I

Ibalizumab (Trogarzo)

Ability to drive, ibalizumab [2] ---> SmPC of [2] of EMA

Dizziness, nausea, fatigue and headache have been reported during treatment with ibalizumab. Patients experiencing these symptoms should be advised to use caution when driving or using machines until symptoms abate.

Breast-feeding, ibalizumab [2] ---> SmPC of [2] of EMA

Consequently, a risk to breast-fed infants cannot be excluded during this short period and ibalizumab should not be used during breast-feeding.

Fertility, ibalizumab [2] ---> SmPC of [2] of EMA

There are no data on the effects of ibalizumab on human fertility.

Ibalizumab [1], pharmacokinetics ---> SmPC of [1] of EMA

Based on the mechanism of action and target-mediated drug disposition of ibalizumab, it is not expected that ibalizumab will have pharmacokinetic drug-drug interactions with other medicinal products.

Ibalizumab [1], pregnancy ---> SmPC of [1] of EMA

Human immunoglobulin (IgG) is known to cross the placental barrier. Ibalizumab is not recommended during pregnancy.

Ibalizumab [1], women of childbearing potential ---> SmPC of [1] of EMA

It is recommended that women of childbearing potential use an effective method of contraception during treatment.

CONTRAINDICATIONS of Ibalizumab (Trogarzo)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/trogarzo-epar-product-information_en.pdf 16/01/2023 (withdrawn)

Ibandronic acid (Ibandronic Acid Sandoz)

Ability to drive, ibandronic acid [2] ---> SmPC of [2] of EMA

On the basis of the pharmacodynamic and pharmacokinetic profile and reported adverse reactions, it is expected that ibandronic acid has no or negligible influence on the ability to drive and use machines.

Absorption of tablets, ibandronic acid [2] ---> SmPC of [2] of EMA

Products containing calcium and other multivalent cations (such as aluminium, magnesium, iron), including milk and food, are likely to interfere with absorption of Ibandronic acid Sandoz tablets.

Acetylsalicylic acid, biphosphonates ---> SmPC of [ibandronic acid] of EMA

Since Acetylsalicylic acid, Nonsteroidal Anti-Inflammatory medicinal products (NSAIDs) and bisphosphonates are associated with gastrointestinal irritation, caution should be taken during concomitant administration

Acetylsalicylic acid, ibandronic acid [2] ---> SmPC of [2] of EMA

Aluminium, ibandronic acid [2] ---> SmPC of [2] of EMA

Possible decreased ibandronic acid absorption. It is recommended to take ibandronic acid at least 30 minutes before taking the other product

Aminoglycoside antibiotics, biphosphonates ---> SmPC of [ibandronic acid] of EMA

Caution is advised when bisphosphonates are administered with aminoglycosides, since both substances can lower serum calcium levels for prolonged periods. Attention should also be paid to the possible existence of simultaneous hypomagnesaemia.

Biphosphonates, NSAID ---> SmPC of [ibandronic acid] of EMA

Breast-feeding, ibandronic acid [2] ---> SmPC of [2] of EMA

Ibandronic acid should not be used during breast-feeding.

Calcium, ibandronic acid [2] ---> SmPC of [2] of EMA

Possible decreased ibandronic acid absorption. It is recommended to take ibandronic acid at least 30 minutes before taking the other product

Cytochrome P450, ibandronic acid [2] ---> SmPC of [2] of EMA

Metabolic interactions are not considered likely, since ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats (see section 5.2).

Fertility, ibandronic acid [2] ---> SmPC of [2] of EMA

In reproductive studies in rats by the oral route, ibandronic acid decreased fertility. In studies in rats using the intravenous route, ibandronic acid decreased fertility at high daily doses (see section 5.3).

Foods, ibandronic acid [2] ---> SmPC of [2] of EMA

It is recommended that the tablets should be taken after an overnight fast (minimum 6 hours) and fasting should continue for at least 30 minutes after the dose has been taken

Gastric pH increasing medication, ibandronic acid [2] ---> SmPC of [2] of EMA

No dosage adjustment is required when ibandronic acid is administered with H2-antagonists or medicinal products that increase gastric pH.

H2 antagonists, ibandronic acid [2] ---> SmPC of [2] of EMA

No dosage adjustment is required when ibandronic acid is administered with H2-antagonists or medicinal products that increase gastric pH.

Ibandronic acid [1], iron ---> SmPC of [1] of EMA

Possible decreased ibandronic acid absorption. It is recommended to take ibandronic acid at least 30 minutes before taking the other product

Ibandronic acid [1], magnesium ---> SmPC of [1] of EMA

Possible decreased ibandronic acid absorption. It is recommended to take ibandronic acid at least 30 minutes before taking the other product

Ibandronic acid [1], metabolic interactions ---> SmPC of [1] of EMA

Ibandronic acid [1], milk ---> SmPC of [1] of EMA

Possible decreased ibandronic acid absorption. It is recommended to take ibandronic acid at least 30 minutes before taking the other product

Ibandronic acid [1], NSAID ---> SmPC of [1] of EMA

Ibandronic acid [1], polyvalent cations ---> SmPC of [1] of EMA

Possible decreased ibandronic acid absorption. It is recommended to take ibandronic acid at least 30 minutes before taking the other product

Ibandronic acid [1], pregnancy ---> SmPC of [1] of EMA

Ibandronic acid should not be used during pregnancy.

Ibandronic acid [1], ranitidine ---> SmPC of [1] of EMA

Intravenous ranitidine causes an increase in ibandronic acid bioavailability. No dosage adjustment is required when is administered with H2-antagonists

CONTRAINDICATIONS of Ibandronic acid (Ibandronic Acid Sandoz)

- Abnormalities of the oesophagus which delay oesophageal emptying such as stricture or achalasia

- Inability to stand or sit upright for at least 60 minutes

- Hypocalcaemia

- Hypersensitivity to ibandronic acid or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/ibandronic-acid-sandoz-epar-product-information_en.pdf 06/07/2022

Other trade names: Abrion, Bondenza, Bondronat, Bonviva, Iasibon, Ibandronic acid Accord, Ibandronic Acid Teva,

Ibritumomab tiuxetan (Zevalin)

Ability to drive, ibritumomab tiuxetan [2] ---> SmPC of [2] of EMA

Zevalin could affect the ability to drive and to use machines, as dizziness has been reported as a common side effect.

Breast-feeding, ibritumomab tiuxetan [2] ---> SmPC of [2] of EMA

Women must discontinue breast-feeding, as the potential for absorption and immunosuppression in the infant is unknown.

Fertility, ibritumomab tiuxetan [2] ---> SmPC of [2] of EMA

Patients should be advised that fertility may be affected and that male patients may wish to consider semen cryopreservation.

Fertility, ibritumomab tiuxetan [2] ---> SmPC of [2] of EMA

There is a potential risk that ionizing radiation by [90Y]-radiolabelled Zevalin could cause toxic effects on female and male gonads (see sections '4.4 and 5.2).

Fludarabine, ibritumomab tiuxetan [2] ---> SmPC of [2] of EMA

The risk of haematological toxicity may be increased when ibritumomab tiuxetan is administered shortly (< 4 months) after fludarabine-containing regimens

Growth factor, ibritumomab tiuxetan [2] ---> SmPC of [2] of EMA

Patients must not receive growth factor treatment for 3 weeks prior and 2 weeks following completion of the treatment with ibritumomab tiuxetan.

Ibritumomab tiuxetan [1], pregnancy ---> SmPC of [1] of EMA

Zevalin is contraindicated during pregnancy. Pregnancy must be excluded before the start of treatment in women.

Ibritumomab tiuxetan [1], vaccinations ---> SmPC of [1] of EMA

A potentially limited ability to generate a primary or anamnestic humoral response to any vaccine following ibritumomab tiuxetan treatment has to be taken into consideration.

Ibritumomab tiuxetan [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Due to the potential risk of developing viral infections it is not recommended to administer live viral vaccines to patients who have recently received ibritumomab tiuxetan.

Ibritumomab tiuxetan [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential as well as males must use effective contraceptive methods during and up to 12 months after treatment with Zevalin.

CONTRAINDICATIONS of Ibritumomab tiuxetan (Zevalin)

- Hypersensitivity to ibritumomab tiuxetan, to yttrium chloride, or to any of the excipients listed in section 6.1.

- Hypersensitivity to rituximab or to other murine-derived proteins

- Pregnancy and lactation

https://www.ema.europa.eu/en/documents/product-information/zevalin-epar-product-information_en.pdf 09/03/2020

Ibrutinib (Imbruvica)

Ability to drive, ibrutinib [2] ---> SmPC of [2] of EMA

Fatigue, dizziness and asthenia have been reported in some patients taking IMBRUVICA and should be considered when assessing a patient's ability to drive or operate machines.

Amiodarone, ibrutinib [2] ---> SmPC of [2] of EMA

If a moderate CYP3A4 inhibitor is indicated, reduce IMBRUVICA dose to 280 mg (two capsules) for the duration of the inhibitor use.

Amprenavir, ibrutinib [2] ---> SmPC of [2] of EMA

If a moderate CYP3A4 inhibitor is indicated, reduce IMBRUVICA dose to 280 mg (two capsules) for the duration of the inhibitor use.

Aprepitant, ibrutinib [2] ---> SmPC of [2] of EMA

If a moderate CYP3A4 inhibitor is indicated, reduce IMBRUVICA dose to 280 mg (two capsules) for the duration of the inhibitor use.

Atazanavir, ibrutinib [2] ---> SmPC of [2] of EMA

If a moderate CYP3A4 inhibitor is indicated, reduce IMBRUVICA dose to 280 mg (two capsules) for the duration of the inhibitor use.

Azithromycin, ibrutinib [2] ---> SmPC of [2] of EMA

The mild CYP3A4 inhibitors azithromycin and fluvoxamine may increase the AUC of ibrutinib by a factor of < 2-fold. No dose adjustment is required in combination with mild inhibitors.

BCRP inhibitors, ibrutinib [2] ---> SmPC of [2] of EMA

As no clinical data are available on this interaction, it cannot be excluded that ibrutinib could inhibit intestinal P-gp and BCRP after a therapeutic dose.

BCRP substrates with narrow therapeutic range, ibrutinib [2] ---> SmPC of [2] of EMA

To minimise the potential for an interaction in the GI tract, oral narrow therapeutic range, P-gp or BCRP substrates such as digoxin or methotrexate should be taken at least 6 hours before or after IMBRUVICA.

Breast-feeding, ibrutinib [2] ---> SmPC of [2] of EMA

It is not known whether ibrutinib or its metabolites are excreted in human milk. A risk to breast-fed children cannot be excluded. Breast-feeding should be discontinued during treatment with IMBRUVICA.

Bupropion, ibrutinib [2] ---> SmPC of [2] of EMA

The exposure to substrates of CYP2B6 (such as efavirenz and bupropion) and of co-regulated enzymes may be reduced upon co-administration with ibrutinib.

Carbamazepine, ibrutinib [2] ---> SmPC of [2] of EMA

Avoid concomitant use of strong or moderate CYP3A4 inducers (e.g., carbamazepine, rifampicin, phenytoin).

Ciprofloxacin, ibrutinib [2] ---> SmPC of [2] of EMA

If a moderate CYP3A4 inhibitor is indicated, reduce IMBRUVICA dose to 280 mg (two capsules) for the duration of the inhibitor use.

Clarithromycin, ibrutinib [2] ---> SmPC of [2] of EMA

Concomitant use of IMBRUVICA and medicinal products that strongly or moderately inhibit CYP3A4 can increase ibrutinib exposure and strong CYP3A4 inhibitors should be avoided.

Cobicistat, ibrutinib [2] ---> SmPC of [2] of EMA

Concomitant use of IMBRUVICA and medicinal products that strongly or moderately inhibit CYP3A4 can increase ibrutinib exposure and strong CYP3A4 inhibitors should be avoided.

Crizotinib, ibrutinib [2] ---> SmPC of [2] of EMA

If a moderate CYP3A4 inhibitor is indicated, reduce IMBRUVICA dose to 280 mg (two capsules) for the duration of the inhibitor use.

Cyclosporine, ibrutinib [2] ---> SmPC of [2] of EMA

Caution should be exercised if co-administering ibrutinib with CYP3A4 substrates administered orally with narrow therapeutic range (such as dihydroergotamine, ergotamine, fentanyl, cyclosporine, sirolimus and tacrolimus).

CYP3A4 inductors, ibrutinib [2] ---> SmPC of [2] of EMA

Mild inducers may be used concomitantly with ibrutinib, however, patients should be monitored for potential lack of efficacy.

CYP3A4 inhibitors, ibrutinib [2] ---> SmPC of [2] of EMA

The mild CYP3A4 inhibitors azithromycin and fluvoxamine may increase the AUC of ibrutinib by a factor of < 2-fold. No dose adjustment is required in combination with mild inhibitors.

Darunavir/ritonavir, ibrutinib [2] ---> SmPC of [2] of EMA

Concomitant use of IMBRUVICA and medicinal products that strongly or moderately inhibit CYP3A4 can increase ibrutinib exposure and strong CYP3A4 inhibitors should be avoided.

Digoxin, ibrutinib [2] ---> SmPC of [2] of EMA

Dihydroergotamine, ibrutinib [2] ---> SmPC of [2] of EMA

Diltiazem, ibrutinib [2] ---> SmPC of [2] of EMA

If a moderate CYP3A4 inhibitor is indicated, reduce IMBRUVICA dose to 280 mg (two capsules) for the duration of the inhibitor use.

Dronedarone, ibrutinib [2] ---> SmPC of [2] of EMA

If a moderate CYP3A4 inhibitor is indicated, reduce IMBRUVICA dose to 280 mg (two capsules) for the duration of the inhibitor use.

Drugs primarily metabolised by CYP2B6, ibrutinib [2] ---> SmPC of [2] of EMA

Based on in vitro data, ibrutinib is a weak CYP2B6 inducer and may have the potential to affect the expression of other enzymes and transporters regulated via the constitutive androstane receptor (CAR), e.g. CYP2C9, CYP2C19, UGT1A1 and MRP2.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, ibrutinib [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP3A4, ibrutinib [2] ---> SmPC of [2] of EMA

There is a risk that ibrutinib may inhibit intestinal CYP3A4 and thereby increasing the exposure of CYP3A4 substrates with a large contribution of intestinal CYP3A4 metabolism to its first pass extraction.

Duvelisib [1], ibrutinib ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Efavirenz, ibrutinib [2] ---> SmPC of [2] of EMA

The exposure to substrates of CYP2B6 (such as efavirenz and bupropion) and of co-regulated enzymes may be reduced upon co-administration with ibrutinib.

Ergotamine, ibrutinib [2] ---> SmPC of [2] of EMA

Erythromycin, ibrutinib [2] ---> SmPC of [2] of EMA

If a moderate CYP3A4 inhibitor is indicated, reduce IMBRUVICA dose to 280 mg (two capsules) for the duration of the inhibitor use.

Fentanyl, ibrutinib [2] ---> SmPC of [2] of EMA

Fertility, ibrutinib [2] ---> SmPC of [2] of EMA

No effects on fertility or reproductive capacities were observed in male or female rats up to the maximum dose tested, 100 mg/kg/day (Human Equivalent Dose [HED] 16 mg/kg/day) (see section 5.3).

Fish oil, ibrutinib [2] ---> SmPC of [2] of EMA

Supplements such as fish oil and vitamin E preparations should be avoided.

Fluconazole, ibrutinib [2] ---> SmPC of [2] of EMA

If a moderate CYP3A4 inhibitor is indicated, reduce IMBRUVICA dose to 280 mg (two capsules) for the duration of the inhibitor use.

Fluvoxamine, ibrutinib [2] ---> SmPC of [2] of EMA

The mild CYP3A4 inhibitors azithromycin and fluvoxamine may increase the AUC of ibrutinib by a factor of < 2-fold. No dose adjustment is required in combination with mild inhibitors.

Fosamprenavir, ibrutinib [2] ---> SmPC of [2] of EMA

If a moderate CYP3A4 inhibitor is indicated, reduce IMBRUVICA dose to 280 mg (two capsules) for the duration of the inhibitor use.

Gastric pH increasing medication, ibrutinib [2] ---> SmPC of [2] of EMA

There is no evidence that the lower Cmax would have clinical significance, and medicinal products that increase stomach pH (e.g., proton pump inhibitors) have been used without restrictions in the pivotal clinical studies.

Grapefruit juice, ibrutinib [2] ---> SmPC of [2] of EMA

Grapefruit and Seville oranges should be avoided during IMBRUVICA treatment, as these contain moderate inhibitors of CYP3A4

Grapefruit, ibrutinib [2] ---> SmPC of [2] of EMA

Grapefruit and Seville oranges should be avoided during IMBRUVICA treatment, as these contain moderate inhibitors of CYP3A4

H2 antagonists, ibrutinib [2] ---> SmPC of [2] of EMA

Ibrutinib [1], imatinib ---> SmPC of [1] of EMA

If a moderate CYP3A4 inhibitor is indicated, reduce IMBRUVICA dose to 280 mg (two capsules) for the duration of the inhibitor use.

Ibrutinib [1], indinavir ---> SmPC of [1] of EMA

Concomitant use of IMBRUVICA and medicinal products that strongly or moderately inhibit CYP3A4 can increase ibrutinib exposure and strong CYP3A4 inhibitors should be avoided.

Ibrutinib [1], itraconazol ---> SmPC of [1] of EMA

Concomitant use of IMBRUVICA and medicinal products that strongly or moderately inhibit CYP3A4 can increase ibrutinib exposure and strong CYP3A4 inhibitors should be avoided.

Ibrutinib [1], ketoconazole ---> SmPC of [1] of EMA

Concomitant use of IMBRUVICA and medicinal products that strongly or moderately inhibit CYP3A4 can increase ibrutinib exposure and strong CYP3A4 inhibitors should be avoided.

Ibrutinib [1], methotrexate ---> SmPC of [1] of EMA

Ibrutinib [1], midazolam ---> SmPC of [1] of EMA

In a drug interaction study in patients with B-cell malignancies, a single 560 mg dose of ibrutinib did not have a clinically meaningful effect on the exposure of the CYP3A4 substrate midazolam.

Ibrutinib [1], moderate CYP3A4 inductors ---> SmPC of [1] of EMA

Ibrutinib is primarily metabolised by cytochrome P450 enzyme 3A4. Administration with inducers of CYP3A4 can decrease ibrutinib plasma concentrations. Avoid concomitant use of moderate CYP3A4 inducers

Ibrutinib [1], moderate CYP3A4 inhibitors ---> SmPC of [1] of EMA

If a moderate CYP3A4 inhibitor is indicated, reduce IMBRUVICA dose to 280 mg (two capsules) for the duration of the inhibitor use.

Ibrutinib [1], nefazodone ---> SmPC of [1] of EMA

Concomitant use of IMBRUVICA and medicinal products that strongly or moderately inhibit CYP3A4 can increase ibrutinib exposure and strong CYP3A4 inhibitors should be avoided.

Ibrutinib [1], nelfinavir ---> SmPC of [1] of EMA

Concomitant use of IMBRUVICA and medicinal products that strongly or moderately inhibit CYP3A4 can increase ibrutinib exposure and strong CYP3A4 inhibitors should be avoided.

Ibrutinib [1], omeprazole ---> SmPC of [1] of EMA

A lower Cmax was observed in fasted healthy subjects administered a single 560 mg dose of ibrutinib after taking omeprazole at 40 mg once daily for 5 days (see section 5.2).

Ibrutinib [1], oral contraceptives ---> SmPC of [1] of EMA

2 weeks of treatment with ibrutinib at 560 mg daily had no clinically relevant effect on the pharmacokinetics of oral contraceptives (ethinylestradiol and levonorgestrel), the CYP3A4 substrate midazolam, nor the CYP2B6

Ibrutinib [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Ibrutinib is a P-gp inhibitor in vitro. As no clinical data are available on this interaction, it cannot be excluded that ibrutinib could inhibit intestinal P-gp after a therapeutic dose.

Ibrutinib [1], P-glycoprotein substrates with small therapeutic index ---> SmPC of [1] of EMA

Ibrutinib [1], P-gp inhibitors ---> SmPC of [1] of EMA

As no clinical data are available on this interaction, it cannot be excluded that ibrutinib could inhibit intestinal P-gp and BCRP after a therapeutic dose.

Ibrutinib [1], phenytoin ---> SmPC of [1] of EMA

Avoid concomitant use of strong or moderate CYP3A4 inducers (e.g., carbamazepine, rifampicin, phenytoin).

Ibrutinib [1], pregnancy ---> SmPC of [1] of EMA

IMBRUVICA should not be used during pregnancy. There are no data from the use of IMBRUVICA in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3).

Ibrutinib [1], proton pump inhibitors ---> SmPC of [1] of EMA

Ibrutinib [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

In a phase 2 study, ECG evaluations showed IMBRUVICA produced a mild decrease in QTcF interval (mean 7.5 ms).

Ibrutinib [1], rifampicin ---> SmPC of [1] of EMA

Avoid concomitant use of strong or moderate CYP3A4 inducers (e.g., carbamazepine, rifampicin, phenytoin).

Ibrutinib [1], rosuvastatin ---> SmPC of [1] of EMA

Ibrutinib may also inhibit BCRP in the liver and increase the exposure of drugs that undergo BCRP-mediated hepatic efflux, such as rosuvastatin.

Ibrutinib [1], saquinavir ---> SmPC of [1] of EMA

Concomitant use of IMBRUVICA and medicinal products that strongly or moderately inhibit CYP3A4 can increase ibrutinib exposure and strong CYP3A4 inhibitors should be avoided.

Ibrutinib [1], Seville orange ---> SmPC of [1] of EMA

Grapefruit and Seville oranges should be avoided during IMBRUVICA treatment, as these contain moderate inhibitors of CYP3A4

Ibrutinib [1], sirolimus ---> SmPC of [1] of EMA

Ibrutinib [1], St. John's wort ---> SmPC of [1] of EMA

Preparations containing St. John's Wort are contraindicated during treatment with ibrutinib, as efficacy may be reduced.

Ibrutinib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Ibrutinib is primarily metabolised by cytochrome P450 enzyme 3A4. Administration with inducers of CYP3A4 can decrease ibrutinib plasma concentrations. Avoid concomitant use of strong CYP3A4 inducers

Ibrutinib [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Concomitant use of IMBRUVICA and medicinal products that strongly or moderately inhibit CYP3A4 can increase ibrutinib exposure and strong CYP3A4 inhibitors should be avoided.

Ibrutinib [1], tacrolimus ---> SmPC of [1] of EMA

Ibrutinib [1], telithromycin ---> SmPC of [1] of EMA

Concomitant use of IMBRUVICA and medicinal products that strongly or moderately inhibit CYP3A4 can increase ibrutinib exposure and strong CYP3A4 inhibitors should be avoided.

Ibrutinib [1], venetoclax ---> SmPC of [1] of EMA

In studies of ibrutinib (420 mg) in combination with venetoclax (400 mg) in CLL patients, an increase in venetoclax exposure (approximately 1.8-fold based on AUC) was observed compared with monotherapy data for venetoclax.

Ibrutinib [1], verapamil ---> SmPC of [1] of EMA

If a moderate CYP3A4 inhibitor is indicated, reduce IMBRUVICA dose to 280 mg (two capsules) for the duration of the inhibitor use.

Ibrutinib [1], vitamin E ---> SmPC of [1] of EMA

Supplements such as fish oil and vitamin E preparations should be avoided.

Ibrutinib [1], vitamin K antagonists ---> SmPC of [1] of EMA

Warfarin or other vitamin K antagonists should not be administered concomitantly with IMBRUVICA.

Ibrutinib [1], voriconazole ---> SmPC of [1] of EMA

Concomitant use of IMBRUVICA and medicinal products that strongly or moderately inhibit CYP3A4 can increase ibrutinib exposure and strong CYP3A4 inhibitors should be avoided.

Ibrutinib [1], warfarin ---> SmPC of [1] of EMA

Warfarin or other vitamin K antagonists should not be administered concomitantly with IMBRUVICA.

Ibrutinib [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of child-bearing potential must use highly effective contraceptive measures while taking IMBRUVICA and for three months after stopping treatment.

Ibrutinib, ketoconazole [2] ---> SmPC of [2] of EMA

Not recommended as it may increase ibrutinib-related toxicity.

Ibrutinib, lefamulin [2] ---> SmPC of [2] of EMA

Lefamulin is a moderate CYP3A inhibitor but has no induction potential. Co-administration of oral lefamulin with agents metabolised by CYP3A may result in increased plasma concentrations of these medicinal products.

Ibrutinib, lopinavir/ritonavir [2] ---> SmPC of [2] of EMA

Co-administration of ibrutinib and Kaletra may increase ibrutinib exposure which may increase the risk of toxicity including risk of tumor lysis syndrome. Co-administration of ibrutinib and Kaletra should be avoided.

Ibrutinib, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Serum concentrations of ibrutinib may be increased due to CYP3A inhibition by ritonavir, resulting in increased risk for toxicity including risk of tumour lysis syndrome. Coadministration of ibrutinib and ritonavir should be avoided.

Ibrutinib, rezafungin [2] ---> SmPC of [2] of EMA

The need for dose adjustments is considered unlikely for tacrolimus, cyclosporine, ibrutinib, mycophenolate mofetil, and venetoclax when administered with rezafungin.

Ibrutinib, ritonavir [2] ---> SmPC of [2] of EMA

Serum concentrations of ibrutinib may be increased due to CYP3A inhibition by ritonavir, resulting in increased risk for toxicity including risk of tumor lysis syndrome. Co-administration of ibrutinib and ritonavir should be avoided.

Ibrutinib, tucatinib [2] ---> SmPC of [2] of EMA

Co-administration of tucatinib with sensitive CYP3A substrates may increase their systemic exposures which may increase the toxicity associated with a CYP3A substrate.

CONTRAINDICATIONS of Ibrutinib (Imbruvica)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Use of preparations containing St. John's Wort is contraindicated in patients treated with IMBRUVICA.

https://www.ema.europa.eu/en/documents/product-information/imbruvica-epar-product-information_en.pdf 27/10/2025

Ibuprofen (Pedea and Algiasdin)

Ability to drive, ibuprofen

Not relevant

Ability to drive, ibuprofen [2] ---> SmPC of [2] of eMC

None expected at recommended doses and duration of therapy.

ACE inhibitors, ibuprofen

The co-administration of ACE inhibitors with long-term NSAIDs may decrease the antihypertensive effect, increase the risk of renal failure and cause hypercaliemia.

Acetylsalicylic acid [1], ibuprofen ---> SmPC of [1] of eMC

Experimental data suggest that ibuprofen may inhibit the effect of low dose acetylsalicylic acid on platelet aggregation when they are dosed concomitantly. Caution should be exercised

AIIRA, ibuprofen

The co-administration may cause a further worsening of renal function. The concomitant use should be done with caution

Aminoglycoside antibiotics, ibuprofen [2] ---> SmPC of [2] of EMA

Ibuprofen may decrease the clearance of aminoglycosides and increase the risk of nephrotoxicity and ototoxicity. Co-administration is not recommended

Aminoglycosides, ibuprofen [2] ---> SmPC of [2] of EMA

Since ibuprofen may decrease the clearance of aminoglycosides, their coadministration may increase the risk of nephrotoxicity and ototoxicity (see section 4.4).

Anticoagulants, ibuprofen [2] ---> SmPC of [2] of EMA

Ibuprofen may increase the effect of anticoagulants and enhance the risk of bleeding.

Antihypertensives, ibuprofen [2] ---> SmPC of [2] of EMA

NSAIDs may reduce the effect of antihypertensive medicinal products.

Atenolol [1], ibuprofen ---> SmPC of [1] of eMC

Concomitant use of prostaglandin synthetase-inhibiting drugs may decrease the hypotensive effects of beta-blockers.

Atenolol/chlortalidone [1], ibuprofen ---> SmPC of [1] of eMC

Concomitant use of prostaglandin synthetase-inhibiting drugs may decrease the hypotensive effects of beta-blockers.

Atenolol/nifedipine [1], ibuprofen ---> SmPC of [1] of eMC

Concomitant use of prostaglandin synthetase-inhibiting drugs, e.g. ibuprofen or indometacin, may decrease the hypotensive effects of beta-blocking drugs.

Bazedoxifene, ibuprofen ---> SmPC of [conjugated oestrogens/bazedoxifene] of EMA

There were no significant pharmacokinetic interactions between bazedoxifene and ibuprofen

Betablockers, ibuprofen ---> SmPC of [atenolol/chlortalidone] of eMC

Concomitant use of prostaglandin synthetase-inhibiting drugs may decrease the hypotensive effects of beta-blockers.

Bilirubin, ibuprofen [2] ---> SmPC of [2] of EMA

Ibuprofen competes with bilirubin for albumin binding in newborn infant serum and, as a consequence, the free fraction of bilirubin may be increased at high ibuprofen concentrations.

Boceprevir [1], ibuprofen ---> SmPC of [1] of EMA

Boceprevir is primarily metabolized by aldo-keto reductase (AKR). In medicine interaction trials conducted with AKR inhibitors, boceprevir exposure did not increase to a clinically significant extent. Boceprevir may be co-administered with AKR inhibitors

Breast-feeding, ibuprofen

Not relevant

Breast-feeding, ibuprofen [2] ---> SmPC of [2] of eMC

In limited studies ibuprofen appears in the breast milk in very low concentrations and is unlikely to affect the breast-fed infant adversely.

Carbamazepine [1], ibuprofen ---> SmPC of [1] of eMC

The plasma concentrations of carbamazepine may be increased

Cardiac glycosides, ibuprofen [2] ---> SmPC of [2] of eMC

NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels.

Cardiac glycosides, tenoxicam ---> SmPC of [ibuprofen] of eMC

NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels when co-administered with cardiac glycosides.

Celiprolol [1], ibuprofen ---> SmPC of [1] of eMC

Drugs inhibiting prostaglandin synthetase may decrease the hypotensive effects of beta-adrenoceptor blocking drugs.

Cholestyramine, ibuprofen

Possible decreased absorption of ibuprofen. Patients should take other drugs at least 1 hour before or 4-6 hours after colestyramine to minimize possible interference with their absorption.

Clopidogrel/acetylsalicylic acid [1], ibuprofen ---> SmPC of [1] of EMA

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly.

Conjugated oestrogens/bazedoxifene [1], ibuprofen ---> SmPC of [1] of EMA

There were no significant pharmacokinetic interactions between bazedoxifene and ibuprofen

Corticosteroids, ibuprofen [2] ---> SmPC of [2] of EMA

Ibuprofen may increase the risk of gastrointestinal bleeding.

Coxibs, ibuprofen [2] ---> SmPC of [2] of eMC

Concomitant use of several NSAIDs should be avoided due to an increased risk of adverse effects, particularly upper gastrointestinal disorders.

Cyclosporine, ibuprofen

The co-administration may increase the risk of nephrotoxicity due to reduced synthesis of renal prostaglandins. Renal function must be closely monitored

CYP2C8 inductors, ibuprofen

The CYP2C8 induction may decrease the ibuprofen effect

CYP2C9 inductors, ibuprofen

The CYP2C9 induction may decrease the ibuprofen effect

Dasabuvir with ombitasvir/paritaprevir/ritonavir, ibuprofen ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

Ombitasvir/paritaprevir/ritonavir administered with or without dasabuvir did not affect the exposures of the CYP2C9 substrate, warfarin. Other CYP2C9 substrates are not expected to require dose adjustments.

Dextromethorphan, ibuprofen

Concomitant use may cause a serotoninergic syndrome. Concomitant use should be avoided within 14 day after taking ibuprofen

Diuretics, ibuprofen [2] ---> SmPC of [2] of EMA

Ibuprofen may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients.

Fluconazole [1], ibuprofen ---> SmPC of [1] of eMC

The Cmax and AUC of the pharmacologically active isomer [S (+)ibuprofen] was increased by 15%% and 82%, respectively, when fluconazole was coadministered with racemic ibuprofen (400 mg) compared to administration of racemic ibuprofen alone.

Foods, ibuprofen

The co-administration of ibuprofen with foods decreases the absorption rate

Fossil tree, ibuprofen

Ginkgo biloba with NSAID may increase the risk of bleeding

Fossil tree, NSAID ---> SmPC of [ibuprofen] of eMC

Ginkgo biloba with NSAID may increase the risk of bleeding

Gadofosveset [1], ibuprofen ---> SmPC of [1] of EMA

Gadofosveset demonstrated no adverse interaction at clinically relevant concentrations.

Ibuprofen [1], lithium ---> SmPC of [1] of eMC

Increased lithium concentrations

Ibuprofen [1], methotrexate ---> SmPC of [1] of eMC

NSAIDs should not be administered prior to, or concomitantly with, high dose methotrexate as fatal methotrexate toxicity has been reported.

Ibuprofen [1], mifepristone ---> SmPC of [1] of eMC

NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effects of mifepristone.

Ibuprofen [1], nitric oxide ---> SmPC of [1] of EMA

Since both medicinal products inhibit platelet function, their combination may in theory increase the risk of bleeding.

Ibuprofen [1], NSAID ---> SmPC of [1] of EMA

The concomitant use of more than one NSAID should be avoided because of the increased risk of adverse reactions. Diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients.

Ibuprofen [1], pregnancy ---> SmPC of [1] of EMA

Not relevant

Ibuprofen [1], pregnancy ---> SmPC of [1] of eMC

Use of ibuprofen should, if possible, be avoided during the first 6 months of pregnancy. During the 3rd trimester, ibuprofen is contraindicated,

Ibuprofen [1], quinolones ---> SmPC of [1] of eMC

Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

Ibuprofen, leflunomide [2] ---> SmPC of [2] of EMA

A771726 displaced ibuprofen from its plasma protein binding, but the unbound fraction is only increased by 10% to 50%. There is no indication that these effects are of clinical relevance.

Ibuprofen, lumacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

A higher dose of ibuprofen may be required to obtain the desired clinical effect. Lumacaftor/ivacaftor may decrease the exposure of ibuprofen, which may reduce its efficacy.

Ibuprofen, magnesium hydroxide

The co-administration may increase the absorption rate of ibuprofen

Ibuprofen, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Ibuprofen, pemetrexed [2] ---> SmPC of [2] of EMA

Caution should be made when administering higher doses of NSAIDs or aspirin, concurrently with pemetrexed to patients with normal function (creatinine clearance ≥ 80 ml/min).

Ibuprofen, pentoxifylline

The co-administration may increase the risk of bleeding. Increase clinical monitoring and check bleeding time more often

Ibuprofen, phenobarbital

The CYP2C8 induction may decrease the ibuprofen effect

Ibuprofen, phenytoin

Ibuprofen may increase phenytoin serum levels and toxicity. Phenytoin, CYP2C8 inductor, may decrease the ibuprofen effect

Ibuprofen, platelet aggregation inhibitors

Increased risk of gastrointestinal bleeding

Ibuprofen, potassium-sparing diuretics ---> SmPC of [amiloride/hydrochlorothiazide] of eMC

Concomitant administration of NSAIDs and potassium-sparing agents may cause hyperkalemia

Ibuprofen, probenecide

The co-administration may delay the elimination of ibuprofen and increase its plasma levels, effects and adverse reactions

Ibuprofen, proteolytic enzymes enriched in bromelain [2] ---> SmPC of [2] of EMA

NexoBrid, when absorbed, is an inhibitor of CYP2C8 and CYP2C9. This should be taken into account if it is used in patients receiving CYP2C9 substrates

Ibuprofen, rifampicin

The CYP2C9 induction may decrease the ibuprofen effect

Ibuprofen, sodium oxybate [2] ---> SmPC of [2] of EMA

Drug interaction studies in healthy adults demonstrated no pharmacokinetic interactions between sodium oxybate and ibuprofen.

Ibuprofen, SSRI

Increased risk of gastrointestinal bleeding

Ibuprofen, strong CYP2C8 inductors

The strong CYP2C8 induction may decrease the ibuprofen effect

Ibuprofen, strong CYP2C9 inhibitors

The potent CYP2C9 inhibition may increase the plasma concentrations of ibuprofen

Ibuprofen, sulfinpyrazone

Sulfinpyrazone may delay the elimination of ibuprofen

Ibuprofen, sulfonylureas

NSAIDs can increase the hypoglycaemic effect of sulfonylureas by displacement from plasma protein binding sites. Caution is recommended

Ibuprofen, sultiame

The co-administration may increase the plasma levels of ibuprofen. Adjustment of the dose may be required

Ibuprofen, tacrolimus [2] ---> SmPC of [2] of EMA

Products known to have nephrotoxic or neurotoxic effects: May enhance nephrotoxic or neurotoxic effects of tacrolimus. Concurrent use of tacrolimus with drugs known to have nephrotoxic effects should be avoided.

Ibuprofen, thiazides

Ibuprofen may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated. Co-administration is not recommended

Ibuprofen, thrombolytics

Increased bleeding risk

Ibuprofen, ticlopidine [2] ---> SmPC of [2] of eMC

It is considered unsafe to take NSAIDs in combination with platelet aggregation inhibitors due to increased risk of bleeding. If coadministration is unavoidable, patient should be closely monitored.

Ibuprofen, treosulfan [2] ---> SmPC of [2] of eMC

In one patient the effect of ibuprofen/chloroquine was reduced with concomitant administration of treosulfan.

Ibuprofen, trimethoprim

The potent CYP2C9 inhibition may increase the plasma concentrations of trimethoprim

Ibuprofen, ustekinumab [2] ---> SmPC of [2] of EMA

The effect of the most frequently used concomitant medicinal products in patients with psoriasis on pharmacokinetics of ustekinumab was explored. There were no indications of an interaction with these concomitantly administered medicinal products.

Ibuprofen, voriconazole [2] ---> SmPC of [2] of EMA

Frequent monitoring for adverse reactions and toxicity related to NSAIDs is recommended. Dose reduction of NSAIDs may be needed.

Ibuprofen, warfarin

Possible increase of plasma concentration and anticoagulant effect of warfarin due to displacement from plasma proteins

Ibuprofen, zidovudine ---> SmPC of [flurbiprofen] of eMC

Increased risk of haematological toxicity when NSAIDs are given with zidovudine

Mifepristone, NSAID ---> SmPC of [ibuprofen] of eMC

NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effects of mifepristone.

Naproxen, quinolones ---> SmPC of [ibuprofen] of eMC

Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking quinolones may have an increased risk of developing convulsions.

Other trade names: Algiasdin, Apirofeno, Aragel, Articalm, Azodermol, Buscafem, Dalsy, Dermilevol, Diltix, Dolencar, Doltra, Espididol, Espidifen, Eudorlin, Febrirol, Gelobufen, Iblasin, Ibudol, Ibufarmalid, Ibufen, Ibukern, Ibukey, Ibumac, Ibupirac, Ibustick, Junifen, Jun

Pedea:

- Hypersensitivity to the active substance or to any of the excipients;

- Life-threatening infection;

- Active bleeding, especially intracranial or gastrointestinal haemorrhage;

- Thrombocytopenia or coagulation defects;

- Significant impairment of renal function;

- Congenital heart disease in which patency of the ductus arteriosus is necessary for satisfactory pulmonary or systemic blood flow (e.g. pulmonary atresia, severe tetralogy of Fallot, severe coarctation of the aorta);

- Known or suspected necrotising enterocolitis;

https://www.ema.europa.eu/en/documents/product-information/pedea-epar-product-information_en.pdf 21/05/2025

--------------

- Hypersensitivity to ibuprofen or any of the constituents in the product.

- Ibuprofen is contra-indicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to aspirin or other non-steroidal anti-inflammatory drugs.

- Active or previous peptic ulcer (two or more episodes of proven ulceration or bleeding).

- History of upper gastrointestinal bleeding or perforation, related to previous NSAID therapy.

- Patients with severe hepatic failure, renal failure or heart failure

- Use in last trimester of pregnancy

http://www.medicines.org.uk/emc/medicine/15681/SPC/Anadin+Ibuprofen+200mg+Tablets/. Stand of information: 15/11/2012. Access date: 04/07/2014

Icatibant (Firazyr)

Ability to drive, icatibant [2] ---> SmPC of [2] of EMA

Fatigue, lethargy, tiredness, somnolence, and dizziness have been reported following the use of Firazyr. These symptoms may occur as a result of an attack of HAE.

ACE inhibitors, icatibant [2] ---> SmPC of [2] of EMA

ACE inhibitors are contraindicated in hereditary angioedema patients due to possible enhancement of bradykinin levels.

Breast-feeding, icatibant [2] ---> SmPC of [2] of EMA

It is recommended that breastfeeding women, who wish to take Firazyr, should not breastfeed for 12 hours after treatment.

CYP450, icatibant [2] ---> SmPC of [2] of EMA

Pharmacokinetic drug interactions involving CYP450 are not expected

Fertility, icatibant [2] ---> SmPC of [2] of EMA

There were no significant effects of icatibant on the concentration of luteal phase progesterone and luteal function, or on menstrual cycle length in females

Icatibant [1], men ---> SmPC of [1] of EMA

There were no significant effects of icatibant on sperm count, motility and morphology in males.

Icatibant [1], pregnancy ---> SmPC of [1] of EMA

Firazyr should be used during pregnancy only, if the potential benefit justifies the potential risk for the foetus, (e.g for treatment of potentially life threatening laryngeal attacks).

CONTRAINDICATIONS of Icatibant (Firazyr)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/firazyr-epar-product-information_en.pdf 15/10/2025

Other trade names: Icatibant Accord,

Icosapent ethyl (Vazkepa)

Ability to drive, icosapent ethyl [2] ---> SmPC of [2] of EMA

On the basis of its pharmacodynamic profile and clinical study adverse reaction data, icosapent ethyl is expected to have no or negligible influence on the ability to drive and use machines.

Acetylsalicylic acid, icosapent ethyl [2] ---> SmPC of [2] of EMA

Patients taking icosapent ethyl along with antithrombotic agents, i.e., antiplatelet agents, including acetylsalicylic acid, and/or anticoagulants, may be at increased risk of bleeding and should be monitored periodically

Anticoagulants, icosapent ethyl [2] ---> SmPC of [2] of EMA

Antiplatelet therapy, icosapent ethyl [2] ---> SmPC of [2] of EMA

Antithrombotics, icosapent ethyl [2] ---> SmPC of [2] of EMA

Atorvastatin, icosapent ethyl [2] ---> SmPC of [2] of EMA

No interactions were observed.

Breast-feeding, icosapent ethyl [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from icosapent ethyl therapy considering the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility, icosapent ethyl [2] ---> SmPC of [2] of EMA

There are no data on fertility in humans from the use of icosapent ethyl. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

Foods, icosapent ethyl [2] ---> SmPC of [2] of EMA

Icosapent ethyl was administered with or following a meal in all clinical studies; no food effect studies were performed (see section 4.2).

Icosapent ethyl [1], omeprazole ---> SmPC of [1] of EMA

No interactions were observed.

Icosapent ethyl [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of icosapent ethyl during pregnancy unless the benefit of use outweighs the potential risk to the foetus.

Icosapent ethyl [1], rosiglitazone ---> SmPC of [1] of EMA

No interactions were observed.

Icosapent ethyl [1], warfarin ---> SmPC of [1] of EMA

No interactions were observed.

CONTRAINDICATIONS of Icosapent ethyl (Vazkepa)

- Hypersensitivity to the active substance, soya or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/vazkepa-epar-product-information_en.pdf 01/08/2024

Idarubicin

Ability to drive, idarubicin [2] ---> SmPC of [2] of eMC

The effect of idarubicin on the ability to drive or use machinery has not been systematically evaluated.

Alcohol, idarubicin

Alcohol may enhance the adverse reactions

Breast-feeding, idarubicin [2] ---> SmPC of [2] of eMC

Mothers should not breast-feed during treatment with idarubicin hydrochloride.

Calcium antagonists, idarubicin [2] ---> SmPC of [2] of eMC

The use of idarubicin in combination chemotherapy with other cardioactive compounds requires monitoring of cardiac function throughout treatment.

Cardioactive drugs, idarubicin [2] ---> SmPC of [2] of eMC

The use of idarubicin in combination chemotherapy with other cardioactive compounds requires monitoring of cardiac function throughout treatment.

Cyclosporine, idarubicin [2] ---> SmPC of [2] of eMC

The coadministration of cyclosporine A as a single chemosensitizer significantly increased idarubicin AUC (1.78-fold) and idarubicinol AUC (2.46-fold) in patients with acute leukaemia.

Fosphenytoin, idarubicin

Decreased phenytoin absorption (worsening of seizures) and increased toxicity or loss of efficacy loss of idarubicin due to metabolic induction

Idarubicin [1], medicines with cardiotoxic effects ---> SmPC of [1] of eMC

Anthracyclines including idarubicin should not be administered in combination with other cardiotoxic agents unless the patient's cardiac function is closely monitored.

Idarubicin [1], myelosuppressive agents ---> SmPC of [1] of eMC

Idarubicin is a potent myelosuppressant and combination chemotherapy regimens including other agents with similar action may be expected to induce additive myelosuppressant effects

Idarubicin [1], oral anticoagulants ---> SmPC of [1] of eMC

At combination of oral anticoagulants and anticancer chemotherapy, increased frequency of the INR (International Normalised Ratio) monitoring is recommended, since the risk for an interaction cannot be excluded.

Idarubicin [1], potentially cardiotoxic drugs ---> SmPC of [1] of eMC

The use of idarubicin in combination chemotherapy with other potentially cardiotoxic drugs requires monitoring of cardiac function throughout treatment.

Idarubicin [1], pregnancy ---> SmPC of [1] of eMC

Idarubicin should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Idarubicin [1], radiotherapy ---> SmPC of [1] of eMC

An additive myelosuppressant effect may occur when radiotherapy is given concomitantly or within 2-3 weeks prior to treatment with idarubicin.

Idarubicin [1], trastuzumab ---> SmPC of [1] of eMC

Trastuzumab may increase the cardiotoxicity of anthracycline. Physicians should avoid anthracycline-based therapy for up to 24 weeks after stopping trastuzumab

Idarubicin [1], vaccinations with live organism vaccines ---> SmPC of [1] of eMC

Concomitant use of live attenuated vaccines (e.g. yellow fever) is not recommended, due to a risk of possibly fatal systemic disease.

Idarubicin, phenytoin

Decreased phenytoin absorption (worsening of seizures) and increased toxicity or loss of efficacy loss of idarubicin due to metabolic induction

Idarubicin, tacrolimus

The co-administration may cause an excessive immunosuppression with risk of lymphoproliferation

Idarubicin, yellow fever vaccine

Concomitant use of idarubicin with yellow fever vaccine is contraindicated

Mitoxantrone, trastuzumab

Trastuzumab may increase the cardiotoxicity of anthracycline. Physicians should avoid anthracycline-based therapy for up to 24 weeks after stopping trastuzumab

Pixantrone, trastuzumab

Trastuzumab may increase the cardiotoxicity of anthracycline. Physicians should avoid anthracycline-based therapy for up to 24 weeks after stopping trastuzumab

CONTRAINDICATIONS of Idarubicin

- hypersensitivity to idarubicin or any other component of the product, other anthracyclines or anthracenediones

- severe hepatic impairment

- severe renal impairment

- uncontrolled infections

- severe cardiomyopathy

- recent myocardial infarction

- severe arrhythmias

- persistent myelosuppression

- previous treatment with maximum cumulative doses of idarubicin and/or other anthracyclines and anthracenediones

- breast-feeding should be stopped during drug therapy

http://www.medicines.org.uk/emc/

Idarucizumab (Praxbind)

Anticoagulants, idarucizumab [2] ---> SmPC of [2] of EMA

Preclinical investigations with idarucizumab have shown no interactions with coagulation other anticoagulants. Thus idarucizumab will not reverse the effects of other anticoagulants.

Breast-feeding, idarucizumab [2] ---> SmPC of [2] of EMA

It is unknown whether idarucizumab/metabolites are excreted in human milk.

Coagulation factors, idarucizumab [2] ---> SmPC of [2] of EMA

Preclinical investigations with idarucizumab have shown no interactions with coagulation factor concentrates, such as prothrombin complex concentrates, activated PCCs (aPCCs) and recombinant factor VIIa.

Dabigatran, idarucizumab [2] ---> SmPC of [2] of EMA

Based on the pharmacokinetic properties and the high specificity in binding to dabigatran, clinically relevant interactions with other medicinal products are considered unlikely.

Fertility, idarucizumab [2] ---> SmPC of [2] of EMA

There are no data on the effect of idarucizumab on fertility (see section 5.3).

Idarucizumab [1], pregnancy ---> SmPC of [1] of EMA

Praxbind may be used during pregnancy, if the expected clinical benefit outweighs the potential risks.

Idarucizumab [1], volume expander ---> SmPC of [1] of EMA

Preclinical investigations with idarucizumab have shown no interactions with volume expanders.

CONTRAINDICATIONS of Idarucizumab (Praxbind)

None.

https://www.ema.europa.eu/en/documents/product-information/praxbind-epar-product-information_en.pdf 21/11/2024

Idebenone (Raxone)

Alfentanyl, idebenone [2] ---> SmPC of [2] of EMA

CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving idebenone.

Aliskiren, idebenone [2] ---> SmPC of [2] of EMA

Idebenone may inhibit P-glycoprotein (p-gp) with possible exposure increases of e.g. dabigatran etexilate, digoxin or aliskiren. Idebenone is not a substrate for p-gp in vitro.

Astemizole, idebenone [2] ---> SmPC of [2] of EMA

CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving idebenone.

Breast-feeding, idebenone [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the mother.

Cisapride, idebenone [2] ---> SmPC of [2] of EMA

CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving idebenone.

Cyclosporine, idebenone [2] ---> SmPC of [2] of EMA

CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving idebenone.

Dabigatran etexilate, idebenone [2] ---> SmPC of [2] of EMA

Idebenone may inhibit P-glycoprotein (p-gp) with possible exposure increases of e.g. dabigatran etexilate, digoxin or aliskiren. Idebenone is not a substrate for p-gp in vitro.

Digoxin, idebenone [2] ---> SmPC of [2] of EMA

Idebenone may inhibit P-glycoprotein (p-gp) with possible exposure increases of e.g. dabigatran etexilate, digoxin or aliskiren. Idebenone is not a substrate for p-gp in vitro.

Dihydroergotamine, idebenone [2] ---> SmPC of [2] of EMA

CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving idebenone.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, idebenone [2] ---> SmPC of [2] of EMA

CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving idebenone.

Ergot derivatives, idebenone [2] ---> SmPC of [2] of EMA

CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving idebenone.

Ergotamine, idebenone [2] ---> SmPC of [2] of EMA

CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving idebenone.

Fentanyl, idebenone [2] ---> SmPC of [2] of EMA

CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving idebenone.

Foods, idebenone [2] ---> SmPC of [2] of EMA

Food increases the bioavailability of idebenone by approximately 5-7-fold and therefore, Raxone should always be administered with food. The tablets should not be broken or chewed.

Idebenone [1], midazolam ---> SmPC of [1] of EMA

After repeated administration Cmax and AUC of midazolam were increased by 28% and 34%, respectively, when midazolam was administered in combination with 300 mg idebenone t.i.d.

Idebenone [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Idebenone may inhibit P-glycoprotein (p-gp) with possible exposure increases of e.g. dabigatran etexilate, digoxin or aliskiren. Idebenone is not a substrate for p-gp in vitro.

Idebenone [1], pimozide ---> SmPC of [1] of EMA

CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving idebenone.

Idebenone [1], pregnancy ---> SmPC of [1] of EMA

Idebenone should only be administered to pregnant women or women of child-bearing age likely to become pregnant if it is considered that the benefit of the therapeutic effect outweighs any potential risk.

Idebenone [1], quinidine ---> SmPC of [1] of EMA

CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving idebenone.

Idebenone [1], sirolimus ---> SmPC of [1] of EMA

CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving idebenone.

Idebenone [1], tacrolimus ---> SmPC of [1] of EMA

CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving idebenone.

Idebenone [1], terfenadine ---> SmPC of [1] of EMA

CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving idebenone.

CONTRAINDICATIONS of Idebenone (Raxone)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/raxone-epar-product-information_en.pdf 20/08/2025

Idecabtagene vicleucel (Abecma)

Ability to drive, idecabtagene vicleucel [2] ---> SmPC of [2] of EMA

Patients receiving Abecma should refrain from driving or operating heavy or potentially dangerous machines for at least 8 weeks after Abecma infusion or until resolution of neurologic adverse reactions.

Breast-feeding, idecabtagene vicleucel [2] ---> SmPC of [2] of EMA

A risk to the breast-fed infant cannot be excluded. Women who are breast-feeding should be advised of the potential risk to the breast-fed child.

Corticosteroids, idecabtagene vicleucel [2] ---> SmPC of [2] of EMA

Prophylactic use of systemic corticosteroids should be avoided as the use may interfere with the activity of Abecma.

Cyclophosphamide, idecabtagene vicleucel [2] ---> SmPC of [2] of EMA

See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive the lymphodepleting chemotherapy.

Duration of contraception, idecabtagene vicleucel [2] ---> SmPC of [2] of EMA

There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with Abecma.

Fertility, idecabtagene vicleucel [2] ---> SmPC of [2] of EMA

There are no data on the effect of idecabtagene vicleucel on fertility. Effects of idecabtagene vicleucel on male and female fertility have not been evaluated in animal studies.

Fludarabine, idecabtagene vicleucel [2] ---> SmPC of [2] of EMA

See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive the lymphodepleting chemotherapy.

Idecabtagene vicleucel [1], lymphocytes ---> SmPC of [1] of EMA

The co-administration of agents known to inhibit T cell function has not been formally studied. The co-administration of agents known to stimulate T cell function has not been investigated and the effects are unknown.

Idecabtagene vicleucel [1], lymphodepleting chemotherapy ---> SmPC of [1] of EMA

See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive the lymphodepleting chemotherapy.

Idecabtagene vicleucel [1], pregnancy ---> SmPC of [1] of EMA

Abecma is not recommended for women who are pregnant or for women of childbearing potential not using contraception. Pregnant women should be advised on the potential risks to the foetus.

Idecabtagene vicleucel [1], tocilizumab ---> SmPC of [1] of EMA

Some patients required tocilizumab or siltuximab and/or corticosteroid for the management of CRS (see section 4.8). The use of tocilizumab or siltuximab and/or corticosteroids for CRS management was more common in patients with higher cellular expansion.

Idecabtagene vicleucel [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Abecma treatment and until immune recovery following treatment with Abecma.

Idecabtagene vicleucel [1], women of childbearing potential ---> SmPC of [1] of EMA

Pregnancy status for women of childbearing potential should be verified using a pregnancy test prior to starting treatment with Abecma.

CONTRAINDICATIONS of Idecabtagene vicleucel (Abecma)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Contraindications of the lymphodepleting chemotherapy must be considered.

https://www.ema.europa.eu/en/documents/product-information/abecma-epar-product-information_en.pdf 04/09/2024

Idelalisib (Zydelig)

Alfentanyl, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with alfentanyl may increase the serum concentrations of alfentanyl. Careful monitoring of adverse reactions (e.g., respiratory depression, sedation) is recommended.

Alfuzosin, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with alfuzosin may increase the serum concentrations of alfuzosin. Idelalisib should not be co-administered with alfuzosin.

Amiodarone, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with amiodarone may increase the serum concentrations of amiodarone. Idelalisib should not be co-administered with amiodarone.

Amlodipine, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with amlodipine may increase the serum concentrations of amlodipine. Clinical monitoring of therapeutic effect and adverse reactions is recommended.

Atorvastatin, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with atorvastatin may increase the serum concentrations of atorvastatin. Clinical monitoring is recommended and a lower starting dose of atorvastatin may be considered.

Bepridil, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with bepridil may increase the serum concentrations of bepridil. Clinical monitoring is recommended.

Boceprevir, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with boceprevir may increase the serum concentrations of boceprevir. Clinical monitoring is recommended.

Bosentan, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with bosentan may increase the serum concentrations of bosentan. Caution should be exercised and patients closely observed for bosentan-related toxicity.

Breast-feeding, idelalisib [2] ---> SmPC of [2] of EMA

Breast-feeding should be discontinued during treatment with Zydelig.

Budesonide, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with budesonide may increase the serum concentrations of budesonide. Clinical monitoring is recommended (inhaled) for increased signs/symptoms of corticosteroid effects (oral).

Buprenorphine/naloxone, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with buprenorphine/naloxone may increase the serum concentrations of buprenorphine/naloxone. Careful monitoring of adverse reactions (e.g., respiratory depression, sedation) is recommended.

Buspirone, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with buspirone may increase the serum concentrations of buspirone. Concentration monitoring of buspirone is recommended and dose reduction may be considered.

Capivasertib [1], idelalisib ---> SmPC of [1] of EMA

Co-administration of TRUQAP with strong CYP3A4 inhibitors increases capivasertib concentration, which may increase the risk of TRUQAP toxicity. Co-administration with strong CYP3A4 inhibitors should be avoided

Carbamazepine, idelalisib [2] ---> SmPC of [2] of EMA

Co-administration of Zydelig with moderate or strong CYP3A inducers such as rifampicin, phenytoin, St. John's wort, or carbamazepine should be avoided as this may result in decreased efficacy (see section 4.4).

Cisapride, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with cisapride may increase the serum concentrations of cisapride. Idelalisib should not be co-administered with cisapride.

Clarithromycin, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with clarithromycin may increase the serum concentrations of clarithromycin. No dose adjustment of clarithromycin is required for patients with normal renal function or mild renal impairment

Colchicine, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with colchicine may increase the serum concentrations of colchicine. Dose reductions of colchicine may be required. Idelalisib should not be co-administered with colchicine to patients with renal or hepatic impairment.

Cyclosporine, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with cyclosporine may increase the serum concentrations of cyclosporine. Therapeutic monitoring is recommended.

CYP2C8 substrates with narrow therapeutic index, idelalisib [2] ---> SmPC of [2] of EMA

Caution is advised if idelalisib is used together with narrow therapeutic index drugs that are substrates of CYP2C8

CYP3A4 inhibitors, idelalisib [2] ---> SmPC of [2] of EMA

No initial dose adjustment of idelalisib is considered necessary when administered with CYP3A/P-gp inhibitors, but an intensified monitoring of adverse reactions is recommended.

Dabigatran etexilate, idelalisib [2] ---> SmPC of [2] of EMA

A risk for P-gp inhibition in the gastrointestinal tract, that could result in increased exposure of sensitive substrates for intestinal P-gp such as dabigatran etexilate, cannot be excluded.

Dasatinib, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with dasatinib may increase the serum concentrations of dasatinib. Careful monitoring of the tolerance to these anti-cancer agents is recommended.

Diazepam, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with diazepam may increase the serum concentrations of diazepam. Concentration monitoring of diazepam is recommended and dose reduction may be considered.

Dihydroergotamine, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with dihydroergotamine may increase the serum concentrations of dihydroergotamine. Idelalisib should not be co-administered with dihydroergotamine.

Diltiazem, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with diltiazem may increase the serum concentrations of diltiazem. Clinical monitoring of therapeutic effect and adverse reactions is recommended.

Dipotassium clorazepate, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with clorazepate may increase the serum concentrations of clorazepate. Concentration monitoring of clorazepate is recommended and dose reduction may be considered.

Disopyramide, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with disopyramide may increase the serum concentrations of disopyramide. Clinical monitoring is recommended.

Drugs metabolised by CYP3A4, idelalisib [2] ---> SmPC of [2] of EMA

Co-administration of idelalisib with CYP3A substrates may increase their systemic exposures and increase or prolong their therapeutic activity and adverse reactions.

Drugs primarily metabolised by CYP3A4, idelalisib [2] ---> SmPC of [2] of EMA

Co-administration of idelalisib with CYP3A substrates may increase their systemic exposures and increase or prolong their therapeutic activity and adverse reactions.

Ergotamine, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with ergotamine may increase the serum concentrations of ergotamine. Idelalisib should not be co-administered with ergotamine.

Estazolam, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with estazolam may increase the serum concentrations of estazolam. Concentration monitoring of estazolam is recommended and dose reduction may be considered.

Felodipine, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with felodipine may increase the serum concentrations of felodipine. Clinical monitoring of therapeutic effect and adverse reactions is recommended.

Fentanyl, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with fentanyl may increase the serum concentrations of fentanyl. Careful monitoring of adverse reactions (e.g., respiratory depression, sedation) is recommended.

Fertility, idelalisib [2] ---> SmPC of [2] of EMA

No human data on the effect of idelalisib on fertility are available. Animal studies indicate the potential for harmful effects of idelalisib on fertility and foetal development (see section 5.3).

Flurazepam, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with flurazepam may increase the serum concentrations of flurazepam. Concentration monitoring of flurazepam is recommended and dose reduction may be considered.

Fluticasone, idelalisib [2] ---> SmPC of [2] of EMA

The co-administration of idelalisib with fluticasone may increase the serum concentrations of fluticasone. Clinical monitoring is recommended.

Fostamatinib [1], idelalisib ---> SmPC of [1] of EMA

Concomitant use of fostamatinib with strong CYP3A4 inhibitors increases exposure to R406 (the major active metabolite), which may increase the risk of adverse reactions.

Hormonal contraceptives, idelalisib [2] ---> SmPC of [2] of EMA

Women using hormonal contraceptives should add a barrier method as a second form of contraception since it is currently unknown whether idelalisib may reduce the effectiveness of hormonal contraceptives.

Idelalisib [1], itraconazol ---> SmPC of [1] of EMA

The co-administration of idelalisib with itraconazol may increase the serum concentrations of itraconazol. Clinical monitoring is recommended.

Idelalisib [1], ketoconazole ---> SmPC of [1] of EMA

No initial dose adjustment of idelalisib is considered necessary when administered with CYP3A/P-gp inhibitors, but an intensified monitoring of adverse reactions is recommended.

Idelalisib [1], lidocaine ---> SmPC of [1] of EMA

The co-administration of idelalisib with lidocaine may increase the serum concentrations of lidocaine. Clinical monitoring is recommended.

Idelalisib [1], lovastatine ---> SmPC of [1] of EMA

The co-administration of idelalisib with lovastatine may increase the serum concentrations of lovastatine. Idelalisib should not be co-administered with lovastatine.

Idelalisib [1], methadone ---> SmPC of [1] of EMA

The co-administration of idelalisib with methadone may increase the serum concentrations of methadone. Careful monitoring of adverse reactions (e.g., respiratory depression, sedation) is recommended.

Idelalisib [1], midazolam ---> SmPC of [1] of EMA

The co-administration of idelalisib with midazolam may increase the serum concentrations of midazolam. Idelalisib should not be co-administered with midazolam (oral)

Idelalisib [1], moderate CYP3A4 inductors ---> SmPC of [1] of EMA

Idelalisib [1], nicardipine ---> SmPC of [1] of EMA

The co-administration of idelalisib with nicardipine may increase the serum concentrations of nicardipine. Clinical monitoring of therapeutic effect and adverse reactions is recommended.

Idelalisib [1], nifedipine ---> SmPC of [1] of EMA

The co-administration of idelalisib with nifedipine may increase the serum concentrations of nifedipine. Clinical monitoring of therapeutic effect and adverse reactions is recommended.

Idelalisib [1], nilotinib ---> SmPC of [1] of EMA

The co-administration of idelalisib with nilotinib may increase the serum concentrations of nilotinib. Careful monitoring of the tolerance to these anti-cancer agents is recommended.

Idelalisib [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

A risk for P-gp inhibition in the gastrointestinal tract, that could result in increased exposure of sensitive substrates for intestinal P-gp such as dabigatran etexilate, cannot be excluded.

Idelalisib [1], P-gp inhibitors ---> SmPC of [1] of EMA

No initial dose adjustment of idelalisib is considered necessary when administered with CYP3A/P-gp inhibitors, but an intensified monitoring of adverse reactions is recommended.

Idelalisib [1], paclitaxel ---> SmPC of [1] of EMA

Caution is advised if idelalisib is used together with narrow therapeutic index drugs that are substrates of CYP2C8

Idelalisib [1], phenytoin ---> SmPC of [1] of EMA

Idelalisib [1], pimozide ---> SmPC of [1] of EMA

The co-administration of idelalisib with pimozide may increase the serum concentrations of pimozide. Idelalisib should not be co-administered with pimozide.

Idelalisib [1], posaconazole ---> SmPC of [1] of EMA

The co-administration of idelalisib with posaconazole may increase the serum concentrations of posaconazole. Clinical monitoring is recommended.

Idelalisib [1], pregnancy ---> SmPC of [1] of EMA

Zydelig is not recommended during pregnancy and in women of childbearing potential not using contraception.

Idelalisib [1], quetiapine ---> SmPC of [1] of EMA

The co-administration of idelalisib with quetiapine may increase the serum concentrations of quetiapine. Idelalisib should not be co-administered with quetiapine.

Idelalisib [1], quinidine ---> SmPC of [1] of EMA

The co-administration of idelalisib with quinidine may increase the serum concentrations of quinidine. Idelalisib should not be co-administered with quinidine.

Idelalisib [1], rifabutin ---> SmPC of [1] of EMA

The co-administration of idelalisib with rifabutin may increase the serum concentrations of rifabutin. Increased monitoring for rifabutin-associated adverse reactions including neutropenia and uveitis is recommended.

Idelalisib [1], rifampicin ---> SmPC of [1] of EMA

Idelalisib [1], salmeterol ---> SmPC of [1] of EMA

Concurrent administration of salmeterol and idelalisib is not recommended. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia.

Idelalisib [1], sildenafil ---> SmPC of [1] of EMA

The co-administration of idelalisib with sildenafil may increase sildenafil serum concentrations. For pulmonary arterial hypertension: Idelalisib should not be co-administered with sildenafil. For erectile dysfunction: Particular caution must be used

Idelalisib [1], simvastatine ---> SmPC of [1] of EMA

The co-administration of idelalisib with simvastatine may increase the serum concentrations of simvastatine. Idelalisib should not be co-administered with simvastatine.

Idelalisib [1], sirolimus ---> SmPC of [1] of EMA

The co-administration of idelalisib with sirolimus may increase the serum concentrations of sirolimus. Therapeutic monitoring is recommended.

Idelalisib [1], St. John's wort ---> SmPC of [1] of EMA

Idelalisib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Idelalisib [1], substrates of inducible enzymes ---> SmPC of [1] of EMA

In vitro, idelalisib was an inducer of several enzymes, and a risk for decreased exposure and thereby decreased efficacy of substrates of inducible enzymes

Idelalisib [1], tacrolimus ---> SmPC of [1] of EMA

The co-administration of idelalisib with tacrolimus may increase the serum concentrations of tacrolimus. Therapeutic monitoring is recommended.

Idelalisib [1], tadalafil ---> SmPC of [1] of EMA

The co-administration of idelalisib with tadalafil may increase tadalafil serum levels. For pulmonary arterial hypertension: Caution should be exercised when co-administering. For erectile dysfunction: Particular caution must be used

Idelalisib [1], telaprevir ---> SmPC of [1] of EMA

The co-administration of idelalisib with telaprevir may increase the serum concentrations of telaprevir. Clinical monitoring is recommended.

Idelalisib [1], telithromycin ---> SmPC of [1] of EMA

The co-administration of idelalisib with telithromycin may increase the serum concentrations of telithromycin. Clinical monitoring is recommended for telithromycin.

Idelalisib [1], trazodone ---> SmPC of [1] of EMA

The co-administration of idelalisib with trazodone may increase the serum concentrations of trazodone. Careful dose titration of the antidepressant and monitoring for antidepressant response is recommended.

Idelalisib [1], triazolam ---> SmPC of [1] of EMA

The co-administration of idelalisib with triazolam may increase the serum concentrations of triazolam. Idelalisib should not be co-administered with triazolam

Idelalisib [1], vinblastine ---> SmPC of [1] of EMA

The co-administration of idelalisib with vinblastine may increase the serum concentrations of vinblastine. Careful monitoring of the tolerance to these anti-cancer agents is recommended.

Idelalisib [1], vincristine ---> SmPC of [1] of EMA

The co-administration of idelalisib with vincristine may increase the serum concentrations of vincristine. Careful monitoring of the tolerance to these anti-cancer agents is recommended.

Idelalisib [1], voriconazole ---> SmPC of [1] of EMA

The co-administration of idelalisib with voriconazole may increase the serum concentrations of voriconazole. Clinical monitoring is recommended.

Idelalisib [1], warfarin ---> SmPC of [1] of EMA

The co-administration of idelalisib with warfarin may increase the serum concentrations of warfarin. It is recommended that the INR be monitored upon co-administration and following ceasing treatment with idelalisib.

Idelalisib [1], women of childbearing potential ---> SmPC of [1] of EMA

Therefore, women of childbearing potential must use highly effective contraception while taking Zydelig and for 1 month after stopping treatment.

Idelalisib [1], zolpidem ---> SmPC of [1] of EMA

The co-administration of idelalisib with zolpidem may increase the serum concentrations of zolpidem. Concentration monitoring of zolpidem is recommended and dose reduction may be considered.

CONTRAINDICATIONS of Idelalisib (Zydelig)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/zydelig-epar-product-information_en.pdf 21/10/2024

Idursulfase (Elaprase)

Breast-feeding, idursulfase [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from idursulfase therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Cytochrome P450, idursulfase [2] ---> SmPC of [2] of EMA

Based on its metabolism in cellular lysosomes, idursulfase would not be a candidate for cytochrome P450 mediated interactions.

Fertility, idursulfase [2] ---> SmPC of [2] of EMA

No effects on male fertility were seen in reproductive studies in male rats.

Idursulfase [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of idursulfase during pregnancy.

CONTRAINDICATIONS of Idursulfase (Elaprase)

- Severe or life-threatening hypersensitivity to the active substance or to any of the excipients if hypersensitivity is not controllable.

https://www.ema.europa.eu/en/documents/product-information/elaprase-epar-product-information_en.pdf 16/04/2025

Iloprost (Ventavis)

Abciximab, iloprost [2] ---> SmPC of [2] of EMA

Since iloprost inhibits platelet function its use with anticoagulants or other inhibitors of platelet aggregation may increase the risk of bleeding. A careful monitoring of the patients is recommended.

Ability to drive, iloprost [2] ---> SmPC of [2] of EMA

Ventavis has major influence on the ability to drive and use machines for patients experiencing hypotensive symptoms such as dizziness.

ACE inhibitors, iloprost [2] ---> SmPC of [2] of EMA

Iloprost may increase the effects of vasodilatators and antihypertensive agents and then favour the risk of hypotension

Acetylsalicylic acid, iloprost [2] ---> SmPC of [2] of EMA

Anagrelide, iloprost [2] ---> SmPC of [2] of EMA

Anticoagulants, iloprost [2] ---> SmPC of [2] of EMA

Antihypertensives, iloprost [2] ---> SmPC of [2] of EMA

Iloprost may increase the effects of vasodilatators and antihypertensive agents and then favour the risk of hypotension (see section 4.4).

Betablockers, iloprost [2] ---> SmPC of [2] of EMA

Iloprost may increase the effects of vasodilatators and antihypertensive agents and then favour the risk of hypotension

Breast-feeding, iloprost [2] ---> SmPC of [2] of EMA

A potential risk to the breast-feeding child cannot be excluded and it is preferable to avoid breast-feeding during Ventavis therapy.

Calcium antagonists, iloprost [2] ---> SmPC of [2] of EMA

Iloprost may increase the effects of vasodilatators and antihypertensive agents and then favour the risk of hypotension

Cilostazol, iloprost [2] ---> SmPC of [2] of EMA

Clopidogrel, iloprost [2] ---> SmPC of [2] of EMA

Coumarin anticoagulants, iloprost [2] ---> SmPC of [2] of EMA

Cytochrome P450, iloprost [2] ---> SmPC of [2] of EMA

In vitro studies investigating the inhibitory potential of iloprost on the activity of cytochrome P450 enzymes revealed that no relevant inhibition of drug metabolism via these enzymes by iloprost is to be expected.

Defibrotide, iloprost [2] ---> SmPC of [2] of EMA

Desirudin [1], iloprost ---> SmPC of [1] of EMA

Desirudin should be used with caution in conjunction with medicinal products which affect platelet function

Digoxin, iloprost [2] ---> SmPC of [2] of EMA

Intravenous infusion of iloprost has no effect either on the pharmacokinetics of multiple oral doses of digoxin or on the pharmacokinetics of co-administered tissue plasminogen activator (t-PA) in patients.

Drotrecogin alfa [1], iloprost ---> SmPC of [1] of EMA

Caution should be employed when using drotrecogin alfa with other drugs that affect haemostasis

Eptifibatide, iloprost [2] ---> SmPC of [2] of EMA

Fertility, iloprost [2] ---> SmPC of [2] of EMA

Animal studies have not shown harmful effect of iloprost on fertility.

GP IIb/IIIa inhibitors, iloprost [2] ---> SmPC of [2] of EMA

Heparin, iloprost [2] ---> SmPC of [2] of EMA

Iloprost [1], NSAID ---> SmPC of [1] of EMA

Iloprost [1], pentoxifylline ---> SmPC of [1] of EMA

Iloprost [1], phosphodiesterase inhibitors ---> SmPC of [1] of EMA

Additive or superadditive effect of the platelet function. Increased risk of bleeding. Careful monitoring is recommended

Iloprost [1], platelet aggregation inhibitors ---> SmPC of [1] of EMA

Iloprost [1], pregnancy ---> SmPC of [1] of EMA

Taking into account the potential maternal benefit, the use of Ventavis during pregnancy may be considered in those women who choose to continue their pregnancy, despite the known risks of pulmonary hypertension during pregnancy.

Iloprost [1], ticlopidine ---> SmPC of [1] of EMA

Iloprost [1], tirofiban ---> SmPC of [1] of EMA

Iloprost [1], tissue-type plasminogen activator ---> SmPC of [1] of EMA

Iloprost [1], vasodilators ---> SmPC of [1] of EMA

Iloprost may increase the effects of vasodilatators and antihypertensive agents and then favour the risk of hypotension (see section 4.4).

Iloprost [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should use effective contraceptive measures during treatment with Ventavis.

CONTRAINDICATIONS of Iloprost (Ventavis)

- Hypersensitivity to the active substance or to any of the excipients

- Conditions where the effects of Ventavis on platelets might increase the risk of haemorrhage (e.g. active peptic ulcers, trauma, intracranial haemorrhage).

- Severe coronary heart disease or unstable angina;

- Myocardial infarction within the last 6 months;

- Decompensated cardiac failure if not under close medical supervision;

- Severe arrhythmias;

- Cerebrovascular events (e.g. transient ischaemic attack, stroke) within the last 3 months.

- Pulmonary hypertension due to venous occlusive disease.

- Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension.

https://www.ema.europa.eu/en/documents/product-information/ventavis-epar-product-information_en.pdf 31/07/2024

Other trade names: Ilomedin,

Imatinib (Glivec)

Ability to drive, imatinib [2] ---> SmPC of [2] of EMA

Patients should be advised that they may experience undesirable effects such as dizziness, blurred vision or somnolence during treatment with imatinib. Therefore, caution should be recommended when driving a car or operating machinery.

Acenocoumarol, imatinib [2] ---> SmPC of [2] of EMA

Imatinib may increase the anticoagulant effect of acenocoumarol (because of known increased risk of bleeding in conjunction with the use of imatinib)

Alfentanyl, imatinib [2] ---> SmPC of [2] of EMA

Imatinib inhibits CYP3A4 and may increase plasma concentration of other CYP3A4 metabolised drugs. Caution is recommended when administering imatinib with CYP3A4 substrates with a narrow therapeutic window

Alprazolam, imatinib [2] ---> SmPC of [2] of EMA

The CYP3A4 inhibition may increase plasma concentrations of the triazolobenzodiazepine

Anisindione, imatinib [2] ---> SmPC of [2] of EMA

Imatinib may increase the anticoagulant effect of anisindione (because of known increased risk of bleeding in conjunction with the use of imatinib)

Anticoagulants, imatinib [2] ---> SmPC of [2] of EMA

Because of known increased risks of bleeding in conjunction with the use of imatinib (e.g. haemorrhage), patients who require anticoagulation should receive low-molecular-weight or standard heparin, instead of coumarin derivatives such as warfarin.

Artesunate [1], imatinib ---> SmPC of [1] of EMA

Co-administration of intravenous artesunate with strong inhibitors of UGT enzymes (e.g. axitinib, vandetanib, imatinib, diclofenac) may increase plasma exposures to DHA. Co-administration should be avoided if possible.

Asparaginase, imatinib [2] ---> SmPC of [2] of EMA

The combination can be associated with increased hepatotoxicity

Azole antifungals, imatinib [2] ---> SmPC of [2] of EMA

Substances that inhibit the cytochrome P450 isoenzyme CYP3A4 activity could decrease metabolism and increase imatinib concentrations. Caution should be taken when administering imatinib with inhibitors of the CYP3A4 family.

Boceprevir, imatinib [2] ---> SmPC of [2] of EMA

Bortezomib, imatinib [2] ---> SmPC of [2] of EMA

Bosutinib [1], imatinib ---> SmPC of [1] of EMA

The concomitant use of bosutinib with moderate CYP3A inhibitors should be avoided, as an increase in bosutinib plasma levels will occur. Selection of an alternate concomitant medicine with no or minimal CYP3A enzyme inhibition potential is recommended.

Breast-feeding, imatinib [2] ---> SmPC of [2] of EMA

Women should not breast-feed during treatment and for at least 15 days after stopping treatment with Glivec.

Brotizolam, imatinib [2] ---> SmPC of [2] of EMA

The CYP3A4 inhibition may increase plasma concentrations of the triazolobenzodiazepine

Calcium antagonists, imatinib [2] ---> SmPC of [2] of EMA

Glivec may increase plasma concentration of other CYP3A4 metabolised drugs (e.g. triazolo-benzodiazepines, dihydropyridine calcium channel blockers, certain HMG-CoA reductase inhibitors, i.e. statins, etc.).

Carbamazepine, imatinib [2] ---> SmPC of [2] of EMA

Substances that are inducers of CYP3A4 activity may significantly reduce exposure to imatinib, potentially increasing the risk of therapeutic failure. Concomitant use of strong CYP3A4 inducers and imatinib should be avoided.

Chemotherapy, imatinib [2] ---> SmPC of [2] of EMA

In Ph+ ALL patients, there is clinical experience of co-administering Glivec with chemotherapy, but drug-drug interactions between imatinib and chemotherapy regimens are not well characterised.

Clarithromycin, imatinib [2] ---> SmPC of [2] of EMA

Cobimetinib [1], imatinib ---> SmPC of [1] of EMA

Caution should be exercised if cobimetinib is coadministered with moderate CYP3A inhibitors. When cobimetinib is co-administered with a moderate CYP3A inhibitor, patients should be carefully monitored for safety.

Coumarin anticoagulants, imatinib [2] ---> SmPC of [2] of EMA

Cyclosporine, imatinib [2] ---> SmPC of [2] of EMA

CYP3A4 inhibitors, imatinib [2] ---> SmPC of [2] of EMA

Daridorexant [1], imatinib ---> SmPC of [1] of EMA

In the absence of clinical data at 50 mg, simultaneous administration of QUVIVIQ with BCRP substrates (e.g., rosuvastatin, imatinib) should be handled with caution.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, imatinib ---> SmPC of [dasabuvir] of EMA

Dasabuvir is an inhibitor of BCRP in vivo. Co-administration of dasabuvir with ombitasvir/paritaprevir/ritonavir together with medicinal products that are substrates of BCRP may increase plasma concentrations of these transporter substrates

Dexamethasone, imatinib [2] ---> SmPC of [2] of EMA

Dicoumarol, imatinib [2] ---> SmPC of [2] of EMA

Imatinib may increase the anticoagulant effect of dicoumarol (because of known increased risk of bleeding in conjunction with the use of imatinib)

Dihydroergotamine, imatinib [2] ---> SmPC of [2] of EMA

Dihydropyridines, imatinib [2] ---> SmPC of [2] of EMA

Docetaxel, imatinib [2] ---> SmPC of [2] of EMA

Drugs metabolised by CYP3A4, imatinib [2] ---> SmPC of [2] of EMA

Imatinib inhibits CYP3A4 and may increase plasma concentration of other CYP3A4 metabolised drugs.

Drugs primarily metabolised by CYP2D6 with narrow therapeutic index, imatinib [2] ---> SmPC of [2] of EMA

Imatinib inhibits CYP2D6 and may increase exposition of other CYP2D6 metabolised drugs. Caution is advised for CYP2D6 substrates with a narrow therapeutic window

Drugs primarily metabolised by CYP2D6, imatinib [2] ---> SmPC of [2] of EMA

Imatinib inhibits CYP2D6 and may increase exposition of other CYP2D6 metabolised drugs. Dose adjustments do not seem to be necessary when imatinib is co-administrated with CYP2D6 substrates

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, imatinib [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP3A4, imatinib [2] ---> SmPC of [2] of EMA

Imatinib inhibits CYP3A4 and may increase plasma concentration of other CYP3A4 metabolised drugs.

Duvelisib [1], imatinib ---> SmPC of [1] of EMA

Dose reduction of duvelisib is not necessary when co-administered with moderate CYP3A4 inhibitors

Eliglustat [1], imatinib ---> SmPC of [1] of EMA

It is predicted that concomitant use of moderate CYP3A inhibitors would increase eliglustat exposure approximately up to 3-fold. Caution should be used with moderate CYP3A inhibitors in intermediate and extensive metabolisers.

Encorafenib [1], imatinib ---> SmPC of [1] of EMA

Moderate CYP3A4 inhibitors should be co-administered with caution. When encorafenib is co-administered with a moderate CYP3A inhibitor, patients should be carefully monitored for safety.

Ergot derivatives, imatinib [2] ---> SmPC of [2] of EMA

Ergotamine, imatinib [2] ---> SmPC of [2] of EMA

Erythromycin, imatinib [2] ---> SmPC of [2] of EMA

Everolimus [1], imatinib ---> SmPC of [1] of EMA

Increase in everolimus concentration is expected. Use caution when co-administration of moderate CYP3A4 inhibitors or PgP inhibitors cannot be avoided.

Fentanyl, imatinib [2] ---> SmPC of [2] of EMA

Fertility, imatinib [2] ---> SmPC of [2] of EMA

Studies on patients receiving Glivec and its effect on fertility and gametogenesis have not been performed. Patients concerned about their fertility on Glivec treatment should consult with their physician.

Foods, imatinib [2] ---> SmPC of [2] of EMA

The prescribed dose should be administered orally with a meal and a large glass of water to minimise the risk of gastrointestinal irritations.

Fosphenytoin, imatinib [2] ---> SmPC of [2] of EMA

Guanfacin [1], imatinib ---> SmPC of [1] of EMA

Co-administration of Intuniv with moderate and strong CYP3A4/5 inhibitors elevates plasma guanfacine concentrations and increases the risk of adverse reactions such as hypotension, bradycardia, and sedation.

Heparin, imatinib [2] ---> SmPC of [2] of EMA

Ibrutinib [1], imatinib ---> SmPC of [1] of EMA

Concomitant use of IMBRUVICA and medicinal products that strongly or moderately inhibit CYP3A4 can increase ibrutinib exposure and strong CYP3A4 inhibitors should be avoided.

Imatinib [1], indinavir ---> SmPC of [1] of EMA

Imatinib [1], itraconazol ---> SmPC of [1] of EMA

Imatinib [1], ketoconazole ---> SmPC of [1] of EMA

There was a significant increase in exposure to imatinib (the mean Cmax and AUC of imatinib rose by 26% and 40%, respectively) in healthy subjects when it was co-administered with a single dose of ketoconazole (a CYP3A4 inhibitor).

Imatinib [1], levothyroxine ---> SmPC of [1] of EMA

In thyroidectomy patients receiving levothyroxine, the plasma exposure to levothyroxine may be decreased when imatinib is co-administered. Caution is therefore recommended.

Imatinib [1], lopinavir/ritonavir ---> SmPC of [1] of EMA

Imatinib [1], metoprolol ---> SmPC of [1] of EMA

Imatinib inhibits CYP2D6 and may increase exposition of other CYP2D6 metabolised drugs. Caution is advised for CYP2D6 substrates with a narrow therapeutic window

Imatinib [1], moderate CYP3A4 inductors ---> SmPC of [1] of EMA

Imatinib [1], moderate CYP3A4 inhibitors ---> SmPC of [1] of EMA

Imatinib [1], nelfinavir ---> SmPC of [1] of EMA

Imatinib [1], oxcarbazepine ---> SmPC of [1] of EMA

The induction of CYP3A4 may significantly decrease the imatinib plasma levels. Concomitant use should be avoided.

Imatinib [1], paracetamol ---> SmPC of [1] of EMA

Caution should therefore be exercised when using high doses of imatinib and paracetamol concomitantly.

Imatinib [1], phenobarbital ---> SmPC of [1] of EMA

Imatinib [1], phenytoin ---> SmPC of [1] of EMA

Imatinib [1], pimozide ---> SmPC of [1] of EMA

Imatinib [1], posaconazole ---> SmPC of [1] of EMA

Imatinib [1], pregnancy ---> SmPC of [1] of EMA

Glivec should not be used during pregnancy unless clearly necessary. If it is used during pregnancy, the patient must be informed of the potential risk to the foetus.

Imatinib [1], primidone ---> SmPC of [1] of EMA

Imatinib [1], protease inhibitors ---> SmPC of [1] of EMA

Imatinib [1], quinidine ---> SmPC of [1] of EMA

Imatinib [1], rifampicin ---> SmPC of [1] of EMA

Pretreatment with multiple doses of rifampicin 600 mg followed by a single 400 mg dose of Glivec resulted in decrease in Cmax and AUC(0-inf) by at least 54% and 74%, of the respective values without rifampicin treatment.

Imatinib [1], ritonavir ---> SmPC of [1] of EMA

Imatinib [1], saquinavir ---> SmPC of [1] of EMA

Imatinib [1], sirolimus ---> SmPC of [1] of EMA

Imatinib [1], St. John's wort ---> SmPC of [1] of EMA

Imatinib [1], statins metabolised by CYP3A4 ---> SmPC of [1] of EMA

Imatinib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Imatinib [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Imatinib [1], tacrolimus ---> SmPC of [1] of EMA

Imatinib [1], telaprevir ---> SmPC of [1] of EMA

Imatinib [1], telithromycin ---> SmPC of [1] of EMA

Imatinib [1], terfenadine ---> SmPC of [1] of EMA

Imatinib [1], triazolobenzodiazepines ---> SmPC of [1] of EMA

Imatinib [1], voriconazole ---> SmPC of [1] of EMA

Imatinib [1], warfarin ---> SmPC of [1] of EMA

Imatinib [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential must be advised to use effective contraception during treatment and for at least 15 days after stopping treatment with Glivec.

Imatinib, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Daunorubicin, doxorubicin, imatinib, irinotecan, lapatinib, mitoxantrone or topotecan: careful monitoring for any occurrence of drug toxicity, and dose reduction if required.

Imatinib, lomitapide [2] ---> SmPC of [2] of EMA

Lomitapide, P-glycoprotein inhibitor, may increase the absorption of the P-glycoprotein substrate

Imatinib, nilotinib [2] ---> SmPC of [2] of EMA

Concomitant administration of nilotinib with imatinib (a substrate and moderator of P-gp and CYP3A4), had a slight inhibitory effect on CYP3A4 and/or P-gp. These changes are unlikely to be clinically important.

Imatinib, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Co-administration of ombitasvir/paritaprevir/ritonavir with or without dasabuvir with medicinal products that are substrates of BCRP may increase plasma concentrations of these transporter substrates

Imatinib, tafamidis [2] ---> SmPC of [2] of EMA

In vitro tafamidis inhibits the efflux transporter CRP breast cancer resistant protein) and may cause drug-drug interactions at clinically relevant concentrations with substrates of this transporter

Imatinib, tedizolid [2] ---> SmPC of [2] of EMA

Orally administered Sivextro can result in inhibition of BCRP at the intestinal level. If possible, an interruption of the co-administered BCRP substrate medicinal product should be considered during the six days of treatment with oral Sivextro.

Imatinib, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Imatinib, triazolam

Imatinib may increase plasma levels of triazolam due to inhibition of CYP3A4. It is recommended caution with the concomitant use

Imatinib, zanubrutinib [2] ---> SmPC of [2] of EMA

If a moderate CYP3A inhibitor must be used, reduce the BRUKINSA dose to 160 mg (two capsules) for the duration of the inhibitor use.

CONTRAINDICATIONS of Imatinib (Glivec)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/glivec-epar-product-information_en.pdf 11/12/2024

Other trade names: Imatinib Accord, Imatinib Actavis, Imatinib Apotex, Imatinib Hetero, Imatinib medac, Imatinib Teva,

Imetelstat (Rytelo)

Ability to drive, imetelstat [2] ---> SmPC of [2] of EMA

Patients should be advised to use caution until any symptoms affecting their ability to drive or operate machines have resolved.

Breast-feeding, imetelstat [2] ---> SmPC of [2] of EMA

Because of the potential for adverse reactions in breast-fed children, women should be advised not to breastfeed during treatment with Rytelo and for 1 week after the last dose.

Embryofoetal toxicity, imetelstat [2] ---> SmPC of [2] of EMA

Pregnant women should be advised of the potential risk to a foetus.

Fertility, imetelstat [2] ---> SmPC of [2] of EMA

Based on findings in animals, imetelstat may impair fertility in females of reproductive potential (see section 5.3). No human data on the effect of imetelstat on fertility are available.

Imetelstat [1], infusion-related reaction ---> SmPC of [1] of EMA

Infusion-related reactions have been reported during treatment with Rytelo and were generally mild or moderate in severity (see section 4.8).

Imetelstat [1], neutropenia ---> SmPC of [1] of EMA

Neutropenia has been reported during treatment with Rytelo, including new or worsening Grade 3 or Grade 4 neutropenia (see section 4.8), and febrile neutropenia may occur.

Imetelstat [1], pregnancy ---> SmPC of [1] of EMA

Studies in animals have shown that imetelstat may cause embryonic or foetal loss (see section 5.3). Imetelstat is not recommended during pregnancy and in women of childbearing potential not using contraception.

Imetelstat [1], thrombocytopenia ---> SmPC of [1] of EMA

Thrombocytopenia has been reported during treatment with Rytelo, including new or worsening Grade 3 or Grade 4 thrombocytopenia (see section 4.8).

Imetelstat [1], women of childbearing potential ---> SmPC of [1] of EMA

The pregnancy status of females of reproductive potential should be verified before starting treatment with Rytelo (see section 4.2).

Imetelstat [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should be advised to use effective contraception during treatment with Rytelo and for at least 1 week after the last dose.

CONTRAINDICATIONS of Imetelstat (Rytelo)

- Hypersensitivity to the active substance or to any of the excipients are listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/rytelo-epar-product-information_en.pdf 15/05/2025

Imidapril

Ability to drive, imidapril [2] ---> SmPC of [2] of eMC

When driving vehicles or operating machines it should be taken into account that occasionally dizziness or weariness may occur.

ACE inhibitors, hyperkalemia ---> SmPC of [imidapril] of eMC

ACE inhibitors must not be associated with hyperkalemic substances, except in hypokalemia.

Acetylsalicylic acid, imidapril [2] ---> SmPC of [2] of eMC

Imidapril may be used concomitantly with acetylsalicylic acid (when used as a thrombolytic), thrombolytics, and beta-blockers.

AIIRA, imidapril

The dual blockade of the RAA-system through the combined use of ACE-inhibitors, AIIRA or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure)

Aliskiren, imidapril

Amiloride, imidapril [2] ---> SmPC of [2] of eMC

Potassium sparing diuretics or supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium (potentially lethal), mainly in conjunction with renal impairment (additive hyperkaliemic effects)

Antacids, imidapril [2] ---> SmPC of [2] of eMC

Antacids may induce decreased bioavailability of imidapril.

Antihypertensives, imidapril [2] ---> SmPC of [2] of eMC

Concomitant use of antihypertensive agents and vasodilators with imidapril may increase the hypotensive effects of imidapril

Betablockers, imidapril [2] ---> SmPC of [2] of eMC

Imidapril may be used concomitantly with acetylsalicylic acid (when used as a thrombolytic), thrombolytics, and beta-blockers.

Breast-feeding, imidapril [2] ---> SmPC of [2] of eMC

Imidapril is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

Coxibs, imidapril [2] ---> SmPC of [2] of eMC

Concomitant use of ACE-inhibitors and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor pre-existing renal function.

Gold, imidapril [2] ---> SmPC of [2] of eMC

Nitritoid reactions following injectable gold have been reported more frequently in patients receiving ACE inhibitor therapy.

Hyperkalemia, imidapril [2] ---> SmPC of [2] of eMC

ACE inhibitors must not be associated with hyperkalemic substances, except in hypokalemia.

Imidapril [1], insulin ---> SmPC of [1] of eMC

The use of ACE inhibitors may increase the hypoglycaemic effect in diabetic patients treated with insulin or hypoglycaemia sulphonamides.

Imidapril [1], lithium ---> SmPC of [1] of eMC

Increased lithium concentration, potentially to toxic levels (decreased renal lithium excretion). Use of imidapril with lithium is not recommended

Imidapril [1], loop diuretics ---> SmPC of [1] of eMC

Risk of sudden hypotension and/or acute renal impairment on initiation of treatment with an ACE inhibitor in patients with pre-existing salt/volume depletion.

Imidapril [1], neuroleptics ---> SmPC of [1] of eMC

Tricyclic antidepressants, neuroleptics: Increased antihypertensive effect and risk of orthostatic hypotension (additive effect)

Imidapril [1], nitroglycerine ---> SmPC of [1] of eMC

Concomitant use of imidapril with nitroglycerin and other nitrates may further reduce blood pressure.

Imidapril [1], non-potassium-sparing diuretics ---> SmPC of [1] of eMC

Risk of sudden hypotension and/or acute renal impairment on initiation of treatment with an ACE inhibitor in patients with pre-existing salt/volume depletion.

Imidapril [1], NSAID ---> SmPC of [1] of eMC

Imidapril [1], oral antidiabetics ---> SmPC of [1] of eMC

The use of ACE inhibitors may increase the hypoglycaemic effect in diabetic patients treated with insulin or hypoglycaemia sulphonamides.

Imidapril [1], organic nitrates ---> SmPC of [1] of eMC

Concomitant use of imidapril with nitroglycerin and other nitrates may further reduce blood pressure.

Imidapril [1], potassium ---> SmPC of [1] of eMC

Imidapril [1], potassium-sparing diuretics ---> SmPC of [1] of eMC

Imidapril [1], pregnancy ---> SmPC of [1] of eMC

The use of ACE inhibitors is not recommended during the first trimester of pregnancy (see section 4.4). The use of ACE inhibitors is contraindicated during the second and third trimester of pregnancy

Imidapril [1], rifampicin ---> SmPC of [1] of eMC

The administration of rifampicin reduced the plasma level of imidaprilat, the active metabolite of imidapril. The antihypertensive effect of imidapril might therefore be reduced.

Imidapril [1], spironolactone ---> SmPC of [1] of eMC

Imidapril [1], sulfonylureas ---> SmPC of [1] of eMC

Concomitant treatment with ACE inhibitors and antidiabetic agents may cause a pronounced hypoglycaemic effect with the risk of hypoglycaemia.

Imidapril [1], sympathomimetics ---> SmPC of [1] of eMC

Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors; patients should be carefully monitored to confirm that the desired effect is obtained.

Imidapril [1], thiazides ---> SmPC of [1] of eMC

Risk of sudden hypotension and/or acute renal impairment on initiation of treatment with an ACE inhibitor in patients with pre-existing salt/volume depletion.

Imidapril [1], thrombolytics ---> SmPC of [1] of eMC

Imidapril may be used concomitantly with acetylsalicylic acid (when used as a thrombolytic), thrombolytics, and beta-blockers.

Imidapril [1], triamterene ---> SmPC of [1] of eMC

Imidapril [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Tricyclic antidepressants, neuroleptics: Increased antihypertensive effect and risk of orthostatic hypotension (additive effect)

Imidapril [1], vasodilators ---> SmPC of [1] of eMC

Concomitant use of antihypertensive agents and vasodilators with imidapril may increase the hypotensive effects of imidapril

CONTRAINDICATIONS of Imidapril

- Hypersensitivity to imidapril or any other ACE inhibitor or to any of the excipients

- History of angioneurotic oedema associated with previous ACE inhibitor therapy

- Hereditary/idiopathic angioedema

- Second and third trimesters of pregnancy

- Renal failure with or without haemodialysis (creatinine clearance < 10 ml/min).

http://www.medicines.org.uk/emc/

Imiglucerase (Cerezyme)

Breast-feeding, imiglucerase [2] ---> SmPC of [2] of EMA

It is not known whether this active substance is excreted in human milk, however, the enzyme is likely to be digested in the child's gastrointestinal tract

Imiglucerase [1], pregnancy ---> SmPC of [1] of EMA

The use of Cerezyme could be beneficial to control the underlying Gaucher disease in pregnancy. Foetal demise has been reported rarely

Imiglucerase [1], pregnancy ---> SmPC of [1] of EMA

Treatment naīve women should be advised to consider commencing therapy prior to conception in order to attain optimal health.

Imiglucerase [1], pregnancy ---> SmPC of [1] of EMA

In women receiving Cerezyme treatment continuation throughout pregnancy should be considered.

Imiglucerase, miglustat [2] ---> SmPC of [2] of EMA

This study also indicated that Zavesca has no or limited effect on the pharmacokinetics of imiglucerase.

CONTRAINDICATIONS of Imiglucerase (Cerezyme)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/cerezyme-epar-product-information_en.pdf 23/05/2024

Imipenem/cilastatin

Ability to drive, imipenem/cilastatin [2] ---> SmPC of [2] of eMC

There are some side effects (such as hallucination, dizziness, somnolence, and vertigo) associated with this product that may affect some patients' ability to drive or operate machinery

Antibiotics, warfarin ---> SmPC of [imipenem/cilastatin] of eMC

There have been many reports of increases in the anti-coagulant effects of orally administered anti-coagulant agents, including warfarin in patients who are concomitantly receiving antibacterial agents.

Beta-lactam antibiotics, warfarin ---> SmPC of [imipenem/cilastatin] of eMC

Breast-feeding, imipenem/cilastatin [2] ---> SmPC of [2] of eMC

Imipenem and cilastatin are excreted into the mother's milk in small quantities. If the use is deemed necessary, the benefit of breast-feeding for the child should be weighed against the possible risk for the child.

Ganciclovir, imipenem/cilastatin [2] ---> SmPC of [2] of eMC

Generalized seizures have been reported in patients who received ganciclovir and imipenem/cilastatin. These medicinal products should not be used concomitantly unless the potential benefit outweighs the risks.

Imipenem/cilastatin [1], oral antidiabetics ---> SmPC of [1] of eMC

Imipenem/cilastatin [1], pregnancy ---> SmPC of [1] of eMC

Imipenem/Cilastatin 500 mg/500 mg Powder for Solution for Infusion should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Imipenem/cilastatin [1], probenecide ---> SmPC of [1] of eMC

Concomitant administration of imipenem/cilastatin and probenecid doubled the plasma level and half-life of cilastatin, but had no effect on urine recovery of cilastatin.

Imipenem/cilastatin [1], sodium valproate ---> SmPC of [1] of eMC

Decreases in valproic acid levels that may fall below the therapeutic range have been reported when valproic acid was co-administered with carbapenem agents. The lowered valproic acid levels can lead to inadequate seizure control

Imipenem/cilastatin [1], valproic acid ---> SmPC of [1] of eMC

Imipenem/cilastatin [1], warfarin ---> SmPC of [1] of eMC

Imipenem/cilastatin, valganciclovir [2] ---> SmPC of [2] of eMC

Convulsions have been reported in patients taking imipenem-cilastatin and ganciclovir. Valganciclovir should not be used concomitantly with imipenem-cilastatin unless the potential benefits outweigh the potential risks

CONTRAINDICATIONS of Imipenem/cilastatin

- Hypersensitivity to the active substances or to any of the excipients

- Hypersensitivity to any other carbapenem antibacterial agent.

- Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other type of betalactam antibacterial agent (e.g. penicillins or cephalosporins).

http://www.medicines.org.uk/emc/

Imipenem/cilastatin/relebactam (Recarbrio)

Ability to drive, imipenem/cilastatin/relebactam [2] ---> SmPC of [2] of EMA

CNS adverse reactions, such as seizures, confusional states, and myoclonic activity, have been reported during treatment with imipenem/cilastatin, components of Recarbrio, especially when recommended dosages of imipenem were exceeded

Breast-feeding, imipenem/cilastatin/relebactam [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breastfeeding or to discontinue Recarbrio therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility, imipenem/cilastatin/relebactam [2] ---> SmPC of [2] of EMA

Tierexperimentelle Studien zeigen keine gesundheitsschädlichen Wirkungen von Imipenem/Cilastatin oder Relebactam auf die Fertilität (siehe Abschnitt 5.3).

Ganciclovir, imipenem/cilastatin/relebactam [2] ---> SmPC of [2] of EMA

Generalised seizures have been reported in patients who received ganciclovir concomitantly with imipenem/cilastatin, components of Recarbrio. Ganciclovir should not be used concomitantly with Recarbrio unless the potential benefits outweigh the risks.

Imipenem/cilastatin/relebactam [1], pregnancy ---> SmPC of [1] of EMA

Recarbrio should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Imipenem/cilastatin/relebactam [1], valproate semisodium ---> SmPC of [1] of EMA

Case reports in the literature have shown that co-administration of carbapenems, including imipenem/cilastatin (components of Recarbrio), to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations.

Imipenem/cilastatin/relebactam [1], valproic acid ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Imipenem/cilastatin/relebactam (Recarbrio)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

- Hypersensitivity to any other carbapenem antibacterial agent.

- Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other type of betalactam antibacterial agent (e.g. penicillins, cephalosporins or monobactams)

https://www.ema.europa.eu/en/documents/product-information/recarbrio-epar-product-information_en.pdf 24/09/2024

Imipramine

Ability to drive, imipramine [2] ---> SmPC of [2] of eMC

Blurred vision, drowsiness and other CNS symptoms may occur.

Adrenaline, imipramine [2] ---> SmPC of [2] of eMC

Imipramine may potentiate the cardiovascular effects of sympathomimetic agent

Alcohol, imipramine [2] ---> SmPC of [2] of eMC

Tricyclic antidepressants may also potentiate the CNS depressant effects of alcohol

Alcohol, tricyclic antidepressant ---> SmPC of [imipramine] of eMC

Tricyclic antidepressants may potentiate the CNS depressant effects of alcohol

Alpha-methyldopa, imipramine [2] ---> SmPC of [2] of eMC

Imipramine may diminish or abolish the antihypertensive effects of adrenergic blocker

Altretamine, imipramine [2] ---> SmPC of [2] of eMC

Concomitant use of imipramine and altretamine should be avoided due to the risk of severe postural hypotension.

Antiadrenergics, imipramine

Imipramine may diminish or abolish the antihypertensive effects of adrenergic blocker

Anticholinergics, imipramine [2] ---> SmPC of [2] of eMC

Tricyclic antidepressants may potentiate the effects of anticholinergic agents on the eye, central nervous system, bowel and bladder.

Anticholinergics, tricyclic antidepressant ---> SmPC of [imipramine] of eMC

Tricyclic antidepressants may potentiate the effects of anticholinergic agents on the eye, central nervous system, bowel and bladder.

Antihistamines, imipramine [2] ---> SmPC of [2] of eMC

Tricyclic antidepressants may potentiate the effects of anticholinergic agents on the eye, central nervous system, bowel and bladder.

Artemether/lumefantrine [1], imipramine ---> SmPC of [1] of eMC

Artemether/lumefantrine is contraindicated in patients who are taking any drug which is metabolised by the cytochrome enzyme CYP2D6. In vitro, lumefantrine significantly inhibits the activity of CYP2D6 at therapeutic plasma concentrations

Asenapine [1], imipramine ---> SmPC of [1] of EMA

In a separate study, co-administration of a single 75 mg dose of imipramine with a single 5 mg dose of asenapine did not affect the plasma concentrations of the metabolite desipramine (a CYP2D6 substrate).

Atomoxetine, imipramine

Drugs that affect noradrenaline should be used cautiously when co-administered with atomoxetine because of the potential for additive or synergistic pharmacological effects.

Atropine, imipramine [2] ---> SmPC of [2] of eMC

Tricyclic antidepressants may potentiate the effects of anticholinergic agents on the eye, central nervous system, bowel and bladder.

Barbiturates, imipramine [2] ---> SmPC of [2] of eMC

Imipramine may potentiate the CNS depressant effects of central depressant drugs. The barbiturate may activate the hepatic mono-oxygenase enzyme system and lower plasma concentrations of imipramine, resulting in decreased efficacy

Benzodiazepines, imipramine [2] ---> SmPC of [2] of eMC

Tricyclic antidepressants may potentiate the CNS depressant effects of central depressant drugs

Betablockers, imipramine

The co-administration may potentiate the hypotensive effects of the beta blocker

Betanidine, imipramine [2] ---> SmPC of [2] of eMC

Imipramine may diminish or abolish the antihypertensive effects of adrenergic blocker

Biperiden, imipramine [2] ---> SmPC of [2] of eMC

Tricyclic antidepressants may potentiate the effects of anticholinergic agents on the eye, central nervous system, bowel and bladder.

Breast-feeding, imipramine [2] ---> SmPC of [2] of eMC

As imipramine is excreted in breast milk, it should not be administered to nursing mothers unless considered essential when the mother should be advised to cease breast feeding.

Bupropion [1], imipramine ---> SmPC of [1] of eMC

Concomitant therapy of bupropion with medicinal products with narrow therapeutic indices that are mainly metabolised by CYP2D6 (bupropion inhibits CYP2D6) should be initiated at the lower end of the dose range of the concomitant medicine.

Carbamazepine, imipramine [2] ---> SmPC of [2] of eMC

Drugs which activate the hepatic mono-oxygenase enzyme system may lower plasma concentrations of imipramine, resulting in decreased efficacy. Plasma levels of carbamazepine may increase, with corresponding adverse effects.

Carteolol, imipramine

Antihypertensive effect and increased risk of orthostatic hypotension (additive effect)

Cholestyramine, imipramine

Cholestyramine may decrease plasma levels of imipramine. Patients should take other drugs at least 1 hour before or 4-6 hours after colestyramine to minimize possible interference with their absorption.

Cimetidine, imipramine [2] ---> SmPC of [2] of eMC

Cimetidine may increase the plasma levels of imipramine whose dosage should therefore be reduced.

Citalopram [1], imipramine ---> SmPC of [1] of eMC

In a pharmacokinetic study no effect was demonstrated on either citalopram or imipramine levels, although the level of desipramine, the primary metabolite of imipramine was increased.

Class IA antiarrhythmic agents, imipramine [2] ---> SmPC of [2] of eMC

Tricyclic antidepressants should not be employed in combination with anti-arrhythmic agents of the quinidine type.

Class IA antiarrhythmic agents, tricyclic antidepressant ---> SmPC of [imipramine] of eMC

Tricyclic antidepressants should not be employed in combination with anti-arrhythmic agents of the quinidine type.

Class III antiarrhythmic agents, imipramine

Tricyclic antidepressants should not be employed in combination with anti-arrhythmic agents of the amiodarone type.

Clonidine, imipramine [2] ---> SmPC of [2] of eMC

Imipramine may diminish or abolish the antihypertensive effects of adrenergic blocker

CNS depressants, imipramine [2] ---> SmPC of [2] of eMC

Tricyclic antidepressants may potentiate the CNS depressant effects of central depressant drugs

Codeine, imipramine

The co-administration may cause additive depression of CNS and may enhance the respiratory depressor effect

Cotrimoxazole, imipramine [2] ---> SmPC of [2] of eMC

Increased risk of ventricular arrhythmias with the combination of imipramine and drugs, which prolong the QT interval.

Coumarin anticoagulants, imipramine [2] ---> SmPC of [2] of eMC

Tricyclic antidepressants may potentiate the anti-coagulant effect of coumarin drugs by inhibiting hepatic metabolism of anticoagulants.

Coumarin anticoagulants, tricyclic antidepressant ---> SmPC of [imipramine] of eMC

Tricyclic antidepressants may potentiate the anti-coagulant effect of coumarin drugs by inhibiting hepatic metabolism of anticoagulants.

Darifenacin [1], imipramine ---> SmPC of [1] of EMA

Darifenacin is a moderate inhibitor of the enzyme CYP2D6. Caution should be exercised when darifenacin is used concomitantly with medicinal products that are predominantly metabolised by CYP2D6 and which have a narrow therapeutic window

Darunavir/cobicistat [1], imipramine ---> SmPC of [1] of EMA

Concomitant use of boosted darunavir/cobicistat (CYP2D6 and/or CYP3A inhibition) and this antidepressant may increase concentrations of the antidepressant.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], imipramine ---> SmPC of [1] of EMA

It is expected to increase these anti-depressant plasma concentrations. CYP2D6 and/or CYP3A inhibition. If this anti-depressant is to be used with Symtuza clinical monitoring is recommended and a dose adjustment of the anti-depressant may be needed.

Debrisoquine, imipramine [2] ---> SmPC of [2] of eMC

Imipramine may diminish or abolish the antihypertensive effects of adrenergic blocker

Dextromethorphan/quinidine [1], imipramine ---> SmPC of [1] of EMA

Quinidine is a potent inhibitor of CYP2D6. Treatment with dextromethorphan/quinidine may therefore result in elevated plasma levels and accumulation of co-administered medicinal products that undergo extensive CYP2D6 metabolism.

Dihydrocodeine [1], imipramine ---> SmPC of [1] of eMC

Opiates potentiate the effects of CNS depressants

Diltiazem, imipramine [2] ---> SmPC of [2] of eMC

Blood levels of imipramine may be increased by calcium channel blockers

Diuretics, imipramine [2] ---> SmPC of [2] of eMC

Concurrent use of a tricyclic antidepressant and a diuretic may increase the risk of postural hypotension.

Dopamine agonists, imipramine [2] ---> SmPC of [2] of eMC

CNS toxicity may be enhanced when tricyclic antidepressants are used in conjunction with dopaminergic.

Dopaminergic drugs, imipramine [2] ---> SmPC of [2] of eMC

CNS toxicity may be enhanced when tricyclic antidepressants are used in conjunction with dopaminergic.

Duloxetine [1], imipramine ---> SmPC of [1] of EMA

Duloxetine is a moderate inhibitor of CYP2D6. Caution is advised if duloxetine is co-administered with medicinal products that are predominantly metabolised by CYP2D6

Electroconvulsive therapy, imipramine [2] ---> SmPC of [2] of eMC

Concomitant treatment with imipramine and electroconvulsive therapy should only be resorted to under careful supervision.

Eliglustat [1], imipramine ---> SmPC of [1] of EMA

Concomitant administration of eliglustat with CYP2D6 substrates may increase the exposition of these substrates. Lower doses of medicinal products that are CYP2D6 substrates may be required.

Enzyme inductors, imipramine [2] ---> SmPC of [2] of eMC

Drugs which activate the hepatic mono-oxygenase enzyme system may accelerate the metabolism and lower plasma concentrations of imipramine, resulting in decreased efficacy.

Ephedrine, imipramine [2] ---> SmPC of [2] of eMC

Imipramine may potentiate the cardiovascular effects of sympathomimetic agent

Epinephrine, imipramine [2] ---> SmPC of [2] of eMC

Imipramine may potentiate the cardiovascular effects of sympathomimetic agent

Esmolol [1], imipramine ---> SmPC of [1] of eMC

Concomitant administration of esmolol and tricyclic antidepressants may increase the blood pressure lowering effect.

Esomeprazole [1], imipramine ---> SmPC of [1] of EMA

Esomeprazole inhibits CYP2C19, the major esomeprazole metabolising enzyme. Thus, when esomeprazole is combined with medicinal products metabolised by CYP2C19, the plasma concentrations of these medicinal products may be increased

Estrogens, imipramine [2] ---> SmPC of [2] of eMC

There is evidence that oestrogens can sometimes paradoxically reduce the effects of imipramine yet at the same time cause imipramine toxicity.

Fluoxetine, imipramine [2] ---> SmPC of [2] of eMC

Combination of SSRIs a. imipramine may lead to additive effects on the serotonergic system. Fluoxetine may increase imipramine plasma levels, resulting in increased plasma levels of tricyclic antidepressants, a lowered convulsion threshold

Fluvoxamine, imipramine [2] ---> SmPC of [2] of eMC

Combination of SSRIs a. imipramine may lead to additive effects on serotonergic system. Fluvoxamine may increase imipramine plasma levels, resulting in increased plasma levels of tricyclic antidepressants, a lowered convulsion threshold

General anesthetics, imipramine [2] ---> SmPC of [2] of eMC

Tricyclic antidepressants may potentiate the CNS depressant effects of central depressant drugs

Guanethidine, imipramine [2] ---> SmPC of [2] of eMC

Imipramine may diminish or abolish the antihypertensive effects of adrenergic blocker

Hydrochlorothiazide, imipramine

Increased hypotensive effect.

IMAOs, imipramine [2] ---> SmPC of [2] of eMC

Imipramine should not be administered for at least 3 weeks after discontinuation of treatment with MAO inhibitors. This also applies when giving a MAO inhibitor after previous treatment with imipramine.

Imipramine [1], isoprenaline ---> SmPC of [1] of eMC

Imipramine may potentiate the cardiovascular effects of sympathomimetic agent

Imipramine [1], labetalol ---> SmPC of [1] of eMC

Blood concentrations of imipramine may be increased by drugs such as labetalol.

Imipramine [1], methylphenidate ---> SmPC of [1] of eMC

Methylphenidate may increase the plasma levels of imipramine whose dosage should therefore be reduced.

Imipramine [1], neuroleptics ---> SmPC of [1] of eMC

Concomitant use of neuroleptics may result in increased plasma levels of tricyclic antidepressants, a lowered convulsion threshold and seizures.

Imipramine [1], nicotine ---> SmPC of [1] of eMC

Drugs which activate the hepatic mono-oxygenase enzyme system may accelerate the metabolism and lower plasma concentrations of imipramine, resulting in decreased efficacy.

Imipramine [1], noradrenaline ---> SmPC of [1] of eMC

Imipramine may potentiate the cardiovascular effects of sympathomimetic agent

Imipramine [1], oral contraceptives ---> SmPC of [1] of eMC

Drugs which activate the hepatic mono-oxygenase enzyme system may accelerate the metabolism and lower plasma concentrations of imipramine, resulting in decreased efficacy.

Imipramine [1], organic nitrates ---> SmPC of [1] of eMC

Reduced salivary secretion may lessen the effectiveness of sub-lingual nitrate preparations.

Imipramine [1], phenelzine ---> SmPC of [1] of eMC

Phenelzine should not be administered at the same time as, or within 3 weeks of, treatment with imipramine

Imipramine [1], phenothiazines ---> SmPC of [1] of eMC

Tricyclic antidepressants may potentiate the effects of anticholinergic agents on the eye, central nervous system, bowel and bladder.

Imipramine [1], phenylephrine ---> SmPC of [1] of eMC

Imipramine may potentiate the cardiovascular effects

Imipramine [1], phenytoin ---> SmPC of [1] of eMC

Drugs which activate the hepatic mono-oxygenase enzyme system may lower plasma concentrations of imipramine, resulting in decreased efficacy. Plasma levels of phenytoin may increase, with corresponding adverse effects.

Imipramine [1], pregnancy ---> SmPC of [1] of eMC

Treatment with imipramine should be avoided during pregnancy, unless the anticipated benefits justify the potential risk to the foetus.

Imipramine [1], propranolol ---> SmPC of [1] of eMC

Blood concentrations of imipramine may be increased by drugs such as propranolol.

Imipramine [1], QT interval prolonging drugs ---> SmPC of [1] of eMC

Increased risk of ventricular arrhythmias with the combination of imipramine and drugs, which prolong the QT interval.

Imipramine [1], quinidine ---> SmPC of [1] of eMC

Tricyclic antidepressants should not be employed in combination with anti-arrhythmic agents of the quinidine type.

Imipramine [1], reserpine ---> SmPC of [1] of eMC

Imipramine may diminish or abolish the antihypertensive effects of adrenergic blocker

Imipramine [1], SSRI ---> SmPC of [1] of eMC

Co-medication of SSRIs and imipramine may lead to additive effects on the serotonergic system.

Imipramine [1], thioridazine ---> SmPC of [1] of eMC

Combination of imipramine with thioridazine may produce severe cardiac arrhythmias.

Imipramine [1], verapamil ---> SmPC of [1] of eMC

Blood levels of imipramine may be increased by calcium channel blockers

Imipramine, indapamide [2] ---> SmPC of [2] of eMC

Antihypertensive effect and increased risk of orthostatic hypotension increased (additive effect).

Imipramine, interferon

Caution should be used when administering interferon with medicines mainly metabolised by hepatic cytochrome P450 and have a narrow therapeutic window

Imipramine, isocarboxazid [2] ---> SmPC of [2] of eMC

Isocarboxazid should not be administered together with imipramine. Hypotensive and other adverse reactions are likely to be increased.

Imipramine, levacetylmethadol [2] ---> SmPC of [2] of EMA

The co-administration of levacetylmethadol with medicinal products that prolong the interval QT is contraindicated

Imipramine, levomepromazine [2] ---> SmPC of [2] of eMC

Co-administration of levomepromazine and drugs primarily metabolised by the CYP2D6 may result in increased plasma concentrations of the drugs that could increase or prolong both therapeutic or adverse effects of those drugs.

Imipramine, lithium

The co-administration may cause additive effects on the serotonergic system

Imipramine, melatonin [2] ---> SmPC of [2] of EMA

Melatonin co-administration resulted in increased feelings of tranquility and difficulty in performing tasks compared to imipramine alone

Imipramine, mephenytoin

Increased hydantoin plasma levels

Imipramine, methadone

Tricyclic antidepressants may potentiate the effects of anticholinergic agents

Imipramine, mirabegron [2] ---> SmPC of [2] of EMA

Caution is advised if mirabegron is co-administered with medicinal products with a narrow therapeutic index and significantly metabolised by CYP2D6. Caution is also advised with CYP2D6 substrates that are individually dose titrated.

Imipramine, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Co-administration of bupropion with drugs that are metabolised by CYP2D6 isozyme should be approached with caution and should be initiated at the lower end of the dose range of the concomitant medicinal product.

Imipramine, nelfinavir [2] ---> SmPC of [2] of EMA

Co-administration of nelfinavir with inhibitors of CYP2C19 may be expected to reduce the conversion of nelfinavir to its major active metabolite M8 (tert-butyl hydroxy nelfinavir) with a concomitant increase in plasma nelfinavir levels

Imipramine, norephedrine

The antidepressant may enhance the cardiovascular effects of sympathomimetic agent resulting in severe arrhytmias, tachycardia, hypertension and hyperpyrexia

Imipramine, paroxetine

Co-medication of SSRIs and imipramine may lead to additive effects on the serotonergic system.

Imipramine, phenylpropanolamine

The antidepressant may enhance the cardiovascular effects of sympathomimetic agent resulting in severe arrhytmias, tachycardia, hypertension and hyperpyrexia

Imipramine, pitolisant [2] ---> SmPC of [2] of EMA

Tri or tetracyclic antidepressants may impair the efficacy of pitolisant because they display histamine H1-receptor antagonist activity and possibly cancel the effect of endogenous histamine released in brain by the treatment.

Imipramine, propiverine [2] ---> SmPC of [2] of eMC

Increased effects of propiverine due to concomitant medication with tricyclic antidepressants (e. g. imipramine)

Imipramine, quetiapine [2] ---> SmPC of [2] of eMC

The pharmacokinetics of quetiapine were not significantly altered by co-administration of the antidepressants imipramine (a known CYP 2D6 inhibitor) or fluoxetine (a known CYP 3A4 and CYP 2D6 inhibitor)

Imipramine, ranolazine [2] ---> SmPC of [2] of EMA

There is a theoretical risk that concomitant treatment of ranolazine with other drugs known to prolong the QTc interval may give rise to a pharmacodynamic interaction and increase the possible risk of ventricular arrhythmias.

Imipramine, riluzole [2] ---> SmPC of [2] of EMA

In vitro studies suggest that CYP1A2 is the principal isozyme involved in the initial oxidative metabolism of riluzole. Inhibitors of CYP1A2 could potentially decrease the rate of riluzole elimination

Imipramine, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as an antiretroviral agent is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of imipramine, amitriptyline, nortriptyline, fluoxetine, paroxetine or sertraline.

Imipramine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Imipramine, serotonergic medicines

The co-administration may cause additive effects on the serotonergic system

Imipramine, sertraline

Co-medication of SSRIs and imipramine may lead to additive effects on the serotonergic system.

Imipramine, SNRIs

The co-administration may cause additive effects on the serotonergic system

Imipramine, stiripentol [2] ---> SmPC of [2] of EMA

Stiripentol is an inhibitor of the enzymes CYP2D6 and may markedly increase the plasma concentrations of substances metabolised by these enzymes and increase the risk of adverse reactions

Imipramine, strong CYP2D6 inhibitors

The CYP2D6 inhibition may increase plasma concentrations of imipramine (narrow therapeutic index)

Imipramine, sultiame

The co-administration may increase the plasma levels of imipramine. Adjustment of the dose may be required

Imipramine, sympathomimetics

The effect of sympathomimetic drugs on the autonomic nervous system may be significantly enhanced by the co-administration of imipramine

Imipramine, tedisamil

Tedisamil, strong CYP2D6 inhibitor, may increase the plasma concentrations of imipramine

Imipramine, terbinafine

Concomitant use of imipramine and terbinafine, strong CYP2D6 inhibitor, may increase the exposition and accumulation of imipramine and terbinafine. Dose adjustment may be required

Imipramine, tetrabenazine [2] ---> SmPC of [2] of eMC

In vitro studies indicate that tetrabenazine may be a CYP2D6 inhibitor and therefore cause increased plasma concentrations of medicinal products metabolised by CYP2D6.

Imipramine, thyroid hormones

Thyroid hormone may enhance effects of imipramine

Imipramine, tiapride

Tiapride should not be combined with drugs that prolong the QT interval. These drugs (with the exception of anti-infectious) should be discontinued, if possible, if they induce torsades de pointes

Imipramine, topiramate [2] ---> SmPC of [2] of eMC

Topiramate inhibits the enzyme CYP 2C19 and may interfere with other substances metabolized via this enzyme

Imipramine, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of imipramine thus increasing risk of toxicity

Imipramine, tricyclic antidepressant

The co-administration may cause additive effects on the serotonergic system

Imipramine, urapidil

Hypotensive effect and risk of orthostatic hypotension

Imipramine, valdecoxib [2] ---> SmPC of [2] of EMA

Valdecoxib, CYP2C19 inhibitor, may increase the plasma concentrations of imipramine

Imipramine, venlafaxine [2] ---> SmPC of [2] of eMC

Caution should be exercised with co-administration of venlafaxine and imipramine.

Imipramine, xipamide [2] ---> SmPC of [2] of eMC

The dosage of other hypotensive drugs may require adjustment when used in conjunction with xipamide

Imipramine, zotepine

The co-administration may increase the plasma levels of both active principles and decrease the convulsion threshold (seizures)

CONTRAINDICATIONS of Imipramine

- Hypersensitivity to imipramine, any of the excipients in the tablets or cross-sensitivity to other tricyclic antidepressants of the dibenzazepine group.

- Any degree of heart block or cardiac arrhythmias; recent myocardial infarction;

- Severe liver disease;

- Porphyria;

- Narrow angle glaucoma;

- Urine retention;

- Mania;

- Concomitant treatment with selective, reversible MAO-A inhibitors, e.g. moclobemide.

- Children under six years of age.

http://www.medicines.org.uk/emc/

Imiquimod (Zyclara)

Breast-feeding, imiquimod [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Zyclara therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility, imiquimod [2] ---> SmPC of [2] of EMA

No clinical data are available, potential risk for human is unknown.

Imiquimod [1], immunosuppressives ---> SmPC of [1] of EMA

Due to its immunostimulating properties, imiquimod cream should be used with caution in patients who are receiving immunosuppressive medicinal products

Imiquimod [1], pregnancy ---> SmPC of [1] of EMA

Zyclara should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Imiquimod [1], systemic medicine ---> SmPC of [1] of EMA

Interactions with systemic medicinal products would be limited by the minimal percutaneous absorption of imiquimod cream.

Imiquimod, imiquimod [2] ---> SmPC of [2] of EMA

Concomitant use of Zyclara and any other imiquimod creams in the same treatment area should be avoided since they contain the same active ingredient (imiquimod) and may increase the risk for and severity of local skin reactions.

CONTRAINDICATIONS of Imiquimod (Zyclara)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/zyclara-epar-product-information_en.pdf 22/07/2025

Other trade names: Aldara, Imunocare crema, Zartra,

Imlifidase (Idefirix)

Adalimumab, imlifidase [2] ---> SmPC of [2] of EMA

Recommended time interval after administration of 0.25 mg/kg imlifidase: 4 days

Alemtuzumab, imlifidase [2] ---> SmPC of [2] of EMA

Recommended time interval after administration of 0.25 mg/kg imlifidase: 4 days

Basiliximab, imlifidase [2] ---> SmPC of [2] of EMA

Recommended time interval after administration of 0.25 mg/kg imlifidase: 4 days

Belatacept, imlifidase [2] ---> SmPC of [2] of EMA

Recommended time interval after administration of 0.25 mg/kg imlifidase: 1 week

Breast-feeding, imlifidase [2] ---> SmPC of [2] of EMA

It is unknown whether imlifidase is excreted in human milk. A risk to the suckling child cannot be excluded. Breast-feeding should be discontinued before imlifidase exposure.

Denosumab, imlifidase [2] ---> SmPC of [2] of EMA

Recommended time interval after administration of 0.25 mg/kg imlifidase: 4 days

Eculizumab, imlifidase [2] ---> SmPC of [2] of EMA

Eculizumab is not cleaved by imlifidase at the recommended dose level. No time interval needed (can be administered concomitantly with imlifidase)

Equine anti-thymocyte globulin, imlifidase [2] ---> SmPC of [2] of EMA

Imlifidase does not degrade equine anti-thymocyte globulin and no time interval between administrations needs to be considered.

Etanercept, imlifidase [2] ---> SmPC of [2] of EMA

Recommended time interval after administration of 0.25 mg/kg imlifidase: 4 days

Fertility, imlifidase [2] ---> SmPC of [2] of EMA

No specific studies on fertility and postnatal development have been conducted

Imlifidase [1], immunoglobulin G ---> SmPC of [1] of EMA

Imlifidase specifically cleaves IgG; the species specificity results in degradation of all subclasses of human and rabbit IgG.

Imlifidase [1], intravenous immunoglobulin ---> SmPC of [1] of EMA

Recommended time interval after administration of 0.25 mg/kg imlifidase: 12 hours

Imlifidase [1], pregnancy ---> SmPC of [1] of EMA

There are no data from use of imlifidase in pregnant women since pregnancy is a contraindication to kidney transplantation. As a precautionary measure, it is preferable to avoid the use of imlifidase during pregnancy.

Imlifidase [1], rabbit anti-human thymocyte globulin ---> SmPC of [1] of EMA

Recommended time interval after administration of 0.25 mg/kg imlifidase: 1 week

Imlifidase [1], rituximab ---> SmPC of [1] of EMA

Recommended time interval after administration of 0.25 mg/kg imlifidase: 4 days

CONTRAINDICATIONS of Imlifidase (Idefirix)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Ongoing serious infection.

- Thrombotic thrombocytopenic purpura (TTP). Patients with this blood disorder may be at risk of developing serum sickness.

https://www.ema.europa.eu/en/documents/product-information/idefirix-epar-product-information_en.pdf 15/07/2024

Inavolisib (Itovebi)

Ability to drive, inavolisib [2] ---> SmPC of [2] of EMA

Itovebi has minor influence on the ability to drive or use machines because fatigue has been reported during treatment with Itovebi.

Alfentanyl, inavolisib [2] ---> SmPC of [2] of EMA

Therefore, inavolisib should be used with caution in combination with sensitive CYP3A4 substrates with a narrow therapeutic index as inavolisib may increase or decrease the systemic exposure of these substrates.

Astemizole, inavolisib [2] ---> SmPC of [2] of EMA

Breast-feeding, inavolisib [2] ---> SmPC of [2] of EMA

A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Itovebi and for 1 week after the last dose of Itovebi.

Cisapride, inavolisib [2] ---> SmPC of [2] of EMA

Cyclosporine, inavolisib [2] ---> SmPC of [2] of EMA

CYP inducers, inavolisib [2] ---> SmPC of [2] of EMA

Clinical study results indicated that the predominant metabolites of inavolisib are not mediated by CYP enzymes, and that hydrolysis was the major metabolic pathway.

CYP inhibitors, inavolisib [2] ---> SmPC of [2] of EMA

Clinical study results indicated that the predominant metabolites of inavolisib are not mediated by CYP enzymes, and that hydrolysis was the major metabolic pathway.

CYP3A4 substrates with narrow therapeutic index, inavolisib [2] ---> SmPC of [2] of EMA

Fertility, inavolisib [2] ---> SmPC of [2] of EMA

No human data on the effect of inavolisib on fertility are available. Based on animal studies, inavolisib may impact fertility in females and males of reproductive potential (see section 5.3).

Inavolisib [1], men ---> SmPC of [1] of EMA

To avoid potential foetal exposure during pregnancy, male patients with female partners of childbearing potential or pregnant female partners should use a condom during treatment with Itovebi and for 1 week after the last dose of Itovebi.

Inavolisib [1], narrow therapeutic margin ---> SmPC of [1] of EMA

In addition, inavolisib induces CYP2B6, CYP2C8, CYP2C9, and CYP2C19 in vitro. Therefore, inavolisib should be used with caution in combination with sensitive substrates of these enzymes with a narrow therapeutic index

Inavolisib [1], paclitaxel ---> SmPC of [1] of EMA

Inavolisib [1], phenytoin ---> SmPC of [1] of EMA

Inavolisib [1], pregnancy ---> SmPC of [1] of EMA

Studies in animals have shown reproductive toxicity (see section 5.3). Itovebi is not recommended during pregnancy and in women of childbearing potential not using contraception.

Inavolisib [1], quinidine ---> SmPC of [1] of EMA

Inavolisib [1], sirolimus ---> SmPC of [1] of EMA

Inavolisib [1], tacrolimus ---> SmPC of [1] of EMA

Inavolisib [1], warfarin ---> SmPC of [1] of EMA

Inavolisib [1], women ---> SmPC of [1] of EMA

Patients should be advised to use effective non-hormonal contraception during treatment with Itovebi and for 1 week after the last dose of Itovebi.

CONTRAINDICATIONS of Inavolisib (Itovebi)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/itovebi-epar-product-information_en.pdf 27/08/2025

Human normal immunoglobulin

Ability to drive, human normal immunoglobulin [2] ---> SmPC of [2] of EMA

The ability to drive and operate machines may be impaired by some adverse reactions associated with KIOVIG.

Breast-feeding, human normal immunoglobulin [2] ---> SmPC of [2] of EMA

Immunoglobulins are excreted into the milk and may contribute to protecting the neonate from pathogens which have a mucosal portal of entry.

Human normal immunoglobulin [1], measles vaccine ---> SmPC of [1] of EMA

Decrease of the immune response to live attenuated virus vaccines for up to 1 year

Human normal immunoglobulin [1], pregnancy ---> SmPC of [1] of EMA

Clinical experience with immunoglobulins suggests that no harmful effects on the course of pregnancy, or on the foetus and the neonate are to be expected.

Human normal immunoglobulin [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

After administration of this product, an interval of 3 months should elapse before vaccination with live attenuated virus vaccines.

Human normal immunoglobulin [1], varicella vaccine ---> SmPC of [1] of EMA

Vaccination should be deferred for at least 5 months

CONTRAINDICATIONS of Human normal immunoglobulin

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Hypersensitivity to human immunoglobulins, especially in patients with antibodies against IgA.

http://www.ema.europa.eu/

Inclisiran (Leqvio)

Atorvastatin, inclisiran [2] ---> SmPC of [2] of EMA

Based on the limited data available, clinically meaningful interactions with atorvastatin, rosuvastatin or other statins are not expected.

Breast-feeding, inclisiran [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from inclisiran therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Cytochrome P450, inclisiran [2] ---> SmPC of [2] of EMA

Therefore, inclisiran is not expected to have clinically significant interactions with other medicinal products.

Fertility, inclisiran [2] ---> SmPC of [2] of EMA

No data on the effect of inclisiran on human fertility are available. Animal studies did not show any effects on fertility (see section 5.3).

Inclisiran [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of inclisiran during pregnancy.

Inclisiran [1], rosuvastatin ---> SmPC of [1] of EMA

Based on the limited data available, clinically meaningful interactions with atorvastatin, rosuvastatin or other statins are not expected.

Inclisiran [1], statins ---> SmPC of [1] of EMA

Based on the limited data available, clinically meaningful interactions with atorvastatin, rosuvastatin or other statins are not expected.

CONTRAINDICATIONS of Inclisiran (Leqvio)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/leqvio-epar-product-information_en.pdf 13/05/2024

Indacaterol (Oslif Breezhaler)

Beta2-adrenergic agonists, betablockers ---> SmPC of [indacaterol] of EMA

Beta-adrenergic blockers and beta2-adrenergic agonists may weaken or antagonise the effect of each other when administered concurrently.

Beta2-adrenergic agonists, indacaterol [2] ---> SmPC of [2] of EMA

Oslif Breezhaler should not be used in conjunction with other long-acting beta2-adrenergic agonists or medicinal products containing long-acting beta2-adrenergic agonists.

Betablockers, indacaterol [2] ---> SmPC of [2] of EMA

Therefore indacaterol should not be given together with beta-adrenergic blockers (including eye drops) unless there are compelling reasons for their use.

Corticosteroids, indacaterol [2] ---> SmPC of [2] of EMA

Concomitant hypokalaemic treatment may potentiate the possible hypokalaemic effect indacaterol. Use with caution

Fertility, indacaterol [2] ---> SmPC of [2] of EMA

A decreased pregnancy rate has been observed in rats. Nevertheless, it is considered unlikely that indacaterol will affect reproductive or fertility performance in humans following inhalation of the maximum recommended dose (see section 5.3).

Glycopyrronium [1], indacaterol ---> SmPC of [1] of EMA

Concomitant administration of glycopyrronium and orally inhaled indacaterol, a beta2-adrenergic agonist, under steady-state conditions of both active substances did not affect the pharmacokinetics of either medicinal product.

Hypokalemia, indacaterol [2] ---> SmPC of [2] of EMA

Concomitant hypokalaemic treatment may potentiate the possible hypokalaemic effect indacaterol. Use with caution

Indacaterol [1], loop diuretics ---> SmPC of [1] of EMA

Concomitant hypokalaemic treatment may potentiate the possible hypokalaemic effect indacaterol. Use with caution

Indacaterol [1], medicinal products ---> SmPC of [1] of EMA

Indacaterol has not been shown to cause interactions with medicinal products administered concomitantly.

Indacaterol [1], P-glycoprotein and CYP3A4 inhibitors ---> SmPC of [1] of EMA

Inhibition of the key contributors of indacaterol clearance, CYP3A4 and P-glycoprotein (P-gp) raises the systemic exposure of indacaterol by up to two-fold.

Indacaterol [1], pregnancy ---> SmPC of [1] of EMA

Oslif Breezhaler should only be used during pregnancy if the expected benefits outweigh the potential risks

Indacaterol [1], sympathomimetics ---> SmPC of [1] of EMA

Concomitant administration of other sympathomimetic medicinal products (alone or as part of combination therapy) may potentiate adverse reactions to Oslif Breezhaler.

Indacaterol [1], thiazides ---> SmPC of [1] of EMA

Concomitant hypokalaemic treatment may potentiate the possible hypokalaemic effect indacaterol. Use with caution

Indacaterol [1], xanthines ---> SmPC of [1] of EMA

Concomitant hypokalaemic treatment may potentiate the possible hypokalaemic effect indacaterol. Use with caution

CONTRAINDICATIONS of Indacaterol (Oslif Breezhaler)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/oslif-breezhaler-epar-product-information_en.pdf 08/09/2021

Other trade names: Hirobriz Breezhaler, Onbrez Breezhaler,

Indacaterol/glycopyrronium (Xoterna Breezhaler)

Ability to drive, indacaterol/glycopyrronium [2] ---> SmPC of [2] of EMA

This medicinal product has no or negligible influence on the ability to drive and use machines. However, the occurrence of dizziness may influence the ability to drive and use machines

Anticholinergics, indacaterol/glycopyrronium [2] ---> SmPC of [2] of EMA

The co-administration of indacaterol/glycopyrronium with other anticholinergic-containing medicinal products has not been studied and is therefore not recommended

Betablockers, indacaterol/glycopyrronium [2] ---> SmPC of [2] of EMA

Indacaterol should not be given together with beta-adrenergic blockers (including eye drops) unless there are compelling reasons for their use

Breast-feeding, indacaterol/glycopyrronium [2] ---> SmPC of [2] of EMA

The use of Xoterna Breezhaler by breast-feeding women should only be considered if the expected benefit to the woman is greater than any possible risk to the infant

Cimetidine, indacaterol/glycopyrronium [2] ---> SmPC of [2] of EMA

No clinically relevant drug interaction is expected when glycopyrronium is co-administered with cimetidine or other inhibitors of the organic cation transport.

Corticosteroids, hypokalemia ---> SmPC of [indacaterol/glycopyrronium] of EMA

Concomitant hypokalaemic treatment with methylxanthine derivatives, steroids, or non-potassium-sparing diuretics may potentiate the possible hypokalaemic effect of beta2-adrenergic agonists, therefore use with caution

CYP3A4 and P-glycoprotein-inhibitors, indacaterol/glycopyrronium [2] ---> SmPC of [2] of EMA

Inhibition of the key contributors of indacaterol clearance, CYP3A4 and P-glycoprotein (P-gp) raises the systemic exposure of indacaterol by up to two-fold.

Fertility, indacaterol/glycopyrronium [2] ---> SmPC of [2] of EMA

Reproduction studies and other data in animals do not indicate a concern regarding fertility in either males or females.

Hypokalemia, indacaterol/glycopyrronium [2] ---> SmPC of [2] of EMA

Concomitant hypokalaemic treatment may potentiate the possible hypokalaemic effect indacaterol. Use with caution

Hypokalemia, non-potassium-sparing diuretics ---> SmPC of [indacaterol/glycopyrronium] of EMA

Hypokalemia, xanthines ---> SmPC of [indacaterol/glycopyrronium] of EMA

Indacaterol/glycopyrronium [1], OCT inhibitors ---> SmPC of [1] of EMA

No clinically relevant drug interaction is expected when glycopyrronium is co-administered with cimetidine or other inhibitors of the organic cation transport.

Indacaterol/glycopyrronium [1], pregnancy ---> SmPC of [1] of EMA

Xoterna Breezhaler should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the foetus.

Indacaterol/glycopyrronium [1], sympathomimetics ---> SmPC of [1] of EMA

Concomitant administration of other sympathomimetic medicinal products (alone or as part of combination therapy) may potentiate adverse reactions to indacaterol.

CONTRAINDICATIONS of Indacaterol/glycopyrronium (Xoterna Breezhaler)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/xoterna-breezhaler-epar-product-information_en.pdf 25/07/2025

Other trade names: Ultibro Breezhaler, Ulunar Breezhaler,

Indacaterol/mometasone (Bemrist Breezhaler)

Beta-adrenergic agonists, betablockers ---> SmPC of [indacaterol/mometasone] of EMA

Beta-adrenergic blockers may weaken or antagonise the effect of beta2-adrenergic agonists. Therefore, this medicinal product should not be given together with beta-adrenergic blockers unless there are compelling reasons for their use.

Beta2-adrenergic agonists, beta2-adrenergic agonists

The co-administration of this medicinal product with other medicinal products containing long-acting beta2-adrenergic agonists has not been studied and is not recommended as it may potentiate adverse reactions

Betablockers, indacaterol/mometasone [2] ---> SmPC of [2] of EMA

Breast-feeding, indacaterol/mometasone [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman

Cobicistat, indacaterol/mometasone [2] ---> SmPC of [2] of EMA

There may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, nelfinavir, ritonavir, cobicistat) are co-administered.

Corticosteroids, hypokalemia ---> SmPC of [indacaterol/mometasone] of EMA

Concomitant hypokalaemic treatment with methylxanthine derivatives, steroids or non-potassium-sparing diuretics may potentiate the possible hypokalaemic effect of beta2-adrenergic agonists

Fertility, indacaterol/mometasone [2] ---> SmPC of [2] of EMA

Reproduction studies and other data in animals did not indicate a concern regarding fertility in either males or females.

Hypokalemia, potassium-sparing diuretics ---> SmPC of [indacaterol/mometasone] of EMA

Concomitant hypokalaemic treatment with methylxanthine derivatives, steroids or non-potassium-sparing diuretics may potentiate the possible hypokalaemic effect of beta2-adrenergic agonists

Hypokalemia, xanthines ---> SmPC of [indacaterol/mometasone] of EMA

Concomitant hypokalaemic treatment with methylxanthine derivatives, steroids or non-potassium-sparing diuretics may potentiate the possible hypokalaemic effect of beta2-adrenergic agonists

IMAOs, indacaterol/mometasone [2] ---> SmPC of [2] of EMA

This medicinal product should be administered with caution to patients being treated with monoamine oxidase inhibitors, as any effect of these on the QT interval may be potentiated.

Indacaterol/mometasone [1], itraconazol ---> SmPC of [1] of EMA

There may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, nelfinavir, ritonavir, cobicistat) are co-administered.

Indacaterol/mometasone [1], ketoconazole ---> SmPC of [1] of EMA

There may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, nelfinavir, ritonavir, cobicistat) are co-administered.

Indacaterol/mometasone [1], nelfinavir ---> SmPC of [1] of EMA

There may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, nelfinavir, ritonavir, cobicistat) are co-administered.

Indacaterol/mometasone [1], P-glycoprotein and CYP3A4 inhibitors ---> SmPC of [1] of EMA

Inhibition of the key contributors of indacaterol clearance (CYP3A4 and P-gp) or mometasone furoate clearance (CYP3A4) raises the systemic exposure of indacaterol or mometasone furoate up to two-fold.

Indacaterol/mometasone [1], pregnancy ---> SmPC of [1] of EMA

This medicinal product should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the foetus.

Indacaterol/mometasone [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

This medicinal product should be administered with caution to patients being treated with medicinal products known to prolong the QT interval, as any effect of these on the QT interval may be potentiated.

Indacaterol/mometasone [1], ritonavir ---> SmPC of [1] of EMA

There may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, nelfinavir, ritonavir, cobicistat) are co-administered.

Indacaterol/mometasone [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

There may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, nelfinavir, ritonavir, cobicistat) are co-administered.

Indacaterol/mometasone [1], tricyclic antidepressant ---> SmPC of [1] of EMA

This medicinal product should be administered with caution to patients being treated with tricyclic antidepressants, as any effect of these on the QT interval may be potentiated.

CONTRAINDICATIONS of Indacaterol/mometasone (Bemrist Breezhaler)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/bemrist-breezhaler-epar-product-information_en.pdf 07/10/2025

Other trade names: Atectura Breezhaler,

Indapamide

Ability to drive, indapamide [2] ---> SmPC of [2] of eMC

In individual cases the hypotensive effect may impact on a patient´s ability to drive and operate machinery, especially at the start of treatment or when another antihypertensive agent is added.

ACE inhibitors, indapamide [2] ---> SmPC of [2] of eMC

Risk of sudden hypotension and/or acute renal failure when treatment with an ACE inhibitor is initiated in the presence of preexisting sodium depletion (particularly in patients with renal artery stenosis).

Amiloride, indapamide [2] ---> SmPC of [2] of eMC

Whilst rational combinations are useful in some patients, hypokalaemia or hyperkalaemia (particularly in patients with renal failure or diabetes) may still occur. Plasma potassium and ECG should be monitored and, if necessary, treatment re

Amiodarone, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Amisulpride, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Amphotericin B, indapamide [2] ---> SmPC of [2] of eMC

Increased risk of hypokalaemia (additive effect).

Amphotericin, indapamide [2] ---> SmPC of [2] of eMC

Increased risk of hypokalaemia (additive effect).

Baclofen, indapamide [2] ---> SmPC of [2] of eMC

Increased antihypertensive effect.

Benzamides, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Bepridil, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Breast-feeding, indapamide [2] ---> SmPC of [2] of eMC

Indapamide is excreted in human milk. Effects on the breast-fed child are likely and therefore indapamide is not recommended during breast-feeding.

Bumetanide, indapamide [2] ---> SmPC of [2] of eMC

The co-administration of indapamide with diuretics which may cause hypokalaemia is not recommended.

Calcium, indapamide [2] ---> SmPC of [2] of eMC

Risk of hypercalcaemia resulting from decreased urinary elimination of calcium

Chlorpromazine, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Cisapride, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Class IA antiarrhythmic agents, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Class III antiarrhythmic agents, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Corticosteroids, indapamide [2] ---> SmPC of [2] of eMC

Increased risk of hypokalaemia (additive effect). Decreased antihypertensive effect (water/sodium retention due to corticosteroids).

Coxibs, indapamide [2] ---> SmPC of [2] of eMC

Possible reduction in the antihypertensive effect of indapamide. Risk of acute renal failure in dehydrated patients (decreased glomerular filtration).

Cyamemazine, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Cyclosporine, indapamide [2] ---> SmPC of [2] of eMC

Risk of increased plasma creatinine without any change in circulating cyclosporin levels, even in the absence of water/sodium depletion.

Digital glycosides, indapamide [2] ---> SmPC of [2] of eMC

Hypokalaemia predisposing to the toxic effects of digitalis. Monitoring of plasma potassium and ECG and, if necessary, adjust the treatment.

Diphemanil, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Disopyramide, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Diuretics, indapamide [2] ---> SmPC of [2] of eMC

The co-administration of indapamide with diuretics which may cause hypokalaemia is not recommended.

Dofetilide, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Droperidol, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Drugs inducing bradycardia, indapamide [2] ---> SmPC of [2] of eMC

Bradycardia is a predisposing factor to the onset of severe arrhythmias, in particular, potentially fatal torsades de pointes

Erythromycin, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Furosemide, indapamide [2] ---> SmPC of [2] of eMC

The co-administration of indapamide with diuretics which may cause hypokalaemia is not recommended.

Glucocorticoids, indapamide [2] ---> SmPC of [2] of eMC

Increased risk of hypokalaemia (additive effect). Decreased antihypertensive effect (water/sodium retention due to corticosteroids).

Halofantrine, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Haloperidol, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Hydroquinine, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Hypokalemia, indapamide [2] ---> SmPC of [2] of eMC

Increased risk of hypokalaemia (additive effect).

Ibutilide, indapamide [2] ---> SmPC of [2] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Imipramine, indapamide [2] ---> SmPC of [2] of eMC

Antihypertensive effect and increased risk of orthostatic hypotension increased (additive effect).

Indapamide [1], iodinated contrast media ---> SmPC of [1] of eMC

In the presence of dehydration caused by diuretics, increased risk of acute renal failure, in particular when large doses of iodinated contrast media are used.

Indapamide [1], levomepromazine ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Indapamide [1], lithium ---> SmPC of [1] of eMC

Increased plasma lithium with signs of overdosage, as with a salt-free diet (decreased urinary lithium excretion).

Indapamide [1], metformin ---> SmPC of [1] of eMC

Increased risk of metformin induced lactic acidosis due to the possibility of functional renal failure associated with diuretics and more particularly with loop diuretics.

Indapamide [1], mineralocorticoids ---> SmPC of [1] of eMC

Increased risk of hypokalaemia (additive effect) with systemic mineralocorticoid

Indapamide [1], mizolastine ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Indapamide [1], moxifloxacin ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Indapamide [1], neuroleptics ---> SmPC of [1] of eMC

Antihypertensive effect and increased risk of orthostatic hypotension increased (additive effect).

Indapamide [1], NSAID ---> SmPC of [1] of eMC

Possible reduction in the antihypertensive effect of indapamide. Risk of acute renal failure in dehydrated patients (decreased glomerular filtration).

Indapamide [1], pentamidine ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Indapamide [1], photosensitizing agents ---> SmPC of [1] of eMC

Cases of photosensitivity reactions have been reported with thiazides and thiazide-related diuretics

Indapamide [1], piretanide ---> SmPC of [1] of eMC

The co-administration of indapamide with diuretics which may cause hypokalaemia is not recommended.

Indapamide [1], potassium-sparing diuretics ---> SmPC of [1] of eMC

Indapamide [1], pregnancy ---> SmPC of [1] of eMC

As a general rule, the administration of diuretics should be avoided in pregnant women and should never be used to treat physiological oedema of pregnancy. Diuretics can cause foetoplacental ischaemia, with a risk of impaired foetal growth

Indapamide [1], quinidine ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Indapamide [1], salicylic acid ---> SmPC of [1] of eMC

High dose salicylic acid (≥3 g/day): Possible reduction in the antihypertensive effect of indapamide. Risk of acute renal failure in dehydrated patients (decreased glomerular filtration).

Indapamide [1], sotalol ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Indapamide [1], sparfloxacin ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Indapamide [1], spironolactone ---> SmPC of [1] of eMC

Indapamide [1], stimulant laxatives ---> SmPC of [1] of eMC

Increased risk of hypokalaemia (additive effect).

Indapamide [1], sulpiride ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Indapamide [1], sultopride ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Indapamide [1], tetracosactide ---> SmPC of [1] of eMC

Increased risk of hypokalaemia (additive effect). Decreased antihypertensive effect (water/sodium retention due to corticosteroids).

Indapamide [1], thiazides ---> SmPC of [1] of eMC

The co-administration of indapamide with diuretics which may cause hypokalaemia is not recommended.

Indapamide [1], thioridazine ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Indapamide [1], tiapride ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Indapamide [1], torsades de pointes inducing drugs ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Indapamide [1], triamterene ---> SmPC of [1] of eMC

Indapamide [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Antihypertensive effect and increased risk of orthostatic hypotension increased (additive effect).

Indapamide [1], trifluoperazine ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Indapamide [1], vincamine ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Indapamide [1], xipamide ---> SmPC of [1] of eMC

The co-administration of indapamide with diuretics which may cause hypokalaemia is not recommended.

Indapamide, loop diuretics [2] ---> SmPC of [2] of eMC

The co-administration of indapamide with diuretics which may cause hypokalaemia is not recommended.

Photosensitizing agents, thiazides ---> SmPC of [indapamide] of eMC

Cases of photosensitivity reactions have been reported with thiazides and thiazide-related diuretics

CONTRAINDICATIONS of Indapamide

- Hypersensitivity to indapamide, other sulphonamides or any ingredients

- Severe renal failure.

- Hepatic encephalopathy or severe impairment of liver function.

- Hypokalaemia.

http://www.medicines.org.uk/emc/

Indinavir

Ability to drive, indinavir [2] ---> SmPC of [2] of EMA

Patients should be informed that dizziness and blurred vision have been reported during treatment with indinavir.

Alfentanyl, indinavir [2] ---> SmPC of [2] of EMA

Indinavir with or without ritonavir should not be administered with medicinal products with narrow therapeutic ranges and which are CYP3A4 substrates. The elevated plasma concentrations of these medicines may cause serious or life-threatening reactions.

Alfentanyl, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Alfuzosin, indinavir [2] ---> SmPC of [2] of EMA

Alfuzosin, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir should not be administered with alfuzosin

Alprazolam, indinavir [2] ---> SmPC of [2] of EMA

Alprazolam, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Amiodarone, indinavir [2] ---> SmPC of [2] of EMA

Amiodarone, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Amlodipine, indinavir ---> SmPC of [amlodipine/valsartan] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.

Amprenavir, indinavir [2] ---> SmPC of [2] of EMA

The appropriate doses for this combination, with respect to efficacy and safety, have not been established.

Amprenavir, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Ritonavir increases the serum levels of amprenavir as a result of CYP3A4 inhibition. The appropriate doses for this combination, with respect to efficacy and safety, have not been established.

Ascorbic acid, indinavir

Ascorbic acid may decrease the plasma levels of indinavir

Astemizole, indinavir [2] ---> SmPC of [2] of EMA

Astemizole, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Atazanavir, indinavir [2] ---> SmPC of [2] of EMA

Combination of atazanavir with or without ritonavir and Crixivan are not recommended due to increased risk of hyperbilirubinemia

Atazanavir/cobicistat [1], indinavir ---> SmPC of [1] of EMA

Indinavir is associated with indirect unconjugated hyperbilirubinaemia due to inhibition of UGT. Co-administration of EVOTAZ and indinavir is not recommended

Atazanavir/ritonavir, indinavir ---> SmPC of [atazanavir] of EMA

Combination of atazanavir with or without ritonavir and Crixivan are not recommended due to increased risk of hyperbilirubinemia

Atenolol/nifedipine [1], indinavir ---> SmPC of [1] of eMC

Drugs known to inhibit the cytochrome P450 3A4 system when administered orally with nifedipine may substantial increase the systemic bioavailability of nifedipine due to a decreased first pass metabolism and a decreased elimination

Atorvastatin, indinavir [2] ---> SmPC of [2] of EMA

Increased atorvastatin concentration. Atorvastatin is less dependent on CYP3A4 for metabolism than lovastatin or simvastatin. Use the lowest possible dose of atorvastatin with careful monitoring. Caution is advised.

Atorvastatin, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Atovaquone [1], indinavir ---> SmPC of [1] of eMC

Concomitant administration of atovaquone and indinavir results in a significant decrease in the C min of indinavir and the AUC. Caution should be exercised on the potential risk of failure of indinavir treatment if co-administered with atovaquone.

Atovaquone, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

The glucuronidation induction by ritonavir may decrease plasma concentrations of atovaquone. Careful monitoring is recommended

Avanafil [1], indinavir ---> SmPC of [1] of EMA

Avanafil is predominantly metabolised by CYP3A4. The strong CYP3A4 inhibitors may increase the exposition of avanafil. Co-administration of avanafil with potent CYP3A4 inhibitors is contraindicated

Axitinib [1], indinavir ---> SmPC of [1] of EMA

Co-administration of axitinib with strong CYP3A4/5 inhibitors may increase axitinib plasma concentrations. Selection of concomitant medicinal products with no or minimal CYP3A4/5 inhibition potential is recommended.

Bepridil, indinavir [2] ---> SmPC of [2] of EMA

Bepridil, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir should not be administered with bepridil

Binimetinib [1], indinavir ---> SmPC of [1] of EMA

UGT1A1 inducers (such as rifampicin and phenobarbital) and inhibitors (such as indinavir, atazanavir, sorafenib) should be co-administered with caution.

Bosutinib [1], indinavir ---> SmPC of [1] of EMA

The concomitant use of bosutinib with potent CYP3A inhibitors should be avoided, as an increase in bosutinib plasma levels will occur. Selection of an alternate concomitant medicine with no or minimal CYP3A enzyme inhibition potential is recommended.

Breast-feeding, indinavir [2] ---> SmPC of [2] of EMA

It is recommended that HIV-infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.

Buprenorphine [1], indinavir ---> SmPC of [1] of eMC

Concomitant administration of buprenorphine and potent CYP3A4 inhibitors can lead to markedly increased plasma concentrations of buprenorphine and norbuprenorphine. The combination should be avoided or monitored closely

Buprenorphine/naloxone [1], indinavir ---> SmPC of [1] of EMA

Medicines that inhibit the enzyme CYP3A4 may give rise to increased concentrations of buprenorphine. A reduction of the buprenorphine/naloxone dose may be needed.

Buspirone, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Indinavir and ritonavir inhibit CYP3A4 and as a result are expected to increase the plasma concentrations of buspirone. Careful monitoring of therapeutic and adverse effects is recommended

Cabazitaxel [1], indinavir ---> SmPC of [1] of EMA

Repeated administration of ketoconazole, a strong CYP3A inhibitor, decreased cabazitaxel clearance. Therefore concomitant administration of strong CYP3A inhibitors should be avoided as an increase of plasma concentrations of cabazitaxel may occur

Carbamazepine, indinavir [2] ---> SmPC of [2] of EMA

Indinavir inhibits CYP3A4 and as a result is expected to increase the plasma concentrations of this anticonvulsant. Concomitant use of medicinal products that are inducers of CYP3A4 may reduce indinavir plasma concentrations.

Carbamazepine, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Ritonavir/ritonavir, CYP3A4 inhibitors, may increase the concentrations of carbamazepine. Careful monitoring of therapeutic and adverse effects is recommended.

Cariprazine [1], indinavir ---> SmPC of [1] of EMA

Metabolism of cariprazine and its major active metabolites is mediated mainly by CYP3A4. The co-administration of cariprazine with strong or moderate inhibitors of CYP3A4 is contraindicated

Cimetidine, indinavir [2] ---> SmPC of [2] of EMA

Indinavir and cimetidine can be co-administered without dose adjustment.

Cinitapride, indinavir

The strong CYP3A4 inhibition may increase the plasma concentrations of cinitapride

Cisapride, indinavir [2] ---> SmPC of [2] of EMA

Cisapride, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Clozapine, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir should not be administered with clozapine

Codergocrin, indinavir

The strong CYP3A4 inhibition may increase the exposition to codergocrin, which may cause a dopaminergic effect. Concomitant use should be avoided

Colchicine [1], indinavir ---> SmPC of [1] of eMC

Colchicine is contraindicated in patients with renal or hepatic impairment who are taking a strong CYP3A4 inhibitor

Crizotinib [1], indinavir ---> SmPC of [1] of EMA

Coadministration of crizotinib with strong CYP3A inhibitors may increase crizotinib plasma concentrations. Therefore, the concomitant use of strong CYP3A inhibitors should be avoided.

Cyclosporine, indinavir [2] ---> SmPC of [2] of EMA

Cyclosporine A (CsA) levels markedly increase in patients on PIs, including indinavir. CsA levels require progressive dose adjustment using therapeutic medicinal product monitoring.

Cyclosporine, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Is expected to increase the plasma concentrations of cyclosporine. Careful monitoring of therapeutic and adverse effects is recommended

Dabrafenib [1], indinavir ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Darunavir/cobicistat, indinavir ---> SmPC of [darunavir] of EMA

Co-administration of darunavir and cobicistat with other medicinal products that inhibit CYP3A may result in increased plasma concentrations of darunavir and cobicistat. Co-administration with strong CYP3A4 inhibitors is not recommended

Darunavir/ritonavir, indinavir ---> SmPC of [darunavir] of EMA

Co-administration of darunavir and ritonavir with other medicinal products that inhibit CYP3A may decrease the clearance of darunavir and ritonavir. Co-administration with strong CYP3A4 inhibitors is not recommended and caution is warranted

Dasabuvir with ombitasvir/paritaprevir/ritonavir, indinavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

Co-administration of ombitasvir/paritaprevir/ritonavir with or without dasabuvir with medicinal products that are strong inhibitors of CYP3A4 is expected to increase paritaprevir plasma concentrations. The coadministration is contraindicated

Delavirdine, indinavir [2] ---> SmPC of [2] of EMA

Dose reduction of CRIXIVAN to 400-600 mg every 8 hours should be considered.

Dexamethasone, indinavir [2] ---> SmPC of [2] of EMA

The CYP3A4 inhibition/induction may increase/decrease the plasma concentrations of dexamethasone/indinavir. Careful monitoring is recommended

Dexamethasone, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

The CYP3A4 inhibition/induction may increase/decrease the plasma concentrations of dexamethasone/indinavir. Careful monitoring is recommended

Dextromethorphan/quinidine [1], indinavir ---> SmPC of [1] of EMA

Concomitant administration of medicines that inhibit CYP3A4 can be expected to increase plasma levels of quinidine, which could increase risk relating to QTc prolongation. Strong and moderate CYP3A4 inhibitors should be avoided during treatment.

Diazepam, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir should not be administered with diazepam

Didanosine, indinavir [2] ---> SmPC of [2] of EMA

Indinavir and didanosine formulations containing buffer should be administered at least 1 hour apart on an empty stomach.

Digitoxin, indinavir

The CYP3A4 inhibition may increase the plasma levels of digitoxin

Digoxin, indinavir [2] ---> SmPC of [2] of EMA

The P-glycoprotein inhibition by ritonavir may increase the plasma concentrations of digoxin. Careful monitoring is recommended

Digoxin, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Ritonavir may increase digoxin levels due to modification of P-glycoprotein mediated digoxin efflux. Careful monitoring of digoxin levels is recommended when digoxin is concomitantly administered with indinavir/ritonavir.

Dihydroergocristine, indinavir [2] ---> SmPC of [2] of EMA

Dihydroergocristine, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Dihydroergotamine, indinavir [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of dihydroergotamine. The co-administration is contraindicated

Dihydroergotamine, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Dihydroergotoxine, indinavir [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the exposition to dihydroergotoxine, which may cause a dopaminergic effect. Concomitant use should be avoided

Dihydroergotoxine, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Dihydropyridines, indinavir [2] ---> SmPC of [2] of EMA

Increased dihydropyridine calcium channel blocker concentration. Calcium channel blockers are metabolized by CYP3A4 which is inhibited by indinavir. Caution is warranted and clinical monitoring of patients is recommended.

Diltiazem, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Dose modification of calcium channel blocker should be considered when coadministered with indinavir/ritonavir as it may result in an increased response.

Dipotassium clorazepate, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir should not be administered with clorazepate

Disopyramide, indinavir [2] ---> SmPC of [2] of EMA

Disopyramide, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Divalproex sodium, ritonavir ---> SmPC of [indinavir] of EMA

Ritonavir, inductor of CYP2C9 and glucuronidation, may decrease the plasma concentrations of divalproex

Divalproex, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Ritonavir induces oxidation by CYP2C9 and glucuronidation and as a result is expected to decrease the plasma concentrations of anticonvulsant.

Docetaxel [1], indinavir ---> SmPC of [1] of EMA

In case of combination of docetaxel with CYP3A4 inhibitors, the occurrence of docetaxel adverse reactions may increase, as a result of reduced metabolism

Droperidol [1], indinavir ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Drugs metabolised by CYP3A4, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Boosted indinavir (indinavir with ritonavir) may have additive pharmacokinetic effects on substances that share the CYP3A4 pathway as both ritonavir and indinavir inhibit the cytochrome P450 enzyme CYP3A4.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, indinavir [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, indinavir/ritonavir ---> SmPC of [indinavir]

Drugs primarily metabolised by CYP3A4, indinavir [2] ---> SmPC of [2] of EMA

Indinavir may have pharmacokinetic effects on substances that share the CYP3A4 pathway as indinavir inhibits the cytochrome P450 enzyme CYP3A4.

Drugs primarily metabolised by CYP3A4, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Dutasteride [1], indinavir ---> SmPC of [1] of eMC

Long-term combination of dutasteride with drugs that are potent inhibitors of the enzyme CYP3A4 may increase serum concentrations of dutasteride.

Efavirenz [1], indinavir ---> SmPC of [1] of EMA

While the clinical significance of decreased indinavir concentrations has not been established, the magnitude of the observed pharmacokinetic interaction should be taken into consideration when choosing a regimen containing both efavirenz and indinavir.

Efavirenz/emtricitabine/tenofovir disoproxil [1], indinavir ---> SmPC of [1] of EMA

Insufficient data are available to make a dosing recommendation for indinavir when dosed with Atripla.

Eletriptan [1], indinavir ---> SmPC of [1] of eMC

In clinical studies with potent inhibitors of CYP3A4 significant increases in eletriptan Cmax and AUC were observed. Eletriptan should not be used together with potent CYP3A4 inhibitors

Eliglustat [1], indinavir ---> SmPC of [1] of EMA

Increased eliglustat exposition would be expected for strong inhibitors of CYP3A. Caution should be used with strong CYP3A inhibitors in intermediate and extensive metabolisers.

Encainide, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir should not be administered with encainide

Enzalutamide [1], indinavir ---> SmPC of [1] of EMA

Enzalutamide, enzymatic inductor, may increase the metabolism of indinavir and decrease its plasma levels and effect

Ergoloid mesylate, indinavir [2] ---> SmPC of [2] of EMA

Ergoloid mesylate, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Ergonovine, indinavir [2] ---> SmPC of [2] of EMA

Ergonovine, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Ergot derivatives, indinavir [2] ---> SmPC of [2] of EMA

Ergot derivatives, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Ergotamine, indinavir [2] ---> SmPC of [2] of EMA

Ergotamine, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Erythromycin, indinavir [2] ---> SmPC of [2] of EMA

Indinavir, CYP3A4 inhibitor, may increase the plasma concentrations of erythromycin. Careful monitoring is recommended

Erythromycin, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, CYP3A4 inhibitors, may increase the plasma concentrations of erythromycin. Careful monitoring is recommended

Estazolam, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir should not be administered with estazolam

Ethinylestradiol/chlormadinone, indinavir

Active principles which inhibit hepatic microsomal enzymes may increase plasma concentrations of ethinylestradiol

Ethinylestradiol/gestodene, indinavir

Substances which inhibit the CYP3A4 may increase the plasma concentrations of ethinylestradiol

Ethinylestradiol/norgestimate [1], indinavir ---> SmPC of [1] of eMC

Increase in plasma hormone levels associated with co-administered drug

Etravirine [1], indinavir ---> SmPC of [1] of EMA

Concomitant use of etravirine with indinavir may cause a significant decrease in the plasma concentration of indinavir and loss of therapeutic effect of indinavir. It is not recommended to co-administer etravirine with indinavir.

Everolimus [1], indinavir ---> SmPC of [1] of EMA

Large increase in everolimus concentration is expected. Concomitant treatment of everolimus and potent CYP3A4 inhibitors is not recommended.

Everolimus, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Ezetimibe/atorvastatin [1], indinavir ---> SmPC of [1] of eMC

Potent CYP3A4 inhibitors have been shown to lead to markedly increased concentrations of atorvastatin. Coadministration of potent CYP3A4 inhibitors should be avoided if possible.

Felodipine, indinavir [2] ---> SmPC of [2] of EMA

Fentanyl, indinavir [2] ---> SmPC of [2] of EMA

Indinavir, CYP3A4 inhibitor, may increase the plasma concentrations of fentanyl. Careful monitoring is recommended

Fentanyl, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, CYP3A4 inhibitors, may increase the plasma concentrations of fentanyl. Careful monitoring is recommended

Fesoterodine [1], indinavir ---> SmPC of [1] of EMA

The maximum dose of fesoterodine should be restricted to 4 mg when used concomitantly with potent CYP3A4 inhibitors

Fexofenadine, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Ritonavir, P-glycoprotein inhibitor, may increase the plasma levels of fexofenadine. Careful monitoring is recommended

Flecainide [1], indinavir ---> SmPC of [1] of eMC

Plasma concentrations are increased by ritonavir, lopinavir and indinavir (increased risk of ventricular arrhythmias) (avoid concomitant use).

Flecainide, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir should not be administered with flecainide

Fluconazole, indinavir [2] ---> SmPC of [2] of EMA

Indinavir and fluconazole can be coadministered without dose adjustment.

Flurazepam, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir should not be administered with flurazepam

Fluvastatin, indinavir [2] ---> SmPC of [2] of EMA

Interaction via effects on transport proteins cannot be excluded.

Foods, indinavir [2] ---> SmPC of [2] of EMA

For optimal absorption, CRIXIVAN should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, CRIXIVAN may be administered with a low-fat, light meal.

Fosamprenavir/ritonavir, indinavir ---> SmPC of [fosamprenavir] of EMA

No dose recommendations can be given.

Fusidic acid, indinavir/ritonavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir should not be administered with fusidic acid

Guanfacin [1], indinavir ---> SmPC of [1] of EMA

Ibrutinib [1], indinavir ---> SmPC of [1] of EMA

Ibrutinib is primarily metabolised by cytochrome P450 enzyme 3A4. Concomitant use of ibrutinib and medicinal products that strongly inhibit CYP3A4 can increase ibrutinib exposure and should be avoided.

Imatinib [1], indinavir ---> SmPC of [1] of EMA

Indinavir [1], isoniazid ---> SmPC of [1] of EMA

Indinavir and isoniazid can be co-administered without dose adjustment.

Indinavir [1], isradipine ---> SmPC of [1] of EMA

Increased concentration of dihydropyridine calcium channel blocker. Calcium channel blockers are metabolized by CYP3A4 which is inhibited by indinavir. Caution is warranted and clinical monitoring of patients is recommended.

Indinavir [1], itraconazol ---> SmPC of [1] of EMA

Dose reduction of indinavir is recommended with administering itraconazole concurrently.

Indinavir [1], ketoconazole ---> SmPC of [1] of EMA

Dose reduction of CRIXIVAN to 600 mg every 8 hours should be considered.

Indinavir [1], lisuride ---> SmPC of [1] of EMA

Indinavir [1], lovastatine ---> SmPC of [1] of EMA

Indinavir inhibits CYP3A4 and as a result is expected to markedly increase the plasma levels of lovastatine, which are highly dependent on CYP3A4 metabolism. Combination contraindicated due to an increased risk of myopathy including rhabdomyolysis.

Indinavir [1], methadone ---> SmPC of [1] of EMA

Indinavir and methadone can be co-administered without dose adjustment.

Indinavir [1], methylergonovine ---> SmPC of [1] of EMA

Indinavir [1], methysergide ---> SmPC of [1] of EMA

Indinavir [1], midazolam ---> SmPC of [1] of EMA

Indinavir, CYP3A4 inhibitor, may increase the plasma concentrations of midazolam: oral contraindicated, caution on parenterally administered

Indinavir [1], nelfinavir ---> SmPC of [1] of EMA

Indinavir [1], nevirapine ---> SmPC of [1] of EMA

The CYP3A4 induction may decrease the plasma concentrations of indinavir. A dose increase of indinavir should be considered if given with nevirapine.

Indinavir [1], nicardipine ---> SmPC of [1] of EMA

Indinavir [1], nicergoline ---> SmPC of [1] of EMA

Indinavir [1], nifedipine ---> SmPC of [1] of EMA

Indinavir [1], norethisterone/ethinylestradiol ---> SmPC of [1] of EMA

Indinavir and norethindrone/ethinyl estradiol 1/35 can be coadministered without dose adjustment.

Indinavir [1], phenobarbital ---> SmPC of [1] of EMA

Indinavir [1], phenytoin ---> SmPC of [1] of EMA

Indinavir [1], pimozide ---> SmPC of [1] of EMA

Indinavir [1], pravastatine ---> SmPC of [1] of EMA

Interaction via effects on transport proteins cannot be excluded. If no alternative treatment is available, use with careful monitoring.

Indinavir [1], pregnancy ---> SmPC of [1] of EMA

Indinavir should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus

Indinavir [1], quetiapine ---> SmPC of [1] of EMA

Concomitant administration of indinavir and quetiapine may increase plasma concentrations of quetiapine leading to quetiapine-related toxicity, including coma. Co-administration of quetiapine with indinavir is contraindicated

Indinavir [1], quinidine ---> SmPC of [1] of EMA

Quinidine concentration expected (CYP3A4 inhibition by indinavir) Caution is warranted and therapeutic concentration monitoring is recommended for quinidine when coadministered with CRIXIVAN. The use of indinavir/ritonavir with quinidine is contraindicated

Indinavir [1], quinine ---> SmPC of [1] of EMA

Indinavir [1], rifabutin ---> SmPC of [1] of EMA

Dose reduction of rifabutin and dose increase of Crixivan has not been confirmed in clinical studies. Therefore coadministration is not recommended. If rifabutin treatment is required, alternative agents for treating HIV infection should be sought.

Indinavir [1], rifampicin ---> SmPC of [1] of EMA

Rifampicin, CYP3A4 inductor, may decrease the plasma concentrations of indinavir. The concomitant use is contraindicated

Indinavir [1], rosuvastatin ---> SmPC of [1] of EMA

Combination not recommended.

Indinavir [1], saquinavir ---> SmPC of [1] of EMA

The appropriate doses for this combination, with respect to efficacy and safety, have not been established.

Indinavir [1], sildenafil ---> SmPC of [1] of EMA

Coadministration of indinavir with sildenafil is likely to result in an increase of sildenafil by competitive inhibition of metabolism.

Indinavir [1], simvastatine ---> SmPC of [1] of EMA

Indinavir inhibits CYP3A4 and as a result is expected to markedly increase the plasma levels of simvastatine, which are highly dependent on CYP3A4 metabolism. Combination contraindicated due to an increased risk of myopathy including rhabdomyolysis.

Indinavir [1], St. John's wort ---> SmPC of [1] of EMA

Concurrent use of indinavir with herbal preparations containing St John 's wort (Hypericum perforatum) is contraindicated

Indinavir [1], stavudine ---> SmPC of [1] of EMA

Indinavir and NRTIs can be co-administered without dose adjustment.

Indinavir [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

The metabolism of indinavir is mediated by the cytochrome P450 enzyme CYP3A4. Therefore, other substances that either share this metabolic pathway or modify CYP3A4 activity may influence the pharmacokinetics of indinavir.

Indinavir [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Indinavir [1], sulfamethoxazol/trimethoprim ---> SmPC of [1] of EMA

Indinavir and sulphamethoxazole/trimethoprim can be coadministered without dose adjustment.

Indinavir [1], tadalafil ---> SmPC of [1] of EMA

Coadministration of indinavir with tadalafil is likely to result in an increase of tadalafil by competitive inhibition of metabolism.

Indinavir [1], terfenadine ---> SmPC of [1] of EMA

Indinavir [1], theophylline ---> SmPC of [1] of EMA

Indinavir and theophylline can be co-administered without dose adjustment.

Indinavir [1], triazolam ---> SmPC of [1] of EMA

Indinavir [1], warfarin ---> SmPC of [1] of EMA

Combined administration may result in increased warfarin levels. Dose adjustment of warfarin may be required.

Indinavir [1], zidovudine ---> SmPC of [1] of EMA

Indinavir and NRTIs can be co-administered without dose adjustment.

Indinavir [1], zidovudine/lamivudine ---> SmPC of [1] of EMA

Indinavir and NRTIs can be co-administered without dose adjustment.

Indinavir, irinotecan [2] ---> SmPC of [2] of EMA

Co-administration of ONIVYDE with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE.

Indinavir, isavuconazole [2] ---> SmPC of [2] of EMA

No dose adjustment of CRESEMBA is necessary when co-administered with strong CYP3A4/5 inhibitors, however caution is advised as adverse drug reactions may increase

Indinavir, ixabepilone

The strong CYP3A4 inhibition may increase the plasma concentrations of ixabepilone. The coadministration should be avoided

Indinavir, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

Less potent UGT1A1 inhibitors (e.g., indinavir, saquinavir) may also increase plasma levels of raltegravir, but to a lesser extent compared with atazanavir.

Indinavir, lopinavir/ritonavir [2] ---> SmPC of [2] of EMA

The appropriate doses for this combination, with respect to efficacy and safety, have not been established.

Indinavir, lurasidone [2] ---> SmPC of [2] of EMA

Lurasidone and its active metabolite ID-14283 are primarily metabolised by CYP3A4. Lurasidone is contraindicated with strong CYP3A4 inhibitors

Indinavir, maraviroc [2] ---> SmPC of [2] of EMA

Indinavir is a potent CYP3A4 inhibitor. Population PK analysis in phase 3 studies suggests dose reduction of maraviroc when co-administered with indinavir gives appropriate maraviroc exposure.

Indinavir, methylergometrine

The strong CYP3A4 inhibition may increase the plasma concentrations of methylergometrine. The concomitant use should be avoided

Indinavir, naloxegol [2] ---> SmPC of [2] of EMA

Concomitant use of naloxegol with CYP3A4 inhibitors increases naloxegol exposition. Concomitant use of naloxegol with strong CYP3A4 inhibitors is contraindicated

Indinavir, neratinib [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4/Pgp inhibitors should be avoided.

Indinavir, nisoldipine

The co-administration of nisoldipine with medicinal products that inhibit the cytochrome P450 3A4-system may increase the bioavailability of nisoldipine. Concomitant use is contraindicated

Indinavir, olaparib [2] ---> SmPC of [2] of EMA

CYP3A4/5 are the isozymes predominantly responsible for the metabolic clearance of olaparib. It is recommended that known strong inhibitors of these isozymes should be avoided with olaparib

Indinavir, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Indinavir, paclitaxel [2] ---> SmPC of [2] of EMA

The metabolism of paclitaxel is catalysed, in part, by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Therefore, caution should be exercised when administering paclitaxel concomitantly with medicines known to inhibit either CYP2C8 or CYP3A4.

Indinavir, palbociclib [2] ---> SmPC of [2] of EMA

Strong inhibitors of CYP3A4 may lead to increased toxicity. Concomitant use of strong CYP3A inhibitors during treatment with palbociclib should be avoided.

Indinavir, pazopanib [2] ---> SmPC of [2] of EMA

Concomitant treatment with strong inhibitors of CYP3A4 should be avoided due to risk of increased exposure to pazopanib

Indinavir, piperaquine/artenimol [2] ---> SmPC of [2] of EMA

Concomitant treatment with medicinal products which inhibit CYP3A4 may lead to a marked increase of piperaquine plasma concentration resulting in an exacerbation of the effect on QTc

Indinavir, ponatinib [2] ---> SmPC of [2] of EMA

Caution should be exercised and a reduction of the starting dose should be considered with concurrent use of ponatinib with strong CYP3A inhibitors (modest increases in ponatinib systemic exposure are possible)

Indinavir, prasugrel [2] ---> SmPC of [2] of EMA

CYP3A inhibitors are not anticipated to have a significant effect on the pharmacokinetics of the prasugrel active metabolite.

Indinavir, protease inhibitors

Generally, dual therapy with protease inhibitors is not recommended

Indinavir, raltegravir [2] ---> SmPC of [2] of EMA

The inhibition of UGT1A1 may increase plasma levels of raltegravir

Indinavir, ribociclib [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors should be avoided and an alternative concomitant medicinal product with less potential to inhibit CYP3A4 inhibition should be considered.

Indinavir, rilpivirine [2] ---> SmPC of [2] of EMA

Not studied. Increased exposure (inhibition of CYP3A enzymes) of rilpivirine is expected. No dose adjustment is required.

Indinavir, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir increases the serum levels of indinavir as a result of CYP3A4 inhibition.

Indinavir, ruxolitinib [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase ruxolitinib exposition. When co-administering with strong CYP3A4 inhibitors the unit dose of ruxolitinib should be reduced

Indinavir, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Low dose ritonavir increases the concentration of indinavir. Increased concentrations of indinavir may result in nephrolithiasis.

Indinavir, sertindole

The concomitant administration of CYP3A inhibitors and sertindole is contraindicated, as this may lead to significant increases in sertindole levels

Indinavir, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Indinavir, sirolimus [2] ---> SmPC of [2] of EMA

Inhibitors of CYP3A4 may decrease the metabolism of sirolimus and increase sirolimus blood levels.

Indinavir, temsirolimus [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors may increase blood concentrations of the active moieties, temsirolimus and its metabolite, sirolimus. Therefore, concomitant treatment with agents that have strong CYP3A4 inhibition potential should be avoided.

Indinavir, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Indinavir, trazodone [2] ---> SmPC of [2] of eMC

It is likely that potent CYP3A4 inhibitors may lead to substantial increases in trazodone plasma concentrations. The co-administration of trazodone and potent CYP3A4 inhibitors should be avoided where possible.

Indinavir, trofosfamide

The inhibition of CYP3A4 may increase the formation of a trofosfamide metabolite which is related with nephrotoxicity and CNS toxicity

Indinavir, vardenafil [2] ---> SmPC of [2] of EMA

The concomitant use of potent CYP3A4 inhibitors can be expected to increase vardenafil plasma levels. Concomitant use of vardenafil with potent CYP3A4 inhibitors should be avoided

Indinavir, venlafaxine [2] ---> SmPC of [2] of eMC

Concomitant use of CYP3A4 inhibitors and venlafaxine may increase levels of venlafaxine and O-desmethylvenlafaxine. Therefore, caution is advised if a patient's therapy includes a CYP3A4 inhibitor and venlafaxine concomitantly.

Indinavir, verapamil [2] ---> SmPC of [2] of eMC

Clinically significant interactions have been reported with inhibitors of CYP3A4 causing elevation of plasma levels of verapamil hydrochloride, therefore, patients should be monitored for drug interactions.

Indinavir, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Indinavir, voriconazole [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary.

Indinavir/ritonavir, itraconazol ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, CYP3A4 inhibitors, may increase the plasma concentrations of itraconazole. Careful monitoring is recommended

Indinavir/ritonavir, ketoconazole ---> SmPC of [indinavir] of EMA

Indinavir and ritonavir inhibit CYP3A4 and as a result are expected to increase the plasma concentrations of ketoconazole. Coadministration of ritonavir and ketoconazole caused an increased incidence of gastrointestinal and hepatic adverse events.

Indinavir/ritonavir, lamotrigine ---> SmPC of [indinavir] of EMA

Ritonavir induces oxidation by CYP2C9 and glucuronidation and as a result is expected to decrease the plasma concentrations of anticonvulsant.

Indinavir/ritonavir, lisuride ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, loratadine ---> SmPC of [indinavir] of EMA

Indinavir and ritonavir inhibit CYP3A4 and as a result are expected to increase the plasma levels of loratidine. Careful monitoring of therapeutic and adverse effects is recommended when loratidine is concomitantly administered with indinavir/ritonavir.

Indinavir/ritonavir, lovastatine ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, CYP3A4 inhibitors, may increase the plasma concentrations of lovastatine. Contraindicated: increased risk of myopathy and rhabdomyolysis

Indinavir/ritonavir, meperidine ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir should not be administered with meperidine

Indinavir/ritonavir, methadone ---> SmPC of [indinavir] of EMA

The glucuronidation induction by ritonavir may decrease the plasma concentrations of methadone. Dose adjustment should be considered based on clinical response to methadone therapy

Indinavir/ritonavir, methylergonovine ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, methysergide ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, midazolam ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, CYP3A4 inhibitors, may increase the plasma concentrations of midazolam: oral contraindicated, caution on parenterally administered

Indinavir/ritonavir, morphine ---> SmPC of [indinavir] of EMA

Ritonavir, glucuronidation inductor, may decrease the plasma concentrations of morphine. Careful monitoring is recommended

Indinavir/ritonavir, nelfinavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, nicergoline ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, phenytoin ---> SmPC of [indinavir] of EMA

Ritonavir induces oxidation by CYP2C9 and glucuronidation and as a result is expected to decrease the plasma concentrations of anticonvulsant. Phenytoin may decrease serum levels of ritonavir.

Indinavir/ritonavir, pimozide ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, piroxicam ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir should not be administered with piroxicam

Indinavir/ritonavir, propafenone ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir should not be administered with propafenone

Indinavir/ritonavir, propoxyphene ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir should not be administered with propoxyphene

Indinavir/ritonavir, quetiapine ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, quinidine ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, CYP3A4 inhibitors, may increase the plasma concentrations of quinidine. The use of indinavir/ritonavir with quinidine is contraindicated.

Indinavir/ritonavir, quinine ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, rifabutin ---> SmPC of [indinavir] of EMA

The CYP3A4 inhibition/induction may increase/decrease the plasma concentrations of rifabutin/indinavir.

Indinavir/ritonavir, rifampicin ---> SmPC of [indinavir] of EMA

Rifampicin, CYP3A4 inductor, may decrease the plasma concentrations of indinavir. The concomitant use is contraindicated

Indinavir/ritonavir, ritonavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, saquinavir ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, sildenafil ---> SmPC of [indinavir] of EMA

Coadministration of indinavir with sildenafil is likely to result in an increase of sildenafil by competitive inhibition of metabolism.

Indinavir/ritonavir, simvastatine ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, sirolimus ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, tacrolimus ---> SmPC of [indinavir] of EMA

Indinavir and ritonavir inhibit CYP3A4 and as a result are expected to increase the plasma concentrations of tacrolimus. Careful monitoring of therapeutic and adverse effects is recommended when tacrolimus is concomitantly administered with indinavir/ritonavir

Indinavir/ritonavir, tadalafil ---> SmPC of [indinavir] of EMA

Coadministration of indinavir with tadalafil is likely to result in an increase of sildenafil by competitive inhibition of metabolism.

Indinavir/ritonavir, terfenadine ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, trazodone ---> SmPC of [indinavir] of EMA

An increase in the incidence in trazodone-related adverse events was noted when coadministered with ritonavir. The combination of trazodone with indinavir/ritonavir should be used with caution

Indinavir/ritonavir, triazolam ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, vardenafil ---> SmPC of [indinavir] of EMA

Vardenafil dose should not exceed a maximum of 2.5 mg in a 72-hour period when given with a boosted protease inhibitor.

Indinavir/ritonavir, warfarin ---> SmPC of [indinavir] of EMA

Ritonavir, inductor of CYP1A2 and CYP2C9, may decrease the levels of R warfarin. Monitoring the anticoagulation parameters.

CONTRAINDICATIONS of Indinavir

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Indinavir with or without ritonavir should not be administered concurrently with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4.

Inhibition of CYP3A4 by both CRIXIVAN and ritonavir could result in elevated plasma concentrations of these medicines, potentially causing serious or life-threatening reactions (see section 4.5).

- CRIXIVAN with or without ritonavir should not be administered concurrently with amiodarone, terfenadine, cisapride, astemizole, quetiapine, alprazolam, triazolam, midazolam administered orally (for caution on parenterally administered midazolam, see section 4.5), pimozide, ergot derivatives, simvastatin or lovastatin

- Combination of rifampicin with CRIXIVAN with or without concomitant low-dose ritonavir is contraindicated (see section 4.5). Concurrent use of indinavir with herbal preparations containing St John's wort (Hypericum perforatum) is contraindicated (see section 4.5).

- In addition, indinavir with ritonavir must not be administered with alfuzosin, meperidine, piroxicam, propoxyphene, bepridil, encainide, flecanide, propafenone, quinidine, fusidic acid, clozapine, clorazepate, diazepam, estazolam and flurazepam

- Indinavir must not be given with ritonavir to patients with decompensated liver disease as ritonavir is principally metabolized and eliminated by the liver (see section 4.4)

- When CRIXIVAN is used with ritonavir, consult the Summary of Product Characteristics of ritonavir for additional contraindications

http://www.ema.europa.eu/

Indometacin

Ability to drive, indometacin [2] ---> SmPC of [2] of eMC

Patients should be warned that they may experience dizziness, drowsiness, visual disturbances or headaches and if they do, should not drive or undertake activities requiring alertness.

ACE inhibitors, indometacin

The combination of AIIRAs and AIIRAs (selective COX-2 inhibitors, ASA (> 3 g/day) and non-selective NSAIDs) may decrease the antihypertensive effect, increase the renal failure risk and cause hypercaliemia

AIIRA, indometacin

Alcohol, indometacin

Enhancement of the adverse effects of the NSAID, especially those of the gastrointestinal tract and CNS

Algeldrate/magnesium hydroxide, indometacin

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Almasilate, indometacin

There are studies which describe an absorption reduction of the active principle co-administered with almasilate

Aluminium hydroxide, indometacin

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Aluminium oxide/magnesium hydroxide, indometacin

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Amikacine [1], indometacin ---> SmPC of [1] of eMC

Indomethacin may increase the plasma concentration of amikacin in neonates.

Amiloride/hydrochlorothiazide, indometacin

Indometacin may decrease the antihypertensive and antidiuretic effect of amiloride/hydrochlorothiazide and increase the risk of hypercaliemia

Aminoglycoside antibiotics, indometacin

Concurrent administration of aminoglycoside antibiotics with indometacin may decrease the renal clearance of antibiotic with risk of toxicity

Antacids, indometacin

Decreased absorption rate of indometacin

Anticoagulants, indometacin [2] ---> SmPC of [2] of eMC

Patients also receiving anticoagulants should be closely observed for alterations of the prothrombin time.

Antihypertensives, indometacin

The co-administration may weaken the hypotensive effect

Atenolol [1], indometacin ---> SmPC of [1] of eMC

Concomitant use of prostaglandin synthetase-inhibiting drugs may decrease the hypotensive effects of beta-blockers.

Atenolol/chlortalidone [1], indometacin ---> SmPC of [1] of eMC

Concomitant use of prostaglandin synthetase-inhibiting drugs may decrease the hypotensive effects of beta-blockers.

Atenolol/nifedipine [1], indometacin ---> SmPC of [1] of eMC

Concomitant use of prostaglandin synthetase-inhibiting drugs, e.g. ibuprofen or indometacin, may decrease the hypotensive effects of beta-blocking drugs.

Azathioprine [1], indometacin ---> SmPC of [1] of eMC

It has been suggested that indomethacin may have myelosuppressive effects which may be enhanced by concomitant administration of azathioprine.

Benazepril, indometacin

It has been shown that the antihypertensive effect of ACE inhibitors may be decreased with the co-administration of indometacin

Benzylpenicillin, indometacin

The co-administration may delay the elimination of the penicillin and increase its plasma levels

Betablockers, indometacin ---> SmPC of [atenolol/chlortalidone] of eMC

Concomitant use of prostaglandin synthetase-inhibiting drugs may decrease the hypotensive effects of beta-blockers.

Breast-feeding, indometacin [2] ---> SmPC of [2] of eMC

Administration of indometacin is not recommended in breast-feeding mothers. Indomethacin is excreted in breast milk.

Captopril [1], indometacin ---> SmPC of [1] of eMC

It has been described NSAIDs and ACE inhibitors exert an additive effect on the increase in serum potassium whereas renal function may decrease. Chronic administration of NSAIDs may reduce the antihypertensive effect of an ACE inhibitor.

Cardiac glycosides, indometacin

NSAID may exacerbate cardiac failure, reduce the glomerular filtration rate and increase plasma levels of the cardiac glycoside

Celiprolol [1], indometacin ---> SmPC of [1] of eMC

Drugs inhibiting prostaglandin synthetase may decrease the hypotensive effects of beta-adrenoceptor blocking drugs.

Cephalexin, indometacin

Delayed renal elimination of cefalexin and increase of its plasma and biliary concentrations

Certoparin, indometacin

The co-administration may enhance the pharmacological effects of certoparin

Chlortalidone [1], indometacin ---> SmPC of [1] of eMC

Concomitant administration of indometacin and chlortalidone may reduce the diuretic and antihypertensive activity of chlortalidone

Cloprednol, indometacin

Increased risk of gastrointestinal haemorrhage

Corticosteroids, indometacin [2] ---> SmPC of [2] of eMC

The risk of gastro-intestinal bleeding and ulceration associated with NSAIDs is increased when used with corticosteroids

Cotrimoxazole, indometacin

The effect of trimethoprim/sulfamethoxazol is enhanced by indometacin, with increased risk of adverse reactions

Coumarin anticoagulants, indometacin [2] ---> SmPC of [2] of eMC

NSAIDs may enhance the effects of oral anti-coagulants (e.g. warfarin, dicoumarol)

Cyclophosphamide, indometacin

The co-administration of cyclophosphamide with indomethacin should be done with great care because it has been observed one case of acute water intoxication

Cyclosporine, indometacin [2] ---> SmPC of [2] of eMC

Administration of non-steroidal anti-inflammatory drugs concomitantly with cyclosporin has been associated with an increase in cyclosporin-induced toxicity, possibly due to decreased synthesis of renal prostacyclin.

Deflazacort, indometacin

Increased risk of gastrointestinal haemorrhage

Diflunisal, indometacin [2] ---> SmPC of [2] of eMC

Co-administration of diflunisal with indometacin increases the plasma level of indomethacin by about a third, with a concomitant decrease in renal clearance. Fatal GI haemorrhage has occurred. The combination should not be used.

Digoxin [1], indometacin ---> SmPC of [1] of eMC

Serum levels of digitoxin may be increased by concomitant administration of indometacin

Dihydralazine, indometacin

The co-administration may weaken the hypotensive effect

Enoxaparin [1], indometacin ---> SmPC of [1] of eMC

The co-administration may enhance the pharmacologic effect and increase the bleeding risk. A close clinical and laboratory monitoring is recommended

Eprosartan [1], indometacin ---> SmPC of [1] of eMC

Concomitant use of losartan with the NSAID indometacin led to a decrease in efficacy of the angiotensin II antagonist; a class effect cannot be excluded.

Febuxostat [1], indometacin ---> SmPC of [1] of EMA

Febuxostat can be co-administered with indomethacin with no dose adjustment of febuxostat or indomethacin being necessary.

Felodipine/metoprolol, indometacin

Indometacin or other prostaglandin synthetase inhibitors may reduce the antihypertensive effects of felodipine/metoprolol

Flucloxacillin, indometacin

The co-administration slows down the excretion of flucloxacillin

Furosemide, indometacin

Furosemide may accelerate the elimination of indometacin

Gentamicin, indometacin

Concurrent administration of aminoglycoside antibiotics with indometacin may decrease the renal clearance of antibiotic with risk of toxicity

Glibenclamide, indometacin

The co-administration may weaken the hypoglycemic effect

Glucagon [1], indometacin ---> SmPC of [1] of eMC

Glucagon may lose its ability to raise blood glucose or may even produce hypoglycaemia

Glycerol trinitrate, indometacin

Weaken of hypotensive effect of nitroglycerin

Haloperidol, indometacin

Increased adverse effects on CNS, such as somnolence and states of confusion

Hydralazine, indometacin

The co-administration may weaken the hypotensive effect

Hydrochlorothiazide, indometacin

NSAIDs may reduce the diuretic, natriuretic and antihypertensive effects of thiazide diuretics

Hydrocortisone, indometacin

Increased risk of gastrointestinal haemorrhages

Hydroxychloroquine, indometacin

Increased risk of sensibilization and retinopathy

Indometacin [1], methotrexate ---> SmPC of [1] of eMC

Caution should be exercised with simultaneous use of indometacin with methotrexate. Indometacin has been reported to decrease the tubular secretion of methotrexate and to potentiate toxicity.

Indometacin [1], pregnancy ---> SmPC of [1] of eMC

Indometacin should be used during the first two trimesters of pregnancy only if the potential benefit justifies the potential risk to the foetus. Use of indometacin during the third trimester of pregnancy is not recommended.

Indometacin [1], probenecide ---> SmPC of [1] of eMC

Co-administration of probenecid may increase plasma levels of indomethacin.

Indometacin [1], quinolones ---> SmPC of [1] of eMC

There have been reports that 4-quinolones may induce convulsions in patients with or without a history of convulsions; taking NSAIDs at the same time may also induce them.

Indometacin [1], thiazides ---> SmPC of [1] of eMC

In some patients, the administration of indometacin can reduce the diuretic and antihypertensive effects of loop, potassium-sparing and thiazide diuretics.

Indometacin [1], triamterene ---> SmPC of [1] of eMC

It has been reported that the addition of triamterene to a maintenance schedule of indometacin resulted in reversible acute renal failure in two of four healthy volunteers. Indometacin and triamterene should not be administered together.

Indometacin, leflunomide [2] ---> SmPC of [2] of EMA

A771726 is an inhibitor of OAT3 in vivo .Therefore, when co-administered leflunomide with substrates of OAT3 caution is recommended.

Indometacin, lesinurad [2] ---> SmPC of [2] of EMA

Based on interaction studies in healthy subjects or gout patients, Zurampic does not have clinically significant interactions with NSAIDs (naproxen and indomethacin), colchicine, repaglinide, tolbutamide, febuxostat or allopurinol.

Indometacin, lisinopril/hydrochlorothiazide [2] ---> SmPC of [2] of eMC

Indometacin may diminish the antihypertensive effect of concomitantly administered lisinopril/hydrochlorothiazide.

Indometacin, lithium ---> SmPC of [lithium carbonate] of eMC

Increased lithium concentrations

Indometacin, losartan ---> SmPC of [eprosartan] of eMC

Concomitant use of losartan with the NSAID indometacin led to a decrease in efficacy of the angiotensin II antagonist

Indometacin, magaldrate

Decreased absorption of indometacin. It is recommended to administer the two substances at least 2-3 hours apart.

Indometacin, magnesium hydroxide

The magnesium hydroxide may decrease the absorption of indometacin. Separate administration by 2-3 hours

Indometacin, methylprednisolone [2] ---> SmPC of [2] of eMC

There may be increased incidence of gastrointestinal bleeding and ulceration when corticosteroids are given with NSAIDs.

Indometacin, metildigoxin

Increased plasma levels of metildigoxin

Indometacin, metoprolol [2] ---> SmPC of [2] of eMC

NSAIDs (especially indometacin) may reduce the antihypertensive effects of beta-blockers possibly by inhibiting renal prostaglandin synthesis and/or causing sodium and fluid retention.

Indometacin, mezlocillin

The co-administration decreases the renal elimination of mezlocillin

Indometacin, nadroparin

The co-administration may increase the nadroparin effect

Indometacin, neuroleptics

Increased adverse effects on CNS, such as somnolence and states of confusion

Indometacin, nitroglycerine

Weaken of hypotensive effect of nitroglycerin

Indometacin, NSAID

Indometacin, oxprenolol

Non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the hypotensive effect of beta-blockade.

Indometacin, penicillamine

Indometacin may increase the plasma levels of penicillamine

Indometacin, penicillins

The co-administration may delay the elimination of the penicillin and increase its plasma levels

Indometacin, phenytoin

Indometacin may increase the plasma levels and effects of phenytoin

Indometacin, piperacillin

Concurrent administration of indometacin and piperacillin produces a longer half-life and lower renal clearance of piperacillin

Indometacin, piretanide

NSAIDs may weaken the antihypertensive and diuretic effect of piretanide

Indometacin, platelet aggregation inhibitors

The co-administration may increase the risk of gastrointestinal bleeding

Indometacin, potassium canrenoate

The co-administration of NSAIDs with potassium canreonate may cause hyperpotassemia and decrease the diuretic effect of potassium canreonate

Indometacin, potassium-sparing diuretics [2] ---> SmPC of [2] of eMC

Indometacin and potassium-sparing diuretics each may be associated with increased plasma potassium levels. The potential effects of indometacin and potassium-sparing diuretics on potassium kinetics and renal function should be considered

Indometacin, prazosin

Indometacin may decrease the hypotensive effect of prazosin

Indometacin, prednisone [2] ---> SmPC of [2] of eMC

The risk of gastrointestinal haemorrhages is increased.

Indometacin, propranolol [2] ---> SmPC of [2] of eMC

NSAIDs notably indometacin, may cause an increase in blood pressure. This may be particularly significant in patients with poorly controlled hypertension.

Indometacin, spironolactone [2] ---> SmPC of [2] of eMC

Indometacin inhibits the excretion of canrenone reducing the diuretic effect.

Indometacin, SSRI

The co-administration may increase the risk of gastrointestinal bleeding

Indometacin, streptokinase [2] ---> SmPC of [2] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Indometacin, streptokinase/streptodornase

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Indometacin, sulfonylureas

NSAIDs can increase the hypoglycaemic effect of sulfonylureas by displacement from plasma protein binding sites. Caution is recommended

Indometacin, sulphamides

Increased sulfonamide effect

Indometacin, sulphonamides

Increased sulfonamide effect

Indometacin, talinolol

Decreased hypotensor effect

Indometacin, teriflunomide [2] ---> SmPC of [2] of EMA

When teriflunomide (OAT3 inhibitor) is coadministered with substrates of OAT3 caution is recommended.

Indometacin, tetracosactide

Increased risk of gastrointestinal haemorrhage and ulceration. Caution is recommended

Indometacin, torasemid [2] ---> SmPC of [2] of eMC

Non-steroidal anti-inflammatory drugs may reduce the diuretic and hypotensive effect of torasemide.

Indometacin, urokinase [2] ---> SmPC of [2] of eMC

Due to increased risk of haemorrhage, concomitant use of urokinase and active substances that affect platelet function should be avoided

Indometacin, valsartan [2] ---> SmPC of [2] of eMC

In drug interaction studies with valsartan, no interactions of clinical significance have been found with valsartan and indometacin

Indometacin, warfarin

The co-administration may enhance the anticoagulant effect

Indometacin, xipamide

Possible decrease of the antihypertensive and diuretic effect of xipamide

CONTRAINDICATIONS of Indometacin

- A history of peptic ulcer or active peptic ulcer; a recurrent history of gastro-intestinal lesions; in patients who have nasal polyps associated with angioneurotic oedema, who show sensitivity to indomethacin or any of the ingredients in this product, or who have experienced acute asthmatic attacks, urticaria or rhinitis as a result of therapy with aspirin or other non-steroidal anti-inflammatory drugs.

- Safety for use in children has not been established.

- 'Indocid' should not be used during pregnancy or lactation

http://www.medicines.org.uk/emc/

Inebilizumab (Uplizna)

Ability to drive, inebilizumab [2] ---> SmPC of [2] of EMA

The pharmacological activity and adverse reactions reported to date suggest that inebilizumab has no or negligible influence on the ability to drive and use machines.

Breast-feeding, inebilizumab [2] ---> SmPC of [2] of EMA

Afterwards, Uplizna could be used during breast feeding if clinically needed. However, if the patient was treated with Uplizna up to the last few months of pregnancy, breast feeding can be started immediately after birth.

Corticosteroids, inebilizumab [2] ---> SmPC of [2] of EMA

Concomitant usage of inebilizumab with immunosuppressants, including systemic corticosteroids, may increase the risk of infection.

Cytochrome P450, inebilizumab [2] ---> SmPC of [2] of EMA

Cytochrome P450 enzymes, efflux pumps, and protein-binding mechanisms are not involved in the clearance of therapeutic antibodies.

Fertility, inebilizumab [2] ---> SmPC of [2] of EMA

There are limited data on the effect of inebilizumab on human fertility; however, studies in animals have shown reduced fertility. The clinical significance of these nonclinical findings is not known (see section 5.3).

Inebilizumab [1], infection ---> SmPC of [1] of EMA

Concomitant usage of inebilizumab with immunosuppressants, including systemic corticosteroids, may increase the risk of infection.

Inebilizumab [1], interactions ---> SmPC of [1] of EMA

Therefore, the potential risk of pharmacokinetic interactions between inebilizumab and other medicinal products is low.

Inebilizumab [1], neoplasia ---> SmPC of [1] of EMA

Immunomodulatory medicinal products may increase the risk of malignancy. However, the possible risk for the development of solid tumours cannot be excluded at this time.

Inebilizumab [1], new-born child ---> SmPC of [1] of EMA

Consequently, newborns should be monitored for B-cell depletion and vaccinations with live virus vaccines, such as Bacillus Calmette-Guérin (BCG) vaccine, should be postponed until the infant's B-cell count has recovered (see section 4.4).

Inebilizumab [1], pregnancy ---> SmPC of [1] of EMA

Treatment with inebilizumab should be avoided during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus.

Inebilizumab [1], pregnancy ---> SmPC of [1] of EMA

In case of exposure during pregnancy, depletion of B cells may be expected in newborns due to the pharmacological properties of the product and findings from animal studies (see section 5.3).

Inebilizumab [1], vaccinations ---> SmPC of [1] of EMA

The response to vaccination could be impaired when B cells are depleted. It is recommended that patients complete immunisations prior to the start of inebilizumab therapy (see section 4.4).

Inebilizumab [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should use effective contraception (methods that result in less than 1% pregnancy rates) while receiving Uplizna and for 6 months after the last administration of Uplizna.

CONTRAINDICATIONS of Inebilizumab (Uplizna)

- Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1

- Severe active infection, including active chronic infection such as hepatitis B

- Active or untreated latent tuberculosis

- History of progressive multifocal leukoencephalopathy (PML)

- Severely immunocompromised state

- Active malignancies

https://www.ema.europa.eu/en/documents/product-information/uplizna-epar-product-information_en.pdf 14/01/2025

Infliximab (Inflectra)

Abatacept, infliximab [2] ---> SmPC of [2] of EMA

The combination of Inflectra with other biological therapeutics used to treat the same conditions as Inflectra, including anakinra and abatacept, is not recommended

Ability to drive, infliximab [2] ---> SmPC of [2] of EMA

Inflectra may have a minor influence on the ability to drive and use machines. Dizziness may occur following administration of infliximab (see section 4.8).

Anakinra, infliximab [2] ---> SmPC of [2] of EMA

Co-administration of anakinra and etanercept has been associated with an increased risk of serious infections and neutropenia. The concurrent administration of anakinra and etanercept or other TNF antagonists is not recommended

Azathioprine, infliximab

Interactions between azathioprine and infliximab in the treatment of Crohn disease have been reported

BCG intravesical, infliximab [2] ---> SmPC of [2] of EMA

The therapeutic infectious agents could result in clinical infections, including disseminated infections. The concurrent administration is not is recommended

Biological medicinal products, infliximab [2] ---> SmPC of [2] of EMA

The co-administration is not recommended because of the possibility of an increased risk of infection, and other potential pharmacological interactions

Breast-feeding, infliximab [2] ---> SmPC of [2] of EMA

Infliximab could be considered for use during breast-feeding.

Corticosteroids, infliximab [2] ---> SmPC of [2] of EMA

Corticosteroids do not appear to affect the pharmacokinetics of infliximab to a clinically relevant extent.

Fertility, infliximab [2] ---> SmPC of [2] of EMA

There are insufficient preclinical data to draw conclusions on the effects of infliximab on fertility and general reproductive function (see section 5.3).

Golimumab [1], infliximab ---> SmPC of [1] of EMA

Caution should be exercised when using any TNF-antagonist in COPD patients, as well as in patients with an increased risk of malignancy due to heavy smoking.

Immunomodulatory agents, infliximab [2] ---> SmPC of [2] of EMA

There are indications that concomitant use of methotrexate and other immunomodulators reduces the formation of antibodies against infliximab and increases the plasma concentrations of infliximab.

Infliximab [1], methotrexate ---> SmPC of [1] of EMA

There are indications that concomitant use of methotrexate and other immunomodulators reduces the formation of antibodies against infliximab and increases the plasma concentrations of infliximab.

Infliximab [1], pregnancy ---> SmPC of [1] of EMA

The available clinical experience is limited. Infliximab should only be used during pregnancy if clearly needed.

Infliximab [1], therapeutic infectious agents ---> SmPC of [1] of EMA

It is recommended that therapeutic infectious agents not be given concurrently with infliximab (see section 4.4).

Infliximab [1], TNF inhibitors ---> SmPC of [1] of EMA

Use of TNF-blocking agents, including infliximab, has been associated with cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disorders

Infliximab [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

It is recommended that live vaccines not be given concurrently with Inflectra. It is also recommended that live vaccines not be given to infants after in utero exposure to infliximab for at least 12 months following birth

Infliximab [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should consider the use of adequate contraception to prevent pregnancy and continue its use for at least 6 months after the last infliximab treatment.

CONTRAINDICATIONS of Infliximab (Inflectra)

- Patients with a history of hypersensitivity to infliximab (see section 4.8), to other murine proteins, or to any of the excipients listed in section 6.1.

- Patients with tuberculosis or other severe infections such as sepsis, abscesses, and opportunistic infections

- Patients with moderate or severe heart failure (NYHA class III/IV)

https://www.ema.europa.eu/en/documents/product-information/inflectra-epar-product-information_en.pdf 27/05/2025

Other trade names: Flixabi, Remicade, Remsima, Zessly,

Ingenol mebutate (Picato)

Breast-feeding, ingenol mebutate [2] ---> SmPC of [2] of EMA

The nursing mother should be instructed that physical contact between her newborn/infant and the treated area should be avoided for a period of 6 hours after application of Picato.

Eye exposure, ingenol mebutate [2] ---> SmPC of [2] of EMA

Patients should wash their hands thoroughly after applying the gel and following any contact with the treated area, to avoid inadvertent transfer of the gel to the eyes.

Fertility, ingenol mebutate [2] ---> SmPC of [2] of EMA

No fertility studies have been performed with ingenol mebutate.

Ingenol mebutate [1], ingestion ---> SmPC of [1] of EMA

Picato must not be ingested. If accidental ingestion occurs the patient should drink plenty of water and seek medical care.

Ingenol mebutate [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of Picato during pregnancy.

Ingenol mebutate [1], skin ---> SmPC of [1] of EMA

It should not be applied to open wounds or damaged skin where the skin barrier is compromised. Picato should not be used near the eyes, on the inside of the nostrils, on the inside of the ears or on the lips.

Ingenol mebutate [1], skin barrier ---> SmPC of [1] of EMA

Administration of Picato is not recommended until the skin is healed from treatment with any previous medicinal product or surgical treatment

Ingenol mebutate [1], sun exposure ---> SmPC of [1] of EMA

However, due to the nature of the disease, excessive exposure to sunlight (including sunlamps and tanning beds) should be avoided or minimised.

CONTRAINDICATIONS of Ingenol mebutate (Picato)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/picato-epar-product-information_en.pdf 04/03/2020 (withdrawn)

Inotersen (Tegsedi)

Acetylsalicylic acid, inotersen [2] ---> SmPC of [2] of EMA

Caution should be used with antithrombotic medicinal products, antiplatelet medicinal products, and medicinal products that may lower platelet count

Aldosterone antagonists, inotersen [2] ---> SmPC of [2] of EMA

Caution should be exercised with concomitant use of nephrotoxic medicinal products and other medicines that may impair renal function, such as sulfonamides

Anilide, inotersen [2] ---> SmPC of [2] of EMA

Caution should be exercised with concomitant use of nephrotoxic medicinal products and other medicines that may impair renal function, such as sulfonamides

Antithrombotics, inotersen [2] ---> SmPC of [2] of EMA

Caution should be used with antithrombotic medicinal products, antiplatelet medicinal products, and medicinal products that may lower platelet count

Apixaban, inotersen [2] ---> SmPC of [2] of EMA

Caution should be used with antithrombotic medicinal products, antiplatelet medicinal products, and medicinal products that may lower platelet count

Breast-feeding, inotersen [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Tegsedi therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Clopidogrel, inotersen [2] ---> SmPC of [2] of EMA

Caution should be used with antithrombotic medicinal products, antiplatelet medicinal products, and medicinal products that may lower platelet count

Dabigatran, inotersen [2] ---> SmPC of [2] of EMA

Caution should be used with antithrombotic medicinal products, antiplatelet medicinal products, and medicinal products that may lower platelet count

Fertility, inotersen [2] ---> SmPC of [2] of EMA

There is no information available on the effects of inotersen on human fertility. Animal studies did not indicate any impact of inotersen on male or female fertility.

Heparin, inotersen [2] ---> SmPC of [2] of EMA

Caution should be used with antithrombotic medicinal products, antiplatelet medicinal products, and medicinal products that may lower platelet count

Inotersen [1], nephrotoxic substances ---> SmPC of [1] of EMA

Caution should be used with nephrotoxic medicinal products and other medicinal products that may impair renal function

Inotersen [1], opiates ---> SmPC of [1] of EMA

Caution should be exercised with concomitant use of nephrotoxic medicinal products and other medicines that may impair renal function, such as sulfonamides

Inotersen [1], platelet aggregation inhibitors ---> SmPC of [1] of EMA

Caution should be used with antithrombotic medicinal products, antiplatelet medicinal products, and medicinal products that may lower platelet count

Inotersen [1], pregnancy ---> SmPC of [1] of EMA

Due to the potential teratogenic risk arising from unbalanced vitamin A levels, inotersen should not be used during pregnancy, unless the clinical condition of the woman requires treatment with inotersen.

Inotersen [1], sulphamides ---> SmPC of [1] of EMA

Caution should be exercised with concomitant use of nephrotoxic medicinal products and other medicines that may impair renal function, such as sulfonamides

Inotersen [1], vitamin A ---> SmPC of [1] of EMA

Inotersen will reduce the plasma levels of vitamin A, which is crucial for normal foetal development. It is not known whether vitamin A supplementation will be sufficient to reduce the risk to the foetus (see section 4.4).

Inotersen [1], warfarin ---> SmPC of [1] of EMA

Caution should be used with antithrombotic medicinal products, antiplatelet medicinal products, and medicinal products that may lower platelet count

Inotersen [1], women of childbearing potential ---> SmPC of [1] of EMA

For this reason, pregnancy should be excluded before initiation of inotersen therapy and Women of child-bearing potential have to use effective contraception during treatment with inotersen.

CONTRAINDICATIONS of (Tegsedi)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Platelet count < 100 x 109/L prior to treatment.

- Urine protein to creatinine ratio (UPCR). 113 mg/mmol (1 g/g) prior to treatment.

- Estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73m2 .

- Severe hepatic impairment.

https://www.ema.europa.eu/en/documents/product-information/tegsedi-epar-product-information_en.pdf 17/01/2024

Inotuzumab ozogamicin (Besponsa)

Ability to drive, inotuzumab ozogamicin [2] ---> SmPC of [2] of EMA

Patients may experience fatigue during treatment with BESPONSA (see section 4.8). Therefore, caution is recommended when driving or operating machines.

Breast-feeding, inotuzumab ozogamicin [2] ---> SmPC of [2] of EMA

Because of the potential for adverse reactions in breast-fed children, women must not breast-feed during treatment with BESPONSA and for at least 2 months after the final dose

Cytochrome P450, inotuzumab ozogamicin [2] ---> SmPC of [2] of EMA

Based on in vitro data, coadministration of inotuzumab ozogamicin with inhibitors or inducers of cytochrome P450 (CYP) to alter exposure to N-acetyl-gamma-calicheamicin dimethylhydrazide.

Fertility, inotuzumab ozogamicin [2] ---> SmPC of [2] of EMA

Based on non-clinical findings, male and female fertility may be compromised by treatment with inotuzumab ozogamicin (see section5.3). Both men and women must seek advice for fertility preservation before treatment.

Inotuzumab ozogamicin [1], medicinal product-metabolising enzymes ---> SmPC of [1] of EMA

Based on in vitro data, coadministration of inotuzumab ozogamicin with uridine diphosphate-glucuronosyltransferase (UGT) drug metabolising enzymes are unlikely to alter exposure to N-acetyl-gamma-calicheamicin dimethylhydrazide.

Inotuzumab ozogamicin [1], men ---> SmPC of [1] of EMA

Men with female partners of childbearing potential should use effective contraception during treatment with BESPONSA and for at least 5months after the final dose.

Inotuzumab ozogamicin [1], pregnancy ---> SmPC of [1] of EMA

There are no data in pregnant women using inotuzumab ozogamicin. Based on non-clinical safety findings, inotuzumab ozogamicin can cause embryo-foetal harm when administered to a pregnant woman. Studies in animals have shown reproductive toxicity

Inotuzumab ozogamicin [1], pregnancy ---> SmPC of [1] of EMA

BESPONSA must not be used during pregnancy unless the potential benefit to the mother outweighs the potential risks to the foetus.

Inotuzumab ozogamicin [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

The concomitant use of inotuzumab ozogamicin with medicinal products known to prolong QT interval or to induce Torsades de Pointes should be carefully considered.

Inotuzumab ozogamicin [1], torsades de pointes inducing drugs ---> SmPC of [1] of EMA

The concomitant use of inotuzumab ozogamicin with medicinal products known to prolong QT interval or to induce Torsades de Pointes should be carefully considered.

Inotuzumab ozogamicin [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Vaccination with live viral vaccines is not recommended for at least 2 weeks prior to the start of BESPONSA treatment, during treatment, and until recovery of B lymphocytes following the last treatment cycle.

Inotuzumab ozogamicin [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should avoid becoming pregnant while receiving BESPONSA. Women should use effective contraception during treatment with BESPONSA and for at least 8 months after the final dose.

CONTRAINDICATIONS of Inotuzumab ozogamicin (Besponsa)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Patients who have experienced prior confirmed severe or ongoing venoocclusive liver disease/sinusoidal obstruction syndrome (VOD/SOS).

- Patients with serious ongoing hepatic disease (e.g., cirrhosis, nodular regenerative hyperplasia, active hepatitis).

https://www.ema.europa.eu/en/documents/product-information/besponsa-epar-product-information_en.pdf 14/02/2024

Human insulin (Actrapid)

Ability to drive, human insulin

Patients should be advised to take precautions to avoid hypoglycaemia while driving. This is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycaemia or have frequent episodes of hypoglycaemia.

Ability to drive, human insulin [2] ---> SmPC of [2] of EMA

The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia.

ACE inhibitors, human insulin [2] ---> SmPC of [2] of EMA

Possible reduction of the patient's insulin requirement

Alcohol, human insulin [2] ---> SmPC of [2] of EMA

Alcohol may intensify or reduce the hypoglycaemic effect of insulin.

Betablockers, human insulin [2] ---> SmPC of [2] of EMA

Possible reduction of the patient's insulin requirement. Beta-blockers may mask the symptoms of hypoglycaemia.

Breast-feeding, human insulin [2] ---> SmPC of [2] of EMA

There is no restriction on treatment with human insulin during breast-feeding. Insulin treatment of the nursing mother presents no risk to the baby. However, the human insulin dose may need to be adjusted.

Corticosteroids, human insulin [2] ---> SmPC of [2] of EMA

Possible increasing in patient's insulin requirement

Danazol, human insulin [2] ---> SmPC of [2] of EMA

Possible increasing in patient's insulin requirement

Estrogens, human insulin [2] ---> SmPC of [2] of EMA

Possible reduction of the patient's insulin requirement

Fertility, human insulin [2] ---> SmPC of [2] of EMA

Animal reproduction studies with human insulin have not revealed any adverse effects on fertility.

Growth hormone, human insulin [2] ---> SmPC of [2] of EMA

Possible increasing in patient's insulin requirement

Human insulin [1], IMAOs ---> SmPC of [1] of EMA

Possible reduction of the patient's insulin requirement

Human insulin [1], lanreotide ---> SmPC of [1] of EMA

Octreotide/lanreotide may either increase or decrease the insulin requirement.

Human insulin [1], octreotide ---> SmPC of [1] of EMA

Octreotide/lanreotide may either increase or decrease the insulin requirement.

Human insulin [1], oral antidiabetics ---> SmPC of [1] of EMA

Possible reduction of the patient's insulin requirement

Human insulin [1], oral contraceptives ---> SmPC of [1] of EMA

Possible increasing in patient's insulin requirement

Human insulin [1], pregnancy ---> SmPC of [1] of EMA

There are no restrictions on treatment of diabetes with insulin during pregnancy, as insulin does not pass the placental barrier.

Human insulin [1], pregnancy ---> SmPC of [1] of EMA

Insulin requirements usually fall in the first trimester and increase subsequently during the second and third trimesters. After delivery, insulin requirements normally return rapidly to pre-pregnancy values.

Human insulin [1], salicylates ---> SmPC of [1] of EMA

Possible reduction of the patient's insulin requirement

Human insulin [1], sulphonamides ---> SmPC of [1] of EMA

Possible reduction of the patient's insulin requirement

Human insulin [1], sympathomimetics ---> SmPC of [1] of EMA

Possible increasing in patient's insulin requirement

Human insulin [1], thiazides ---> SmPC of [1] of EMA

Possible increasing in patient's insulin requirement

Human insulin [1], thyroid hormones ---> SmPC of [1] of EMA

Possible increasing in patient's insulin requirement

CONTRAINDICATIONS of Human insulin (Actrapid)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/outside-eu-product-information/actrapid-product-information_en.pdf 22/07/2022

Other trade names: Actraphane, Exubera, Insulin Human Winthrop, Insulatard, Insuman, Mixtard, Protaphane, Solumarv,

Insulin aspart (NovoRapid)

Ability to drive, insulin aspart [2] ---> SmPC of [2] of EMA

The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia.

ACE inhibitors, insulin aspart [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements

Alcohol, insulin aspart [2] ---> SmPC of [2] of EMA

Alcohol may intensify or reduce the hypoglycaemic effect of insulin.

Anabolic steroids, insulin aspart [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements

Betablockers, insulin aspart [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements. Beta-blockers may mask the symptoms of hypoglycaemia.

Breast-feeding, insulin aspart [2] ---> SmPC of [2] of EMA

Insulin treatment of the nursing mother presents no risk to the baby. However, the NovoRapid dose may need to be adjusted.

Danazol, insulin aspart [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

Fertility, insulin aspart [2] ---> SmPC of [2] of EMA

Animal reproduction studies have not revealed any differences between insulin aspart and human insu-lin regarding fertility.

Glucocorticoids, insulin aspart [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

Growth hormone, insulin aspart [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

IMAOs, insulin aspart [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements

Insulin aspart [1], lanreotide ---> SmPC of [1] of EMA

Lanreotide may either increase or decrease the insulin requirement.

Insulin aspart [1], octreotide ---> SmPC of [1] of EMA

Octreotide may either increase or decrease the insulin requirement.

Insulin aspart [1], oral antidiabetics ---> SmPC of [1] of EMA

Possible reduction of the insulin requirements

Insulin aspart [1], oral contraceptives ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

Insulin aspart [1], pregnancy ---> SmPC of [1] of EMA

NovoRapid (insulin aspart) can be used in pregnancy.

Insulin aspart [1], salicylates ---> SmPC of [1] of EMA

Possible reduction of the insulin requirements

Insulin aspart [1], sulphonamides ---> SmPC of [1] of EMA

Possible reduction of the insulin requirements

Insulin aspart [1], sympathomimetics ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

Insulin aspart [1], thiazides ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

Insulin aspart [1], thyroid hormones ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

CONTRAINDICATIONS of Insulin aspart (NovoRapid)

- Hypersensitivity to the active substance or to any of the excipients (see section 6.1).

https://www.ema.europa.eu/en/documents/product-information/novorapid-epar-product-information_en.pdf 28/05/2025

Other trade names: Fiasp, Insulin aspart Sanofi, NovoMix,

Insulin degludec (Tresiba)

Ability to drive, insulin degludec [2] ---> SmPC of [2] of EMA

The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia.

ACE inhibitors, insulin degludec [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements

Alcohol, insulin degludec [2] ---> SmPC of [2] of EMA

Alcohol may intensify or reduce the hypoglycaemic effect of insulin.

Anabolic steroids, insulin degludec [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements

Betablockers, insulin degludec [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements. Beta-blockers may mask the symptoms of hypoglycaemia.

Danazol, insulin degludec [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

GLP-1 receptor agonists, insulin degludec [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements

Glucocorticoids, insulin degludec [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

Growth hormone, insulin degludec [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

IMAOs, insulin degludec [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements

Insulin degludec [1], octreotide ---> SmPC of [1] of EMA

Octreotide/lanreotide may either increase or decrease the insulin requirement.

Insulin degludec [1], oral antidiabetics ---> SmPC of [1] of EMA

Possible reduction of the insulin requirements

Insulin degludec [1], oral contraceptives ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

Insulin degludec [1], pregnancy ---> SmPC of [1] of EMA

In general, intensified blood glucose control and monitoring of pregnant women with diabetes are recommended throughout pregnancy and when contemplating pregnancy.

Insulin degludec [1], salicylates ---> SmPC of [1] of EMA

Possible reduction of the insulin requirements

Insulin degludec [1], sulphonamides ---> SmPC of [1] of EMA

Possible reduction of the insulin requirements

Insulin degludec [1], sympathomimetics ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

Insulin degludec [1], thiazides ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

Insulin degludec [1], thyroid hormones ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

CONTRAINDICATIONS of Insulin degludec (Tresiba)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/tresiba-epar-product-information_en.pdf 10/10/2024

Insulin degludec/insulin aspart (Ryzodeg)

Ability to drive, insulin degludec/insulin aspart [2] ---> SmPC of [2] of EMA

The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia.

ACE inhibitors, insulin degludec/insulin aspart [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements

Alcohol, insulin degludec/insulin aspart [2] ---> SmPC of [2] of EMA

Alcohol may intensify or reduce the hypoglycaemic effect of insulin.

Anabolic steroids, insulin degludec/insulin aspart [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements

Betablockers, insulin degludec/insulin aspart [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements. Beta-blockers may mask the symptoms of hypoglycaemia.

Breast-feeding, insulin degludec/insulin aspart [2] ---> SmPC of [2] of EMA

No metabolic effects are anticipated in the breast-fed newborn/infant.

Danazol, insulin degludec/insulin aspart [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

Fertility, insulin degludec/insulin aspart [2] ---> SmPC of [2] of EMA

Animal reproduction studies with insulin degludec have not revealed any adverse effects on fertility.

Glucocorticoids, insulin degludec/insulin aspart [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

Growth hormone, insulin degludec/insulin aspart [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

IMAOs, insulin degludec/insulin aspart [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements

Insulin degludec/insulin aspart [1], lanreotide ---> SmPC of [1] of EMA

Octreotide/lanreotide may either increase or decrease the insulin requirement.

Insulin degludec/insulin aspart [1], octreotide ---> SmPC of [1] of EMA

Octreotide/lanreotide may either increase or decrease the insulin requirement.

Insulin degludec/insulin aspart [1], oral antidiabetics ---> SmPC of [1] of EMA

Possible reduction of the insulin requirements

Insulin degludec/insulin aspart [1], oral contraceptives ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

Insulin degludec/insulin aspart [1], pregnancy ---> SmPC of [1] of EMA

In general, intensified blood glucose control and monitoring of pregnant women with diabetes are recommended throughout pregnancy and when contemplating pregnancy.

Insulin degludec/insulin aspart [1], salicylates ---> SmPC of [1] of EMA

Possible reduction of the insulin requirements

Insulin degludec/insulin aspart [1], sulphonamides ---> SmPC of [1] of EMA

Possible reduction of the insulin requirements

Insulin degludec/insulin aspart [1], sympathomimetics ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

Insulin degludec/insulin aspart [1], thiazides ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

Insulin degludec/insulin aspart [1], thyroid hormones ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

CONTRAINDICATIONS of Insulin degludec/insulin aspart (Ryzodeg)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/ryzodeg-epar-product-information_en.pdf 13/05/2024

Insulin degludec/liraglutide (Xultophy)

Ability to drive, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia. This may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or using machines).

ACE inhibitors, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

Possible reduction of the Xultophy requirements

Alcohol, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

Alcohol may intensify or reduce the hypoglycaemic effect of Xultophy.

Anabolic steroids, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

Possible reduction of the Xultophy requirements

Atorvastatin, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

Liraglutide did not change the overall exposure of atorvastatin to a clinically relevant degree following single dose administration of atorvastatin. Therefore, no dose adjustment of atorvastatin is required when given with liraglutide.

Betablockers, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

Possible reduction of the Xultophy requirements. Beta-blockers may mask the symptoms of hypoglycaemia.

Breast-feeding, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

Because of lack of experience, Xultophy should not be used during breast-feeding.

Coumarin anticoagulants, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

Upon initiation of liraglutide treatment in patients on warfarin or other coumarin derivatives, more frequent monitoring of INR (International Normalised Ratio) is recommended.

CYP interaction, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

In vitro data suggest that the potential for pharmacokinetic drug interactions related to CYP interaction and protein binding is low for both liraglutide and insulin degludec.

Danazol, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

Possible increase of the Xultophy requirements

Digoxin, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

A single dose administration of digoxin 1 mg with liraglutide resulted in a reduction of digoxin AUC by 16%. No adjustment of digoxin dose is required

Drugs with high protein binding, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

In vitro data suggest that the potential for pharmacokinetic drug interactions related to CYP interaction and protein binding is low for both liraglutide and insulin degludec.

Fertility, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

Animal reproduction studies with insulin degludec have not revealed any adverse effects on fertility. Apart from a slight decrease in the number of live implants, animal studies with liraglutide did not indicate harmful effects with respect to fertility.

Gastric emptying, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

The small delay of gastric emptying with liraglutide may influence absorption of concomitantly administered oral medicinal products. Interaction studies did not show any clinically relevant delay of absorption.

Glucocorticoids, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

Possible increase of the Xultophy requirements

Griseofulvin, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

Dose adjustments of griseofulvin and other compounds with low solubility and high permeability are not required.

Growth hormone, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

Possible increase of the Xultophy requirements

IMAOs, insulin degludec/liraglutide [2] ---> SmPC of [2] of EMA

Possible reduction of the Xultophy requirements

Insulin degludec/liraglutide [1], lanreotide ---> SmPC of [1] of EMA

Octreotide/lanreotide may either increase or decrease the Xultophy requirement.

Insulin degludec/liraglutide [1], lisinopril ---> SmPC of [1] of EMA

A single dose administration of lisinopril 20 mg with liraglutide resulted in a reduction of lisinopril AUC by 15%. No dose adjustment of lisinopril is required

Insulin degludec/liraglutide [1], octreotide ---> SmPC of [1] of EMA

Octreotide/lanreotide may either increase or decrease the Xultophy requirement.

Insulin degludec/liraglutide [1], oral antidiabetics ---> SmPC of [1] of EMA

Possible reduction of the Xultophy requirements

Insulin degludec/liraglutide [1], oral contraceptives ---> SmPC of [1] of EMA

Possible increase of the Xultophy requirements. The contraceptive effect is anticipated to be unaffected when co-administered with liraglutide.

Insulin degludec/liraglutide [1], paracetamol ---> SmPC of [1] of EMA

Liraglutide did not change the overall exposure of paracetamol following a single dose of 1 000 mg. Paracetamol Cmax was decreased by 31% and median tmax was delayed up to 15 min. No dose adjustment for concomitant use of paracetamol is required.

Insulin degludec/liraglutide [1], pregnancy ---> SmPC of [1] of EMA

If a patient wishes to become pregnant, or pregnancy occurs, treatment with insulin Xultophy should be discontinued.

Insulin degludec/liraglutide [1], salicylates ---> SmPC of [1] of EMA

Possible reduction of the Xultophy requirements

Insulin degludec/liraglutide [1], sulphonamides ---> SmPC of [1] of EMA

Possible reduction of the Xultophy requirements

Insulin degludec/liraglutide [1], sympathomimetics ---> SmPC of [1] of EMA

Possible increase of the Xultophy requirements

Insulin degludec/liraglutide [1], thiazides ---> SmPC of [1] of EMA

Possible increase of the Xultophy requirements

Insulin degludec/liraglutide [1], thyroid hormones ---> SmPC of [1] of EMA

Possible increase of the Xultophy requirements

Insulin degludec/liraglutide [1], warfarin ---> SmPC of [1] of EMA

No interaction study has been performed. A clinically relevant interaction with active substances with poor solubility or with narrow therapeutic index such as warfarin cannot be excluded.

Insulin degludec/liraglutide [1], warfarin ---> SmPC of [1] of EMA

Upon initiation of Xultophy treatment in patients on warfarin or other coumarin derivatives more frequent monitoring of INR (International Normalised Ratio) is recommended.

CONTRAINDICATIONS of Insulin degludec/liraglutide (Xultophy)

- Hypersensitivity to either or both active substances or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/xultophy-epar-product-information_en.pdf 11/03/2024

Insulin detemir (Levemir)

Ability to drive, insulin detemir [2] ---> SmPC of [2] of EMA

ACE inhibitors, insulin detemir [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements

Alcohol, insulin detemir [2] ---> SmPC of [2] of EMA

Alcohol may intensify or reduce the hypoglycaemic effect of insulin.

Anabolic steroids, insulin detemir [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements

Betablockers, insulin detemir [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements. Beta-blockers may mask the symptoms of hypoglycaemia.

Breast-feeding, insulin detemir [2] ---> SmPC of [2] of EMA

Breast-feeding women may require adjustments in insulin dose and diet.

Danazol, insulin detemir [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

Fertility, insulin detemir [2] ---> SmPC of [2] of EMA

Animal studies do not indicate harmful effects with respect to fertility.

GLP-1 receptor agonists, insulin detemir [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements

Glucocorticoids, insulin detemir [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

Growth hormone, insulin detemir [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

IMAOs, insulin detemir [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements

Insulin detemir [1], lanreotide ---> SmPC of [1] of EMA

Octreotide/lanreotide may either increase or decrease the insulin requirement.

Insulin detemir [1], octreotide ---> SmPC of [1] of EMA

Octreotide/lanreotide may either increase or decrease the insulin requirement.

Insulin detemir [1], oral antidiabetics ---> SmPC of [1] of EMA

Possible reduction of the insulin requirements

Insulin detemir [1], oral contraceptives ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

Insulin detemir [1], pregnancy ---> SmPC of [1] of EMA

Treatment with Levemir can be considered during pregnancy, if clinically needed.

Insulin detemir [1], pregnancy ---> SmPC of [1] of EMA

Insulin requirements usually fall in the first trimester and increase subsequently during the second and third trimester. After delivery, insulin requirements normally return rapidly to pre-pregnancy values.

Insulin detemir [1], salicylates ---> SmPC of [1] of EMA

Possible reduction of the insulin requirements

Insulin detemir [1], sulphonamides ---> SmPC of [1] of EMA

Possible reduction of the insulin requirements

Insulin detemir [1], sympathomimetics ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

Insulin detemir [1], thiazides ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

Insulin detemir [1], thyroid hormones ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

CONTRAINDICATIONS of Insulin detemir (Levemir)

- Hypersensitivity to the active substance or to any of the excipients (see section 6.1).

https://www.ema.europa.eu/en/documents/product-information/levemir-epar-product-information_en.pdf 13/07/2021

Insulin glargin (Toujeo)

Ability to drive, insulin glargin [2] ---> SmPC of [2] of EMA

Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is particularly important in those who have reduced or absent awareness of the warning symptoms of hypoglycaemia or have frequent episodes of hypoglycaemia.

Ability to drive, insulin glargin [2] ---> SmPC of [2] of EMA

The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or hyperglycaemia or, for example, as a result of visual impairment.

ACE inhibitors, insulin glargin [2] ---> SmPC of [2] of EMA

Enhanced blood-glucose-lowering effect and increased susceptibility to hypoglycaemia

Adrenaline, insulin glargin [2] ---> SmPC of [2] of EMA

Reduced blood-glucose-lowering effect

Alcohol, insulin glargin [2] ---> SmPC of [2] of EMA

Alcohol may either potentiate or weaken the blood-glucose-lowering effect of insulin.

Anabolic steroids, insulin glargin [2] ---> SmPC of [2] of EMA

Possible reduction of the insulin requirements

Betablockers, insulin glargin [2] ---> SmPC of [2] of EMA

Beta-blockers may either potentiate or weaken the blood-glucose-lowering effect of insulin. Under the influence of sympatholytic medicinal products such as beta-blockers, the signs of adrenergic counter-regulation may be reduced or absent.

Breast-feeding, insulin glargin [2] ---> SmPC of [2] of EMA

Breast-feeding women may require adjustments in insulin dose and diet.

Clonidine, insulin glargin [2] ---> SmPC of [2] of EMA

Clonidine may either potentiate or weaken the blood-glucose-lowering effect of insulin. Under the influence of clonidin, the signs of adrenergic counter-regulation may be reduced or absent.

Clozapine, insulin glargin [2] ---> SmPC of [2] of EMA

Reduced blood-glucose-lowering effect

Corticosteroids, insulin glargin [2] ---> SmPC of [2] of EMA

Reduced blood-glucose-lowering effect

Danazol, insulin glargin [2] ---> SmPC of [2] of EMA

Reduced blood-glucose-lowering effect

Diazoxide, insulin glargin [2] ---> SmPC of [2] of EMA

Possible increase of the insulin requirements

Disopyramide, insulin glargin [2] ---> SmPC of [2] of EMA

Enhanced blood-glucose-lowering effect and increased susceptibility to hypoglycaemia

Diuretics, insulin glargin [2] ---> SmPC of [2] of EMA

Reduced blood-glucose-lowering effect

Epinephrine, insulin glargin [2] ---> SmPC of [2] of EMA

Reduced blood-glucose-lowering effect

Estrogens, insulin glargin [2] ---> SmPC of [2] of EMA

Reduced blood-glucose-lowering effect

Fertility, insulin glargin [2] ---> SmPC of [2] of EMA

Animal studies do not indicate direct harmful effects with respect to fertility.

Fibrates, insulin glargin [2] ---> SmPC of [2] of EMA

Enhanced blood-glucose-lowering effect and increased susceptibility to hypoglycaemia

Fluoxetine, insulin glargin [2] ---> SmPC of [2] of EMA

Enhanced blood-glucose-lowering effect and increased susceptibility to hypoglycaemia

Gestagens, insulin glargin [2] ---> SmPC of [2] of EMA

Reduced blood-glucose-lowering effect

Glucagon, insulin glargin [2] ---> SmPC of [2] of EMA

Reduced blood-glucose-lowering effect

Growth hormone, insulin glargin [2] ---> SmPC of [2] of EMA

Reduced blood-glucose-lowering effect

Guanethidine, insulin glargin [2] ---> SmPC of [2] of EMA

Under the influence of guanethidine, the signs of adrenergic counter-regulation may be reduced or absent.

IMAOs, insulin glargin [2] ---> SmPC of [2] of EMA

Enhanced blood-glucose-lowering effect and increased susceptibility to hypoglycaemia

Insulin glargin [1], isoniazid ---> SmPC of [1] of EMA

Reduced blood-glucose-lowering effect

Insulin glargin [1], lithium ---> SmPC of [1] of EMA

Lithium salts may either potentiate or weaken the blood-glucose-lowering effect of insulin.

Insulin glargin [1], olanzapine ---> SmPC of [1] of EMA

Reduced blood-glucose-lowering effect

Insulin glargin [1], oral antidiabetics ---> SmPC of [1] of EMA

Enhanced blood-glucose-lowering effect and increased susceptibility to hypoglycaemia

Insulin glargin [1], oral contraceptives ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

Insulin glargin [1], pentamidine ---> SmPC of [1] of EMA

Pentamidine may cause hypoglycaemia, which may sometimes be followed by hyperglycaemia.

Insulin glargin [1], pentoxifylline ---> SmPC of [1] of EMA

Enhanced blood-glucose-lowering effect and increased susceptibility to hypoglycaemia

Insulin glargin [1], phenothiazines ---> SmPC of [1] of EMA

Reduced blood-glucose-lowering effect

Insulin glargin [1], pregnancy ---> SmPC of [1] of EMA

The use of Toujeo may be considered during pregnancy, if clinically needed.

Insulin glargin [1], pregnancy ---> SmPC of [1] of EMA

Insulin requirements may decrease during the first trimester and generally increase during the second and third trimesters. Immediately after delivery, insulin requirements decline rapidly (increased risk of hypoglycaemia).

Insulin glargin [1], propoxyphene ---> SmPC of [1] of EMA

Enhanced blood-glucose-lowering effect and increased susceptibility to hypoglycaemia

Insulin glargin [1], protease inhibitors ---> SmPC of [1] of EMA

Reduced blood-glucose-lowering effect

Insulin glargin [1], reserpine ---> SmPC of [1] of EMA

Under the influence of reserpine, the signs of adrenergic counter-regulation may be reduced or absent.

Insulin glargin [1], salbutamol ---> SmPC of [1] of EMA

Reduced blood-glucose-lowering effect

Insulin glargin [1], salicylates ---> SmPC of [1] of EMA

Enhanced blood-glucose-lowering effect and increased susceptibility to hypoglycaemia

Insulin glargin [1], somatotropin ---> SmPC of [1] of EMA

Reduced blood-glucose-lowering effect

Insulin glargin [1], sulphonamides ---> SmPC of [1] of EMA

Enhanced blood-glucose-lowering effect and increased susceptibility to hypoglycaemia

Insulin glargin [1], sympatholytic drug ---> SmPC of [1] of EMA

In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent.

Insulin glargin [1], sympathomimetics ---> SmPC of [1] of EMA

Reduced blood-glucose-lowering effect

Insulin glargin [1], terbutaline ---> SmPC of [1] of EMA

Reduced blood-glucose-lowering effect

Insulin glargin [1], thiazides ---> SmPC of [1] of EMA

Possible increase of the insulin requirements

Insulin glargin [1], thyroid hormones ---> SmPC of [1] of EMA

Reduced blood-glucose-lowering effect

CONTRAINDICATIONS of Insulin glargin (Toujeo)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/toujeo-epar-product-information_en.pdf 05/03/2026

Other trade names: Abasaglar (previously Abasria), Lantus, Lusduna, Semglee, Toujeo (previously Optisulin),

Insulin glargine/lixisenatide (Suliqua)

Ability to drive, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or hyperglycaemia or, for example, as a result of visual impairment.

ACE inhibitors, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may enhance the blood-glucose-lowering effect and increase susceptibility to hypoglycaemia.

Adrenaline, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may reduce the blood-glucose-lowering effect.

Alcohol, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This combination may either potentiate or weaken the blood-glucose-lowering effect of insulin.

Antiadrenergics, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

Under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent

Antibiotics, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

For oral medicinal products that are particularly dependent on threshold concentrations for efficacy, such as antibiotics, patients should be advised to take those medicinal products at least 1 hour before or 4 hours after lixisenatide injection.

Atorvastatin, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

The changes are not clinically relevant and, therefore, no dose adjustment for atorvastatin is required when co-administered with lixisenatide.

Atypical neuroleptics, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may reduce the blood-glucose-lowering effect.

Betablockers, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This combination may either potentiate or weaken the blood-glucose-lowering effect of insulin. The signs of adrenergic counter-regulation may be reduced or absent.

Breast-feeding, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

It is unknown whether insulin glargine or lixisenatide are excreted in human milk. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Suliqua.

Clonidine, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This combination may either potentiate or weaken the blood-glucose-lowering effect of insulin.

Corticosteroids, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may reduce the blood-glucose-lowering effect.

Coumarin anticoagulants, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

No dose adjustment for warfarin is required when co-administered with lixisenatide; however, frequent monitoring of INR in patients on warfarin and/or coumarin derivatives is recommended at the time of initiation or ending of lixisenatide treatment.

Cytochrome P450, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

Lixisenatide is a peptide and is not metabolised by cytochrome P450. In in vitro studies, lixisenatide did not affect the activity of cytochrome P450 isozymes or human transporters tested. No pharmacokinetic interactions are known for insulin glargine.

Danazol, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may reduce the blood-glucose-lowering effect.

Diazoxide, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may reduce the blood-glucose-lowering effect.

Digoxin, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

No dose adjustment for digoxin is required when co-administered with lixisenatide.

Disopyramide, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may enhance the blood-glucose-lowering effect and increase susceptibility to hypoglycaemia.

Diuretics, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may reduce the blood-glucose-lowering effect.

Drugs with a narrow therapeutic window, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

Patients receiving medicinal products of either a narrow therapeutic ratio or medicinal products that require careful clinical monitoring should be followed closely, especially at the time of initiation of lixisenatide treatment.

Epinephrine, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may reduce the blood-glucose-lowering effect.

Estrogens, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may reduce the blood-glucose-lowering effect.

Fertility, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

Animal studies with lixisenatide or insulin glargine do not indicate direct harmful effects with respect to fertility.

Fibrates, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may enhance the blood-glucose-lowering effect and increase susceptibility to hypoglycaemia.

Fluoxetine, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may enhance the blood-glucose-lowering effect and increase susceptibility to hypoglycaemia.

Foods, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

If such medicinal products are to be administered with food, patients should be advised to, if possible, take them with a meal when lixisenatide is not administered.

Gastric emptying, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

The delay of gastric emptying with lixisenatide may reduce the rate of absorption of orally administered medicinal products.

Gastro-resistant formulations, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

Gastro-resistant formulations containing substances sensitive to stomach degradation, should be administered 1 hour before or 4 hours after lixisenatide injection.

Glucagon, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may reduce the blood-glucose-lowering effect.

Guanethidine, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

Under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent

Hypoglycemic drugs, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may enhance the blood-glucose-lowering effect and increase susceptibility to hypoglycaemia.

IMAOs, insulin glargine/lixisenatide [2] ---> SmPC of [2] of EMA

This substance may enhance the blood-glucose-lowering effect and increase susceptibility to hypoglycaemia.

Insulin glargine/lixisenatide [1], isoniazid ---> SmPC of [1] of EMA

This substance may reduce the blood-glucose-lowering effect.

Insulin glargine/lixisenatide [1], lithium ---> SmPC of [1] of EMA

This combination may either potentiate or weaken the blood-glucose-lowering effect of insulin.

Insulin glargine/lixisenatide [1], olanzapine ---> SmPC of [1] of EMA

This substance may reduce the blood-glucose-lowering effect.

Insulin glargine/lixisenatide [1], oral contraceptives ---> SmPC of [1] of EMA

The reduction in Cmax is of limited clinical relevance and no dose adjustment for oral contraceptives is required.

Insulin glargine/lixisenatide [1], orally administered medicinal products ---> SmPC of [1] of EMA

The delay of gastric emptying with lixisenatide may reduce the rate of absorption of orally administered medicinal products.

Insulin glargine/lixisenatide [1], paracetamol ---> SmPC of [1] of EMA

Based on these results, no dose adjustment for paracetamol is required but the delayed tmax observed when paracetamol is administered 1-4 hours after lixisenatide should be taken into account when a rapid onset of action is required for efficacy.

Insulin glargine/lixisenatide [1], pentamidine ---> SmPC of [1] of EMA

Pentamidine may cause hypoglycaemia, which may sometimes be followed by hyperglycaemia.

Insulin glargine/lixisenatide [1], pentoxifylline ---> SmPC of [1] of EMA

This substance may enhance the blood-glucose-lowering effect and increase susceptibility to hypoglycaemia.

Insulin glargine/lixisenatide [1], phenothiazines ---> SmPC of [1] of EMA

This substance may reduce the blood-glucose-lowering effect.

Insulin glargine/lixisenatide [1], pregnancy ---> SmPC of [1] of EMA

Suliqua should not be used during pregnancy. If a patient wishes to become pregnant, or pregnancy occurs, treatment with Suliqua should be discontinued.

Insulin glargine/lixisenatide [1], progestagens ---> SmPC of [1] of EMA

This substance may reduce the blood-glucose-lowering effect.

Insulin glargine/lixisenatide [1], propoxyphene ---> SmPC of [1] of EMA

This substance may enhance the blood-glucose-lowering effect and increase susceptibility to hypoglycaemia.

Insulin glargine/lixisenatide [1], protease inhibitors ---> SmPC of [1] of EMA

This substance may reduce the blood-glucose-lowering effect.

Insulin glargine/lixisenatide [1], ramipril ---> SmPC of [1] of EMA

No dose adjustment for ramipril is required when co-administered with lixisenatide.

Insulin glargine/lixisenatide [1], reserpine ---> SmPC of [1] of EMA

Under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent

Insulin glargine/lixisenatide [1], salbutamol ---> SmPC of [1] of EMA

This substance may reduce the blood-glucose-lowering effect.

Insulin glargine/lixisenatide [1], salicylates ---> SmPC of [1] of EMA

This substance may enhance the blood-glucose-lowering effect and increase susceptibility to hypoglycaemia.

Insulin glargine/lixisenatide [1], somatropin ---> SmPC of [1] of EMA

This substance may reduce the blood-glucose-lowering effect.

Insulin glargine/lixisenatide [1], sulphonamides ---> SmPC of [1] of EMA

This substance may enhance the blood-glucose-lowering effect and increase susceptibility to hypoglycaemia.

Insulin glargine/lixisenatide [1], sympathomimetics ---> SmPC of [1] of EMA

This substance may reduce the blood-glucose-lowering effect.

Insulin glargine/lixisenatide [1], terbutaline ---> SmPC of [1] of EMA

This substance may reduce the blood-glucose-lowering effect.

Insulin glargine/lixisenatide [1], threshold concentrations ---> SmPC of [1] of EMA

Insulin glargine/lixisenatide [1], thyroid hormones ---> SmPC of [1] of EMA

This substance may reduce the blood-glucose-lowering effect.

Insulin glargine/lixisenatide [1], warfarin ---> SmPC of [1] of EMA

Insulin glargine/lixisenatide [1], women of childbearing potential ---> SmPC of [1] of EMA

Suliqua is not recommended in women of childbearing potential not using contraception.

CONTRAINDICATIONS of Insulin glargine/lixisenatide (Suliqua)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/suliqua-epar-product-information_en.pdf 25/10/2024

Insulin glulisin (Apidra)

Ability to drive, insulin glulisin [2] ---> SmPC of [2] of EMA

Patients should be advised to take precautions to avoid hypoglycaemia whilst driving.

Ability to drive, insulin glulisin [2] ---> SmPC of [2] of EMA

The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or hyperglycaemia or, for example, as a result of visual impairment.

ACE inhibitors, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible enhancement of blood-glucose-lowering activity and increased susceptibility to hypoglycaemia

Adrenaline, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible decrease in blood-glucose-lowering activity

Alcohol, insulin glulisin [2] ---> SmPC of [2] of EMA

Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the blood-glucose-lowering activity of insulin.

Antiadrenergics, insulin glulisin [2] ---> SmPC of [2] of EMA

The signs of adrenergic counter-regulation may be reduced or absent.

Atypical neuroleptics, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible decrease in blood-glucose-lowering activity

Betablockers, insulin glulisin [2] ---> SmPC of [2] of EMA

Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the blood-glucose-lowering activity of insulin.

Breast-feeding, insulin glulisin [2] ---> SmPC of [2] of EMA

It is unknown whether insulin glulisine is excreted in human milk, but in general insulin does not pass into breast milk and is not absorbed after oral administration. Breast-feeding mothers may require adjustments in insulin dose and diet.

Clonidine, insulin glulisin [2] ---> SmPC of [2] of EMA

Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the blood-glucose-lowering activity of insulin.

Clozapine, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible decrease in blood-glucose-lowering activity

Corticosteroids, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible decrease in blood-glucose-lowering activity

Danazol, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible decrease in blood-glucose-lowering activity

Diazoxide, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible decrease in blood-glucose-lowering activity

Disopyramide, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible enhancement of blood-glucose-lowering activity and increased susceptibility to hypoglycaemia

Diuretics, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible decrease in blood-glucose-lowering activity

Epinephrine, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible decrease in blood-glucose-lowering activity

Estrogens, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible decrease in blood-glucose-lowering activity

Fertility, insulin glulisin [2] ---> SmPC of [2] of EMA

Animal reproduction studies with insulin glulisine have not revealed any adverse effects on fertility.

Fibrates, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible enhancement of blood-glucose-lowering activity and increased susceptibility to hypoglycaemia

Fluoxetine, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible enhancement of blood-glucose-lowering activity and increased susceptibility to hypoglycaemia

Gestagens, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible decrease in blood-glucose-lowering activity

Glucagon, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible decrease in blood-glucose-lowering activity

Guanethidine, insulin glulisin [2] ---> SmPC of [2] of EMA

The signs of adrenergic counter-regulation may be reduced or absent.

IMAOs, insulin glulisin [2] ---> SmPC of [2] of EMA

Possible enhancement of blood-glucose-lowering activity and increased susceptibility to hypoglycaemia

Insulin glulisin [1], isoniazid ---> SmPC of [1] of EMA

Possible decrease in blood-glucose-lowering activity

Insulin glulisin [1], lithium ---> SmPC of [1] of EMA

Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the blood-glucose-lowering activity of insulin.

Insulin glulisin [1], olanzapine ---> SmPC of [1] of EMA

Possible decrease in blood-glucose-lowering activity

Insulin glulisin [1], oral antidiabetics ---> SmPC of [1] of EMA

Possible enhancement of blood-glucose-lowering activity and increased susceptibility to hypoglycaemia

Insulin glulisin [1], oral contraceptives ---> SmPC of [1] of EMA

Possible decrease in blood-glucose-lowering activity

Insulin glulisin [1], pentamidine ---> SmPC of [1] of EMA

Pentamidine may cause hypoglycaemia, which may sometimes be followed by hyperglycaemia.

Insulin glulisin [1], pentoxifylline ---> SmPC of [1] of EMA

Possible enhancement of blood-glucose-lowering activity and increased susceptibility to hypoglycaemia

Insulin glulisin [1], phenothiazines ---> SmPC of [1] of EMA

Possible decrease in blood-glucose-lowering activity

Insulin glulisin [1], pregnancy ---> SmPC of [1] of EMA

Caution should be exercised when prescribing to pregnant women. Careful monitoring of glucose control is essential.

Insulin glulisin [1], pregnancy ---> SmPC of [1] of EMA

Insulin requirements may decrease during the first trimester and generally increase during the second and third trimesters. Immediately after delivery, insulin requirements decline rapidly.

Insulin glulisin [1], propoxyphene ---> SmPC of [1] of EMA

Possible enhancement of blood-glucose-lowering activity and increased susceptibility to hypoglycaemia

Insulin glulisin [1], protease inhibitors ---> SmPC of [1] of EMA

Possible decrease in blood-glucose-lowering activity

Insulin glulisin [1], reserpine ---> SmPC of [1] of EMA

The signs of adrenergic counter-regulation may be reduced or absent.

Insulin glulisin [1], salbutamol ---> SmPC of [1] of EMA

Possible decrease in blood-glucose-lowering activity

Insulin glulisin [1], salicylates ---> SmPC of [1] of EMA

Possible enhancement of blood-glucose-lowering activity and increased susceptibility to hypoglycaemia

Insulin glulisin [1], somatropin ---> SmPC of [1] of EMA

Possible decrease in blood-glucose-lowering activity

Insulin glulisin [1], sulphonamides ---> SmPC of [1] of EMA

Possible enhancement of blood-glucose-lowering activity and increased susceptibility to hypoglycaemia

Insulin glulisin [1], sympatholytic drug ---> SmPC of [1] of EMA

In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent.

Insulin glulisin [1], sympathomimetics ---> SmPC of [1] of EMA

Possible decrease in blood-glucose-lowering activity

Insulin glulisin [1], terbutaline ---> SmPC of [1] of EMA

Possible decrease in blood-glucose-lowering activity

Insulin glulisin [1], thyroid hormones ---> SmPC of [1] of EMA

Possible decrease in blood-glucose-lowering activity

CONTRAINDICATIONS of Insulin glulisin (Apidra)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Hypoglycaemia.

https://www.ema.europa.eu/en/documents/product-information/apidra-epar-product-information_en.pdf 05/03/2026

Insulin icodec (Awiqli)

Ability to drive, Insulin icodec [2] ---> SmPC of [2] of EMA

The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or hyperglycaemia or, for example, as a result of visual impairment.

ACE inhibitors, Insulin icodec [2] ---> SmPC of [2] of EMA

Medicinal products that may reduce the insulin requirement

Alcohol, Insulin icodec [2] ---> SmPC of [2] of EMA

Alcohol may intensify or reduce the hypoglycaemic effect of insulin.

Anabolic steroids, Insulin icodec [2] ---> SmPC of [2] of EMA

Medicinal products that may reduce the insulin requirement

Antidiabetics, Insulin icodec [2] ---> SmPC of [2] of EMA

Medicinal products that may reduce the insulin requirement

Betablockers, Insulin icodec [2] ---> SmPC of [2] of EMA

Medicinal products that may reduce the insulin requirement. Beta-blockers may mask the symptoms of hypoglycaemia.

Breast-feeding, Insulin icodec [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from insulin icodec therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Danazol, Insulin icodec [2] ---> SmPC of [2] of EMA

This substance may increase the insulin requirement

Fertility, Insulin icodec [2] ---> SmPC of [2] of EMA

Animal reproduction studies with insulin icodec have not revealed any adverse reactions on fertility.

GLP-1 receptor agonists, Insulin icodec [2] ---> SmPC of [2] of EMA

Medicinal products that may reduce the insulin requirement

Glucocorticoids, Insulin icodec [2] ---> SmPC of [2] of EMA

This substance may increase the insulin requirement

Growth hormone, Insulin icodec [2] ---> SmPC of [2] of EMA

This substance may increase the insulin requirement

IMAOs, Insulin icodec [2] ---> SmPC of [2] of EMA

Medicinal products that may reduce the insulin requirement

Insulin icodec [1], lanreotide ---> SmPC of [1] of EMA

Octreotide/lanreotide may either increase or decrease the insulin requirement.

Insulin icodec [1], octreotide ---> SmPC of [1] of EMA

Octreotide/lanreotide may either increase or decrease the insulin requirement.

Insulin icodec [1], oral contraceptives ---> SmPC of [1] of EMA

This substance may increase the insulin requirement

Insulin icodec [1], pioglitazone ---> SmPC of [1] of EMA

Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for development of congestive heart failure.

Insulin icodec [1], pregnancy ---> SmPC of [1] of EMA

There is no clinical experience with use of insulin icodec in pregnant women. Animal reproduction studies with insulin icodec have not revealed any effects regarding embryotoxicity and teratogenicity.

Insulin icodec [1], salicylates ---> SmPC of [1] of EMA

Medicinal products that may reduce the insulin requirement

Insulin icodec [1], sulfonylureas ---> SmPC of [1] of EMA

Medicinal products that may reduce the insulin requirement

Insulin icodec [1], sulphonamides ---> SmPC of [1] of EMA

Medicinal products that may reduce the insulin requirement

Insulin icodec [1], sympathomimetics ---> SmPC of [1] of EMA

This substance may increase the insulin requirement

Insulin icodec [1], thiazides ---> SmPC of [1] of EMA

This substance may increase the insulin requirement

Insulin icodec [1], thyroid hormones ---> SmPC of [1] of EMA

This substance may increase the insulin requirement

Insulin icodec [1], women of childbearing potential ---> SmPC of [1] of EMA

Because of lack of experience during pregnancy, women of childbearing potential should be advised to discontinue Awiqli, if they become pregnant or wish to become pregnant.

CONTRAINDICATIONS of Insulin icodec (Awiqli)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/awiqli-epar-product-information_en.pdf 03/06/2024

Insulin lispro (Humalog)

Ability to drive, insulin lispro [2] ---> SmPC of [2] of EMA

The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia.

Acetylsalicylic acid, insulin lispro [2] ---> SmPC of [2] of EMA

Insulin requirements may be reduced in the presence of medicinal products with hypoglycaemic activity

AIIRA, insulin lispro [2] ---> SmPC of [2] of EMA

Insulin requirements may be reduced in the presence of medicinal products with hypoglycaemic activity

Alcohol, insulin lispro [2] ---> SmPC of [2] of EMA

Insulin requirements may be reduced in the presence of medicinal products with hypoglycaemic activity

Beta2-adrenergic agonists, insulin lispro [2] ---> SmPC of [2] of EMA

Insulin requirements may be increased by medicinal products with hyperglycaemic activity

Betablockers, insulin lispro [2] ---> SmPC of [2] of EMA

Insulin requirements may be reduced in the presence of medicinal products with hypoglycaemic activity

Breast-feeding, insulin lispro [2] ---> SmPC of [2] of EMA

Patients with diabetes who are breast-feeding may require adjustments in insulin dose, diet or both.

Captopril, insulin lispro [2] ---> SmPC of [2] of EMA

Insulin requirements may be reduced in the presence of medicinal products with hypoglycaemic activity

Corticosteroids, insulin lispro [2] ---> SmPC of [2] of EMA

Insulin requirements may be increased by medicinal products with hyperglycaemic activity

Danazol, insulin lispro [2] ---> SmPC of [2] of EMA

Insulin requirements may be increased by medicinal products with hyperglycaemic activity

Enalapril, insulin lispro [2] ---> SmPC of [2] of EMA

Insulin requirements may be reduced in the presence of medicinal products with hypoglycaemic activity

Fertility, insulin lispro [2] ---> SmPC of [2] of EMA

Insulin lispro did not induce fertility impairment in animal studies (see section 5.3).

IMAOs, insulin lispro [2] ---> SmPC of [2] of EMA

Insulin requirements may be reduced in the presence of medicinal products with hypoglycaemic activity

Insulin lispro [1], octreotide ---> SmPC of [1] of EMA

Insulin requirements may be reduced in the presence of medicinal products with hypoglycaemic activity

Insulin lispro [1], oral antidiabetics ---> SmPC of [1] of EMA

Insulin requirements may be reduced in the presence of medicinal products with hypoglycaemic activity

Insulin lispro [1], oral contraceptives ---> SmPC of [1] of EMA

Insulin requirements may be increased by medicinal products with hyperglycaemic activity

Insulin lispro [1], pregnancy ---> SmPC of [1] of EMA

Data on a large number of exposed pregnancies do not indicate any adverse effect of insulin lispro on pregnancy or on the health of the foetus/newborn.

Insulin lispro [1], ritodrine ---> SmPC of [1] of EMA

Insulin requirements may be increased by medicinal products with hyperglycaemic activity

Insulin lispro [1], salbutamol ---> SmPC of [1] of EMA

Insulin requirements may be increased by medicinal products with hyperglycaemic activity

Insulin lispro [1], salicylates ---> SmPC of [1] of EMA

Insulin requirements may be reduced in the presence of medicinal products with hypoglycaemic activity

Insulin lispro [1], SSRI ---> SmPC of [1] of EMA

Insulin requirements may be reduced in the presence of medicinal products with hypoglycaemic activity

Insulin lispro [1], sulphonamides ---> SmPC of [1] of EMA

Insulin requirements may be reduced in the presence of medicinal products with hypoglycaemic activity

Insulin lispro [1], terbutaline ---> SmPC of [1] of EMA

Insulin requirements may be increased by medicinal products with hyperglycaemic activity

Insulin lispro [1], thyroid hormones ---> SmPC of [1] of EMA

Insulin requirements may be increased by medicinal products with hyperglycaemic activity

CONTRAINDICATIONS of Insulin lispro (Humalog)

- Hypersensitivity to insulin lispro or to any of the excipients.

- Hypoglycaemia.

https://www.ema.europa.eu/en/documents/product-information/humalog-epar-product-information_en.pdf. 09/01/2024

Other trade names: Insulin lispro Sanofi, Liprolog, Liumjev,

Interferon alfa-2b (IntronA)

Ability to drive, interferon alfa-2b [2] ---> SmPC of [2] of EMA

Patients are to be advised that they may develop fatigue, somnolence, or confusion during treatment with IntronA, and therefore it is recommended that they avoid driving or operating machinery.

Aminophylline, interferon alfa-2b [2] ---> SmPC of [2] of EMA

Interferons may affect the oxidative metabolic process. This must be considered during concomitant therapy with medicinal products metabolised by this route, such as the xanthine derivatives theophylline or aminophylline.

Antineoplastics, interferon alfa-2b [2] ---> SmPC of [2] of EMA

Administration of interferon alfa-2b in combination with other chemotherapeutic agents (e.g., Ara-C, cyclophosphamide, doxorubicin, teniposide) may lead to increased risk of toxicity (severity and duration)

Breast-feeding, interferon alfa-2b [2] ---> SmPC of [2] of EMA

Because of the potential for adverse reactions in nursing infants, nursing should be discontinued prior to initiation of treatment.

Contraceptives, interferon alfa-2b [2] ---> SmPC of [2] of EMA

Decreased serum estradiol and progesterone concentrations have been reported in women treated with human leukocyte interferon.

Cyclophosphamide, interferon alfa-2b [2] ---> SmPC of [2] of EMA

Cytosine arabinoside, interferon alfa-2b [2] ---> SmPC of [2] of EMA

Doxorubicine, interferon alfa-2b [2] ---> SmPC of [2] of EMA

Epirubicin [1], interferon alfa-2b ---> SmPC of [1] of eMC

The co-administration of epirubicin with interferon alfa-2b may cause a reduction in both the terminal half-life and the total clearance of epirubicin.

Hypnotics, interferon alfa-2b [2] ---> SmPC of [2] of EMA

Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with IntronA.

Interferon alfa-2b [1], medicinal products ---> SmPC of [1] of EMA

Interactions between IntronA and other medicinal products have not been fully evaluated. Caution must be exercised when administering IntronA in combination with other potentially myelosuppressive agents.

Interferon alfa-2b [1], men ---> SmPC of [1] of EMA

IntronA must be used with caution in fertile men. Male patients or their female partners must use an effective contraceptive during treatment and for 7 months after treatment has been concluded

Interferon alfa-2b [1], myelosuppressive agents ---> SmPC of [1] of EMA

Caution must be exercised when administering interferon alfa-2b in combination with other potentially myelosuppressive agents.

Interferon alfa-2b [1], narcotics ---> SmPC of [1] of EMA

Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with IntronA.

Interferon alfa-2b [1], pregnancy ---> SmPC of [1] of EMA

IntronA is to be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. Combination therapy with ribavirin: Ribavirin therapy is contraindicated in women who are pregnant.

Interferon alfa-2b [1], sedatives ---> SmPC of [1] of EMA

Narcotics, hypnotics or sedatives must be administered with caution when used concomitantly with IntronA.

Interferon alfa-2b [1], shosaikoto ---> SmPC of [1] of EMA

Pulmonary infiltrates, pneumonitis, and pneumonia, occasionally resulting in fatality, have been observed rarely in interferon alpha treated patients, including those treated with IntronA. The aetiology has not been defined.

Interferon alfa-2b [1], telbivudine ---> SmPC of [1] of EMA

The co-administration may increase the risk of peripheral neuropathy. The combination of telbivudine with any interferon alfa-containing product is contraindicated

Interferon alfa-2b [1], teniposide ---> SmPC of [1] of EMA

Interferon alfa-2b [1], theophylline ---> SmPC of [1] of EMA

Interferon alfa-2b [1], women of childbearing potential ---> SmPC of [1] of EMA

Females of childbearing potential must use an effective contraceptive during treatment and for 4 months after treatment has been concluded.

Interferon alfa-2b [1], women of childbearing potential ---> SmPC of [1] of EMA

Extreme care must be taken to avoid pregnancy in female patients or in partners of male patients taking IntronA in combination with ribavirin.

Interferon alfa-2b [1], xanthines ---> SmPC of [1] of EMA

Interferon alfa-2b/ribavirin, nucleoside and nucleotide reverse transcriptase inhibitors ---> SmPC of [ribavirin]

Caution should be taken in HIV-positive subjects co-infected with HCV who receive nucleoside reverse transcriptase inhibitor (NRTI) treatment (especially ddI and d4T) and associated interferon alfa-2b/ribavirin treatment.

Interferon alfa-2b/ribavirin, pregnancy

The therapy of interferon alfa-2b with ribavirin is contraindicated in women who are pregnant.

CONTRAINDICATIONS of Interferon alfa-2b (IntronA)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- A history of severe pre-existing cardiac disease, e.g., uncontrolled congestive heart failure, recent myocardial infarction, severe arrhythmic disorders.

- Severe renal or hepatic dysfunction; including that caused by metastases.

- Epilepsy and/or compromised central nervous system (CNS) function

- Chronic hepatitis with decompensated cirrhosis of the liver.

- Chronic hepatitis in patients who are being or have been treated recently with immunosuppressive agents excluding short term corticosteroid withdrawal.

- Autoimmune hepatitis; or history of autoimmune disease; immunosuppressed transplant recipients.

- Pre-existing thyroid disease unless it can be controlled with conventional treatment.

- Combination of IntronA with telbivudine.

- Children and adolescents: Existence of, or history of severe psychiatric condition, particularly severe depression, suicidal ideation or suicide attempt

- Combination therapy with ribavirin: Also see ribavirin SPC if IntronA is to be administered in combination with ribavirin in patients with chronic hepatitis C.

https://www.ema.europa.eu/en/documents/product-information/introna-epar-product-information_en.pdf. 14/12/2022

Interferon beta-1a (Rebif)

Ability to drive, interferon beta-1a [2] ---> SmPC of [2] of EMA

Central nervous system-related adverse events associated with the use of interferon beta (e.g. dizziness) might influence the patient's ability to drive or use machines

ACTH, interferon beta-1a [2] ---> SmPC of [2] of EMA

Clinical studies indicate that multiple sclerosis patients can receive Rebif and corticosteroids or ACTH during relapses.

Antiepileptics, interferon beta-1a [2] ---> SmPC of [2] of EMA

Caution should be exercised when administering Rebif in combination with medicines that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance, e.g. antiepileptics and some classes of antidepressants

Breast-feeding, interferon beta-1a [2] ---> SmPC of [2] of EMA

No harmful effects on the breastfed newborn/infant are anticipated. Rebif can be used during breast-feeding.

Corticosteroids, interferon beta-1a [2] ---> SmPC of [2] of EMA

Clinical studies indicate that multiple sclerosis patients can receive Rebif and corticosteroids or ACTH during relapses.

Cytochrome P450, interferon beta-1a [2] ---> SmPC of [2] of EMA

Interferons have been reported to reduce the activity of hepatic cytochrome P450-dependent enzymes in humans and animals.

Dimethyl fumarate [1], interferon beta-1a ---> SmPC of [1] of EMA

Commonly used medicinal products in patients with multiple sclerosis were clinically tested for potential interactions with dimethyl fumarate and did not alter the pharmacokinetic profile of dimethyl fumarate.

Drugs with narrow therapeutic index and are largely dependent on the hepatic CYP450 for clearance, interferon beta

Fertility, interferon beta-1a [2] ---> SmPC of [2] of EMA

The effects of Rebif on fertility have not been investigated.

Interferon beta-1a [1], pregnancy ---> SmPC of [1] of EMA

If clinically needed, the use of Rebif may be considered during pregnancy

CONTRAINDICATIONS of Interferon beta-1a (Rebif)

- Hypersensitivity to natural or recombinant interferon beta or to any of the excipients listed in section 6.1.

- Current severe depression and/or suicidal ideation

https://www.ema.europa.eu/en/documents/product-information/rebif-epar-product-information_en.pdf 01/06/2023

Other trade names: Avonex,

Interferon beta-1b (Extavia)

Ability to drive, interferon beta-1b [2] ---> SmPC of [2] of EMA

Central nervous system-related adverse events may influence the ability to drive and use machines in susceptible patients.

Antiepileptics, interferon beta-1b [2] ---> SmPC of [2] of EMA

Caution should be exercised when interferon beta-1b is administered with drugs that have a narrow therapeutic index and are largely dependent on the P450 for clearance

Breast-feeding, interferon beta-1b [2] ---> SmPC of [2] of EMA

No harmful effects on the breast-fed newborn/infant are anticipated. Extavia can be used during breast-feeding.

Corticosteroids, interferon beta-1b [2] ---> SmPC of [2] of EMA

Corticosteroid or ACTH treatment of relapses for periods of up to 28 days has been well tolerated in patients receiving Extavia.

Fertility, interferon beta-1b [2] ---> SmPC of [2] of EMA

No investigations on fertility have been conducted (see section 5.3).

Immunomodulatory agents, interferon beta-1b [2] ---> SmPC of [2] of EMA

Due to the lack of clinical experience, the use of interferon beta-1b together with immunomodulators other than corticosteroids or ACTH is not recommended.

Interferon beta-1b [1], narrow therapeutic window ---> SmPC of [1] of EMA

Caution should be exercised when interferon beta-1b is administered with drugs that have a narrow therapeutic index and are largely dependent on the P450 for clearance

Interferon beta-1b [1], pregnancy ---> SmPC of [1] of EMA

If clinically needed, the use of Extavia may be considered during pregnancy.

Interferon beta-1b, zidovudine

The interferon increases the effect and toxicity of zidovudine

CONTRAINDICATIONS of Interferon beta-1b (Extavia)

- Hypersensitivity to natural or recombinant interferon beta, human albumin or to any of the excipients listed in section 6.1.

- Patients with current severe depression and/or suicidal ideation

- Patients with decompensated liver disease

https://www.ema.europa.eu/en/documents/product-information/extavia-epar-product-information_en.pdf 30/04/2025 (withdrawn)

Other trade names: Betaferon, Interferon beta-1b (Extavia)

Iodixanol

Ability to drive, iodixanol

It is not recommended to drive and use machines during the first 24 hours after an intrathecal exploration

Aldesleukin, iodixanol

There was a greater frequency of late reactions to contrast media in patients who were treated 2 weeks before examination with iodinated contrast agents with interleukin-2 (flulike symptoms or skin reactions)

Breast-feeding, iodixanol

Iodixanol is excreted into the breast milk in insignificant quantities and only minimal quantities in the gut are absorbed. A harmful effect of the infant is improbable

Interleukin-2, iodixanol

Iodixanol, metformin

Use of iodinated contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking metformin

Iodixanol, phenothiazines

Medicinal products that reduce the convulsant threshold may cause interactions. It is recommended that these drugs should be discontinued 48 hours before and up to 24 hours after examination

Iodixanol, pregnancy

An exposure to radiation should be avoided during pregnancy

Iodixanol, seizure-threshold lowering drugs

Medicinal products that reduce the convulsant threshold may cause interactions. It is recommended that these drugs should be discontinued 48 hours before and up to 24 hours after examination

Iodixanol, tricyclic antidepressants

Medicinal products that reduce the convulsant threshold may cause interactions. It is recommended that these drugs should be discontinued 48 hours before and up to 24 hours after examination

Iomeprol, metformin

Use of iodinated contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking metformin

Ioxaglic acid, metformin

Use of iodinated contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking metformin

Ioflupane (DaTSCAN)

Amantadine, ioflupane [2] ---> SmPC of [2] of EMA

Medicines shown during clinical trials not to interfere with DaTSCAN imaging include amantadine, trihexyphenidyl, budipine, levodopa, metoprolol, primidone, propranolol and selegiline.

Amphetamine, ioflupane [2] ---> SmPC of [2] of EMA

Ioflupane binds to the dopamine transporter. Medicines that bind to the dopamine transporter with high affinity may therefore interfere with DaTSCAN diagnosis.

Benzatropine, ioflupane [2] ---> SmPC of [2] of EMA

Ioflupane binds to the dopamine transporter. Medicines that bind to the dopamine transporter with high affinity may therefore interfere with DaTSCAN diagnosis.

Breast-feeding, ioflupane [2] ---> SmPC of [2] of EMA

If administration is considered necessary, breast-feeding should be interrupted for 3 days and substituted by formula feeding. During this time, breast milk should be expressed at regular intervals and the expressed feeds should be discarded.

Budipine, ioflupane [2] ---> SmPC of [2] of EMA

Medicines shown during clinical trials not to interfere with DaTSCAN imaging include amantadine, trihexyphenidyl, budipine, levodopa, metoprolol, primidone, propranolol and selegiline.

Bupropion, ioflupane [2] ---> SmPC of [2] of EMA

Ioflupane binds to the dopamine transporter. Medicines that bind to the dopamine transporter with high affinity may therefore interfere with DaTSCAN diagnosis.

Cocaine, ioflupane [2] ---> SmPC of [2] of EMA

Ioflupane binds to the dopamine transporter. Medicines that bind to the dopamine transporter with high affinity may therefore interfere with DaTSCAN diagnosis.

Dopamine agonists, ioflupane [2] ---> SmPC of [2] of EMA

Dopamine agonists and antagonists acting on the postsynaptic dopamine receptors are not expected to interfere with DaTSCAN imaging and can therefore be continued if desired.

Dopamine antagonists, ioflupane [2] ---> SmPC of [2] of EMA

Dopamine agonists and antagonists acting on the postsynaptic dopamine receptors are not expected to interfere with DaTSCAN imaging and can therefore be continued if desired.

Fertility, ioflupane [2] ---> SmPC of [2] of EMA

No fertility studies have been performed. No data are available.

Ioflupane [1], levodopa ---> SmPC of [1] of EMA

Medicines shown during clinical trials not to interfere with DaTSCAN imaging include amantadine, trihexyphenidyl, budipine, levodopa, metoprolol, primidone, propranolol and selegiline.

Ioflupane [1], mazindol ---> SmPC of [1] of EMA

Ioflupane binds to the dopamine transporter. Medicines that bind to the dopamine transporter with high affinity may therefore interfere with DaTSCAN diagnosis.

Ioflupane [1], methylphenidate ---> SmPC of [1] of EMA

Ioflupane binds to the dopamine transporter. Medicines that bind to the dopamine transporter with high affinity may therefore interfere with DaTSCAN diagnosis.

Ioflupane [1], metoprolol ---> SmPC of [1] of EMA

Medicines shown during clinical trials not to interfere with DaTSCAN imaging include amantadine, trihexyphenidyl, budipine, levodopa, metoprolol, primidone, propranolol and selegiline.

Ioflupane [1], pergolide ---> SmPC of [1] of EMA

Medicinal products shown in animal studies not to interfere with DaTSCAN imaging include pergolide.

Ioflupane [1], phentermine ---> SmPC of [1] of EMA

Ioflupane binds to the dopamine transporter. Medicines that bind to the dopamine transporter with high affinity may therefore interfere with DaTSCAN diagnosis.

Ioflupane [1], pregnancy ---> SmPC of [1] of EMA

DaTSCAN is contraindicated in pregnancy

Ioflupane [1], primidone ---> SmPC of [1] of EMA

Medicines shown during clinical trials not to interfere with DaTSCAN imaging include amantadine, trihexyphenidyl, budipine, levodopa, metoprolol, primidone, propranolol and selegiline.

Ioflupane [1], propranolol ---> SmPC of [1] of EMA

Medicines shown during clinical trials not to interfere with DaTSCAN imaging include amantadine, trihexyphenidyl, budipine, levodopa, metoprolol, primidone, propranolol and selegiline.

Ioflupane [1], selegiline ---> SmPC of [1] of EMA

Medicines shown during clinical trials not to interfere with DaTSCAN imaging include amantadine, trihexyphenidyl, budipine, levodopa, metoprolol, primidone, propranolol and selegiline.

Ioflupane [1], sertraline ---> SmPC of [1] of EMA

Ioflupane binds to the dopamine transporter. Medicines that bind to the dopamine transporter with high affinity may therefore interfere with DaTSCAN diagnosis.

Ioflupane [1], women of childbearing potential ---> SmPC of [1] of EMA

Where it is necessary to administer radioactive medicinal products to women of childbearing potential, information should always be sought about pregnancy.

CONTRAINDICATIONS of Ioflupane (DaTSCAN)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6,1.

- Pregnancy

https://www.ema.europa.eu/en/documents/product-information/datscan-epar-product-information_en.pdf 19/02/2024

Other trade names: Celsunax, Striascan,

Iohexol

Ability to drive, iohexol

It is not recommended to drive and use machines during the first 24 hours after an intrathecal exploration

Aldesleukin, iohexol

Patients treated with interleukin-2 less than two weeks previously have been associated with an increased risk for delayed reactions (flu-like symptoms or skin reactions).

Betablockers, iohexol

The use of betablocker increases the risk of hypersensitivity reactions to contrast media

Breast-feeding, iohexol

Breast feeding may be continued normally when iodinated contrast media are given to the mother.

Interleukin-2, iohexol

Patients treated with interleukin-2 less than two weeks previously have been associated with an increased risk for delayed reactions (flu-like symptoms or skin reactions).

Iohexol, metformin

Use of iodinated contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking metformin

Iohexol, monoamine oxidase inhibitors

Medicinal products that reduce the convulsant threshold may cause interactions. It is recommended that these drugs should be discontinued 48 hours before and up to 24 hours after examination

Iohexol, phenothiazines

Medicinal products that reduce the convulsant threshold may cause interactions. It is recommended that these drugs should be discontinued 48 hours before and up to 24 hours after examination

Iohexol, pregnancy

Iohexol should not be used in pregnancy unless the benefit outweighs the risk and it is considered essential by the physician.

Iohexol, seizure-threshold lowering drugs

Medicinal products that reduce the convulsant threshold may cause interactions. It is recommended that these drugs should be discontinued 48 hours before and up to 24 hours after examination

Iohexol, tricyclic antidepressants

Medicinal products that reduce the convulsant threshold may cause interactions. It is recommended that these drugs should be discontinued 48 hours before and up to 24 hours after examination

Iomeprol

Ability to drive, iomeprol [2] ---> SmPC of [2] of eMC

There is no known effect on the ability to drive and operate machines. After intrathecal administration, it is recommended that the patient should wait 24 hours before driving or operating machinery.

ACE inhibitors, iomeprol [2] ---> SmPC of [2] of eMC

It has been reported that cardiac and/or hypertensive patients under treatment with diuretics, ACE-inhibitors, and/or beta blocking agents are at higher risk of adverse reactions when administered iodinated contrast media.

Betablockers, iomeprol [2] ---> SmPC of [2] of eMC

Breast-feeding, iomeprol [2] ---> SmPC of [2] of eMC

Adverse effects on the nursing infant are unlikely to occur. Stopping breastfeeding is unnecessary.

Corticosteroids, iomeprol [2] ---> SmPC of [2] of eMC

Epidural and intrathecal corticosteroids should never be concurrently administered when iodinated contrast media are used, because corticosteroids may promote and affect the signs and symptoms of arachnoiditis

Diuretics, iomeprol [2] ---> SmPC of [2] of eMC

Iomeprol [1], neuroleptics ---> SmPC of [1] of eMC

Treatment with drugs that lower the seizure threshold should be discontinued 48 hours before the examination. Treatment should not be resumed until 24 hours post-procedure.

Iomeprol [1], pregnancy ---> SmPC of [1] of eMC

Since, wherever possible, exposure to radiation should be avoided during pregnancy, the benefits of any X-ray examination, whether with or without contrast material, should be carefully weighed against the possible risk.

Iomeprol [1], vasoconstrictors ---> SmPC of [1] of eMC

Vasopressor agents should not be administered prior to iomeprol.

Iomeprol, metformin

Use of iodinated contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking metformin

Iomeprol, phenothiazines [2] ---> SmPC of [2] of eMC

Treatment with drugs that lower the seizure threshold should be discontinued 48 hours before the examination. Treatment should not be resumed until 24 hours post-procedure.

Iomeprol, seizure-threshold lowering drugs [2] ---> SmPC of [2] of eMC

Treatment with drugs that lower the seizure threshold should be discontinued 48 hours before the examination. Treatment should not be resumed until 24 hours post-procedure.

Iomeprol, tricyclic antidepressant [2] ---> SmPC of [2] of eMC

Treatment with drugs that lower the seizure threshold should be discontinued 48 hours before the examination. Treatment should not be resumed until 24 hours post-procedure.

CONTRAINDICATIONS of Iomeprol

- Hypersensitivity to the active substance or any of the excipients

- Intrathecal concomitant administration of corticosteroids with contrast media is contraindicated.

http://www.medicines.org.uk/emc/

Iopamidol

Aldesleukin, iopamidol

Antihistamines, iopamidol

Medicinal products that reduce the convulsant threshold should be discontinued 48 hours before and up to 24 hours after examination

Betablockers, iopamidol [2] ---> SmPC of [2] of eMC

Concomitant administration of iopamidol and betablockers can exacerbate severe hypersensitivity reactions.

Biguanides, iopamidol

Use of iodinated contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking biguanide

Biguanides, radiologic contrasts

Use of iodinated contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking biguanide

Breast-feeding, iopamidol [2] ---> SmPC of [2] of eMC

Due to the low level of absorption of Iopamidol from the gastrointestinal tract, it is unlikely that a foetus could be exposed to significant levels.

Diuretics, iopamidol ---> SmPC of [aliskiren/hydrochlorothiazide] of EMA

In case of diuretic-induced dehydration, there is an increased risk of acute renal failure, especially with high doses of iodine products. Patients should be rehydrated before administration.

Interleukin-2, iopamidol

Iopamidol [1], pregnancy ---> SmPC of [1] of eMC

As a precautionary measure, it is preferable to avoid the use of Iopamidol solution during pregnancy.

Iopamidol, metformin

Use of iodinated contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking metformin

Iopamidol, neuroleptics

Medicinal products that reduce the convulsant threshold should be discontinued 48 hours before and up to 24 hours after examination

Iopamidol, papaverine

Arterial thrombosis may occur, if iopamidol is administered after papaverine

Iopamidol, phenothiazines

Medicinal products that reduce the convulsant threshold should be discontinued 48 hours before and up to 24 hours after examination

Iopamidol, QT interval prolonging drugs

Due to increased risk of cardiotoxicity, iopamidol should not be administered with medicinal products that may prolong the interval QT

Iopamidol, seizure-threshold lowering drugs

Medicinal products that reduce the convulsant threshold should be discontinued 48 hours before and up to 24 hours after examination

Iopamidol, vasoconstrictors

The administration of vasopressors strongly potentiates the neurological effect of the intra-arterial contrast media

CONTRAINDICATIONS of Iopamidol

- Hypersensitivity to the active ingredient iopamidol and/or iodine preparations or to any of the excipients.

- It must not be used for parenteral administration.

http://www.medicines.org.uk/emc/

Iopromide

Aldesleukin, iopromide

Previous treatment (up to several weeks) with Interleukin-2 is associated with an increased risk of delayed reactions

Betablockers, iopromide

The use of betablocker increases the risk of hypersensitivity reactions to contrast media

Biguanides, iopromide

In patients with acute kidney failure or severe chronic kidney disease biguanide elimination can be reduced leading to accumulation and the development of lactic acidosis.

Breast-feeding, iopromide

Harm to the nursed infant is unlikely

Interleukin-2, iopromide

Previous treatment (up to several weeks) with Interleukin-2 is associated with an increased risk of delayed reactions

Iopromide, monoamine oxidase inhibitors

Medicinal products that reduce the convulsant threshold may cause interactions. It is recommended that these drugs should be discontinued 48 hours before and up to 24 hours after examination

Iopromide, neuroleptics

Medicinal products that reduce the convulsant threshold may cause interactions. It is recommended that these drugs should be discontinued 48 hours before and up to 24 hours after examination

Iopromide, pregnancy

Adequate and well-controlled studies in pregnant women have not been conducted.

Iopromide, seizure-threshold lowering drugs

Medicinal products that reduce the convulsant threshold may cause interactions. It is recommended that these drugs should be discontinued 48 hours before and up to 24 hours after examination

Iopromide, tricyclic antidepressants

Medicinal products that reduce the convulsant threshold may cause interactions. It is recommended that these drugs should be discontinued 48 hours before and up to 24 hours after examination

Ipilimumab (Yervoy)

Ability to drive, ipilimumab [2] ---> SmPC of [2] of EMA

Because of potential adverse reactions such as fatigue (see section 4.8), patients should be advised to use caution when driving or operating machinery until they are certain that ipilimumab does not adversely affect them.

Anticoagulants, ipilimumab [2] ---> SmPC of [2] of EMA

Since gastrointestinal haemorrhage is an adverse reaction with ipilimumab, patients who require concomitant anticoagulant therapy should be monitored closely.

Breast-feeding, ipilimumab [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue from YERVOY therapy taking into account the benefit of breast-feeding for the child and the benefit of YERVOY therapy for the woman.

Corticosteroids, ipilimumab [2] ---> SmPC of [2] of EMA

However, systemic corticosteroids or other immunosuppressants can be used after starting ipilimumab to treat immune-related adverse reactions.

Corticosteroids, ipilimumab [2] ---> SmPC of [2] of EMA

The use of systemic corticosteroids at baseline, before starting ipilimumab, should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of ipilimumab.

Dacarbazine, ipilimumab [2] ---> SmPC of [2] of EMA

No clinically relevant pharmacokinetic drug-drug interaction was observed between ipilimumab and paclitaxel/carboplatin, dacarbazine or its metabolite, 5-aminoimidazole-4-carboxamide (AIC).

Fertility, ipilimumab [2] ---> SmPC of [2] of EMA

Studies to evaluate the effect of ipilimumab on fertility have not been performed. Thus, the effect of ipilimumab on male and female fertility is unknown.

Ipilimumab [1], pharmacokinetics ---> SmPC of [1] of EMA

No clinically relevant pharmacokinetic drug-drug interaction was observed between ipilimumab and paclitaxel/carboplatin, dacarbazine or its metabolite, 5-aminoimidazole-4- carboxamide (AIC).

Ipilimumab [1], pregnancy ---> SmPC of [1] of EMA

YERVOY is not recommended during pregnancy or in women of childbearing potential not using effective contraception, unless the clinical benefit outweighs the potential risk.

Ipilimumab, vemurafenib [2] ---> SmPC of [2] of EMA

In a Phase I trial, asymptomatic grade 3 increases in transaminases (ALT/AST >5 x ULN) and bilirubin (total bilirubin >3x ULN) were reported with concurrent administration of ipilimumab and vemurafenib. Concurrent administration is not recommended.

CONTRAINDICATIONS of Ipilimumab (Yervoy)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/yervoy-epar-product-information_en.pdf 21/03/2024

Ipratropium

Ability to drive, ipratropium

Dizziness, accommodation disorder, mydriasis and blurred vision may occur

Anticholinergics, ipratropium

Ipratropium may enhance the anticholinergic effects of other drugs

Beta-adrenergic agonists, ipratropium [2] ---> SmPC of [2] of eMC

There is evidence that the administration of ipratropium bromide with beta-adrenergic may produce an additive bronchodilatory effect.

Beta2-adrenergic agonists, ipratropium

The risk of acute glaucoma in patients with a history of narrow-angle glaucoma may be increased when nebulized ipratropium bromide and beta2-agonists are administered simultaneously.

Breast-feeding, ipratropium [2] ---> SmPC of [2] of eMC

It is not known whether ipratropium is excreted into breast milk. It is unlikely that ipratropium would reach the infant to an important extent, however caution should be exercised when ipratropium is administered to nursing mothers.

Butylscopolamine [1], ipratropium ---> SmPC of [1] of eMC

The anticholinergic effect may be intensified by hyoscine butylbromide

Ipratropium [1], pregnancy ---> SmPC of [1] of eMC

The benefits of using ipratropium bromide during a confirmed or suspected pregnancy must be weighed against the possible hazards to the unborn child.

Ipratropium [1], xanthines ---> SmPC of [1] of eMC

There is evidence that the administration of ipratropium bromide with xanthine preparations may produce an additive bronchodilatory effect.

Ipratropium, pilocarpine [2] ---> SmPC of [2] of eMC

Pilocarpine might antagonise the anticholinergic effects of other drugs used concomitantly

Ipratropium, scopolamine

Scopolamine may enhance the anticholinergic effect

CONTRAINDICATIONS of Ipratropium

- Known hypersensitivity to atropine or ipratropium bromide.

http://www.medicines.org.uk/emc/

Iptacopan (Fabhalta)

Breast-feeding, iptacopan [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from FABHALTA therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Carbamazepine, iptacopan [2] ---> SmPC of [2] of EMA

Caution should be exercised if co-administration of iptacopan with sensitive CYP3A4 substrates is required, especially for those with a narrow therapeutic index

Cyclosporine, iptacopan [2] ---> SmPC of [2] of EMA

Caution should be exercised if co-administration of iptacopan with sensitive CYP3A4 substrates is required, especially for those with a narrow therapeutic index

CYP2C8 substrates, iptacopan [2] ---> SmPC of [2] of EMA

In vitro data showed iptacopan has potential for time-dependent inhibition of CYP2C8 and may increase the exposure of sensitive CYP2C8 substrates, such as repaglinide, dasabuvir or paclitaxel. Caution should be exercised

CYP3A4 substrates with narrow therapeutic index, iptacopan [2] ---> SmPC of [2] of EMA

Caution should be exercised if co-administration of iptacopan with sensitive CYP3A4 substrates is required, especially for those with a narrow therapeutic index

CYP3A4 substrates, iptacopan [2] ---> SmPC of [2] of EMA

In vitro data showed iptacopan has potential for induction of CYP3A4 and may decrease the exposure of sensitive CYP3A4 substrates.

Dasabuvir, iptacopan [2] ---> SmPC of [2] of EMA

Ergotamine, iptacopan [2] ---> SmPC of [2] of EMA

Caution should be exercised if co-administration of iptacopan with sensitive CYP3A4 substrates is required, especially for those with a narrow therapeutic index

Fentanyl, iptacopan [2] ---> SmPC of [2] of EMA

Caution should be exercised if co-administration of iptacopan with sensitive CYP3A4 substrates is required, especially for those with a narrow therapeutic index

Fertility, iptacopan [2] ---> SmPC of [2] of EMA

There are no data on the effect of iptacopan on human fertility. Available non-clinical data do not suggest an effect of iptacopan treatment on fertility (see section 5.3).

Hemolysis, iptacopan [2] ---> SmPC of [2] of EMA

The patient should be instructed to seek prompt medical care if they experience any sign or symptom of serious infection or serious haemolysis following treatment discontinuation.

Infection, iptacopan [2] ---> SmPC of [2] of EMA

The use of complement inhibitors, such as iptacopan, may predispose individuals to serious, life-threatening or fatal infections caused by encapsulated bacteria.

Iptacopan [1], paclitaxel ---> SmPC of [1] of EMA

Iptacopan [1], pimozide ---> SmPC of [1] of EMA

Caution should be exercised if co-administration of iptacopan with sensitive CYP3A4 substrates is required, especially for those with a narrow therapeutic index

Iptacopan [1], pregnancy ---> SmPC of [1] of EMA

The use of iptacopan in pregnant women or women planning to become pregnant may only be considered following a careful assessment of the risk and benefits, if necessary.

Iptacopan [1], quinidine ---> SmPC of [1] of EMA

Caution should be exercised if co-administration of iptacopan with sensitive CYP3A4 substrates is required, especially for those with a narrow therapeutic index

Iptacopan [1], repaglinide ---> SmPC of [1] of EMA

Iptacopan [1], rifampicin ---> SmPC of [1] of EMA

The coadministration of iptacopan with strong inducers of CYP2C8, UGT1A1, PgP, BCRP and OATP1B1/3, such as rifampicin , concomitant use with iptacopan is not recommended due to the potential for reduced efficacy of iptacopan

Iptacopan [1], sirolimus ---> SmPC of [1] of EMA

Caution should be exercised if co-administration of iptacopan with sensitive CYP3A4 substrates is required, especially for those with a narrow therapeutic index

Iptacopan [1], tacrolimus ---> SmPC of [1] of EMA

Caution should be exercised if co-administration of iptacopan with sensitive CYP3A4 substrates is required, especially for those with a narrow therapeutic index

Iptacopan [1], vaccinations ---> SmPC of [1] of EMA

Vaccines should be administered at least 2 weeks prior to administration of the first dose of iptacopan.

Iptacopan [1], vaccinations ---> SmPC of [1] of EMA

If treatment must be initiated prior to vaccination, patients should be vaccinated as soon as possible and provided with antibacterial prophylaxis until 2 weeks after vaccine administration.

CONTRAINDICATIONS of Iptacopan (Fabhalta)

- Patients who are not currently vaccinated against Neisseria meningitidis and Streptococcus pneumoniae, unless the risk of delaying treatment outweighs the risk of developing an infection from these encapsulated bacteria (see section 4.4).

- Patients with unresolved infection caused by encapsulated bacteria, including Neisseria meningitidis, Streptococcus pneumoniae or Haemophilus influenzae type B, at treatment initiation.

https://www.ema.europa.eu/en/documents/product-information/fabhalta-epar-product-information_en.pdf 14/06/2024

Irbesartan (Aprovel)

Ability to drive, irbesartan [2] –––> SmPC of [2] of EMA

Based on its pharmacodynamic properties, irbesartan is unlikely to affect the ability to drive and use machines. When driving vehicles or operating machines, it should be taken into account that dizziness or weariness may occur during treatment.

Ability to drive, irbesartan [2] –––> SmPC of [2] of EMA

When driving vehicles or operating machines, it should be taken into account that occasionally dizziness or weariness may occur during treatment of hypertension.

ACE inhibitors, irbesartan [2] –––> SmPC of [2] of EMA

The dual blockade of the RAA–system through the combined use of ACE–inhibitors, AIIRA or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure)

ACE inhibitors, teratogenicity –––> SmPC of [irbesartan] of EMA

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded.

Acetylsalicylic acid, AIIRA –––> SmPC of [irbesartan] of EMA

The combination of AIIRAs and AIIRAs (selective COX–2 inhibitors, ASA (> 3 g/day) and non–selective NSAIDs) may decrease the antihypertensive effect, increase the renal failure risk and cause hypercaliemia

Acetylsalicylic acid, irbesartan [2] –––> SmPC of [2] of EMA

AIIRA, irbesartan [2] –––> SmPC of [2] of EMA

Whilst there is no controlled epidemiological data on the risk with Angiotensin II Receptor Antagonists (AIIRAs), similar risks may exist for this class of drugs.

AIIRA, NSAID –––> SmPC of [irbesartan] of EMA

Aliskiren, irbesartan [2] –––> SmPC of [2] of EMA

Antihypertensives, irbesartan [2] –––> SmPC of [2] of EMA

Other antihypertensive agents may increase the hypotensive effects of irbesartan; however Aprovel has been safely administered with other antihypertensive agents, such as beta–blockers, long–acting calcium channel blockers, and thiazide diuretics.

Betablockers, irbesartan [2] –––> SmPC of [2] of EMA

Breast–feeding, irbesartan [2] –––> SmPC of [2] of EMA

Because no information is available regarding the use of Aprovel during breast–feeding, Aprovel is not recommended

Bulevirtide [1], irbesartan –––> SmPC of [1] of EMA

In vitro, it has been shown, that certain medicinal products can inhibit bulevirtide target sodium– taurocholate co–transporting polypeptide (NTCP). The co–administration of such medicinal products is not recommended.

Calcium antagonists, irbesartan [2] –––> SmPC of [2] of EMA

Coxibs, irbesartan [2] –––> SmPC of [2] of EMA

Digoxin, irbesartan [2] –––> SmPC of [2] of EMA

The pharmacokinetic of digoxin was not altered by coadministration of irbesartan.

Diuretics, irbesartan [2] –––> SmPC of [2] of EMA

Prior treatment with high dose diuretics may result in volume depletion and a risk of hypotension when initiating therapy with Aprovel (see section 4.4).

Diuretics, irbesartan [2] –––> SmPC of [2] of EMA

Fertility, irbesartan [2] –––> SmPC of [2] of EMA

Irbesartan had no effect upon fertility of treated rats and their offspring up to the dose levels inducing the first signs of parental toxicity (see section 5.3).

Heparin, irbesartan [2] –––> SmPC of [2] of EMA

Concomitant use of irbesartan und potassium–sparing diuretics, potassium supplements, salt substitutes containing potassium or other medicinal products that may increase serum potassium levels is not recommended

Hydrochlorothiazide, irbesartan [2] –––> SmPC of [2] of EMA

In clinical studies, the pharmacokinetic of irbesartan is not affected by hydrochlorothiazide.

Hyperkalemia, irbesartan [2] –––> SmPC of [2] of EMA

Irbesartan [1], lithium –––> SmPC of [1] of EMA

Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors. This combination is not recommended

Irbesartan [1], NSAID –––> SmPC of [1] of EMA

Irbesartan [1], nursing –––> SmPC of [1] of EMA

Infants whose mothers have taken AIIRAs should be closely observed for hypotension (see sections 4.3 and 4.4).

Irbesartan [1], potassium –––> SmPC of [1] of EMA

Irbesartan [1], potassium–sparing diuretics –––> SmPC of [1] of EMA

Irbesartan [1], pregnancy –––> SmPC of [1] of EMA

The use of AIIRAs is not recommended during the first trimester of pregnancy. The use of AIIRAs is contraindicated during the second and third trimesters of pregnancy

Irbesartan [1], repaglinide –––> SmPC of [1] of EMA

Irbesartan has the potential to inhibit OATP1B1. Therefore, dose adjustment of antidiabetic treatment such as repaglinide may be required (see section 4.4).

Irbesartan [1], rifampicin –––> SmPC of [1] of EMA

The effects of CYP2C9 inducers such as rifampicin on the pharmacokinetic of irbesartan have not been evaluated.

Irbesartan [1], thiazides –––> SmPC of [1] of EMA

Irbesartan [1], warfarin –––> SmPC of [1] of EMA

Irbesartan is mainly metabolised by CYP2C9 and to a lesser extent by glucuronidation. No significant pharmacokinetic or pharmacodynamic interactions were observed when irbesartan was coadministered with warfarin, a medicinal product metabolised by CYP2C9

Irbesartan, patiromer [2] –––> SmPC of [2] of EMA

In vitro studies have shown no potential interaction of patiromer with the other active substances

Irbesartan, pilocarpine

En estudios in vitro, se ha observado que la pilocarpina es un inhibidor de CYP2A6. Por consiguiente, no debe descartarse la inhibición in vivo y la interacción con sustratos del CYP2A6 (por ejemplo irbesartán, cumarina)

CONTRAINDICATIONS of Irbesartan (Aprovel)

– Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

– Second and third trimesters of pregnancy

– The concomitant use of Aprovel with aliskiren–containing products is contraindicated in patients with diabetes mellitus or renal impairment (glomerular filtration rate (GFR) < 60 ml/min/1.73 m²)

https://www.ema.europa.eu/en/documents/product-information/aprovel-epar-product-information_en.pdf 11/02/2025

Other trade names: Fensoberax, Ifirmasta (previously Irbesartan Krka), Irbesartan BMS, Irbesartan Teva, Irbesartan Zentiva (previously Irbesartan Winthrop), Karvea, Sabervel,

Irbesartan/hydrochlorothiazide (CoAprovel)

Ability to drive, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

When driving vehicles or operating machines, it should be taken into account that occasionally dizziness or weariness may occur during treatment of hypertension.

ACE inhibitors, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Dual blockade of the renin-angiotensin-aldosterone system (RAAS) through the combined use is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function

Acetylsalicylic acid, AIIRA ---> SmPC of [irbesartan/hydrochlorothiazide] of EMA

When AIIRA are administered simultaneously with non-steroidal anti-inflammatory drugs (i.e. selective COX-2 inhibitors, acetylsalicylic acid (> 3 g/day) and non-selective NSAIDs), attenuation of the antihypertensive effect may occur.

ACTH, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Electrolyte depletion, particularly hypokalaemia, may be increased;

AIIRA, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

AIIRA, non-selective NSAIDs ---> SmPC of [irbesartan/hydrochlorothiazide] of EMA

AIIRA, NSAID ---> SmPC of [irbesartan/hydrochlorothiazide] of EMA

Concomitant use of AIIRAs and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor pre-existing renal function.

AIIRA, pregnancy ---> SmPC of [irbesartan/hydrochlorothiazide] of EMA

The use of AIIRAs is not recommended during the first trimester of pregnancy (see section 4.4). The use of AIIRAs is contraindicated during the second and third trimesters of pregnancy (see sections 4.3 and 4.4).

Alcohol, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Potentiation of orthostatic hypotension may occur;

Aliskiren, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Allopurinol, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Co-administration of thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol;

Amantadine, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Thiazides may increase the risk of adverse effects caused by amantadine.

Amphotericin, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

The effect of hydrochlorothiazide on serum potassium would be expected to be potentiated by other medicinal products associated with potassium loss and hypokalaemia

Anticholinergics, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Anticholinergic agents (e.g. atropine, biperiden) may increase the bioavailability of thiazide type diuretics by decreasing gastrointestinal motility and stomach emptying rate.

Antigout preparations, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Dosage adjustments of antigout medicinal products may be necessary as hydrochlorothiazide may raise the level of serum uric acid.

Antihypertensives, irbesartan/hydrochlorothiazide

Irbesartan and hydrochlorothiazide (at doses up to 300 mg irbesartan/25 mg hydrochlorothiazide) have been safely administered with other antihypertensive agents including calcium channel blockers and beta-adrenergic blockers.

Antihypertensives, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

The antihypertensive effect may be increased with the concomitant use of other antihypertensive agents.

Atropine, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Anticholinergic agents (e.g. atropine, biperiden) may increase the bioavailability of thiazide type diuretics by decreasing gastrointestinal motility and stomach emptying rate.

Betablockers, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Biperiden, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Anticholinergic agents (e.g. atropine, biperiden) may increase the bioavailability of thiazide type diuretics by decreasing gastrointestinal motility and stomach emptying rate.

Breast-feeding, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Because no information is available regarding the use of CoAprovel during breast-feeding, CoAprovel is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable

Calcium antagonists, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Calcium salts, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Thiazide diuretics may increase serum calcium levels due to decreased excretion.

Calcium salts, thiazides ---> SmPC of [irbesartan/hydrochlorothiazide] of EMA

Thiazide diuretics may increase serum calcium levels due to decreased excretion.

Carbamazepine, hydrochlorothiazide ---> SmPC of [irbesartan/hydrochlorothiazide] of EMA

Concomitant use of carbamazepine and hydrochlorothiazide has been associated with the risk of symptomatic hyponatraemia. Electrolytes should be monitored during concomitant use. If possible, another class of diuretics should be used;

Carbenoxolone, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

The effect of hydrochlorothiazide on serum potassium would be expected to be potentiated by other medicinal products associated with potassium loss and hypokalaemia

Cholestyramine, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

The absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. CoAprovel should be taken at least one hour before or four hours after these medications;

Class IA antiarrhythmic agents, irbesartan/hydrochlorothiazide ---> SmPC of [irbesartan/hydrochlorothiazide] of EM

Class III antiarrhythmic agents, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Periodic monitoring of serum potassium is recommended when CoAprovel is administered with medicinal products affected by serum potassium disturbances (e.g. digitalis glycosides, antiarrhythmics).

Colestipol, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

The absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. CoAprovel should be taken at least one hour before or four hours after these medications;

Corticosteroids, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Electrolyte depletion, particularly hypokalaemia, may be increased;

Coxibs, irbesartan/hydrochlorothiazide ---> SmPC of [irbesartan/hydrochlorothiazide] of EMA

Cyclophosphamide, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Thiazides may reduce the renal excretion of cytotoxic medicinal products (e.g. cyclophosphamide, methotrexate) and potentiate their myelosuppressive effects.

Cyclophosphamide, thiazides ---> SmPC of [irbesartan/hydrochlorothiazide] of EMA

Thiazides may reduce the renal excretion of cytotoxic medicinal products (e.g. cyclophosphamide, methotrexate) and potentiate their myelosuppressive effects.

Cytotoxic agents, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Thiazides may reduce the renal excretion of cytotoxic medicinal products (e.g. cyclophosphamide, methotrexate) and potentiate their myelosuppressive effects.

Cytotoxic agents, thiazides ---> SmPC of [irbesartan/hydrochlorothiazide] of EMA

Thiazides may reduce the renal excretion of cytotoxic medicinal products (e.g. cyclophosphamide, methotrexate) and potentiate their myelosuppressive effects.

Diazoxide, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

The hyperglycaemic effect of beta-blockers and diazoxide may be enhanced by thiazides.

Digital glycosides, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Periodic monitoring of serum potassium is recommended when CoAprovel is administered with medicinal products affected by serum potassium disturbances (e.g. digitalis glycosides, antiarrhythmics).

Digital glycosides, thiazides ---> SmPC of [irbesartan/hydrochlorothiazide] of EMA

Thiazide induced hypokalaemia or hypomagnesaemia favour the onset of digitalis-induced cardiac arrhythmias (see section 4.4);

Digoxin, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

The pharmacokinetic of digoxin was not altered by co-administration of irbesartan.

Diuretics, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Prior treatment with high dose diuretics may result in volume depletion and a risk of hypotension when initiating therapy with irbesartan with or without thiazide diuretics unless the volume depletion is corrected first

Fertility, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Irbesartan had no effect upon fertility of treated rats and their offspring up to the dose levels inducing the first signs of parental toxicity (see section 5.3).

Heparin, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

The concomitant may lead to increases in serum potassium. Adequate monitoring of serum potassium in patients at risk is recommended

Hydrochlorothiazide, muscle relaxants (non-depolarizing) ---> SmPC of [irbesartan/hydrochlorothiazide] of EMA

The effect of nondepolarizing skeletal muscle relaxants may be potentiated by hydrochlorothiazide;

Hydrochlorothiazide, tubocuranine ---> SmPC of [irbesartan/hydrochlorothiazide] of EMA

The effect of nondepolarizing skeletal muscle relaxants may be potentiated by hydrochlorothiazide;

Hyperkalemia, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

The concomitant may lead to increases in serum potassium. Adequate monitoring of serum potassium in patients at risk is recommended

Hypokalemia, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

The effect of hydrochlorothiazide on serum potassium would be expected to be potentiated by other medicinal products associated with potassium loss and hypokalaemia

Insulin, irbesartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Dosage adjustment of the antidiabetic medicinal product may be required (see section 4.4);

Irbesartan/hydrochlorothiazide [1], kaliuretic medicines ---> SmPC of [1] of EMA

The effect of hydrochlorothiazide on serum potassium would be expected to be potentiated by other medicinal products associated with potassium loss and hypokalaemia

Irbesartan/hydrochlorothiazide [1], laxatives ---> SmPC of [1] of EMA

The effect of hydrochlorothiazide on serum potassium would be expected to be potentiated by other medicinal products associated with potassium loss and hypokalaemia

Irbesartan/hydrochlorothiazide [1], lithium ---> SmPC of [1] of EMA

Irbesartan/hydrochlorothiazide [1], muscle relaxants (non-depolarizing) ---> SmPC of [1] of EMA

The effect of nondepolarizing skeletal muscle relaxants may be potentiated by hydrochlorothiazide;

Irbesartan/hydrochlorothiazide [1], noradrenaline ---> SmPC of [1] of EMA

The effect of pressor amines may be decreased, but not sufficiently to preclude their use;

Irbesartan/hydrochlorothiazide [1], NSAID ---> SmPC of [1] of EMA

NSAIDs may reduce the diuretic, natriuretic and antihypertensive effects of thiazide diuretics and the antihypertensive effects of angiotensin II receptor antagonists.

Irbesartan/hydrochlorothiazide [1], oral antidiabetics ---> SmPC of [1] of EMA

Dosage adjustment of the antidiabetic medicinal product may be required (see section 4.4);

Irbesartan/hydrochlorothiazide [1], penicillin G ---> SmPC of [1] of EMA

The effect of hydrochlorothiazide on serum potassium would be expected to be potentiated by other medicinal products associated with potassium loss and hypokalaemia

Irbesartan/hydrochlorothiazide [1], potassium ---> SmPC of [1] of EMA

The concomitant may lead to increases in serum potassium. Adequate monitoring of serum potassium in patients at risk is recommended

Irbesartan/hydrochlorothiazide [1], potassium-sparing diuretics ---> SmPC of [1] of EMA

The concomitant may lead to increases in serum potassium. Adequate monitoring of serum potassium in patients at risk is recommended

Irbesartan/hydrochlorothiazide [1], pregnancy ---> SmPC of [1] of EMA

It is not recommended during the first trimester of pregnancy. Is contraindicated during the second and third trimesters of pregnancy.

Irbesartan/hydrochlorothiazide [1], pressor amines ---> SmPC of [1] of EMA

The effect of pressor amines may be decreased, but not sufficiently to preclude their use;

Irbesartan/hydrochlorothiazide [1], probenecide ---> SmPC of [1] of EMA

Increase in dosage of probenecid or sulfinpyrazone may be necessary.

Irbesartan/hydrochlorothiazide [1], repaglinide ---> SmPC of [1] of EMA

Dose adjustment of antidiabetic treatment such as repaglinide may be required (see section 4.4).

Irbesartan/hydrochlorothiazide [1], rifampicin ---> SmPC of [1] of EMA

The effects of CYP2C9 inducers such as rifampicin on the pharmacokinetic of irbesartan have not been evaluated.

Irbesartan/hydrochlorothiazide [1], tubocuranine ---> SmPC of [1] of EMA

The effect of nondepolarizing skeletal muscle relaxants may be potentiated by hydrochlorothiazide;

Irbesartan/hydrochlorothiazide [1], warfarin ---> SmPC of [1] of EMA

No significant pharmacokinetic or pharmacodynamic interactions were observed when irbesartan was coadministered with warfarin, a medicinal product metabolised by CYP2C9.

Irbesartan/hydrochlorothiazide, methotrexate [2] ---> SmPC of [2] of EMA

Thiazides may reduce the renal excretion of cytotoxic medicinal products (e.g. cyclophosphamide, methotrexate) and potentiate their myelosuppressive effects.

Irbesartan/hydrochlorothiazide, thiazides ---> SmPC of [irbesartan/hydrochlorothiazide] of EMA

Furthermore, renal clearance of lithium is reduced by thiazides so the risk of lithium toxicity could be increased with CoAprovel. Therefore, the combination of lithium and CoAprovel is not recommended

Methotrexate, thiazides ---> SmPC of [irbesartan/hydrochlorothiazide] of EMA

Thiazides may reduce the renal excretion of cytotoxic medicinal products (e.g. cyclophosphamide, methotrexate) and potentiate their myelosuppressive effects.

NSAID, thiazides ---> SmPC of [irbesartan/hydrochlorothiazide] of EMA

The administration of a non-steroidal anti-inflammatory drug may reduce the diuretic, natriuretic and antihypertensive effects of thiazide diuretics in some patients

CONTRAINDICATIONS of Irbesartan/hydrochlorothiazide (CoAprovel)

- Hypersensitivity to the active substances, to any of the excipients, or to other sulfonamide-derived substances (hydrochlorothiazide is a sulfonamide-derived substance)

- Second and third trimester of pregnancy

- Severe renal impairment (creatinine clearance < 30 ml/min)

- Refractory hypokalaemia, hypercalcaemia

- Severe hepatic impairment, biliary cirrhosis and cholestasis

- The concomitant use of CoAprovel with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (glomerular filtration rate (GFR) < 60 ml/min/1.73 m²)

https://www.ema.europa.eu/en/documents/product-information/coaprovel-epar-product-information_en.pdf 25/09/2025

Other trade names: Ifirmacombi, Irbesartan Hydrochlorothiazide BMS, Irbesartan Hydrochlorothiazide Zentiva (previously Irbesartan Hydrochlorothiazide Winthrop), Irbesartan/Hydrochlorothiazide Teva, Karvezide,

Irinotecan (Onivyde pegylated liposomal)

Ability to drive, irinotecan [2] ---> SmPC of [2] of EMA

ONIVYDE pegylated liposomal has moderate influence on the ability to drive and use machines. During treatment patients should observe caution when driving or using machines.

Anticholinesterase, irinotecan [2] ---> SmPC of [2] of eMC

Since irinotecan has anticholinesterase activity, drugs with anticholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium and the neuromuscular blockade of non-depolarising drugs may be antagonised.

Antineoplastics, irinotecan [2] ---> SmPC of [2] of EMA

Adverse effects of irinotecan, such as myelosuppression, may be exacerbated by other antineoplastic agents having a similar adverse-effect profile.

Antineoplastics, irinotecan/fluorouracil/leucovorin/panitumumab

High incidence of severe diarrhea. Concomitant use of panitumumab and IFL is not recommended

Aprepitant [1], irinotecan ---> SmPC of [1] of EMA

Concomitant administration of aprepitant with irinotecan should be approached with particular caution as the combination might result in increased toxicity.

Atazanavir [1], irinotecan ---> SmPC of [1] of EMA

Co-administration of ONIVYDE pegylated liposomal with other inhibitors of UGT1A1 (e.g. atazanavir, gemfibrozil, indinavir, regorafenib) may also increase systemic exposure of ONIVYDE pegylated liposomal.

Bevacizumab [1], irinotecan ---> SmPC of [1] of EMA

Results from a dedicated drug-drug interaction trial demonstrated no significant effect of bevacizumab on the pharmacokinetics of irinotecan and its active metabolite SN38.

Breast-feeding, irinotecan [2] ---> SmPC of [2] of EMA

ONIVYDE pegylated liposomal is contraindicated during breast-feeding (see section 4.3). Patients should not breast-feed until one month after the last dose.

Carbamazepine, irinotecan [2] ---> SmPC of [2] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with inducers of CYP3A4 may reduce systemic exposure of ONIVYDE pegylated liposomal.

Clarithromycin, irinotecan [2] ---> SmPC of [2] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE pegylated liposomal.

Crizotinib [1], irinotecan ---> SmPC of [1] of EMA

Crizotinib, UGT1A1 inhibitor, may increase the plasma concentrations of the medicinal products mainly metabolized by UGT1A1

Erlotinib, irinotecan

Erlotinib, UGT1A1 inhibitor, may increase the plasma concentrations of irinotecan. Patients should be closely monitored

Fertility, irinotecan [2] ---> SmPC of [2] of EMA

Non-liposomal irinotecan was shown to cause atrophy of male and female reproductive organs after multiple daily irinotecan doses in animals (see section 5.3).

Fluorouracil, irinotecan [2] ---> SmPC of [2] of eMC

Co-administration of ONIVYDE pegylated liposomal +5-FU/LV does not alter the pharmacokinetics of ONIVYDE pegylated liposomal based on the population pharmacokinetic analysis.

Folinic acid, irinotecan [2] ---> SmPC of [2] of eMC

Co-administration of ONIVYDE pegylated liposomal +5-FU/LV does not alter the pharmacokinetics of ONIVYDE pegylated liposomal based on the population pharmacokinetic analysis.

Fosaprepitant [1], irinotecan ---> SmPC of [1] of EMA

Concomitant administration of fosaprepitant with irinotecan should be approached with particular caution as the combination might result in increased toxicity.

Gemfibrozil, irinotecan [2] ---> SmPC of [2] of EMA

Grapefruit juice, irinotecan [2] ---> SmPC of [2] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE pegylated liposomal.

Indinavir, irinotecan [2] ---> SmPC of [2] of EMA

Irinotecan [1], itraconazol ---> SmPC of [1] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE pegylated liposomal.

Irinotecan [1], ketoconazole ---> SmPC of [1] of EMA

Patients receiving concomitant non-liposomal irinotecan and ketoconazole, a CYP3A4 and UGT1A1 inhibitor, have increased SN-38 exposure by 109%.

Irinotecan [1], lopinavir ---> SmPC of [1] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE pegylated liposomal.

Irinotecan [1], meal ---> SmPC of [1] of EMA

Avoid eating grapefruits and drinking grapefruit juice while you are receiving ONIVYDE pegylated liposomal as it may increase the level of irinotecan in your body.

Irinotecan [1], men ---> SmPC of [1] of EMA

Males should use condoms during ONIVYDE pegylated liposomal treatment and 4 months thereafter.

Irinotecan [1], muscle relaxants (non-depolarizing) ---> SmPC of [1] of eMC

Irinotecan [1], nefazodone ---> SmPC of [1] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE pegylated liposomal.

Irinotecan [1], nelfinavir ---> SmPC of [1] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE pegylated liposomal.

Irinotecan [1], phenobarbital ---> SmPC of [1] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with inducers of CYP3A4 may reduce systemic exposure of ONIVYDE pegylated liposomal.

Irinotecan [1], phenytoin ---> SmPC of [1] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with inducers of CYP3A4 may reduce systemic exposure of ONIVYDE pegylated liposomal.

Irinotecan [1], pregnancy ---> SmPC of [1] of EMA

Therefore, based on results from animal studies and the mechanism of action of irinotecan, ONIVYDE pegylated liposomal should not be used during pregnancy unless clearly necessary.

Irinotecan [1], pregnancy ---> SmPC of [1] of EMA

If ONIVYDE pegylated liposomal is used during pregnancy or if the patient becomes pregnant while receiving therapy, the patient should be informed about the potential hazard to the foetus.

Irinotecan [1], radiotherapy ---> SmPC of [1] of EMA

Tell your doctor, pharmacist or nurse if you are already having, or have recently had chemotherapy and/or radiotherapy or treatment with the antifungal medicine flucytosine.

Irinotecan [1], rifampicin ---> SmPC of [1] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with inducers of CYP3A4 may reduce systemic exposure of ONIVYDE pegylated liposomal.

Irinotecan [1], ritonavir ---> SmPC of [1] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE pegylated liposomal.

Irinotecan [1], saquinavir ---> SmPC of [1] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE pegylated liposomal.

Irinotecan [1], St. John's wort ---> SmPC of [1] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with inducers of CYP3A4 may reduce systemic exposure of ONIVYDE pegylated liposomal.

Irinotecan [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with inducers of CYP3A4 may reduce systemic exposure of ONIVYDE pegylated liposomal.

Irinotecan [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE pegylated liposomal.

Irinotecan [1], telaprevir ---> SmPC of [1] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE pegylated liposomal.

Irinotecan [1], UGT1A1 inhibitors ---> SmPC of [1] of EMA

Based on the drug interaction of non-liposomal irinotecan and ketoconazole, co-administration of ONIVYDE with other inhibitors of UGT1A1 may also increase systemic exposure of ONIVYDE.

Irinotecan [1], vaccinations ---> SmPC of [1] of EMA

Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic medicinal products including ONIVYDE pegylated liposomal may result in serious or fatal infections

Irinotecan [1], voriconazole ---> SmPC of [1] of EMA

Therefore, co-administration of ONIVYDE pegylated liposomal with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE pegylated liposomal.

Irinotecan [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should use effective contraception during ONIVYDE pegylated liposomal treatment and 7 months thereafter.

Irinotecan, isavuconazole [2] ---> SmPC of [2] of EMA

Irinotecan, lapatinib [2] ---> SmPC of [2] of EMA

Co-administration of lapatinib with irinotecan (when administered as part of the FOLFIRI regimen) resulted in an approximate 40% increase in the AUC of SN-38, the active metabolite of irinotecan.

Irinotecan, mitapivat [2] ---> SmPC of [2] of EMA

If co-administration is unavoidable, patients should be monitored for loss of therapeutic effect of substrates of these enzymes, especially for those with a narrow therapeutic index

Irinotecan, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Netupitant is a moderate CYP3A4 inhibitor and can increase the exposure of chemotherapeutic agents that are substrates for CYP3A4. Therefore, patients should be monitored for increased toxicity of chemotherapeutic agents that are substrates for CYP3A4

Irinotecan, niraparib [2] ---> SmPC of [2] of EMA

Caution is recommended when niraparib is combined with substrates of BCRP (irinotecan, rosuvastatin, simvastatin, atorvastatin, and methotrexate).

Irinotecan, pazopanib [2] ---> SmPC of [2] of EMA

Concomitant administration of pazopanib with uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) substrates (e.g. irinotecan) should be undertaken with caution since pazopanib is an inhibitor of UGT1A1

Irinotecan, pitolisant [2] ---> SmPC of [2] of EMA

With other CYP3A4, CYP2B6 (e.g. efavirenz, bupropion), CYP2C (e.g. repaglinide, phenytoin, warfarin), P-gp (e.g. dabigatran, digoxin) and UGT (e.g. morphine, paracetamol, irinotecan) substrates, caution should be made

Irinotecan, ramucirumab [2] ---> SmPC of [2] of EMA

The pharmacokinetics of irinotecan and its active metabolite, SN-38, were not affected when co-administered with ramucirumab.

Irinotecan, ranolazine

Ranolazine, P-glycoprotein and CYP3A4 inhibitor, may increase the plasma concentrations of irinotecan

Irinotecan, regorafenib [2] ---> SmPC of [2] of EMA

Irinotecan, ripretinib [2] ---> SmPC of [2] of EMA

QINLOCK is to be used with caution with BCRP substrates (e.g. rosuvastatin, sulfasalazine and irinotecan) and MATE-1 substrates (e.g. metformin) as co-administration of QINLOCK with BCRP and MATE-1 substrates may lead to an increase of their exposure.

Irinotecan, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant is an inhibitor of Breast-Cancer-Resistance Protein (BCRP). Increased plasma concentrations of BCRP substrates may result in potential adverse reactions.

Irinotecan, rucaparib [2] ---> SmPC of [2] of EMA

Caution should be used when rucaparib is co-administered with UGT1A1 substrates (i.e. irinotecan) to patients with UGT1A1*28 (poor metabolizer) due to a possible increase in the exposure of SN-38 and associated toxicities.

Irinotecan, sonidegib [2] ---> SmPC of [2] of EMA

Sonidegib is a breast cancer resistance protein (BCRP) inhibitor. BCRP substrates with narrow therapeutic range (e.g. methotrexate, mitoxantrone, irinotecan, topotecan) should be avoided.

Irinotecan, sorafenib [2] ---> SmPC of [2] of EMA

Caution is recommended when administering sorafenib with compounds that are metabolised/eliminated predominantly by the UGT1A1 (e.g. irinotecan) or UGT1A9 pathways

Irinotecan, succinylcholine [2] ---> SmPC of [2] of eMC

Since irinotecan has anticholinesterase activity, drugs with anticholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Irinotecan, suxamethonium [2] ---> SmPC of [2] of eMC

Since irinotecan has anticholinesterase activity, drugs with anticholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Irinotecan, thiotepa

Thiotepa, weak inhibitor for CYP2B6, may increase plasma concentrations of irinotecan

Irinotecan/fluorouracil/leucovorin, panitumumab [2] ---> SmPC of [2] of EMA

Patients receiving panitumumab in combination with the IFL regimen [bolus 5-fluorouracil, leucovorin and irinotecan] experienced a high incidence of severe diarrhoea. Therefore administration of panitumumab in combination with IFL should be avoided

CONTRAINDICATIONS of Irinotecan (Onivyde pegylated liposomal)

- History of severe hypersensitivity to irinotecan or to any of the excipients listed in section 6.1.

- Breast-feeding

https://www.ema.europa.eu/en/documents/product-information/onivyde-pegylated-liposomal-epar-product-information_en.pdf 15/10/2024

Other trade names: Irinotecán Actavis, Irinotecán Aldial, Campto, Irinotecán Fair-Med Healthcare, Irinotecán Fresenius, Irinotecán GP-Pharm, Irinotecán Hospira, Irinotecán Kabi, Irinotecán Kewl, Onivyde pegylated liposomal (previously known as Onivyde),

Isatuximab (Sarclisa)

Breast-feeding, isatuximab [2] ---> SmPC of [2] of EMA

A risk to the breast-fed child cannot be excluded during this short period just after birth. Afterwards, isatuximab could be used during breastfeeding if clinically needed.

Fertility, isatuximab [2] ---> SmPC of [2] of EMA

No human and animal data are available to determine potential effects of isatuximab on fertility in males and females (see section 5.3).

Isatuximab [1], pomalidomide ---> SmPC of [1] of EMA

Isatuximab has no impact on the pharmacokinetics of pomalidomide or carfilzomib, or vice versa.

Isatuximab [1], pregnancy ---> SmPC of [1] of EMA

Immunoglobulin G1 monoclonal antibodies are known to cross the placenta after the first trimester of pregnancy. The use of isatuximab in pregnant women is not recommended.

Isatuximab [1], serologic tests ---> SmPC of [1] of EMA

Because CD38 protein is expressed on the surface of red blood cells, isatuximab, an anti-CD38 antibody, may interfere with blood bank serologic tests with potential false positive reactions

Isatuximab [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential treated with isatuximab should use effective contraception during treatment and for 5 months after cessation of treatment.

CONTRAINDICATIONS of Isatuximab (Sarclisa)

- Hypersensitivity to the active substance or to any of its excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/sarclisa-epar-product-information_en.pdf 29/07/2024

Isavuconazole (Cresemba)

Ability to drive, isavuconazole [2] ---> SmPC of [2] of EMA

Isavuconazole has a moderate potential to influence the ability to drive and use machines. Patients should avoid driving or operating machinery if symptoms of confusional state, somnolence, syncope, and/or dizziness are experienced.

Alfentanyl, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Short-acting opiates (alfentanyl, fentanyl): careful monitoring for any occurrence of drug toxicity, and dose reduction if required.

Amprenavir, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Protease inhibitors: careful monitoring for any occurrence of drug toxicity and /or lack of antiviral efficacy, and dose adjustment if required.

Aprepitant, isavuconazole [2] ---> SmPC of [2] of EMA

Co-administration with mild CYP3A4/5 inducers may result in mild to moderate decreases of isavuconazole plasma levels; co-administration with mild CYP3A4/5 inducers should be avoided unless the potential benefit is considered to outweigh the risk

Atorvastatin, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Based on results with atorvastatin, no statin dose adjustment required. Monitoring of adverse reactions typical of statins is advised.

BCRP substrates, isavuconazole [2] ---> SmPC of [2] of EMA

Isavuconazole is an inhibitor in vitro of BCRP, and plasma concentrations of substrates of BCRP may therefore be increased. Caution is advised when CRESEMBA is given concomitantly with substrates of BCRP.

Breast-feeding, isavuconazole [2] ---> SmPC of [2] of EMA

Available pharmacodynamic/toxicological data in animals have shown excretion of isavuconazole/metabolites in milk (see section 5.3). Breast-feeding should be discontinued during treatment

Bupropion, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Bupropion: dose increase if required.

Caffeine, isavuconazole [2] ---> SmPC of [2] of EMA

No isavuconazole dose adjustment necessary. Caffeine: no dose adjustment required.

Carbamazepine, isavuconazole [2] ---> SmPC of [2] of EMA

Co-administration of CRESEMBA with potent/moderate CYP3A4/5 inducers is contraindicated, since these medicinal products can significantly decrease plasma concentrations of isavuconazole

Clarithromycin, isavuconazole [2] ---> SmPC of [2] of EMA

No dose adjustment of CRESEMBA is necessary when co-administered with strong CYP3A4/5 inhibitors, however caution is advised as adverse drug reactions may increase

Colchicine, isavuconazole [2] ---> SmPC of [2] of EMA

Dose adjustment of medicinal products that are P-gp substrates, especially medicinal products with a narrow therapeutic index such as digoxin, colchicine and dabigatran etexilate, may be needed when concomitantly administered with CRESEMBA

Cyclophosphamide, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Cyclophosphamide: careful monitoring for any occurrence of lack of efficacy, and dose increase if required.

Cyclosporine, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Ciclosporin, sirolimus, tacrolimus: monitoring of plasma levels and appropriate dose adjustment if required. No CRESEMBA dose adjustment

CYP3A4 inductors, isavuconazole [2] ---> SmPC of [2] of EMA

CYP3A4 inhibitors, isavuconazole [2] ---> SmPC of [2] of EMA

No dose adjustment is warranted for moderate to mild CYP3A4/5 inhibitors.

Dabigatran etexilate, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Dabigatran etexilate has a narrow therapeutic index and should be monitored, and dose reduction if required.

Darunavir/cobicistat [1], isavuconazole ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the antifungal plasma concentrations, and darunavir and/or cobicistat plasma concentrations may be increased by the antifungal (CYP3A inhibition)

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], isavuconazole ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this antifungal plasma concentration, and darunavir, cobicistat and/or tenofovir alafenamide plasma concentrations may be increased by the antifungals. CYP3A and/or P-gp inhibition

Daunorubicin, isavuconazole [2] ---> SmPC of [2] of EMA

Decrease the QT interval, isavuconazole [2] ---> SmPC of [2] of EMA

Caution is warranted when prescribing CRESEMBA to patients taking other medicinal products known to decrease the QT interval, such as rufinamide.

Delavirdine, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. NNRTIs: careful monitoring for any occurrence of drug toxicity and/or lack of anti-viral efficacy, and dose adjustment if required.

Dextromethorphan, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Dextromethorphan: no dose adjustment required.

Digoxin, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Digoxin (P-gp substrate): serum digoxin concentrations should be monitored and used for titration of the digoxin dose.

Dolutegravir/rilpivirine [1], isavuconazole ---> SmPC of [1] of EMA

May cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). No dose adjustment is required.

Doxorubicine, isavuconazole [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP2B6, isavuconazole [2] ---> SmPC of [2] of EMA

Isavuconazole is a mild CYP2B6 inducer; co-administration of CRESEMBA may result in decreased plasma concentrations of CYP2B6 substrates.

Drugs primarily metabolised by CYP3A4, isavuconazole [2] ---> SmPC of [2] of EMA

Isavuconazole is a moderate inhibitor of CYP3A4/5; co-administration of CRESEMBA with medicinal products which are substrates of CYP3A4/5 may result in increased plasma concentrations of these medicinal products.

Drugs primarily metabolised by glucuronidation, isavuconazole [2] ---> SmPC of [2] of EMA

Isavuconazole is a mild inhibitor of UGT. Co-administration of CRESEMBA with medicinal products which are substrates of UGT may result in mildly increased plasma concentrations of these medicinal products.

Efavirenz, isavuconazole [2] ---> SmPC of [2] of EMA

Co-administration of CRESEMBA with potent/moderate CYP3A4/5 inducers is contraindicated, since these medicinal products can significantly decrease plasma concentrations of isavuconazole

Empagliflozin/metformin [1], isavuconazole ---> SmPC of [1] of EMA

Co-administration of metformin with Inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration.

Emtricitabine/tenofovir alafenamide [1], isavuconazole ---> SmPC of [1] of EMA

Co-administration of fluconazole or isavuconazole may increase plasma concentrations of tenofovir alafenamide.

Ertugliflozin/metformin [1], isavuconazole ---> SmPC of [1] of EMA

Inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration.

Esomeprazole, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Esomeprazole: no dose adjustment required.

Ethinyl estradiol, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Ethinyl oestradiol and norenthrindone: no dose adjustment required.

Etravirine, isavuconazole [2] ---> SmPC of [2] of EMA

Co-administration of CRESEMBA with potent/moderate CYP3A4/5 inducers is contraindicated, since these medicinal products can significantly decrease plasma concentrations of isavuconazole

Fentanyl, isavuconazole [2] ---> SmPC of [2] of EMA

No CRESEMBA dose adjustment necessary. Short-acting opiates (alfentanyl, fentanyl): careful monitoring for any occurrence of drug toxicity, and dose reduction if required.

Fertility, isavuconazole [2] ---> SmPC of [2] of EMA

There are no data on the effect of isavuconazole on human fertility. Studies in animals did not show impairment of fertility in male or female rats (see section 5.3).

Fosamprenavir, isavuconazole [2] ---> SmPC of [2] of EMA

No isavuconazole dose adjustment necessary. Protease inhibitors: careful monitoring for any occurrence of drug toxicity and /or lack of antiviral efficacy, and dose adjustment if required.

Imatinib, isavuconazole [2] ---> SmPC of [2] of EMA

Indinavir, isavuconazole [2] ---> SmPC of [2] of EMA

No dose adjustment of CRESEMBA is necessary when co-administered with strong CYP3A4/5 inhibitors, however caution is advised as adverse drug reactions may increase

Irinotecan, isavuconazole [2] ---> SmPC of [2] of EMA

Isavuconazole [1], ketoconazole ---> SmPC of [1] of EMA

Co-administration of CRESEMBA with the strong CYP3A4/5 inhibitor ketoconazole is contraindicated, since this medicinal product can significantly increase plasma concentrations of isavuconazole

Isavuconazole [1], lapatinib ---> SmPC of [1] of EMA

Isavuconazole [1], lopinavir/ritonavir ---> SmPC of [1] of EMA

No dose adjustment of CRESEMBA is necessary when co-administered with strong CYP3A4/5 inhibitors, however caution is advised as adverse drug reactions may increase

Isavuconazole [1], methadone ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Methadone: no dose adjustment required.

Isavuconazole [1], methotrexate ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Methotrexate: no dose adjustment required.

Isavuconazole [1], midazolam ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Midazolam: careful monitoring of clinical signs and symptoms recommended, and dose reduction if required.

Isavuconazole [1], mitoxantrone ---> SmPC of [1] of EMA

Isavuconazole [1], moderate CYP3A4 inductors ---> SmPC of [1] of EMA

Co-administration of CRESEMBA with potent/moderate CYP3A4/5 inducers is contraindicated, since these medicinal products can significantly decrease plasma concentrations of isavuconazole

Isavuconazole [1], nafcillin ---> SmPC of [1] of EMA

Co-administration of CRESEMBA with potent/moderate CYP3A4/5 inducers is contraindicated, since these medicinal products can significantly decrease plasma concentrations of isavuconazole

Isavuconazole [1], nelfinavir ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Protease inhibitors: careful monitoring for any occurrence of drug toxicity and /or lack of antiviral efficacy, and dose adjustment if required.

Isavuconazole [1], nevirapine ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. NNRTIs: careful monitoring for any occurrence of drug toxicity and/or lack of anti-viral efficacy, and dose adjustment if required.

Isavuconazole [1], norethisterone ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Ethinyl oestradiol and norenthrindone: no dose adjustment required.

Isavuconazole [1], OCT2 substrates ---> SmPC of [1] of EMA

Isavuconazole is a mild inhibitor of the organic cation transporter 2 (OCT2). Co-administration of CRESEMBA with medicinal products which are substrates of OCT2 may result in increased plasma concentrations of these medicinal products.

Isavuconazole [1], omeprazole ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Omeprazole: no dose adjustment required.

Isavuconazole [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Isavuconazole is a mild inhibitor of P-glycoprotein (P-gp); co-administration with CRESEMBA may result in increased plasma concentrations of P-gp substrates.

Isavuconazole [1], P-glycoprotein substrates with small therapeutic index ---> SmPC of [1] of EMA

Isavuconazole [1], phenobarbital ---> SmPC of [1] of EMA

Co-administration of CRESEMBA with potent/moderate CYP3A4/5 inducers is contraindicated, since these medicinal products can significantly decrease plasma concentrations of isavuconazole

Isavuconazole [1], phenytoin ---> SmPC of [1] of EMA

Co-administration of CRESEMBA with potent/moderate CYP3A4/5 inducers is contraindicated, since these medicinal products can significantly decrease plasma concentrations of isavuconazole

Isavuconazole [1], pioglitazone ---> SmPC of [1] of EMA

Isavuconazole [1], prednisone ---> SmPC of [1] of EMA

Isavuconazole [1], pregnancy ---> SmPC of [1] of EMA

CRESEMBA must not be used during pregnancy except in patients with severe or potentially life-threatening fungal infections, in whom isavuconazole may be used if the anticipated benefits outweigh the possible risks to the foetus.

Isavuconazole [1], protease inhibitors ---> SmPC of [1] of EMA

No isavuconazole dose adjustment necessary. Protease inhibitors: careful monitoring for any occurrence of drug toxicity and /or lack of antiviral efficacy, and dose adjustment if required.

Isavuconazole [1], repaglinide ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Repaglinide: no dose adjustment required.

Isavuconazole [1], rifabutin ---> SmPC of [1] of EMA

Co-administration of CRESEMBA with potent/moderate CYP3A4/5 inducers is contraindicated, since these medicinal products can significantly decrease plasma concentrations of isavuconazole

Isavuconazole [1], rifampicin ---> SmPC of [1] of EMA

Co-administration of CRESEMBA with potent/moderate CYP3A4/5 inducers is contraindicated, since these medicinal products can significantly decrease plasma concentrations of isavuconazole

Isavuconazole [1], ritonavir ---> SmPC of [1] of EMA

Co-administration with high-dose ritonavir (>200 mg twice daily) is contraindicated, as at high doses ritonavir may induce CYP3A4/5 and decrease isavuconazole plasma concentrations

Isavuconazole [1], rufinamide ---> SmPC of [1] of EMA

Caution is warranted when prescribing CRESEMBA to patients taking other medicinal products known to decrease the QT interval, such as rufinamide.

Isavuconazole [1], saquinavir ---> SmPC of [1] of EMA

No dose adjustment of CRESEMBA is necessary when co-administered with strong CYP3A4/5 inhibitors, however caution is advised as adverse drug reactions may increase

Isavuconazole [1], sirolimus ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Ciclosporin, sirolimus, tacrolimus: monitoring of plasma levels and appropriate dose adjustment if required. No CRESEMBA dose adjustment

Isavuconazole [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of CRESEMBA with potent/moderate CYP3A4/5 inducers is contraindicated, since these medicinal products can significantly decrease plasma concentrations of isavuconazole

Isavuconazole [1], statins ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Based on results with atorvastatin, no statin dose adjustment required. Monitoring of adverse reactions typical of statins is advised.

Isavuconazole [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Co-administration of CRESEMBA with potent/moderate CYP3A4/5 inducers is contraindicated, since these medicinal products can significantly decrease plasma concentrations of isavuconazole

Isavuconazole [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

No dose adjustment of CRESEMBA is necessary when co-administered with strong CYP3A4/5 inhibitors, however caution is advised as adverse drug reactions may increase

Isavuconazole [1], topotecan ---> SmPC of [1] of EMA

Isavuconazole [1], UGT substrates ---> SmPC of [1] of EMA

Co-administration of CRESEMBA with medicinal products which are substrates of UGT may result in mildly increased plasma concentrations of these medicinal products.

Isavuconazole [1], vinblastine ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Vinca alkaloids: careful monitoring for any occurrence of drug toxicity, and dose reduction if required.

Isavuconazole [1], vincristine ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Vinca alkaloids: careful monitoring for any occurrence of drug toxicity, and dose reduction if required.

Isavuconazole [1], warfarin ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Warfarin (CYP2C9 substrate): no dose adjustment required

Isavuconazole [1], women of childbearing potential ---> SmPC of [1] of EMA

CRESEMBA is not recommended for women of childbearing potential who are not using contraception.

Isavuconazole, ivosidenib [2] ---> SmPC of [2] of EMA

Coadministration of moderate or strong CYP3A4 inhibitors increases ivosidenib plasma levels. This may increase the risk of QTc interval prolongation and suitable alternatives that are not moderate or strong CYP3A4 inhibitors should be considered

Isavuconazole, metformin ---> SmPC of [ertugliflozin/metformin] of EMA

Inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration.

Isavuconazole, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Co-administration of metformin with inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration;

Isavuconazole, mycophenolate mofetil [2] ---> SmPC of [2] of EMA

Concomitant administration of drugs affecting glucuronidation of MPA may change MPA exposure. Caution is therefore recommended when administering these drugs concomitantly with mycophenolate mofetil.

Isavuconazole, tacrolimus [2] ---> SmPC of [2] of EMA

May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation). A rapid increase in tacrolimus level may occur. Monitor tacrolimus whole blood trough levels frequently,

CONTRAINDICATIONS of Isavuconazole (Cresemba)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Co-administration with ketoconazole

- Co-administration with high-dose ritonavir (>200 mg every 12 hours)

- Co-administration with strong CYP3A4/5 inducers such as rifampicin, rifabutin, carbamazepine, longacting barbiturates (e.g. phenobarbital), phenytoin and St. John's wort or with moderate CYP3A4/5 inducers such as efavirenz, nafcillin and etravirine (see section 4.5).

- Patients with familial short QT syndrome

https://www.ema.europa.eu/en/documents/product-information/cresemba-epar-product-information_en.pdf 24/07/2025

Isoflurane

Ability to drive, isoflurane [2] ---> SmPC of [2] of eMC

Patients should be advised that performance of activities requiring mental alertness, such as operating a motor vehicle or hazardous machinery, may be impaired for 2-4 days after anaesthesia with isoflurane.

ACE inhibitors, isoflurane [2] ---> SmPC of [2] of eMC

Chronic treatment with other vasodilators like ACE inhibitors (e. g. captopril, enalapril, lisinopril) or alfa1-adrenergic receptor blocker (e.g. prazosin) may cause an unforeseeable hypotension

Adrenaline, isoflurane [2] ---> SmPC of [2] of eMC

Alpha- and beta-sympathomimetic agents like adrenaline and noradrenaline should be used with caution during isoflurane narcosis, due to a potential risk of ventricular arrhythmia.

Alfa and beta-adrenergic agonists, isoflurane [2] ---> SmPC of [2] of eMC

Alpha- and beta-sympathomimetic agents like adrenaline and noradrenaline should be used with caution during isoflurane narcosis, due to a potential risk of ventricular arrhythmia.

Alfa1-adrenergic receptor blockers, isoflurane [2] ---> SmPC of [2] of eMC

Chronic treatment with other vasodilators like ACE inhibitors (e. g. captopril, enalapril, lisinopril) or alfa1-adrenergic receptor blocker (e.g. prazosin) may cause an unforeseeable hypotension

Amphetamine, isoflurane [2] ---> SmPC of [2] of eMC

Beta-sympathomimetic agents should be used with caution during isoflurane narcosis, due to a potential risk of ventricular arrhythmia.

Anorexics, isoflurane [2] ---> SmPC of [2] of eMC

Beta-sympathomimetic agents should be used with caution during isoflurane narcosis, due to a potential risk of ventricular arrhythmia.

Atracurium [1], isoflurane ---> SmPC of [1] of eMC

The neuromuscular block produced by atracurium besilate may be increased by the concomitant use of inhalational anaesthetics

Benzodiazepines, isoflurane [2] ---> SmPC of [2] of eMC

Opioids, benzodiazepines and other sedative agents are associated with respiratory depression, and caution should be exercised when concomitantly administered with isoflurane.

Beta-adrenergic agonists, isoflurane [2] ---> SmPC of [2] of eMC

Beta-sympathomimetic agents should be used with caution during isoflurane narcosis, due to a potential risk of ventricular arrhythmia.

Betablockers, isoflurane [2] ---> SmPC of [2] of eMC

Cardiovascular compensation reactions may be impaired by beta-blockers.

Breast-feeding, isoflurane [2] ---> SmPC of [2] of eMC

It is not known whether isoflurane/metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when isoflurane is administered to a nursing woman.

Calcium antagonists, isoflurane [2] ---> SmPC of [2] of eMC

Calcium antagonists, in particular dihydropyridine derivates: isoflurane may lead to marked hypotension in patients treated with calcium antagonists.

Cisatracurium [1], isoflurane ---> SmPC of [1] of eMC

Anaesthetics increase the magnitude and/or duration of action of non-depolarising neuromuscular blocking agents

CNS depressants, isoflurane [2] ---> SmPC of [2] of eMC

Opioids, benzodiazepines and other sedative agents are associated with respiratory depression, and caution should be exercised when concomitantly administered with isoflurane.

CYP2E1 inductors, isoflurane

The CYP2E1 induction may decrease plasma concentrations of isoflurane

Depolarizing muscle relaxants, isoflurane [2] ---> SmPC of [2] of eMC

Muscle relaxants are markedly potentiated by isoflurane.

Dexmedetomidine [1], isoflurane ---> SmPC of [1] of EMA

Specific studies have confirmed that the co-administration of dexmedetomidine with isoflurane, propofol, alfentanil, and midazolam enhances the effects

Dihydropyridines, isoflurane [2] ---> SmPC of [2] of eMC

Calcium antagonists, in particular dihydropyridine derivates: isoflurane may lead to marked hypotension in patients treated with calcium antagonists.

Doxapram [1], isoflurane ---> SmPC of [1] of eMC

The active principles that sensitize the myocard to catecholamines should be discontinued at least 10 minutes before the use of doxapram

Ephedrine, isoflurane [2] ---> SmPC of [2] of eMC

Risk of perioperative hypertension. In patients undergoing elective surgery, treatment should ideally be discontinued several days before surgery.

Epinephrine, isoflurane [2] ---> SmPC of [2] of eMC

Alpha- and beta-sympathomimetic agents like adrenaline and noradrenaline should be used with caution during isoflurane narcosis, due to a potential risk of ventricular arrhythmia.

Esketamine, isoflurane

Enhancement of anesthetic effect

Etilefrine, isoflurane

The co-administration may enhance the sympathicomimetic effect on the cardiac muscle and cause heart rhythm disorders

Indirect sympathomimetics [1], isoflurane ---> SmPC of [1] of eMC

Beta-sympathomimetic agents should be used with caution during isoflurane narcosis, due to a potential risk of ventricular arrhythmia.

Irreversible non-selective MAO-inhibitors, isoflurane [2] ---> SmPC of [2] of eMC

Non-selective MAO-inhibitors and isoflurane: Risk of crisis during the operation. Treatment should be stopped 15 days prior to surgery.

Isoflurane [1], isoniazid ---> SmPC of [1] of eMC

Use of isoflurane and isoniazid can increase the risk of potentiation of the hepatotoxic effects.

Isoflurane [1], muscle relaxants (non-depolarizing) ---> SmPC of [1] of eMC

Muscle relaxants are markedly potentiated by isoflurane.

Isoflurane [1], nitrous oxide ---> SmPC of [1] of eMC

MAC (minimum alveolar concentration) is reduced by concomitant administration of N20 in adults

Isoflurane [1], opiates ---> SmPC of [1] of eMC

Opioids, benzodiazepines and other sedative agents are associated with respiratory depression, and caution should be exercised when concomitantly administered with isoflurane.

Isoflurane [1], opioid analgesics ---> SmPC of [1] of eMC

Opioids, benzodiazepines and other sedative agents are associated with respiratory depression, and caution should be exercised when concomitantly administered with isoflurane.

Isoflurane [1], pregnancy ---> SmPC of [1] of eMC

Isoflurane should only be used during pregnancy if the benefit outweighs the potential risk.

Isoflurane [1], psychostimulants ---> SmPC of [1] of eMC

Risk of perioperative hypertension. In patients undergoing elective surgery, treatment should ideally be discontinued several days before surgery.

Isoflurane [1], reversible non-selective MAO-inhibitors ---> SmPC of [1] of eMC

Non-selective MAO-inhibitors and isoflurane: Risk of crisis during the operation. Treatment should be stopped 15 days prior to surgery.

Isoflurane [1], sedatives ---> SmPC of [1] of eMC

Opioids, benzodiazepines and other sedative agents are associated with respiratory depression, and caution should be exercised when concomitantly administered with isoflurane.

Isoflurane [1], vasodilators ---> SmPC of [1] of eMC

Chronic treatment with other vasodilators like ACE inhibitors (e. g. captopril, enalapril, lisinopril) or alfa1-adrenergic receptor blocker (e.g. prazosin) may cause an unforeseeable hypotension

Isoflurane, mivacurium [2] ---> SmPC of [2] of eMC

The neuromuscular block produced by mivacurium may be increased by the concomitant use of inhalational anaesthetics

Isoflurane, pancuronium [2] ---> SmPC of [2] of eMC

The anaesthetic may potentiate the neuromuscular blocking activity of pancuronium

Isoflurane, piperaquine/artenimol [2] ---> SmPC of [2] of EMA

Piperaquine, CYP2E1 inductor, may decrease the plasma concentrations of the medicinal products metabolized by CYP2E1

Isoflurane, succinylcholine ---> SmPC of [suxamethonium] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Isoflurane, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

CONTRAINDICATIONS of Isoflurane

- Isoflurane is contra-indicated in patients with known sensitivity to isoflurane or other halogenated anaesthetics.

- It is also contraindicated in patients with known or suspected genetic susceptibility to malignant hyperthermia.

http://www.medicines.org.uk/emc/

Isoniazid

Ability to drive, isoniazid [2] ---> SmPC of [2] of eMC

Patients should be warned of the possibility of convulsions, psychosis and optic neuritis

Acarbose, isoniazid

The combined active ingredient with acarbose may cause hyperglycaemia, what may attenuate the acarbose effects. Monitorization of the blood-sugar concentration is recommended

Adrenaline, isoniazid

Increased adverse effects of sympathomimetic agent

Alcohol, isoniazid

Decreased alcohol tolerance, higher incidence of adverse reactions on the CNS, additive hepatotoxicity

Algeldrate/magnesium hydroxide, isoniazid

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Almasilate, isoniazid

The antacid can decrease the gastrointestinal absorption of isoniazide

Aluminium hydroxide, isoniazid

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Aluminium oxide/magnesium hydroxide, isoniazid

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Aluminium, isoniazid

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Aminophylline [1], isoniazid ---> SmPC of [1] of eMC

Isoniazid may decrease aminophylline clearance resulting in increased plasma theophylline concentrations and the potential for increased toxicity

Aminosalicyclic acid, isoniazid

Prolonged exposition to isoniazid

Antacids, isoniazid

Decreased isoniazid absorption. Administer antacid at least 2 hours after

Atropine, isoniazid

Increased toxicity of atropine

Barbiturates, isoniazid

Isoniazid, enzymatic inhibitor, may increase the plasma levels of barbiturate

BCG intravesical [1], isoniazid ---> SmPC of [1] of eMC

The treatment with anti-tuberculosis drugs is contraindicated

Bedaquiline [1], isoniazid ---> SmPC of [1] of EMA

The short-term coadministration of bedaquiline with isoniazid/pyrazinamide in healthy subjects did not result in clinically relevant changes in the exposure (AUC) to bedaquiline, isoniazid or pyrazinamide. No dose-adjustment is required

Benzodiazepines, isoniazid ---> SmPC of [lorazepam] of eMC

Inhibitors reduce clearance and may potentiate the action of benzodiazepines.

Betablockers, isoniazid

Metabolism inhibition of isoniazid and increase of its plasma levels

Breast-feeding, isoniazid [2] ---> SmPC of [2] of eMC

Isoniazid is excreted in breast milk at concentrations equivalent to those found in maternal plasma

Carbaldrate, isoniazid

The aluminium salt decreases the absorption of the co-administered active principle. Separate administration by at least 2 hours

Carbamazepine, isoniazid [2] ---> SmPC of [2] of eMC

Concomitant use of carbamazepine and isoniazid has been reported to increase isoniazid-induced hepatotoxicity.

Chenodeoxycholic acid, isoniazid

Increased elimination of isoniazid due to acetylation acceleration

Chloroquine, isoniazid

The co-administration of chloroquine with hepatotoxic medicinal products is not recommended

Chlorpromazine, isoniazid

Metabolism inhibition of isoniazid and increase of its plasma levels

Chlorprothixene, isoniazid

The enzymatic inhibition increases the plasma levels of chlorprothixene

CNS stimulants, isoniazid

States of excitement

Colchicine, isoniazid

The co-administration may decrease the effect of colchicine and/or increase its toxicity

Cotrimoxazole, isoniazid

Co-trimoxazole may inhibit the metabolism of isoniazid

Coumarin anticoagulants, isoniazid

Increased anticoagulant effect with haemorrhagic diathesis

Cycloserine, isoniazid [2] ---> SmPC of [2] of eMC

The adverse CNS effects of cycloserine are increased by isoniazid.

Dihydralazine, isoniazid

The co-administration may enhance the effect by competition for the degradation path

Disulfiram, isoniazid [2] ---> SmPC of [2] of eMC

Isoniazid is known to inhibit certain cytochrome P-450 enzymes and can inhibit the hepatic metabolism of disulfiram.

Eliglustat [1], isoniazid ---> SmPC of [1] of EMA

Caution should be used with weak CYP3A inhibitors in poor metabolisers.

Ethosuximide [1], isoniazid ---> SmPC of [1] of eMC

The plasma concentrations of ethosuximide may be increased by isoniazid.

Fenyramidol, isoniazid

Metabolism inhibition of isoniazid and increase of its plasma levels

Fludrocortisone [1], isoniazid ---> SmPC of [1] of eMC

Isoniazid serum concentrations may be decreased.

Fluorouracil, isoniazid

The co-administration may enhance the effect of fluorouracil

Foods, isoniazid

Decreased absorption of isoniazid. Isoniazid must therefore be taken on an empty stomach

Fosphenytoin [1], isoniazid ---> SmPC of [1] of eMC

Isoniazid may increase phenytoin serum levels

Glibenclamide [1], isoniazid ---> SmPC of [1] of EMA

Weakening of the blood-glucose- lowering effect

Gliquidone, isoniazid

Hyperglycemic reactions may occur as expression of weakening effect of gliquidone with gliquidone is co-administered with isoniazid

Glucocorticoids, isoniazid

Increased hepatic metabolism of isoniazid and decreased metabolism of glucocorticoid

Halogenated anaesthetics, isoniazid [2] ---> SmPC of [2] of eMC

General anaesthetics possibly potentiate hepatotoxicity of isoniazid

Haloperidol, isoniazid

Mutual potentiation of effects. Relevant increase of plasma levels of haloperidol

Hepatotoxic drugs, isoniazid

The co-administration of hepatotoxic medicinal products increase the probability of hepatotoxic effects

Hydralazine, isoniazid

The co-administration may enhance the effect by competition for the degradation path

Hydrotalcite, isoniazid

The co-administration of hydrotalcite with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 1-2 hours

IMAOs, isoniazid

Mutual enhancement of effects

Indandione, isoniazid

Increased anticoagulant effect

Indinavir [1], isoniazid ---> SmPC of [1] of EMA

Indinavir and isoniazid can be co-administered without dose adjustment.

Insulin glargin [1], isoniazid ---> SmPC of [1] of EMA

Reduced blood-glucose-lowering effect

Insulin glargine/lixisenatide [1], isoniazid ---> SmPC of [1] of EMA

This substance may reduce the blood-glucose-lowering effect.

Insulin glulisin [1], isoniazid ---> SmPC of [1] of EMA

Possible decrease in blood-glucose-lowering activity

Insulin, isoniazid

Possible increase of the insulin requirements. Increased plasma levels of isoniazid

Isoflurane [1], isoniazid ---> SmPC of [1] of eMC

Use of isoflurane and isoniazid can increase the risk of potentiation of the hepatotoxic effects.

Isoniazid [1], prednisolone ---> SmPC of [1] of eMC

Prednisolone can lower plasma levels of isoniazid.

Isoniazid [1], pregnancy ---> SmPC of [1] of eMC

There is a possibility of an increased risk of foetal malformations occurring when isoniazid is given in early pregnancy. If pregnancy cannot be excluded possible risks should be balanced against therapeutic benefits.

Isoniazid [1], primidone ---> SmPC of [1] of eMC

Isoniazid is known to inhibit certain cytochrome P-450 enzymes and can inhibit the hepatic metabolism of primidone

Isoniazid [1], rifampicin ---> SmPC of [1] of eMC

When rifampicin is given concomitantly with isoniazid, the potential for hepatotoxicity is increased. Patients receiving both rifampicin and isoniazid should be monitored closely for hepatotoxicity.

Isoniazid [1], tyramine ---> SmPC of [1] of eMC

Isoniazid is an inhibitor of monoamine oxidase (MAO) and diamine oxidase (DAO), and hence can reduce tyramine and histamine metabolism. Patients should therefore be advised against ingesting foods rich in tyramine and/or histamine

Isoniazid, itraconazol [2] ---> SmPC of [2] of eMC

Coadministration of itraconazole with potent enzyme inducers of CYP3A4 may decrease the bioavailability of itraconazole and hydroxy-itraconazole to such an extent that efficacy may be largely reduced.

Isoniazid, ketoconazole [2] ---> SmPC of [2] of EMA

Ketoconazole HRA is mainly metabolised by cytochrome CYP3A4. Enzyme-inducing drugs may significantly reduce the bioavailability of ketoconazole. Use of Ketoconazole HRA with potent enzyme inducers is not recommended.

Isoniazid, levodopa ---> SmPC of [levodopa/carbidopa] of eMC

Isoniazid may reduce the therapeutic effects of levodopa.

Isoniazid, levodopa/carbidopa [2] ---> SmPC of [2] of EMA

Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone), benzodiazepines and isoniazid may reduce the therapeutic effects of levodopa.

Isoniazid, lomitapide [2] ---> SmPC of [2] of EMA

Weak CYP3A4 inhibitors are expected to increase the exposure of lomitapide when taken simultaneously. Separate the dose of the medications by 12 hours OR decrease the dose of Lojuxta by half.

Isoniazid, lorazepam [2] ---> SmPC of [2] of eMC

Inhibitors reduce clearance and may potentiate the action of benzodiazepines.

Isoniazid, lymecycline

The co-administration of tetracyclines with other potentially hepatotoxic medicinal products should be avoided

Isoniazid, meperidine

Isoniazid inhibits monoamine oxidase causing hypotensive episode or CNS depression

Isoniazid, mephenytoin

Increased hydantoin plasma levels

Isoniazid, metformin

Decreased hypoglycemic effect

Isoniazid, noradrenaline

Increased adverse effects of sympathomimetic agent

Isoniazid, norepinephrine

Increased adverse effects of sympathomimetic agent

Isoniazid, para-aminosalicylic acid

Increased half-time of isoniazid

Isoniazid, paracetamol

The enzymatic inductor may decrease the plasma levels of paracetamol and increase its hepatotoxicity. Caution is recommended

Isoniazid, phenothiazines

Isoniazid, enzymatic inhibitor, may increase the plasma levels of phenothiazine

Isoniazid, phenytoin [2] ---> SmPC of [2] of eMC

Isoniazid may increase phenytoin serum levels

Isoniazid, phytomenadione

Possible bleeding in newborn due to vitamin K deficiency

Isoniazid, prednisone

Decreased plasma concentrations of isoniazid

Isoniazid, propiverine [2] ---> SmPC of [2] of eMC

Reduced blood pressure in patients treated with isoniazid.

Isoniazid, prothionamide

Increased plasma levels of protionamide and enhancement of hepatotoxic effects

Isoniazid, pyrazinamide

The co-administration may increase the risk of hepatotoxicity

Isoniazid, pyridoxine

Isoniazid may increase the pyridoxine requirements

Isoniazid, rifabutin [2] ---> SmPC of [2] of eMC

Clinical studies have shown that rifabutin does not affect the pharmacokinetics of isoniazid

Isoniazid, salicylates

Increased half-time of isoniazid

Isoniazid, sevoflurane [2] ---> SmPC of [2] of eMC

Concomitant use of sevoflurane and isoniazid can potentiate the hepatotoxic effects of isoniazid.

Isoniazid, sympathomimetics

Increased adverse effects of sympathomimetic agent

Isoniazid, tacrolimus [2] ---> SmPC of [2] of EMA

Isoniazid has the potential to decrease tacrolimus concentrations.

Isoniazid, terizidone

Increased proconvulsiveness

Isoniazid, theophylline [2] ---> SmPC of [2] of eMC

Isoniazid is known to inhibit certain cytochrome P-450 enzymes and can inhibit the hepatic metabolism of theophylline

Isoniazid, thiopental [2] ---> SmPC of [2] of eMC

General anaesthetics possibly potentiate hepatotoxicity of isoniazid

Isoniazid, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Isoniazid, triamcinolone acetonide [2] ---> SmPC of [2] of eMC

Isoniazid serum concentrations may be decreased.

Isoniazid, triamcinolone [2] ---> SmPC of [2] of eMC

Isoniazid serum concentrations may be decreased.

Isoniazid, triazolam

Caution is advised when combining triazolam with isoniazid

Isoniazid, tuberculosis vaccine

BCG bacteria are susceptible to tuberculostatic agents

Isoniazid, valproic acid

Isoniazid, enzymatic inhibitor, may increase the plasma levels of valproic acid

Isoniazid, vincristine

The co-administration of vincristine and neurotoxic drugs may cause severe and long-lasting peripheral neuropathy

Isoniazid, vitamin B6

Isoniazid may increase the requirements for pyridoxine

Isoniazid, vitamin D

Decreased metabolism of vitamin D

Isoniazid, vitamin K

Possible bleeding in newborn due to vitamin K deficiency

Isoniazid, warfarin

The enzymatic inhibitor may decrease the metabolism of warfarin and increase its plasma levels, the anticoagulant effect and the bleeding risk

CONTRAINDICATIONS of Isoniazid

- Hypersensitivity to the active substance or to any of the excipients

http://www.medicines.org.uk/emc/

Isoprenaline

Adrenaline, isoprenaline

Isoprenaline should not be coadministered with sympathomimetic agents like adrenalin, due to the combined effect can induce arrythmias

Betablockers, isoprenaline

Betablocker may counteract the isoprenaline effect.

Bisoprolol [1], isoprenaline ---> SmPC of [1] of eMC

Combination of beta-sympathomimetic agents with bisoprolol may reduce the effect of both agents.

Breast-feeding, isoprenaline

It is not known whether isoprenaline passes into breast milk. The expected benefits of therapy should therefore be weighed against the potential risk of breast-feeding.

Brinzolamide/brimonidine [1], isoprenaline ---> SmPC of [1] of EMA

Caution is advised when initiating (or changing the dose of) a concomitant systemic medicinal products (irrespective of pharmaceutical form) which may interact with alfa-adrenergic agonists or interfere with their activity

Catecholamine-O-methyltransferase inhibitors, isoprenaline

The COMT-inhibition may increase the plasma levels of isoprenaline

Clomipramine [1], isoprenaline ---> SmPC of [1] of eMC

Clomipramine may potentiate the cardiovascular effects of isoprenaline

Cyclopropane, isoprenaline

Isoprenaline should be used with caution in patients receiving inhalation anesthetics or cyclopropane, due to arrythmias may occur

Entacapone [1], isoprenaline ---> SmPC of [1] of EMA

Because of its mechanism of action, entacapone may interfere with the metabolism of medicinal products containing a catechol group and potentiate their action

Epinephrine, isoprenaline

Isoprenaline should not be coadministered with sympathomimetic agents like adrenalin, due to the combined effect can induce arrythmias

Halogenated anaesthetics, isoprenaline

Isoprenaline should be used with caution in patients receiving inhalation anesthetics or cyclopropane, due to arrythmias may occur

IMAOs, isoprenaline

Isoprenaline should not be coadministered with MAO inhibitors, due to the combined effect can induce arrythmias

Imipramine [1], isoprenaline ---> SmPC of [1] of eMC

Imipramine may potentiate the cardiovascular effects of sympathomimetic agent

Isoprenaline, lofepramine [2] ---> SmPC of [2] of eMC

Lofepramine should not be given with sympathomimetic agents since their cardiovascular effects may be potentiated.

Isoprenaline, melitracen

The antidepressant may enhance the cardiovascular effects of sympathomimetic agent resulting in severe arrhytmias, tachycardia, hypertension and hyperpyrexia

Isoprenaline, nadolol [2] ---> SmPC of [2] of eMC

Beta-adrenoceptor stimulants such as isoprenaline and verapamil, or alpha-adrenoceptor stimulants such as noradrenaline and adrenaline, will reverse the hypotensive effects and increase vasoconstrictor activity.

Isoprenaline, nicotine

Decrease of circulating catecholamines. It can be necessary to increase the dose of isoprenaline

Isoprenaline, non-selective betablockers ---> SmPC of [oxprenolol] of eMC

Non-cardioselective beta-blockers enhance the pressor response to sympathomimetic drugs, resulting in hypertension and bradycardia.

Isoprenaline, oxprenolol [2] ---> SmPC of [2] of eMC

Non-cardioselective beta-blockers enhance the pressor response to sympathomimetic drugs, resulting in hypertension and bradycardia.

Isoprenaline, pregnancy

Due to the inhibitor effect of uterine contraction of isoprenaline, it should be used with caution close to delivery

Isoprenaline, propranolol

Betablocker may counteract the isoprenaline effect.

Isoprenaline, sotalol

The co-administration may require increasing the dose of beta2-adrenergic agonist

Isoprenaline, sympathomimetics

Isoprenaline should not be coadministered with sympathomimetic agents like adrenalin, due to the combined effect can induce arrythmias

Isoprenaline, tetracyclic antidepressant

The antidepressant may enhance the cardiovascular effects of sympathomimetic agent resulting in severe arrhytmias, tachycardia, hypertension and hyperpyrexia

Isoprenaline, theophylline

Isoprenaline increases the elimination of theophylline (bronchodilator) and can enhance the hypokaliemia, hyperglycaemia, tachycardia and hypertension

Isoprenaline, tolcapone [2] ---> SmPC of [2] of EMA

Tolcapone, COMT inhibitor, may increase the plasma concentrations of drugs metabolised by COMT

Isoprenaline, tricyclic antidepressant

Isoprenaline should not be coadministered with tricyclic antidepressants, due to the combined effect can induce arrythmias

Isoprenaline, trimipramine [2] ---> SmPC of [2] of eMC

Trimipramine should not be given with sympathomimetic agents

Isosorbide dinitrate

Ability to drive, isosorbide dinitrate [2] ---> SmPC of [2] of eMC

Headaches, tiredness, dizziness. These may affect the ability to drive and operate machinery.

ACE inhibitors, isosorbide dinitrate [2] ---> SmPC of [2] of eMC

Concurrent intake of drugs with blood pressure lowering properties may potentiate the hypotensive effect

Alcohol, isosorbide dinitrate [2] ---> SmPC of [2] of eMC

Concurrent intake of drugs with blood pressure lowering properties may potentiate the hypotensive effect

Antihypertensives, isosorbide dinitrate [2] ---> SmPC of [2] of eMC

Concurrent intake of drugs with blood pressure lowering properties may potentiate the hypotensive effect

Betablockers, isosorbide dinitrate [2] ---> SmPC of [2] of eMC

Concurrent intake of drugs with blood pressure lowering properties may potentiate the hypotensive effect

Breast-feeding, isosorbide dinitrate [2] ---> SmPC of [2] of eMC

This product should not be used during lactation unless considered essential by the physician.

Calcium antagonists, isosorbide dinitrate [2] ---> SmPC of [2] of eMC

Concurrent intake of drugs with blood pressure lowering properties may potentiate the hypotensive effect

Dihydroergotamine, isosorbide dinitrate [2] ---> SmPC of [2] of eMC

Reports suggest that when administered concomitantly, nitrates may increase the blood level of dihydroergotamine and its hypertensive effect.

Diuretics, isosorbide dinitrate [2] ---> SmPC of [2] of eMC

Concurrent intake of drugs with blood pressure lowering properties may potentiate the hypotensive effect

IMAOs, isosorbide dinitrate

Concurrent intake of drugs with blood pressure lowering properties may potentiate the hypotensive effect

Isosorbide dinitrate [1], neuroleptics ---> SmPC of [1] of eMC

Concurrent intake of drugs with blood pressure lowering properties may potentiate the hypotensive effect

Isosorbide dinitrate [1], PDE5 inhibitors ---> SmPC of [1] of eMC

The hypotensive effect of nitrates is potentiated by concurrent administration of phosphodiesterase inhibitors

Isosorbide dinitrate [1], pregnancy ---> SmPC of [1] of eMC

This product should not be used during pregnancy unless considered essential by the physician.

Isosorbide dinitrate [1], sildenafil ---> SmPC of [1] of eMC

The hypotensive effect of nitrates is potentiated by concurrent administration of phosphodiesterase inhibitors

Isosorbide dinitrate [1], tadalafil ---> SmPC of [1] of eMC

The hypotensive effect of nitrates is potentiated by concurrent administration of phosphodiesterase inhibitors

Isosorbide dinitrate [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Concurrent intake of drugs with blood pressure lowering properties may potentiate the hypotensive effect

Isosorbide dinitrate [1], vardenafil ---> SmPC of [1] of eMC

The hypotensive effect of nitrates is potentiated by concurrent administration of phosphodiesterase inhibitors

Isosorbide dinitrate [1], vasodilators ---> SmPC of [1] of eMC

Concurrent intake of drugs with blood pressure lowering properties may potentiate the hypotensive effect

Organic nitrates, PDE5 inhibitors ---> SmPC of [isosorbide dinitrate] of eMC

PDE5 inhibitors may potentiate the hypotensive effects of nitrates, thus contraindicated in patients who are concomitantly treated with nitrates

CONTRAINDICATIONS of Isosorbide dinitrate

This product should not be given to patients with

- a known sensitivity to nitrates (or any other ingredient in this product),

- very low blood pressure,

- acute myocardial infarction with low filling pressure,

- marked anaemia,

- head trauma,

- cerebral haemorrhage,

- acute circulatory failure,

- severe hypotension or

- hypovolaemia.

- Phosphodiesterase inhibitors (e.g. Sildenafil) have been shown to potentiate the hypotensive effects of nitrates, and their co-administration with nitrates or nitric oxide donors is therefore contraindicated.

http://www.medicines.org.uk/emc/

Isosorbide mononitrate

Ability to drive, isosorbide mononitrate [2] ---> SmPC of [2] of eMC

Isosorbide mononitrate may, owing to side effects (e.g. dizziness), affect the ability to drive and use machines to a slight or moderate extent. This action is potentiated by intake of alcohol.

ACE inhibitors, isosorbide mononitrate [2] ---> SmPC of [2] of eMC

The hypotensive effects of nitrates are potentiated by concurrent administration of ACE inhibitors.

Alcohol, isosorbide mononitrate [2] ---> SmPC of [2] of eMC

Alcohol can accentuate cerebral ischaemia associated with postural hypotension.

Antihypertensives, isosorbide mononitrate

The co-administration may potentiate the antihypertensive effect of isosorbide mononitrate

Betablockers, isosorbide mononitrate [2] ---> SmPC of [2] of eMC

Beta-blocking drugs have a different pharmacological action in angina and may have a complimentary effect when co-administered with isosorbide mononitrate.

Breast-feeding, isosorbide mononitrate [2] ---> SmPC of [2] of eMC

It is not advisable to use this drug during lactation.

Calcium antagonists, isosorbide mononitrate

The co-administration may potentiate the antihypertensive effect of isosorbide mononitrate and cause orthostatic dysregulation

Dihydroergotamine, isosorbide mononitrate

The co-administration may enhance the effects and adverse effects of dihydroergotamine. The concomitant use should be done with caution

Isosorbide mononitrate [1], PDE5 inhibitors ---> SmPC of [1] of eMC

Phosphodiesterase type-5 inhibitors have been shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitrates or nitric oxide donors is therefore contra-indicated.

Isosorbide mononitrate [1], pregnancy ---> SmPC of [1] of eMC

It is not advisable to use this drug during pregnancy.

Isosorbide mononitrate [1], sildenafil ---> SmPC of [1] of eMC

Phosphodiesterase type-5 inhibitors have been shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitrates or nitric oxide donors is therefore contra-indicated.

Isosorbide mononitrate [1], tadalafil ---> SmPC of [1] of eMC

Phosphodiesterase type-5 inhibitors have been shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitrates or nitric oxide donors is therefore contra-indicated.

Isosorbide mononitrate [1], vardenafil ---> SmPC of [1] of eMC

Phosphodiesterase type-5 inhibitors have been shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitrates or nitric oxide donors is therefore contra-indicated.

Isosorbide mononitrate, levosimendan

The co-administration may significantly enhance the orthostatic hypotensive effect

Isosorbide mononitrate, neuroleptics

The co-administration may potentiate the antihypertensive effect of isosorbide mononitrate

Isosorbide mononitrate, sapropterin

The co-administration may potentiate the antihypertensive effect of isosorbide mononitrate

Isosorbide mononitrate, tricyclic antidepressant

The co-administration may potentiate the antihypertensive effect of isosorbide mononitrate and cause a strong anticholinergic effect

Isosorbide mononitrate, vasodilators

The co-administration may potentiate the antihypertensive effect of isosorbide mononitrate

CONTRAINDICATIONS of Isosorbide mononitrate

- Known hypersensitivity to isosorbide dinitrate or mononitrate; to other nitrates or to any of the excipients;

- acute circulatory failure (shock, vascular collapse);

- angina caused by hypertrophic obstructive cardiomyopathy;

- very low blood pressure or low filling pressure;

- severe anaemia;

- cerebral haemorrhage;

- head trauma.

- Phosphodiesterase type-5 inhibitors (eg sildenafil, tadalafil, vardenafil) have been shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitrates or nitric oxide donors is therefore contra-indicated.

http://www.medicines.org.uk/emc/

Isotretinoin

Abacavir/lamivudine [1], isotretinoin ---> SmPC of [1] of EMA

Possible interaction given common pathway (retinoids and abacavir) of elimination via alcohol dehydrogenase.

Abacavir/lamivudine/zidovudine [1], isotretinoin ---> SmPC of [1] of EMA

Possible interaction given common pathway (retinoids and abacavir) of elimination via alcohol dehydrogenase.

Ability to drive, isotretinoin [2] ---> SmPC of [2] of eMC

A number of cases of decreased night vision have occurred during isotretinoin therapy and in rare instances have persisted after therapy

Acitretin, isotretinoin [2] ---> SmPC of [2] of eMC

Risk of A hypervitaminosis. The co-administration should be avoided.

Alitretinoin, isotretinoin

Risk of A hypervitaminosis. The co-administration should be avoided.

Breast-feeding, isotretinoin [2] ---> SmPC of [2] of eMC

Due to the potential for adverse effects in the child exposed via mothers' milk, the use of isotretinoin is contraindicated in nursing mothers.

Carbamazepine [1], isotretinoin ---> SmPC of [1] of eMC

The carbamazepine plasma levels may be decreased.

Dolutegravir/abacavir/lamivudine [1], isotretinoin ---> SmPC of [1] of EMA

Possible interaction due to common metabolic pathway through alcohol dehydrogenase (abacavir-component).

Isotretinoin [1], keratolytics ---> SmPC of [1] of eMC

Concurrent administration of isotretinoin with topical keratolytic or exfoliative anti-acne agents should be avoided as local irritation may increase

Isotretinoin [1], pregnancy ---> SmPC of [1] of eMC

Pregnancy is an absolute contraindication to treatment with isotretinoin

Isotretinoin [1], retinoids ---> SmPC of [1] of eMC

Patients should not take vitamin A as concurrent medication due to the risk of developing hypervitaminosis A.

Isotretinoin [1], tetracyclines ---> SmPC of [1] of eMC

Cases of benign intracranial hypertension (pseudotumor cerebri) have been reported with concomitant use of isotretinoin and tetracyclines. Therefore, concomitant treatment with tetracyclines must be avoided

Isotretinoin [1], vitamin A ---> SmPC of [1] of eMC

Patients should not take vitamin A as concurrent medication due to the risk of developing hypervitaminosis A.

Isotretinoin, lomitapide [2] ---> SmPC of [2] of EMA

Caution should be exercised when lomitapide is used with other medicinal products known to have potential for hepatotoxicity

Isotretinoin, methotrexate

Concomitant use of methotrexat with other drugs with nephrotoxic or hepatotoxic potential should generally be avoided, unless considered clinically justified, in which case the patient should be closely monitored.

CONTRAINDICATIONS of Isotretinoin

- Isotretinoin is contraindicated in women who are pregnant or breastfeeding

- Isotretinoin is contraindicated in women of childbearing potential unless all of the conditions of the Pregnancy Prevention Programme are met

- Isotretinoin is also contraindicated in patients with hypersensitivity to isotretinoin or to any of the excipients. The medicinal product 10 mg contains soya oil, partially hydrogenated soya oil, and hydrogenated soya oil. Therefore, is contraindicated in patients allergic to peanut or soya.

- Isotretinoin is also contraindicated in patients

- With hepatic insufficiency

- With excessively elevated blood lipid values

- With hypervitaminosis A

- Receiving concomitant treatment with tetracyclines

http://www.medicines.org.uk/emc/

Isradipine

Ability to drive, isradipine [2] ---> SmPC of [2] of eMC

As with other calcium channel blockers, syncope, dizziness, hypotension, visual disturbances and blurred vision are known adverse reactions associated with the use of isradipine.

Anticoagulants, isradipine

Isradipine doesn't bind specifically to proteins; however, caution is recommended in combination with anticoagulants and anticonvulsants

Antiepileptics, isradipine

Isradipine doesn't bind specifically to proteins; however, caution is recommended in combination with anticoagulants and anticonvulsants

Antihypertensives, isradipine

The co-administration may enhance the hypotensive effect

Azole antifungals, isradipine [2] ---> SmPC of [2] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

Baclofen, isradipine [2] ---> SmPC of [2] of eMC

As with all antihypertensives, concomitant treatment with oral baclofen is likely to further increase a possible fall in blood pressure. It may therefore be necessary to monitor blood pressure and adjust the dosage of the antihypertensive

Betablockers, isradipine

The co-administration may enhance the negative inotropic effect

Breast-feeding, isradipine [2] ---> SmPC of [2] of eMC

Women being treated with isradipine should not breast-feed.

Carbamazepine, isradipine [2] ---> SmPC of [2] of eMC

Concurrent administration of isradipine with enzyme-inducing drugs may reduce the plasma concentrations of isradipine. Concomitant administration of isradipine with enzyme-inducing drugs should be avoided.

Cimetidine, isradipine [2] ---> SmPC of [2] of eMC

Concurrent administration of cimetidine increases the bioavailability of isradipine by about 50%. When isradipine is given concurrently with cimetidine, the dosage of isradipine should be reduced by 50%.

Clarithromycin, isradipine [2] ---> SmPC of [2] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

Cyclosporine, isradipine

The co-administration may increase the cyclosporine plasma levels. Possible renal impairment

Delavirdine, isradipine [2] ---> SmPC of [2] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

Diclofenac, isradipine [2] ---> SmPC of [2] of eMC

The peak plasma concentration of isradipine increases by about 20% during co-administration with diclofenac but this is not expected to be clinically significant, as steady state exposure remained unchanged.

Digoxin [1], isradipine ---> SmPC of [1] of eMC

Isradipine causes no change in serum digoxin levels.

Enzyme inductors, isradipine [2] ---> SmPC of [2] of eMC

Erythromycin, isradipine [2] ---> SmPC of [2] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

Fentanyl, isradipine

The co-administration may decrease strongly the blood pressure

Fluconazole [1], isradipine ---> SmPC of [1] of eMC

Isradipine is metabolized by CYP3A4. Fluconazole has the potential to increase the systemic exposure of isradipine. Frequent monitoring for adverse events is recommended.

Grapefruit juice, isradipine [2] ---> SmPC of [2] of eMC

The concomitant intake of grapefruit juice may increase the bioavailability of isradipine.

Grapefruit, isradipine [2] ---> SmPC of [2] of eMC

The concomitant intake of grapefruit juice may increase the bioavailability of isradipine.

Indinavir [1], isradipine ---> SmPC of [1] of EMA

Isradipine [1], itraconazol ---> SmPC of [1] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

Isradipine [1], ketoconazole ---> SmPC of [1] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

Isradipine [1], nelfinavir ---> SmPC of [1] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

Isradipine [1], phenobarbital ---> SmPC of [1] of eMC

Isradipine [1], phenytoin ---> SmPC of [1] of eMC

Based on an isradipine case report and on the known risks related to the co-administration of phenytoin with calcium channel blockers, concomitant administration with phenytoin should be avoided.

Isradipine [1], pregnancy ---> SmPC of [1] of eMC

There is insufficient experience with the drug in pregnant women to justify its use during pregnancy unless the benefit to the mother is expected to outweigh any potential risk to the infant.

Isradipine [1], propranolol ---> SmPC of [1] of eMC

Concurrent administration of isradipine with propranolol increases the bioavailability (AUC) of propranolol.

Isradipine [1], protease inhibitors ---> SmPC of [1] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

Isradipine [1], rifampicin ---> SmPC of [1] of eMC

Concurrent administration of isradipine with rifampicin greatly reduces the plasma concentrations of isradipine. Concomitant administration of isradipine with enzyme-inducing drugs should be avoided.

Isradipine [1], ritonavir ---> SmPC of [1] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

Isradipine [1], strong CYP3A4 inhibitors ---> SmPC of [1] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

Isradipine [1], troleandomycin ---> SmPC of [1] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

Isradipine [1], voriconazole ---> SmPC of [1] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

Isradipine, negative inotropic drugs

The co-administration may enhance the negative inotropic effect

Isradipine, quinidine

The co-administration of dihydropyridines with quinidine may decrease the plasma levels of quinidine

Isradipine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Possible increase in the plasma concentrations of calcium channel antagonist. Careful monitoring of therapeutic and adverse effects is recommended.

Isradipine, theophylline

The co-administration may increase the theophylline plasma levels

Isradipine, tricyclic antidepressant

The co-administration may enhance the hypotensive effect

CONTRAINDICATIONS of Isradipine

- Known hypersensitivity to isradipine, to other calcium channel blockers of the dihydropyridine type or to any of the excipients

As with other calcium channel blockers of the dihydropyridine type, isradipine should not be used in patients with any of the following conditions:

- Cardiogenic shock,

- Unstable angina,

- During or within one month after myocardial infarction,

- Treatment of hypertensive crisis.

http://www.medicines.org.uk/emc/

Itraconazol

Abemaciclib [1], itraconazol ---> SmPC of [1] of EMA

Use of strong CYP3A4 inhibitors together with abemaciclib should be avoided. If strong CYP3A4 inhibitors need to be co-administered, the dose of abemaciclib should be reduced, followed by careful monitoring of toxicity.

Ability to drive, itraconazol [2] ---> SmPC of [2] of eMC

Possibility of adverse reactions such as dizziness, visual disturbances and hearing loss may occur

Afatinib [1], itraconazol ---> SmPC of [1] of EMA

Increased exposure to afatinib. It is recommended to administer strong P-gp inhibitors using staggered dosing, preferably 6 hours or 12 hours apart from afatinib

Alectinib [1], itraconazol ---> SmPC of [1] of EMA

Appropriate monitoring is recommended for patients taking concomitant strong CYP3A inhibitors

Alfentanyl [1], itraconazol ---> SmPC of [1] of eMC

Alfentanil is metabolised mainly via the human cytochrome P450 3A4 enzyme. In vitro data suggest that cytochrome P450 3A4 enzyme inhibitors may inhibit the metabolism of alfentanil

Alfuzosin [1], itraconazol ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of alfuzosin

Aliskiren [1], itraconazol ---> SmPC of [1] of EMA

The concomitant use of aliskiren with ciclosporin and itraconazole, two highly potent P-gp inhibitors, and other potent P-gp inhibitors (e.g. quinidine), is contraindicated

Aliskiren/amlodipine [1], itraconazol ---> SmPC of [1] of EMA

The concomitant use of aliskiren with ciclosporin and itraconazole, two highly potent P-gp inhibitors, and other potent P-gp inhibitors (e.g. quinidine), is contraindicated

Aliskiren/amlodipine/hydrochlorothiazide [1], itraconazol ---> SmPC of [1] of EMA

The strong inhibition of P-glycoprotein increases the plasma levels of aliskiren. The concomitant use is contra-indicated

Aliskiren/hydrochlorothiazide [1], itraconazol ---> SmPC of [1] of EMA

The concomitant use of aliskiren with ciclosporin and itraconazole, two highly potent P-gp inhibitors, and other potent P-gp inhibitors (e.g. quinidine), is contraindicated

Alprazolam [1], itraconazol ---> SmPC of [1] of eMC

The CYP3A4 inhibition may increase the plasma concentrations of alprazolam. Co-administration is not recommended

Aluminium hydroxide, itraconazol [2] ---> SmPC of [2] of eMC

The antacid may decrease the absorption and effect of itraconazole, it should be administered at least 2 hours after the intake of itraconazole

Amitriptyline, itraconazol

The strong CYP3A4 inhibition may increase the plasma concentrations of amitriptyline

Amlodipine, itraconazol ---> SmPC of [amlodipine/valsartan] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.

Amlodipine/valsartan [1], itraconazol ---> SmPC of [1] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.

Amlodipine/valsartan/hydrochlorothiazide [1], itraconazol ---> SmPC of [1] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.

Amprenavir [1], itraconazol ---> SmPC of [1] of EMA

The CYP3A4 inhibition by amprenavir may increase the plasma concentrations of itraconazole

Amprenavir/ritonavir, itraconazol ---> SmPC of [amprenavir] of EMA

The CYP3A4 inhibition by amprenavir may increase the plasma concentrations of ketoconazole

Antacids, itraconazol [2] ---> SmPC of [2] of eMC

Medicinal products that reduce the gastric acidity impair the absorption of itraconazole. It is recommended that these medicinal products be used with caution when coadministered with itraconazole

Apixaban [1], itraconazol ---> SmPC of [1] of EMA

The use of apixaban is not recommended in patients receiving concomitant systemic treatment with strong inhibitors of both CYP3A4 and P-gp

Aprepitant [1], itraconazol ---> SmPC of [1] of EMA

Concomitant administration of aprepitant with active substances that inhibit CYP3A4 activity should be approached cautiously, as the combination is expected to result several-fold in increased plasma concentrations of aprepitant

Aripiprazole [1], itraconazol ---> SmPC of [1] of EMA

Strong inhibitors of CYP3A4 may increase the AUC of aripiprazole. A dose reduction should, therefore, be applied

Astemizole, itraconazol [2] ---> SmPC of [2] of eMC

The co-administration of itraconazole with CYP3A4 metabolised substrates that can prolong the QT-interval is contraindicated

Atazanavir/cobicistat [1], itraconazol ---> SmPC of [1] of EMA

Itraconazole is a potent inhibitor and a substrate of CYP3A4. Itraconazole, and/or cobicistat levels may be increased with coadministration of itraconazole with EVOTAZ. The mechanism is CYP3A4 inhibition by atazanavir, cobicistat and itraconazole.

Atazanavir/ritonavir, itraconazol ---> SmPC of [atazanavir] of EMA

Atazanavir/ritonavir is expected to increase itraconazole concentrations.

Atenolol/nifedipine [1], itraconazol ---> SmPC of [1] of eMC

Atorvastatin [1], itraconazol ---> SmPC of [1] of eMC

Potent CYP3A4 inhibitors have been shown to lead to markedly increased concentrations of atorvastatin. Co-administration of potent CYP3A4 inhibitors should be avoided if possible.

Avanafil [1], itraconazol ---> SmPC of [1] of EMA

Avanafil is predominantly metabolised by CYP3A4. The strong CYP3A4 inhibitors may increase the exposition of avanafil. Co-administration of avanafil with potent CYP3A4 inhibitors is contraindicated

Axitinib [1], itraconazol ---> SmPC of [1] of EMA

Barnidipine, itraconazol

The strong CYP3A4 inhibition may increase the plasma concentrations of barnidipine. Barnidipine should not be concomitantly prescribed with strong CYP3A4 inhibitors.

Bepridil, itraconazol [2] ---> SmPC of [2] of eMC

The co-administration of itraconazole with CYP3A4 metabolised substrates that can prolong the QT-interval is contraindicated

Bexarotene [1], itraconazol ---> SmPC of [1] of EMA

On the basis of the oxidative metabolism of bexarotene by cytochrome P450 3A4 (CYP3A4), coadministration with other CYP3A4 substrates may theoretically lead to an increase in plasma bexarotene concentrations.

Bictegravir/emtricitabine/tenofovir alafenamide [1], itraconazol ---> SmPC of [1] of EMA

No dose adjustment is required upon co-administration.

Boceprevir [1], itraconazol ---> SmPC of [1] of EMA

The inhibition of CYP3A4 and P-glycoprotein may increase the plasma concentrations of boceprevir. Caution should be exercised when boceprevir is combined with azole antifungals

Bosentan [1], itraconazol ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of bosentan. Co-administration is not recommended

Bosutinib [1], itraconazol ---> SmPC of [1] of EMA

Breast-feeding, itraconazol [2] ---> SmPC of [2] of eMC

A very small amount of itraconazole is excreted in human milk. The expected benefits of therapy should therefore be weighed against the potential risk of breast-feeding.

Brinzolamide [1], itraconazol ---> SmPC of [1] of EMA

It is expected that inhibitors of CYP3A4 will inhibit the metabolism of brinzolamide by CYP3A4. Caution is advised if CYP3A4 inhibitors are given concomitantly.

Brinzolamide/brimonidine [1], itraconazol ---> SmPC of [1] of EMA

It is expected that inhibitors of CYP3A4 will inhibit the metabolism of brinzolamide by CYP3A4. Caution is advised if CYP3A4 inhibitors are given concomitantly.

Brinzolamide/timolol [1], itraconazol ---> SmPC of [1] of EMA

It is expected that inhibitors of CYP3A4 will inhibit the metabolism of brinzolamide by CYP3A4. Caution is advised if CYP3A4 inhibitors are given concomitantly.

Bromperidol, itraconazol

The co-administration of bromperidol with itraconazol (strong CYP3A4 inhibitor) may increase the plasma levels of bromperidol

Brotizolam, itraconazol [2] ---> SmPC of [2] of eMC

Itraconazole may increase the plasma concentrations of brotizolam. Use with caution

Budesonide [1], itraconazol ---> SmPC of [1] of EMA

Co-treatment with potent CYP3A inhibitors may cause a marked increase of the plasma concentration of budesonide and is expected to increase the risk of systemic adverse reactions. Therefore, concomitant use should be avoided

Budesonide/formoterol [1], itraconazol ---> SmPC of [1] of EMA

Potent inhibitors of CYP3A4 are likely to markedly increase plasma levels of budesonide and concomitant use should be avoided.

Budipine, itraconazol

The co-administration of budipine with drugs known to prolong QT interval is contraindicated

Buprenorphine [1], itraconazol ---> SmPC of [1] of eMC

Buprenorphine/naloxone [1], itraconazol ---> SmPC of [1] of EMA

Medicines that inhibit the enzyme CYP3A4 may give rise to increased concentrations of buprenorphine. A reduction of the buprenorphine/naloxone dose may be needed.

Buspirone [1], itraconazol ---> SmPC of [1] of eMC

If buspirone is administered with a potent CYP3A4 inhibitor, the initial dose should be lowered and only increased gradually after medical evaluation

Busulfan [1], itraconazol ---> SmPC of [1] of EMA

The administration of itraconazole to patients receiving high-dose busulfan may result in reduced busulfan clearance.

Cabazitaxel [1], itraconazol ---> SmPC of [1] of EMA

Cabozantinib [1], itraconazol ---> SmPC of [1] of EMA

Co-administration of cabozantinib with strong CYP3A4 inhibitors (increased plasma cabozantinib exposure (AUC) should be approached with caution.

Calcium antagonists, itraconazol [2] ---> SmPC of [2] of eMC

Calcium channel blockers can have negative inotropic effects which may be additive to those of itraconazole. In addition, itraconazole can inhibit the metabolism of calcium channel blockers.

Carbamazepine, itraconazol [2] ---> SmPC of [2] of eMC

Cariprazine [1], itraconazol ---> SmPC of [1] of EMA

Metabolism of cariprazine and its major active metabolites is mediated mainly by CYP3A4. The co-administration of cariprazine with strong or moderate inhibitors of CYP3A4 is contraindicated

Ceritinib [1], itraconazol ---> SmPC of [1] of EMA

If it is not possible to avoid concomitant use with strong CYP3A inhibitors, reduce the ceritinib dose by approximately one third, rounded to the nearest multiple of the 150 mg dosage strength.

Ciclesonide [1], itraconazol ---> SmPC of [1] of eMC

The concomitant administration of ciclesonide with potent inhibitors of CYP 3A4 should be avoided unless the benefit outweighs the increased risk of systemic side effects of corticosteroids.

Cilostazol [1], itraconazol ---> SmPC of [1] of EMA

Cilostazol is extensively metabolised by CYP3A4 and CYP2C19 and to a lesser extent CYP1A2. Drugs inhibiting CYP3A4 increase the total pharmacological activity and could have the potential to enhance the undesirable effects of cilostazol.

Cimetidine [1], itraconazol ---> SmPC of [1] of eMC

Cimetidine increases the pH und decreases the absorption of itraconazol.

Cinacalcet [1], itraconazol ---> SmPC of [1] of EMA

Cinacalcet is metabolised in part by the enzyme CYP3A4. Co-administration of a strong inhibitor of CYP3A4 may increase cinacalcet levels. Dose adjustment of cinacalcet may be required

Cinitapride, itraconazol

The strong CYP3A4 inhibition may increase the plasma concentrations of cinitapride

Cisapride, itraconazol [2] ---> SmPC of [2] of eMC

The co-administration of itraconazole with CYP3A4 metabolised substrates that can prolong the QT-interval is contraindicated

Clarithromycin [1], itraconazol ---> SmPC of [1] of eMC

Both clarithromycin and itraconazole are substrates and inhibitors of CYP3A, leading to a bidirectional drug interaction. Clarithromycin may increase the plasma levels of itraconazole, while itraconazole may increase the plasma levels of clarithromycin.

Clobetasol, itraconazol

The co-administration of clobetasol with CYP3A4 inhibitors inhibits the metabolism of corticosteroid and increases its systemic bioavailability

Clobetasone [1], itraconazol ---> SmPC of [1] of eMC

Co-administered drugs that can inhibit CYP3A4 have been shown to inhibit the metabolism of corticosteroids leading to increased systemic exposure.

Cloprednol, itraconazol

The strong CYP3A4 inhibition may increase the plasma concentrations of cloprednol

Cobicistat [1], itraconazol ---> SmPC of [1] of EMA

Concentrations of itraconazole may be increased when co-administered with cobicistat.

Cobimetinib [1], itraconazol ---> SmPC of [1] of EMA

Avoid concurrent use of strong CYP3A inhibitors during treatment with cobimetinib. If concomitant use of a strong CYP3A inhibitor is unavoidable, patients should be carefully monitored for safety.

Colchicine [1], itraconazol ---> SmPC of [1] of eMC

Colchicine is contraindicated in patients with renal or hepatic impairment who are taking a strong CYP3A4 inhibitor

Conjugated oestrogens/bazedoxifene [1], itraconazol ---> SmPC of [1] of EMA

In a clinical drug-drug interaction study, repeat administration of 200 mg itraconazole, a strong CYP3A4 inhibitor, had minimal impact on the pharmacokinetics of CE and bazedoxifene when administered with a single dose of CE 0.45 mg/bazedoxifene 20 mg.

Coumarin anticoagulants [1], itraconazol ---> SmPC of [1] of eMC

Itraconazole may increase the plasma concentrations of coumarin

Crizotinib [1], itraconazol ---> SmPC of [1] of EMA

Coadministration of crizotinib with strong CYP3A inhibitors may increase crizotinib plasma concentrations. Therefore, the concomitant use of strong CYP3A inhibitors should be avoided.

Cyclophosphamide, itraconazol

The co-administration may delay the activation and decrease the efficacy of cyclophosphamide.

Cyclosporine [1], itraconazol ---> SmPC of [1] of eMC

Inhibitors of CYP3A4 may lead to increased levels of cyclosporine.

Cyproterone [1], itraconazol ---> SmPC of [1] of eMC

Since cyproterone acetate is metabolised by CYP3A4, it is expected strong inhibitors of CYP3A4 inhibit the metabolism of cyproterone acetate.

Dabigatran etexilate [1], itraconazol ---> SmPC of [1] of EMA

Dabigatran is a substrate for the efflux transporter P-gp. Concomitant administration of strong P-gp inhibitors is expected to result in increased dabigatran plasma concentrations. The coadministration with itraconazol is contraindicated

Dabigatran [1], itraconazol ---> SmPC of [1] of EMA

Dabrafenib [1], itraconazol ---> SmPC of [1] of EMA

Dabrafenib is a substrate for the metabolising enzymes CYP3A4. Medicines that are strong inhibitors of CYP3A4 are therefore likely to increase dabrafenib concentrations. Use caution if strong inhibitors are coadministered with dabrafenib.

Daclatasvir [1], itraconazol ---> SmPC of [1] of EMA

Strong inhibitors of CYP3A4 may increase the plasma levels of daclatasvir. Dose adjustment of daclatasvir is recommended when coadministered with strong inhibitors of CYP3A4

Dalbavancin [1], itraconazol ---> SmPC of [1] of EMA

It is not known if dalbavancin is a substrate for hepatic uptake and efflux transporters. Co-administration with inhibitors of these transporters may increase the exposure to dalbavancin.

Dapoxetine [1], itraconazol ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of dapoxetine. Concomitant use of dapoxetine and potent CYP3A4 inhibitors is contraindicated

Darifenacin [1], itraconazol ---> SmPC of [1] of EMA

Concomitant treatment of darifenacin with potent CYP3A4 inhibitors is contraindicated

Darunavir/cobicistat [1], itraconazol ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], itraconazol ---> SmPC of [1] of EMA

Darunavir/ritonavir, itraconazol ---> SmPC of [darunavir] of EMA

Dasabuvir with ombitasvir/paritaprevir/ritonavir, itraconazol ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

Dasatinib [1], itraconazol ---> SmPC of [1] of EMA

In vitro studies indicate that dasatinib is a CYP3A4 substrate. Concomitant use of dasatinib and medicinal products which potently inhibit CYP3A4 may increase exposure to dasatinib. Systemic administration of a potent CYP3A4 inhibitor is not recommended.

Deflazacort, itraconazol

The strong CYP3A4 inhibition may increase the plasma concentrations of glucocorticoid

Dexamethasone, itraconazol

The co-administration may increase the plasma levels of dexamethasone. The dosage should be reduced if necessary

Dextromethorphan/quinidine [1], itraconazol ---> SmPC of [1] of EMA

Diazepam [1], itraconazol ---> SmPC of [1] of eMC

The CYP3A4 inhibition may increase the plasma levels of diazepam.

Didanosine, itraconazol

Itraconazol should be administered 2 hours before didanosine

Digoxin, itraconazol [2] ---> SmPC of [2] of eMC

Itraconazole may increase the plasma concentrations of digoxin. Use with caution

Dihydroergotamine, itraconazol [2] ---> SmPC of [2] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of dihydroergotamine. The co-administration is contraindicated

Disopyramide, itraconazol [2] ---> SmPC of [2] of eMC

Itraconazole may increase the plasma concentrations of disopyramide. Coadministration is contraindicated

Docetaxel [1], itraconazol ---> SmPC of [1] of EMA

In case of combination of docetaxel with CYP3A4 inhibitors, the occurrence of docetaxel adverse reactions may increase, as a result of reduced metabolism

Dofetilide, itraconazol [2] ---> SmPC of [2] of eMC

The co-administration of itraconazole with CYP3A4 metabolised substrates that can prolong the QT-interval is contraindicated

Dolutegravir [1], itraconazol ---> SmPC of [1] of EMA

The inhibition of CYP3A4 may increase plasma levels of dolutegravir. No dose adjustment is necessary. Based on data from other CYP3A4 inhibitors, a marked increase is not expected.

Dolutegravir/rilpivirine [1], itraconazol ---> SmPC of [1] of EMA

May cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). No dose adjustment is required.

Donepezil [1], itraconazol ---> SmPC of [1] of eMC

The strong CYP3A4-inhibition may increase the plasma levels of donepezil

Dronedarone [1], itraconazol ---> SmPC of [1] of EMA

Concomitant use of dronedarone with strong CYP3A4 inhibitors increases dronedarone exposure. The combination of dronedarone with strong CYP3A4 inhibitors is contraindicated

Droperidol [1], itraconazol ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Drugs metabolised by CYP3A4, itraconazol [2] ---> SmPC of [2] of eMC

Itraconazole and its major metabolite, hydroxy-itraconazole, can inhibit the metabolism of active ingredients metabolised by CYP3A4, which may result in increased plasma concentrations

Drugs primarily metabolised by CYP3A4, itraconazol [2] ---> SmPC of [2] of eMC

Itraconazole and its major metabolite, hydroxy-itraconazole, can inhibit the metabolism of active ingredients metabolised by CYP3A4, which may result in increased plasma concentrations

Dutasteride [1], itraconazol ---> SmPC of [1] of eMC

Long-term combination of dutasteride with drugs that are potent inhibitors of the enzyme CYP3A4 may increase serum concentrations of dutasteride.

Ebastine, itraconazol

The co-administration with CYP3A4 inhibitors may increase the plasma levels of ebastine and should be done with caution

Efavirenz [1], itraconazol ---> SmPC of [1] of EMA

The CYP3A4 induction decreases the plasma concentrations of itraconazol. Concomitant use should be avoided

Efavirenz/emtricitabine/tenofovir disoproxil [1], itraconazol ---> SmPC of [1] of EMA

The CYP3A4 induction decreases the plasma concentrations of itraconazol. Since no dose recommendation can be made for itraconazole when used with Atripla, an alternative antifungal treatment should be considered.

Eletriptan [1], itraconazol ---> SmPC of [1] of eMC

In clinical studies with potent inhibitors of CYP3A4 significant increases in eletriptan Cmax and AUC were observed. Eletriptan should not be used together with potent CYP3A4 inhibitors

Eliglustat [1], itraconazol ---> SmPC of [1] of EMA

Increased eliglustat exposition would be expected for strong inhibitors of CYP3A. Caution should be used with strong CYP3A inhibitors in intermediate and extensive metabolisers.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], itraconazol ---> SmPC of [1] of EMA

Concentrations of itraconazole, fluconazole and posaconazole may be increased when co-administered with cobicistat.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], itraconazol ---> SmPC of [1] of EMA

Concentrations of itraconazole may be increased when co-administered with cobicistat.

Emtricitabine/rilpivirine/tenofovir alafenamide [1], itraconazol ---> SmPC of [1] of EMA

Co-administration of this antifungal agent is expected to increase plasma concentrations of rilpivirine (inhibition of CYP3A) and tenofovir alafenamide (inhibition of P-gp). Co-administration is not recommended.

Emtricitabine/rilpivirine/tenofovir disoproxil [1], itraconazol ---> SmPC of [1] of EMA

Concomitant use of Eviplera with azole antifungal agents may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). At a dose of 25 mg of rilpivirine, dose adjustment is required.

Emtricitabine/tenofovir alafenamide [1], itraconazol ---> SmPC of [1] of EMA

Co-administration of ketoconazole or itraconazole, which are potent P-gp inhibitors, is expected to increase plasma concentrations of tenofovir alafenamide.

Encorafenib [1], itraconazol ---> SmPC of [1] of EMA

Concomitant administration of encorafenib with strong CYP3A4 inhibitors should be avoided (due to increased encorafenib exposure and potential increase in toxicity, see section 5.2).

Enzalutamide [1], itraconazol ---> SmPC of [1] of EMA

CYP3A4 plays a minor role in the metabolism of enzalutamide. No dose adjustment is necessary when enzalutamide is co-administered with inhibitors of CYP3A4.

Enzyme inductors, itraconazol

The enzymatic induction may decrease the plasma concentrations of itraconazole.

Eplerenone [1], itraconazol ---> SmPC of [1] of eMC

Strong CYP3A4 inhibitors may increase the AUC of eplerenone. The concomitant use of eplerenone with strong CYP3A4 inhibitors is contra-indicated

Ergometrine, itraconazol [2] ---> SmPC of [2] of eMC

Itraconazole, strong CYP3A4 inhibitor, may increase the plasma concentrations of ergot derivate. The co-administration is contraindicated.

Ergonovine, itraconazol [2] ---> SmPC of [2] of eMC

Itraconazole, strong CYP3A4 inhibitor, may increase the plasma concentrations of ergot derivate. The co-administration is contraindicated.

Ergot derivatives, itraconazol [2] ---> SmPC of [2] of eMC

Itraconazole, strong CYP3A4 inhibitor, may increase the plasma concentrations of ergot derivate. The co-administration is contraindicated.

Ergotamine, itraconazol [2] ---> SmPC of [2] of eMC

Itraconazole, strong CYP3A4 inhibitor, may increase the plasma concentrations of ergot derivate. The co-administration is contraindicated.

Erlotinib [1], itraconazol ---> SmPC of [1] of EMA

Erlotinib is metabolised in the liver by the hepatic cytochromes in humans, primarily CYP3A4 and to a lesser extent by CYP1A2. Potent inhibitors of CYP3A4 activity decrease erlotinib metabolism and increase erlotinib plasma concentrations.

Erythromycin, itraconazol [2] ---> SmPC of [2] of eMC

Potent inhibitors of CYP3A4 may increase the bioavailability of itraconazole.

Esomeprazole [1], itraconazol ---> SmPC of [1] of EMA

Esomeprazole may decrease the absorption of itraconazole

Estrogens, itraconazol ---> SmPC of [conjugated oestrogens/bazedoxifene] of EMA

Inhibitors of CYP3A4 may increase plasma concentrations of oestrogens and may result in adverse reactions.

Ethinylestradiol/norgestimate [1], itraconazol ---> SmPC of [1] of eMC

Increase in plasma hormone levels associated with co-administered drug

Etravirine [1], itraconazol ---> SmPC of [1] of EMA

Possible increase of plasma concentrations of etravirine and decreased plasma concentrations of itraconazole. The co-administration can be used without dose adjustments.

Everolimus [1], itraconazol ---> SmPC of [1] of EMA

Large increase in everolimus concentration is expected. Concomitant treatment of everolimus and potent CYP3A4 inhibitors is not recommended.

Ezetimibe/atorvastatin [1], itraconazol ---> SmPC of [1] of eMC

Potent CYP3A4 inhibitors have been shown to lead to markedly increased concentrations of atorvastatin. Coadministration of potent CYP3A4 inhibitors should be avoided if possible.

Ezetimibe/simvastatine [1], itraconazol ---> SmPC of [1] of eMC

Potent inhibitors of cytochrome P450 3A4 with simvastatine increase the risk of myopathy and rhabdomyolysis. The co-administration of simvastatine with potent inhibitors of CYP3A4 is contraindicated

Famotidine, itraconazol

Decreased absorption of itraconazol. Itraconazole should be administered 2 hours before famotidine

Felodipine/metoprolol, itraconazol

It has been shown that inhibitors of cytochrome P450-3A4 system increase the plasma concentrations of felodipine. The concomitant use with strong CYP3A4 inhibitors should be avoided

Felodipine/ramipril [1], itraconazol ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition may increase the plasma levels of felodipine. The co-administration of felodipine with strong CYP3A4 inhibitors should be avoided

Fenofibrate/simvastatin [1], itraconazol ---> SmPC of [1] of EMA

Potent inhibitors of cytochrome P450 3A4 increase the risk of myopathy and rhabdomyolysis by increasing the concentration of HMG-CoA reductase inhibitory activity in plasma during simvastatin therapy. Concomitant use is contraindicated

Fentanyl [1], itraconazol ---> SmPC of [1] of EMA

The concomitant use of fentanyl with strong CYP3A4 inhibitors may result in increased fentanyl plasma concentrations, potentially causing serious adverse drug reactions including fatal respiratory depression.

Fesoterodine [1], itraconazol ---> SmPC of [1] of EMA

The maximum dose of fesoterodine should be restricted to 4 mg when used concomitantly with potent CYP3A4 inhibitors

Flunitrazepam, itraconazol

Substances that inhibit hepatic enzymes may enhance the effect of benzodiazepines. Interactions with strong CYP3A4 inhibitors cannot be excluded

Fluticasone, itraconazol

The co-administration may increase the plasma levels of fluticasone. The dosage should be reduced if necessary

Fluvastatin [1], itraconazol ---> SmPC of [1] of eMC

Concomitant administration of fluvastatin with the potent cytochrome P450 (CYP) 3A4 inhibitors itraconazole and erythromycin has minimal effects on the bioavailability of fluvastatin.

Foods, itraconazol [2] ---> SmPC of [2] of eMC

A maximum oral bioavailability is achieved if itraconazole is taken directly after a meal.

Fosamprenavir/ritonavir, itraconazol ---> SmPC of [fosamprenavir] of EMA

The CYP3A4 inhibition by fosamprenavir/ritonavir may increase the plasma concentrations of itraconazole

Fosaprepitant [1], itraconazol ---> SmPC of [1] of EMA

Concomitant administration of fosaprepitant with active substances that inhibit CYP3A4 activity should be approached cautiously as the combination is expected to result in increased plasma concentrations of aprepitant

Fosphenytoin [1], itraconazol ---> SmPC of [1] of eMC

CYP2C9 inhibition may increase plasma phenytoin concentrations

Gastric pH increasing medication, itraconazol [2] ---> SmPC of [2] of eMC

Absorption of itraconazole is impaired when gastric acidity is reduced. It is advisable to administer itraconazole with an acidic beverage (such as non-diet cola)

Gefitinib [1], itraconazol ---> SmPC of [1] of EMA

Concomitant administration with potent inhibitors of CYP3A4 activity may increase gefitinib plasma concentrations. The increase may be clinically relevant since adverse reactions are related to dose and exposure.

Glecaprevir/pibrentasvir [1], itraconazol ---> SmPC of [1] of EMA

Co-administration of Maviret with medicinal products that inhibit P-gp and BCRP may slow elimination of glecaprevir and pibrentasvir and thereby increase plasma exposure of the antivirals.

Guanfacin [1], itraconazol ---> SmPC of [1] of EMA

H2 antagonists, itraconazol [2] ---> SmPC of [2] of eMC

Acid secretion suppressors impair the absorption of itraconazole. It is recommended that itraconazole be administered with an acidic beverage (such as non-diet cola)

Halofantrine, itraconazol

Itraconazole may increase the plasma concentrations of halofantrine. Coadministration is contraindicated

Haloperidol [1], itraconazol ---> SmPC of [1] of eMC

Inhibition of the CYP3A4 by another drug may result in increased haloperidol concentrations and an increased risk of adverse events, including QT-prolongation.

Hydrocortisone [1], itraconazol ---> SmPC of [1] of EMA

Potent CYP 3A4 inhibitors can inhibit the metabolism of hydrocortisone, and thus increase blood levels.

Hydroquinidine, itraconazol

Concomitant use may cause hearing impairment and chinchonism due to itraconazol decreases the hepatic metabolism of hydroquinidine

Ibrutinib [1], itraconazol ---> SmPC of [1] of EMA

Idelalisib [1], itraconazol ---> SmPC of [1] of EMA

The co-administration of idelalisib with itraconazol may increase the serum concentrations of itraconazol. Clinical monitoring is recommended.

Imatinib [1], itraconazol ---> SmPC of [1] of EMA

Indinavir [1], itraconazol ---> SmPC of [1] of EMA

Dose reduction of indinavir is recommended with administering itraconazole concurrently.

Indinavir/ritonavir, itraconazol ---> SmPC of [indinavir] of EMA

Indinavir/ritonavir, CYP3A4 inhibitors, may increase the plasma concentrations of itraconazole. Careful monitoring is recommended

Irinotecan [1], itraconazol ---> SmPC of [1] of EMA

Co-administration of ONIVYDE with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE.

Isoniazid, itraconazol [2] ---> SmPC of [2] of eMC

Isradipine [1], itraconazol ---> SmPC of [1] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

Itraconazol [1], levacetylmethadol ---> SmPC of [1] of eMC

The co-administration of itraconazole with CYP3A4 metabolised substrates that can prolong the QT-interval is contraindicated

Itraconazol [1], metabolized by CYP3A4 and prolong QT ---> SmPC of [1] of eMC

The co-administration of itraconazole with CYP3A4 metabolised substrates that can prolong the QT-interval is contraindicated

Itraconazol [1], methylergometrine ---> SmPC of [1] of eMC

Itraconazole, strong CYP3A4 inhibitor, may increase the plasma concentrations of ergot derivate. The co-administration is contraindicated.

Itraconazol [1], methylergonovine ---> SmPC of [1] of eMC

Itraconazole, strong CYP3A4 inhibitor, may increase the plasma concentrations of ergot derivate. The co-administration is contraindicated.

Itraconazol [1], methylprednisolone ---> SmPC of [1] of eMC

Itraconazole may increase the plasma concentrations of methylprednisolone. Use with caution

Itraconazol [1], mizolastine ---> SmPC of [1] of eMC

The co-administration of itraconazole with CYP3A4 metabolised substrates that can prolong the QT-interval is contraindicated

Itraconazol [1], P-glycoprotein substrates ---> SmPC of [1] of eMC

Itraconazole can inhibit the transport of active ingredients by P-glycoprotein, which may result in increased plasma concentrations

Itraconazol [1], phenobarbital ---> SmPC of [1] of eMC

Itraconazol [1], phenytoin ---> SmPC of [1] of eMC

Itraconazol [1], pimozide ---> SmPC of [1] of eMC

The co-administration of itraconazole with CYP3A4 metabolised substrates that can prolong the QT-interval is contraindicated

Itraconazol [1], pregnancy ---> SmPC of [1] of eMC

Itraconazole must not be used during pregnancy except for life-threatening cases where the potential benefit to the mother outweighs the potential harm to the fetus

Itraconazol [1], proton pump inhibitors ---> SmPC of [1] of eMC

Acid secretion suppressors impair the absorption of itraconazole. It is recommended that itraconazole be administered with an acidic beverage (such as non-diet cola)

Itraconazol [1], quinidine ---> SmPC of [1] of eMC

The co-administration of itraconazole with CYP3A4 metabolised substrates that can prolong the QT-interval is contraindicated

Itraconazol [1], rifabutin ---> SmPC of [1] of eMC

Itraconazol [1], rifampicin ---> SmPC of [1] of eMC

Itraconazol [1], sertindole ---> SmPC of [1] of eMC

The co-administration of itraconazole with CYP3A4 metabolised substrates that can prolong the QT-interval is contraindicated

Itraconazol [1], St. John's wort ---> SmPC of [1] of eMC

Itraconazol [1], strong CYP3A4 inductors ---> SmPC of [1] of eMC

Itraconazol [1], strong CYP3A4 inhibitors ---> SmPC of [1] of eMC

Potent inhibitors of CYP3A4 may increase the bioavailability of itraconazole.

Itraconazol [1], terfenadine ---> SmPC of [1] of eMC

The co-administration of itraconazole with CYP3A4 metabolised substrates that can prolong the QT-interval is contraindicated

Itraconazol [1], triamcinolone ---> SmPC of [1] of eMC

Corticosteroid clearance may be decreased, resulting in increased effects.

Itraconazol [1], triazolam ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition increases the plasma concentrations of triazolam. The co-administration with oral triazolam is contraindicated

Itraconazol [1], verapamil ---> SmPC of [1] of eMC

Calcium channel blockers can have negative inotropic effects which may be additive to those of itraconazole. In addition, itraconazole can inhibit the metabolism of calcium channel blockers.

Itraconazol [1], vinca alkaloids ---> SmPC of [1] of eMC

Itraconazole may increase the plasma concentrations of vinca alkaloids

Itraconazol, ivabradine [2] ---> SmPC of [2] of EMA

The concomitant use of ivabradine and potent CYP3A4 inhibitors increases plasma concentrations of ivabradine (may be associated with the risk of excessive bradycardia). The concomitant use of ivabradine with these medicinal products is contraindicated

Itraconazol, ivacaftor [2] ---> SmPC of [2] of EMA

Ivacaftor is a sensitive CYP3A substrate. A reduction of the Kalydeco dose to 150 mg twice a week is recommended for co-administration with strong CYP3A inhibitors

Itraconazol, lacidipine [2] ---> SmPC of [2] of eMC

Lacidipine is known to be metabolised by cytochrome CYP3A4 and, therefore, significant inhibitors and inducers of CYP3A4 administered concurrently may interact with the metabolism and elimination of lacidipine.

Itraconazol, lacosamide [2] ---> SmPC of [2] of EMA

Caution is recommended in concomitant treatment of lacosamide with strong inhibitors of CYP3A4, which may lead to increased systemic exposure of lacosamide.

Itraconazol, lansoprazole [2] ---> SmPC of [2] of eMC

Administration of lansoprazole may result in subtherapeutic concentrations of itraconazole and the combination should be avoided.

Itraconazol, lapatinib [2] ---> SmPC of [2] of EMA

Lapatinib is predominantly metabolised by CYP3A. The strong CYP3A4 inhibition increases the exposition to lapatinib. Co-administration of lapatinib with strong inhibitors of CYP3A4 should be avoided.

Itraconazol, lercanidipine [2] ---> SmPC of [2] of eMC

The strong CYP3A4 inhibition increases plasma concentrations of lercanidipine. Co-administration of lercanidipine with inhibitors of CYP3A4 should be avoided

Itraconazol, letermovir [2] ---> SmPC of [2] of EMA

Caution is advised if P-gp/BCRP inhibitors are added to letermovir combined with cyclosporine.

Itraconazol, lomitapide [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase lomitapide AUC. The combination of lomitapide with strong CYP3A4 inhibitors is contra-indicated

Itraconazol, loperamide [2] ---> SmPC of [2] of eMC

The concomitant administration of loperamide (4 mg single dose) and itraconazole, an inhibitor of CYP3A4 and P-glycoprotein, resulted in a 3 to 4-fold increase in loperamide plasma concentrations.

Itraconazol, lopinavir/ritonavir [2] ---> SmPC of [2] of EMA

Lopinavir/ritonavir, CYP3A4 inhibitors, may increase the plasma levels of itraconazole. High doses of itraconazole are not recommended.

Itraconazol, lovastatine [2] ---> SmPC of [2] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of lovastatin. The co-administration is contraindicated

Itraconazol, lumacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Co-administration of lumacaftor/ivacaftor with itraconazole, a strong CYP3A inhibitor, did not impact the exposure of lumacaftor, but increased ivacaftor exposure by 4.3-fold.

Itraconazol, lurasidone [2] ---> SmPC of [2] of EMA

Lurasidone and its active metabolite ID-14283 are primarily metabolised by CYP3A4. Lurasidone is contraindicated with strong CYP3A4 inhibitors

Itraconazol, macitentan [2] ---> SmPC of [2] of EMA

Caution should be exercised when macitentan (by CYP3A4 metabolized) is administered concomitantly with strong CYP3A4 inhibitors

Itraconazol, manidipine

Manidipine should not be administered with CYP3A4 inhibitors

Itraconazol, maraviroc [2] ---> SmPC of [2] of EMA

Itraconazole is a potent CYP3A4 inhibitor and would be expected to increase the exposure of maraviroc.

Itraconazol, methadone

The strong CYP3A4 inhibition may increase the plasma concentrations of methadone

Itraconazol, metildigoxin

Increased plasma levels of metildigoxin

Itraconazol, micafungin [2] ---> SmPC of [2] of EMA

Patients receiving itraconazol in combination with micafungin should be monitored for itraconazol toxicity and the itraconazol dosage should be reduced if necessary

Itraconazol, miconazole

Oral miconazole is contraindicated with medicinal products that are metabolised by CYP3A4 and may prolong also the QT interval

Itraconazol, midazolam [2] ---> SmPC of [2] of EMA

Fluconazole and itraconazole both increased the plasma concentrations of intravenous midazolam by 2 to 3-fold associated with an increase in terminal half-life by 2.4-fold for itraconazole and 1.5-fold for fluconazole.

Itraconazol, midostaurin [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors may increase midostaurin blood concentrations.

Itraconazol, mifepristone [2] ---> SmPC of [2] of eMC

On the basis of this drug's metabolism by CYP3A4, it is possible that strong CYP3A4 inhibitors may inhibit its metabolism (increasing serum levels of mifepristone).

Itraconazol, mirabegron [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the exposition of mirabegron. No dose-adjustment is needed when mirabegron is combined with inhibitors of CYP3A and/or P-gp.

Itraconazol, mometasone [2] ---> SmPC of [2] of eMC

There may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors are co-administered

Itraconazol, naloxegol [2] ---> SmPC of [2] of EMA

Concomitant use of naloxegol with CYP3A4 inhibitors increases naloxegol exposition. Concomitant use of naloxegol with strong CYP3A4 inhibitors is contraindicated

Itraconazol, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

Like with other drugs that decrease the intragastric acidity, the absorption of itraconazole can decrease

Itraconazol, neratinib [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4/Pgp inhibitors should be avoided.

Itraconazol, nevirapine [2] ---> SmPC of [2] of EMA

A dose increase for itraconazole should be considered when these two agents are administered concomitantly.

Itraconazol, nifedipine [2] ---> SmPC of [2] of eMC

Nifedipine is metabolised via the cytochrome P450 3A4 system. Therefore, there are theoretical interactions with drugs known to inhibit this enzyme system.

Itraconazol, nilotinib [2] ---> SmPC of [2] of EMA

Significant prolongation of the QT interval may occur when nilotinib is inappropriately taken with strong CYP3A4 inhibitors. Prolongation of the QT interval may expose patients to the risk of fatal outcome.

Itraconazol, niraparib [2] ---> SmPC of [2] of EMA

No dose adjustment for Zejula is required when administered concomitantly with medicinal products known to inhibit (e.g. itraconazole, ritonavir, and clarithromycin) or induce CYP enzymes (e.g. rifampin, carbamazepine, and phenytoin)

Itraconazol, nisoldipine

Concomitant use of itraconazol and nisoldipine is contraindicated

Itraconazol, olaparib [2] ---> SmPC of [2] of EMA

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

Itraconazol, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

CYP3A4/P-gp inhibition by itraconazol and paritaprevir/ ritonavir/ ombitasvir. Concomitant use is contraindicated

Itraconazol, omeprazole [2] ---> SmPC of [2] of eMC

Acid secretion suppressors impair the absorption of itraconazole. It is recommended that itraconazole be administered with an acidic beverage (such as non-diet cola)

Itraconazol, osimertinib [2] ---> SmPC of [2] of EMA

Itraconazole (a strong CYP3A4 inhibitor) had no clinically significant effect on the exposure of osimertinib. Therefore, CYP3A4 inhibitors are not likely to affect the exposure of osimertinib.

Itraconazol, palbociclib [2] ---> SmPC of [2] of EMA

Strong inhibitors of CYP3A4 may lead to increased toxicity. Concomitant use of strong CYP3A inhibitors during treatment with palbociclib should be avoided.

Itraconazol, panobinostat [2] ---> SmPC of [2] of EMA

In patients who take concomitant medicinal products which are strong CYP3A and/or Pgp inhibitors, the dose of panobinostat should be reduced

Itraconazol, pazopanib [2] ---> SmPC of [2] of EMA

Concomitant treatment with strong inhibitors of CYP3A4 should be avoided due to risk of increased exposure to pazopanib

Itraconazol, pitavastatin

Itraconazol and Saint John's wort, strong inhibitors of CYP3A4, had no clinically meaningful effect on the plasma concentrations of pitavastatin.

Itraconazol, ponatinib [2] ---> SmPC of [2] of EMA

Itraconazol, prednisolone

Medicinal products that inhibit the hepatic metabolism of prednisolone may enhance the corticoid effect

Itraconazol, prednisone

The strong CYP3A4 inhibition may increase the plasma concentrations of prednisone

Itraconazol, protease inhibitors

The co-administration may increase the plasma levels of protease inhibitor. The dosage should be reduced if necessary

Itraconazol, rabeprazole [2] ---> SmPC of [2] of eMC

Acid secretion suppressors impair the absorption of itraconazole. It is recommended that itraconazole be administered with an acidic beverage (such as non-diet cola)

Itraconazol, ranolazine [2] ---> SmPC of [2] of EMA

Ranolazine is a substrate of cytochrome CYP3A4. Inhibitors of CYP3A4 increase plasma concentrations of ranolazine. Combining ranolazine with potent CYP3A4 inhibitors is contraindicated

Itraconazol, regorafenib [2] ---> SmPC of [2] of EMA

It is recommended to avoid concomitant use of strong inhibitors of CYP3A4 activity, as their influence on the steady-state exposure of regorafenib and its metabolites has not been studied.

Itraconazol, repaglinide [2] ---> SmPC of [2] of EMA

Itraconazole may enhance and/or prolong the hypoglycaemic effect of repaglinide.

Itraconazol, ribociclib [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors should be avoided and an alternative concomitant medicinal product with less potential to inhibit CYP3A4 inhibition should be considered.

Itraconazol, rilpivirine [2] ---> SmPC of [2] of EMA

Not studied. Concomitant use of rilpivirine with azole antifungal agents (inhibition of CYP3A enzymes) may cause an increase in the plasma concentrations of rilpivirine. No dose adjustment is required.

Itraconazol, rimonabant [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the exposition of rimonabant. Caution is advised during concomitant use of rimonabant and potent CYP3A4 inhibitors

Itraconazol, riociguat [2] ---> SmPC of [2] of EMA

Concomitant use of riociguat with strong multi-pathway CYP and P-gp/BCRP inhibitors is not recommended

Itraconazol, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent inhibits CYP3A4 and as a result is expected to increase the plasma concentrations of itraconazole.

Itraconazol, rivaroxaban [2] ---> SmPC of [2] of EMA

Co-administration of rivaroxaban with strong inhibitors of both CYP3A4 and P-gp may lead to an increased bleeding risk. The use of rivaroxaban with inhibitors of both CYP3A4 and P-gp is not recommended

Itraconazol, rupatadine [2] ---> SmPC of [2] of eMC

The concomitant administration of rupatadine with inhibitors of the isozyme CYP3A4 increases the systemic exposure to rupatadine. Rupatadine should be used with caution when it is administered concomitantly with inhibitors of CYP3A4.

Itraconazol, ruxolitinib [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase ruxolitinib exposition. When co-administering with strong CYP3A4 inhibitors the unit dose of ruxolitinib should be reduced

Itraconazol, salmeterol [2] ---> SmPC of [2] of eMC

The co-administration with strong CYP3A4 inhibitors with salmeterol may significant increase the plasma salmeterol exposure, what may cause a QTc interval prolongation. The co-administration should be avoided

Itraconazol, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

Co-treatment with potent CYP3A inhibitors, such as itraconazole, and moderate CYP3A inhibitors, such as erythromycin, is also expected to increase the systemic fluticasone propionate exposure and the risk of systemic undesirable effects.

Itraconazol, saquinavir [2] ---> SmPC of [2] of EMA

Itraconazole is a moderately potent inhibitor of CYP3A4. An interaction is possible. Monitoring for saquinavir toxicity recommended.

Itraconazol, sibutramine [2] ---> SmPC of [2] of eMC

Caution should be exercised on concomitant administration of sibutramine with drugs which affect CYP3A4 enzyme activity (increased plasma concentrations (AUC) of sibutramine active metabolites)

Itraconazol, sildenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis of clinical trial data indicated a reduction in sildenafil clearance when co-administered with CYP3A4 inhibitors

Itraconazol, silodosin [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the plasma levels of silodosin. Concomitant use of silodosin with potent CYP3A4 inhibitors is not recommended

Itraconazol, simeprevir [2] ---> SmPC of [2] of EMA

Co-administration of simeprevir with moderate or strong inhibitors of CYP3A4 may significantly increase the plasma exposure of simeprevir. Co-administration of simeprevir with these inhibitors is not recommended.

Itraconazol, simvastatine ---> SmPC of [fenofibrate/simvastatin] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of simvastatine and the risk of myopathy and rhabdomyolysis. The co-administration is contraindicated

Itraconazol, sirolimus [2] ---> SmPC of [2] of EMA

Inhibitors of CYP3A4 may decrease the metabolism of sirolimus and increase sirolimus blood levels.

Itraconazol, sitagliptin [2] ---> SmPC of [2] of EMA

It is possible that potent CYP3A4 inhibitors (i.e. ketoconazole, itraconazole, ritonavir, clarithromycin) could alter the pharmacokinetics of sitagliptin in patients with severe renal impairment or ESRD.

Itraconazol, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

It is possible that potent CYP3A4 inhibitors (i.e., ketoconazole, itraconazole, ritonavir, clarithromycin) could alter the pharmacokinetics of sitagliptin in patients with severe renal impairment or ESRD.

Itraconazol, solifenacin [2] ---> SmPC of [2] of eMC

The CYP3A4 inhibition may increase the plasma levels of solifenacin. Simultaneous treatment of solifenacin and a potent CYP3A4 inhibitor is contra-indicated in patients with severe renal impairment or moderate hepatic impairment

Itraconazol, sonidegib [2] ---> SmPC of [2] of EMA

Sonidegib undergoes metabolism primarily by CYP3A4, and concomitant administration of strong inhibitors of CYP3A4 can increase sonidegib concentrations significantly. The sonidegib dose should be reduced to 200 mg every other day

Itraconazol, sufentanil [2] ---> SmPC of [2] of EMA

Sufentanil is primarily metabolised by the CYP3A4. Ketoconazole, a potent CYP3A4 inhibitor, can significantly increase the systemic exposure to sublingual sufentanil. Similar effects with other potent CYP3A4 inhibitors cannot be excluded.

Itraconazol, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inhibitors may increase sunitinib concentrations. Combination with CYP3A4 inhibitors should therefore be avoided

Itraconazol, tacrolimus [2] ---> SmPC of [2] of EMA

Concomitant use of substances known to inhibit CYP3A4 may affect the metabolism of tacrolimus and thereby increase tacrolimus blood levels.

Itraconazol, tadalafil [2] ---> SmPC of [2] of EMA

Tadalafil is principally metabolised by CYP3A4. CYP3A4 inhibitors should be co-administered with caution as they would be expected to increase plasma concentrations of tadalafil

Itraconazol, telaprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 inhibition increases the plasma levels of itraconazol and telaprevir.

Itraconazol, telithromycin [2] ---> SmPC of [2] of EMA

Itraconazol, CYP3A4 inhibitor, may increase the telithromycin plasma levels. No dosage adjustment necessary (contraindicated with severe renal/or hepatic dysfunction)

Itraconazol, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

It cannot be ruled out that strong inhibitors of CYP3A4 may increase the plasma concentrations of amlodipine. Amlodipine should be used with caution together with CYP3A4 inhibitors.

Itraconazol, temsirolimus [2] ---> SmPC of [2] of EMA

Itraconazol, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration of Vemlidy with strong inhibitors of P-gp (e.g. itraconazole and ketoconazole) may increase tenofovir alafenamide plasma concentrations. Co-administration is not recommended.

Itraconazol, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

When co-administered with strong CYP3A inhibitors, the dose should be adjusted to one Symkevi tablet twice a week, taken approximately 3 to 4 days apart.

Itraconazol, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Based on theoretical considerations tipranavir, is expected to increase plasma concentrations of the active principles

Itraconazol, tolterodine [2] ---> SmPC of [2] of eMC

Concomitant systemic medication with potent CYP3A4 inhibitors is not recommended due to increased serum concentrations of tolterodine in poor CYP2D6 metabolisers with (subsequent) risk of overdosage

Itraconazol, toremifene [2] ---> SmPC of [2] of EMA

Theoretically the metabolism of toremifene is inhibited by drugs known to inhibit the CYP3A enzyme system which is reported to be responsible for its main metabolic pathways. Concomitant use should be carefully considered.

Itraconazol, trametinib [2] ---> SmPC of [2] of EMA

As it cannot be excluded that strong inhibition of hepatic P-gp may result in increased levels of trametinib, caution is advised when coadministering trametinib with medicinal products that are strong inhibitors of P-gp

Itraconazol, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Itraconazol, trazodone [2] ---> SmPC of [2] of eMC

Itraconazol, trimetrexate

The co-administration may increase the plasma levels of trimetrexate. The dosage should be reduced if necessary

Itraconazol, trofosfamide

The inhibition of CYP3A4 may increase the formation of a trofosfamide metabolite which is related with nephrotoxicity and CNS toxicity

Itraconazol, umeclidinium/vilanterol [2] ---> SmPC of [2] of EMA

Concomitant administration of strong CYP3A4 inhibitors may inhibit the metabolism of, and increase the systemic exposure to, vilanterol. Care is advised

Itraconazol, vandetanib [2] ---> SmPC of [2] of EMA

In healthy subjects, no clinically significant interaction was shown between vandetanib (a single dose of 300 mg) and the potent CYP3A4 inhibitor, itraconazole

Itraconazol, vardenafil [2] ---> SmPC of [2] of EMA

Concomitant use of vardenafil with potent CYP3A4 inhibitors such as itraconazole and ketoconazole (oral form) should be avoided as very high plasma concentrations of vardenafil are reached if the medicinal products are combined

Itraconazol, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

Itraconazol, venetoclax [2] ---> SmPC of [2] of EMA

Concomitant use of venetoclax with strong CYP3A inhibitors at initiation and during the dose-titration phase is contraindicated due to increased risk for TLS

Itraconazol, venlafaxine [2] ---> SmPC of [2] of eMC

Itraconazol, vilanterol ---> SmPC of [umeclidinium/vilanterol] of EMA

Concomitant administration of strong CYP3A4 inhibitors may inhibit the metabolism of, and increase the systemic exposure to, vilanterol. Care is advised

Itraconazol, vincristine [2] ---> SmPC of [2] of eMC

Co-administration of vincristine and itraconazole has been reported to cause an earlier onset and/or an increased severity of neuromuscular side-effects. It is presumed to be related to inhibition of the metabolism of vincristine.

Itraconazol, vinflunine [2] ---> SmPC of [2] of EMA

The concomitant use of vinflunine and potent CYP3A4 inhibitors should be avoided since they may increase vinflunine and DVFL concentrations

Itraconazol, vinorelbine [2] ---> SmPC of [2] of eMC

The strong CYP3A4 and P-glycoprotein inhibition may increase the plasma levels of the vinca alkaloid and increases its neurotoxicity. The combination is not recommended

Itraconazol, vismodegib [2] ---> SmPC of [2] of EMA

Itraconazole (a strong CYP3A4 inhibitor) 200 mg daily did not influence vismodegib AUC0-24 h after 7 days co-treatment in healthy volunteers.

Itraconazol, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Itraconazol, vortioxetine [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the AUC of vortioxetine. No dosage adjustment necessary. It is caution recommended with CYP2D6 poor metabolisers

Itraconazol, warfarin [2] ---> SmPC of [2] of eMC

Itraconazole may increase the plasma concentrations of warfarin

Itraconazol, zafirlukast [2] ---> SmPC of [2] of eMC

Co-administration with itraconazole, a strong CYP3A4 inhibitor, caused no change in plasma levels of zafirlukast.

Itraconazol, ziprasidone

The co-administration of ziprasidone with P glycoprotein inhibitors may increase the plasma concentrations of ziprasidone

Itraconazol, zolpidem [2] ---> SmPC of [2] of eMC

When zolpidem tartrate was administered with itraconazole (a CYP3A4 inhibitor) its pharmacokinetics and pharmacodynamics were not significantly modified.

Itraconazol, zopiclone [2] ---> SmPC of [2] of eMC

Since zopiclone is metabolised by the cytochrome P450 (CYP) 3A4, plasma levels of zopiclone may be increased when co-administered with CYP3A4 inhibitors

CONTRAINDICATIONS of Itraconazol

- Itraconazole is contraindicated in patients with known hypersensitivity to the active substance or to any of the excipients

- Co-administration of a number of CYP3A4 substrates is contraindicated with itraconazole. Increased plasma concentrations of these active ingredients, caused by coadministration with itraconazole, may increase or prolong both therapeutic and adverse effects to such an extent that a potentially serious situation may occur. For example, increased plasma concentrations of some of these active ingredients can lead to QT prolongation and ventricular tachyarrhythmias including occurrences of torsade de pointes, a potentially fatal arrhythmia.

- Itraconazole should not be administered to patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF except for the treatment of life-threatening or other serious infections

- Itraconazole must not be used during pregnancy, except for life-threatening cases

- Women of childbearing potential taking itraconazole should use contraceptive precautions. Effective contraception should be continued until the menstrual period following the end of itraconazole therapy.

http://www.medicines.org.uk/emc/

Ivabradine (Corlentor)

Ability to drive, ivabradine [2] ---> SmPC of [2] of EMA

In post-marketing experience, cases of impaired driving ability due to visual symptoms have been reported. Ivabradine may cause transient luminous phenomena consisting mainly of phosphenes

ACE inhibitors, ivabradine [2] ---> SmPC of [2] of EMA

In pivotal phase III clinical trials the ACE inhibitors were routinely combined with ivabradine with no evidence of safety concerns

Acetylsalicylic acid, ivabradine [2] ---> SmPC of [2] of EMA

In pivotal phase III clinical trials aspirin and other anti-platelet medicinal products were routinely combined with ivabradine with no evidence of safety concerns

AIIRA, ivabradine [2] ---> SmPC of [2] of EMA

In pivotal phase III clinical trials the angiotensin II antagonists were routinely combined with ivabradine with no evidence of safety concerns

Aldosterone antagonists, ivabradine [2] ---> SmPC of [2] of EMA

In pivotal phase III clinical trials anti-aldosterone agents were routinely combined with ivabradine with no evidence of safety concerns

Amiodarone, ivabradine [2] ---> SmPC of [2] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Amlodipine, ivabradine [2] ---> SmPC of [2] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the dihydropyridine calcium channel blockers on pharmacokinetics and pharmacodynamics of ivabradine

Antihypertensives, ivabradine [2] ---> SmPC of [2] of EMA

Limited data are available in patients with mild to moderate hypotension, and ivabradine should therefore be used with caution in these patients. Ivabradine is contra-indicated in patients with severe hypotension (blood pressure < 90/50 mmHg)

Azole antifungals, ivabradine [2] ---> SmPC of [2] of EMA

Barbiturates, ivabradine [2] ---> SmPC of [2] of EMA

Ivabradine is metabolised by CYP3A4 only. CYP3A4 inducers may decrease ivabradine exposure and activity. The concomitant use of CYP3A4 inducing medicinal products may require an adjustment of the dose of ivabradine.

Bepridil, ivabradine [2] ---> SmPC of [2] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Betablockers, ivabradine [2] ---> SmPC of [2] of EMA

In pivotal phase III clinical trials betablockers were routinely combined with ivabradine with no evidence of safety concerns

Breast-feeding, ivabradine [2] ---> SmPC of [2] of EMA

Ivabradine is contra-indicated during breast-feeding. Women that need treatment with ivabradine should stop breast-feeding

Cisapride, ivabradine [2] ---> SmPC of [2] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Clarithromycin, ivabradine [2] ---> SmPC of [2] of EMA

CYP3A4 inductors, ivabradine [2] ---> SmPC of [2] of EMA

Digoxin, ivabradine [2] ---> SmPC of [2] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the digoxine on pharmacokinetics and pharmacodynamics of ivabradine

Dihydropyridines, ivabradine [2] ---> SmPC of [2] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the dihydropyridine calcium channel blockers on pharmacokinetics and pharmacodynamics of ivabradine

Diltiazem, ivabradine [2] ---> SmPC of [2] of EMA

Diltiazem or verapamil resulted in an increase in ivabradine exposure (2 to 3 fold increase in AUC) and an additional heart rate reduction of 5 bpm. The concomitant use of ivabradine with these medicinal products is contraindicated

Disopyramide, ivabradine [2] ---> SmPC of [2] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Diuretics, ivabradine [2] ---> SmPC of [2] of EMA

In pivotal phase III clinical trials diuretics were routinely combined with ivabradine with no evidence of safety concerns

Erythromycin, ivabradine [2] ---> SmPC of [2] of EMA

The concomitant use of ivabradine with intravenous erythromycin (QT prolongation) should be avoided and with oral erythromycin is contra-indicated (potent CYP3A4 inhibitor)

Fertility, ivabradine [2] ---> SmPC of [2] of EMA

Studies in rats have shown no effect on fertility in males and females (see section 5.3).

Fibrates, ivabradine [2] ---> SmPC of [2] of EMA

In pivotal phase III clinical trials fibrates were routinely combined with ivabradine with no evidence of safety concerns

Fingolimod [1], ivabradine ---> SmPC of [1] of EMA

Treatment with Gilenya should not be initiated in patients receiving beta blockers, or other substances which may decrease heart rate because of the potential additive effects on heart rate

Fluconazole, ivabradine [2] ---> SmPC of [2] of EMA

The concomitant use of ivabradine with moderate CYP3A4 inhibitors may be considered at the starting dose of 2.5 mg twice daily and if resting heart rate is above 70 bpm, with monitoring of heart rate.

Foods, ivabradine [2] ---> SmPC of [2] of EMA

The intake during meals is recommended

Grapefruit juice, ivabradine [2] ---> SmPC of [2] of EMA

Ivabradine exposure was increased by 2-fold following the co-administration with grapefruit juice. Therefore the intake of grapefruit juice should be avoided.

Halofantrine, ivabradine [2] ---> SmPC of [2] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Ibutilide, ivabradine [2] ---> SmPC of [2] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Itraconazol, ivabradine [2] ---> SmPC of [2] of EMA

Ivabradine [1], josamycin ---> SmPC of [1] of EMA

Ivabradine [1], ketoconazole ---> SmPC of [1] of EMA

Ivabradine [1], lacidipine ---> SmPC of [1] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the dihydropyridine calcium channel blockers on pharmacokinetics and pharmacodynamics of ivabradine

Ivabradine [1], lansoprazole ---> SmPC of [1] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the proton pump inhibitors on pharmacokinetics and pharmacodynamics of ivabradine

Ivabradine [1], loop diuretics ---> SmPC of [1] of EMA

Hypokalemia can increase the risk of arrhythmia. As ivabradine may cause bradycardia, the resulting combination of hypokalemia and bradycardia is a predisposing factor to the onset of severe arrhythmias, especially in patients with long QT syndrome

Ivabradine [1], macrolide antibiotics ---> SmPC of [1] of EMA

Ivabradine [1], mefloquine ---> SmPC of [1] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Ivabradine [1], moderate CYP3A4 inhibitors ---> SmPC of [1] of EMA

Ivabradine [1], nefazodone ---> SmPC of [1] of EMA

Ivabradine [1], nelfinavir ---> SmPC of [1] of EMA

Ivabradine [1], omeprazole ---> SmPC of [1] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the proton pump inhibitors on pharmacokinetics and pharmacodynamics of ivabradine

Ivabradine [1], oral antidiabetics ---> SmPC of [1] of EMA

In pivotal phase III clinical trials oral antidiabetics were routinely combined with ivabradine with no evidence of safety concerns

Ivabradine [1], organic nitrates ---> SmPC of [1] of EMA

In pivotal phase III clinical trials short and long acting nitrates were routinely combined with ivabradine with no evidence of safety concerns

Ivabradine [1], pentamidine ---> SmPC of [1] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Ivabradine [1], phenytoin ---> SmPC of [1] of EMA

Ivabradine [1], pimozide ---> SmPC of [1] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Ivabradine [1], platelet aggregation inhibitors ---> SmPC of [1] of EMA

In pivotal phase III clinical trials aspirin and other anti-platelet medicinal products were routinely combined with ivabradine with no evidence of safety concerns

Ivabradine [1], pregnancy ---> SmPC of [1] of EMA

Ivabradine is contra-indicated during pregnancy

Ivabradine [1], protease inhibitors ---> SmPC of [1] of EMA

Ivabradine [1], proton pump inhibitors ---> SmPC of [1] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the proton pump inhibitors on pharmacokinetics and pharmacodynamics of ivabradine

Ivabradine [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Ivabradine [1], quinidine ---> SmPC of [1] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Ivabradine [1], rifampicin ---> SmPC of [1] of EMA

Ivabradine [1], ritonavir ---> SmPC of [1] of EMA

Ivabradine [1], sertindole ---> SmPC of [1] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Ivabradine [1], sildenafil ---> SmPC of [1] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the sildenafil on pharmacokinetics and pharmacodynamics of ivabradine

Ivabradine [1], simvastatine ---> SmPC of [1] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the HMG CoA reductase inhibitors on pharmacokinetics and pharmacodynamics of ivabradine

Ivabradine [1], sotalol ---> SmPC of [1] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Ivabradine [1], St. John's wort ---> SmPC of [1] of EMA

The combination of ivabradine 10 mg twice daily with St John's Wort was shown to reduce ivabradine AUC by half. The intake of St John's Wort should be restricted during the treatment with ivabradine.

Ivabradine [1], statins ---> SmPC of [1] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the HMG CoA reductase inhibitors on pharmacokinetics and pharmacodynamics of ivabradine

Ivabradine [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Ivabradine [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Ivabradine [1], telithromycin ---> SmPC of [1] of EMA

Ivabradine [1], thiazides ---> SmPC of [1] of EMA

Ivabradine [1], verapamil ---> SmPC of [1] of EMA

Ivabradine [1], warfarin ---> SmPC of [1] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the warfarin on pharmacokinetics and pharmacodynamics of ivabradine

Ivabradine [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of child-bearing potential should use appropriate contraceptive measures during treatment (see section 4.3).

Ivabradine [1], ziprasidone ---> SmPC of [1] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Ivabradine, siponimod [2] ---> SmPC of [2] of EMA

Concomitant use of these substances during treatment initiation may be associated with severe bradycardia and heart block.

Ivabradine, voriconazole [2] ---> SmPC of [2] of EMA

The combination of voriconazole, CYP3A4 inhibitor, with drugs metabolized by CYP3A4 and may prolong the QTc interval is contraindicated and rare occurrences of torsades de pointes

CONTRAINDICATIONS of Ivabradine (Corlentor)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Resting heart rate below 70 beats per minute prior to treatment

- Cardiogenic shock

- Acute myocardial infarction

- Severe hypotension (< 90/50 mmHg)

- Severe hepatic insufficiency

- Sick sinus syndrome

- Sino-atrial block

- Unstable or acute heart failure

- Pacemaker dependent (heart rate imposed exclusively by the pacemaker)

- Unstable angina.

- AV-block of 3rd degree.

- Combination with strong cytochrome P450 3A4 inhibitors such as azole antifungals (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, erythromycin per os josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone (see sections 4.5 and 5.2)

- Combination with verapamil or diltiazem which are moderate CYP3A4 inhibitors with heart rate reducing properties (see section 4.5)

- Pregnancy, lactation and women of child-bearing potential not using appropriate contraceptive measures (see section 4.6)

https://www.ema.europa.eu/en/documents/product-information/corlentor-epar-product-information_en.pdf 11/12/2024

Other trade names: Ivabradine Accord, Ivabradine Anpharm, Ivabradine JensonR, Ivabradine Zentiva, Procoralan,

Ivacaftor (Kalydeco)

Ability to drive, ivacaftor [2] ---> SmPC of [2] of EMA

Ivacaftor may cause dizziness and, therefore, patients experiencing dizziness should be advised not to drive or use machines until symptoms abate.

Alprazolam, ivacaftor [2] ---> SmPC of [2] of EMA

No dose adjustment of CYP3A substrates, such as midazolam, alprazolam, diazepam or triazolam, is required when these are co-administered with ivacaftor.

BCRP inhibitors, ivacaftor [2] ---> SmPC of [2] of EMA

It is not expected to alter exposure of ivacaftor and M1-IVA, while any potential changes in M6-IVA exposures are not expected to be clinically relevant.

BCRP substrates, ivacaftor [2] ---> SmPC of [2] of EMA

Due to its high intrinsic permeability and low likelihood of being excreted intact, co-administration of BCRP inhibitors is not expected to alter exposure of ivacaftor

Breast-feeding, ivacaftor [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from ivacaftor therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Carbamazepine, ivacaftor [2] ---> SmPC of [2] of EMA

Co-administration of ivacaftor with strong CYP3A inducers, such as rifampicin, rifabutin, phenobarbital, carbamazepine, phenytoin and St. John's wort (Hypericum perforatum), is not recommended (see section 4.4).

Ciprofloxacin, ivacaftor [2] ---> SmPC of [2] of EMA

Co-administration of ciprofloxacin with ivacaftor did not affect exposure of ivacaftor. No dose adjustment is required when ivacaftor is co-administered with ciprofloxacin.

Clarithromycin, ivacaftor [2] ---> SmPC of [2] of EMA

A reduction of the ivacaftor dose is recommended for co-administration with strong CYP3A inhibitors, such as ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin and clarithromycin (see Table 2 in section 4.2 and section 4.4).

Cyclosporine, ivacaftor [2] ---> SmPC of [2] of EMA

When used concomitantly with digoxin or other substrates of P-gp with a narrow therapeutic index, such as ciclosporin, everolimus, sirolimus or tacrolimus, caution and appropriate monitoring should be used.

CYP3A4 inductors, ivacaftor [2] ---> SmPC of [2] of EMA

No dose adjustment is recommended when ivacaftor is used with moderate or weak CYP3A inducers.

Diazepam, ivacaftor [2] ---> SmPC of [2] of EMA

No dose adjustment of CYP3A substrates, such as midazolam, alprazolam, diazepam or triazolam, is required when these are co-administered with ivacaftor.

Digoxin, ivacaftor [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP2C9, ivacaftor [2] ---> SmPC of [2] of EMA

Administration of ivacaftor may increase systemic exposure of medicinal products that are sensitive substrates of CYP2C9, and/or P-gp, and/or CYP3A which may increase or prolong their therapeutic effect and adverse reactions.

Drugs primarily metabolised by CYP3A4, ivacaftor [2] ---> SmPC of [2] of EMA

Erythromycin, ivacaftor [2] ---> SmPC of [2] of EMA

A reduction of the ivacaftor dose is recommended for patients taking concomitant moderate CYP3A inhibitors, such as fluconazole, erythromycin, and verapamil (see Table 2 in section 4.2 and section 4.4).

Everolimus, ivacaftor [2] ---> SmPC of [2] of EMA

Fertility, ivacaftor [2] ---> SmPC of [2] of EMA

There are no data available on the effect of ivacaftor on fertility in humans. Ivacaftor had an effect on fertility in rats (see section 5.3).

Fluconazole, ivacaftor [2] ---> SmPC of [2] of EMA

Foods, ivacaftor [2] ---> SmPC of [2] of EMA

Ivacaftor tablets should be taken with fat-containing food. Food or drink containing grapefruit should be avoided during treatment (see section 4.5).

Glimepiride, ivacaftor [2] ---> SmPC of [2] of EMA

Other medicinal products for which exposure may be increased include glimepiride and glipizide; these medicinal products should be used with caution.

Glipizide, ivacaftor [2] ---> SmPC of [2] of EMA

Other medicinal products for which exposure may be increased include glimepiride and glipizide; these medicinal products should be used with caution.

Grapefruit juice, ivacaftor [2] ---> SmPC of [2] of EMA

Co-administration of ivacaftor with grapefruit juice, which contains one or more components that moderately inhibit CYP3A, may increase exposure to ivacaftor. Food or drink containing grapefruit should be avoided during treatment with ivacaftor

Grapefruit, ivacaftor [2] ---> SmPC of [2] of EMA

Co-administration of ivacaftor with grapefruit juice, which contains one or more components that moderately inhibit CYP3A, may increase exposure to ivacaftor. Food containing grapefruit or Seville oranges should be avoided during treatment with ivacaftor

Itraconazol, ivacaftor [2] ---> SmPC of [2] of EMA

Ivacaftor [1], ketoconazole ---> SmPC of [1] of EMA

Ivacaftor [1], midazolam ---> SmPC of [1] of EMA

No dose adjustment of CYP3A substrates, such as midazolam, alprazolam, diazepam or triazolam, is required when these are co-administered with ivacaftor.

Ivacaftor [1], moderate CYP3A4 inductors ---> SmPC of [1] of EMA

No dose adjustment is recommended when ivacaftor is used with moderate or weak CYP3A inducers.

Ivacaftor [1], moderate CYP3A4 inhibitors ---> SmPC of [1] of EMA

Ivacaftor [1], oral contraceptives ---> SmPC of [1] of EMA

Ivacaftor has been studied with an oestrogen/progesterone oral contraceptive and was found to have no significant effect on the exposures of the oral contraceptive. Therefore, no dose adjustment of oral contraceptives is necessary.

Ivacaftor [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Ivacaftor [1], phenobarbital ---> SmPC of [1] of EMA

Ivacaftor [1], phenytoin ---> SmPC of [1] of EMA

Ivacaftor [1], posaconazole ---> SmPC of [1] of EMA

Ivacaftor [1], pregnancy ---> SmPC of [1] of EMA

Animals studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of ivacaftor during pregnancy.

Ivacaftor [1], rifabutin ---> SmPC of [1] of EMA

Ivacaftor [1], rifampicin ---> SmPC of [1] of EMA

Ivacaftor [1], sirolimus ---> SmPC of [1] of EMA

Ivacaftor [1], St. John's wort ---> SmPC of [1] of EMA

Ivacaftor [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Ivacaftor [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Ivacaftor [1], tacrolimus ---> SmPC of [1] of EMA

Ivacaftor [1], telithromycin ---> SmPC of [1] of EMA

Ivacaftor [1], triazolam ---> SmPC of [1] of EMA

No dose adjustment of CYP3A substrates, such as midazolam, alprazolam, diazepam or triazolam, is required when these are co-administered with ivacaftor.

Ivacaftor [1], verapamil ---> SmPC of [1] of EMA

Ivacaftor [1], voriconazole ---> SmPC of [1] of EMA

Ivacaftor [1], warfarin ---> SmPC of [1] of EMA

Ivacaftor may inhibit CYP2C9. Therefore, monitoring of the international normalised ratio (INR) is recommended during co-administration of warfarin with ivacaftor.

CONTRAINDICATIONS of Ivacaftor (Kalydeco)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/kalydeco-epar-product-information_en.pdf 13/06/2024

Ivacaftor/tezacaftor/elexacaftor (Kaftrio)

Ability to drive, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

Patients experiencing dizziness should be advised not to drive or use machines until symptoms abate.

BCRP inhibitors, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

Exposure to elexacaftor is not expected to be affected significantly by concomitant use of P-gp and BCRP inhibitors due to its high intrinsic permeability and low likelihood of being excreted intact.

BCRP substrates, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

Co-administration of IVA/TEZ/ELX and ivacaftor may increase exposures of medicinal products that are substrates of BCRP, such as rosuvastatin.

Breast-feeding, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from IVA/TEZ/ELX therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Carbamazepine, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

Elexacaftor and tezacaftor exposures are also expected to decrease during co-administration with strong CYP3A inducers; therefore, co-administration with strong CYP3A inducers is not recommended.

Clarithromycin, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

The dose of IVA/TEZ/ELX and ivacaftor should be reduced when co-administered with strong CYP3A inhibitors (see Table 1 in section 4.2 and section 4.4).

Cyclosporine, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

When used concomitantly with digoxin or other substrates of P-gp with a narrow therapeutic index such as ciclosporin, everolimus, sirolimus, and tacrolimus, caution and appropriate monitoring should be used.

Digoxin, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP2C9, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

Ivacaftor may inhibit CYP2C9;

Erythromycin, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

The dose of IVA/TEZ/ELX and ivacaftor should be reduced when co-administered with moderate CYP3A inhibitors (see Table 2 in section 4.2 and section 4.4).

Ethinyl estradiol/levonorgestrel, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

IVA/TEZ/ELX in combination with ivacaftor has been studied with ethinyl estradiol/levonorgestrel and was found to have no clinically relevant effect on the exposures of the oral contraceptive.

Everolimus, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

Fertility, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

TEZ had no effects on fertility and reproductive performance indices in male and female rats at clinically relevant exposures. ELX and IVA had an effect on fertility in rats (see section 5.3).

Fluconazole, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

The dose of IVA/TEZ/ELX and ivacaftor should be reduced when co-administered with moderate CYP3A inhibitors (see Table 2 in section 4.2 and section 4.4).

Foods, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

Kaftrio tablets should be taken with fat-containing food. Food or drink containing grapefruit should be avoided during treatment with Kaftrio (see section 4.5).

Glimepiride, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

Other medicinal products for which exposure may be increased include glimepiride and glipizide; these medicinal products should be used with caution.

Glipizide, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

Other medicinal products for which exposure may be increased include glimepiride and glipizide; these medicinal products should be used with caution.

Glyburide, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

Coadministration may increase exposures of substrates of these transporters, such as statins, glyburide, nateglinide and repaglinide. When used concomitantly with substrates of OATP1B1 or OATP1B3, caution and appropriate monitoring should be used.

Grapefruit juice, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

Co-administration with grapefruit juice, which contains one or more components that moderately inhibit CYP3A, may increase exposure of elexacaftor, tezacaftor and ivacaftor.

Grapefruit, ivacaftor/tezacaftor/elexacaftor [2] ---> SmPC of [2] of EMA

Food or drink containing grapefruit should be avoided during treatment with Kaftrio

Itraconazol [1], ivacaftor/tezacaftor/elexacaftor ---> SmPC of [1] of EMA

The dose of IVA/TEZ/ELX and ivacaftor should be reduced when co-administered with strong CYP3A inhibitors (see Table 1 in section 4.2 and section 4.4).

Ivacaftor/tezacaftor/elexacaftor [1], ketoconazole ---> SmPC of [1] of EMA

The dose of IVA/TEZ/ELX and ivacaftor should be reduced when co-administered with strong CYP3A inhibitors (see Table 1 in section 4.2 and section 4.4).

Ivacaftor/tezacaftor/elexacaftor [1], moderate CYP3A4 inhibitors ---> SmPC of [1] of EMA

The dose of IVA/TEZ/ELX and ivacaftor should be reduced when co-administered with moderate CYP3A inhibitors (see Table 2 in section 4.2 and section 4.4).

Ivacaftor/tezacaftor/elexacaftor [1], nateglinide ---> SmPC of [1] of EMA

Ivacaftor/tezacaftor/elexacaftor [1], OATP1B1 substrates ---> SmPC of [1] of EMA

Ivacaftor/tezacaftor/elexacaftor [1], OATP1B3 substrates ---> SmPC of [1] of EMA

Ivacaftor/tezacaftor/elexacaftor [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Administration of IVA/TEZ/ELX and ivacaftor may increase systemic exposure of medicinal products that are sensitive substrates of P-gp, which may increase or prolong their therapeutic effect and adverse reactions.

Ivacaftor/tezacaftor/elexacaftor [1], P-glycoprotein substrates with small therapeutic index ---> SmPC of [1] of E

Ivacaftor/tezacaftor/elexacaftor [1], P-gp inhibitors ---> SmPC of [1] of EMA

Caution should be used when P-gp inhibitors (e.g. ciclosporin) are used with IVA/TEZ/ELX.

Ivacaftor/tezacaftor/elexacaftor [1], phenobarbital ---> SmPC of [1] of EMA

Elexacaftor and tezacaftor exposures are also expected to decrease during co-administration with strong CYP3A inducers; therefore, co-administration with strong CYP3A inducers is not recommended.

Ivacaftor/tezacaftor/elexacaftor [1], phenytoin ---> SmPC of [1] of EMA

Elexacaftor and tezacaftor exposures are also expected to decrease during co-administration with strong CYP3A inducers; therefore, co-administration with strong CYP3A inducers is not recommended.

Ivacaftor/tezacaftor/elexacaftor [1], posaconazole ---> SmPC of [1] of EMA

The dose of IVA/TEZ/ELX and ivacaftor should be reduced when co-administered with strong CYP3A inhibitors (see Table 1 in section 4.2 and section 4.4).

Ivacaftor/tezacaftor/elexacaftor [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of IVA/TEZ/ELX during pregnancy.

Ivacaftor/tezacaftor/elexacaftor [1], repaglinide ---> SmPC of [1] of EMA

Ivacaftor/tezacaftor/elexacaftor [1], rifabutin ---> SmPC of [1] of EMA

Elexacaftor and tezacaftor exposures are also expected to decrease during co-administration with strong CYP3A inducers; therefore, co-administration with strong CYP3A inducers is not recommended.

Ivacaftor/tezacaftor/elexacaftor [1], rifampicin ---> SmPC of [1] of EMA

Elexacaftor and tezacaftor exposures are also expected to decrease during co-administration with strong CYP3A inducers; therefore, co-administration with strong CYP3A inducers is not recommended.

Ivacaftor/tezacaftor/elexacaftor [1], rosuvastatin ---> SmPC of [1] of EMA

Co-administration of IVA/TEZ/ELX and ivacaftor may increase exposures of medicinal products that are substrates of BCRP, such as rosuvastatin.

Ivacaftor/tezacaftor/elexacaftor [1], sirolimus ---> SmPC of [1] of EMA

Ivacaftor/tezacaftor/elexacaftor [1], St. John's wort ---> SmPC of [1] of EMA

Elexacaftor and tezacaftor exposures are also expected to decrease during co-administration with strong CYP3A inducers; therefore, co-administration with strong CYP3A inducers is not recommended.

Ivacaftor/tezacaftor/elexacaftor [1], statins ---> SmPC of [1] of EMA

Ivacaftor/tezacaftor/elexacaftor [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Elexacaftor and tezacaftor exposures are also expected to decrease during co-administration with strong CYP3A inducers; therefore, co-administration with strong CYP3A inducers is not recommended.

Ivacaftor/tezacaftor/elexacaftor [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

The dose of IVA/TEZ/ELX and ivacaftor should be reduced when co-administered with strong CYP3A inhibitors (see Table 1 in section 4.2 and section 4.4).

Ivacaftor/tezacaftor/elexacaftor [1], tacrolimus ---> SmPC of [1] of EMA

Ivacaftor/tezacaftor/elexacaftor [1], telithromycin ---> SmPC of [1] of EMA

The dose of IVA/TEZ/ELX and ivacaftor should be reduced when co-administered with strong CYP3A inhibitors (see Table 1 in section 4.2 and section 4.4).

Ivacaftor/tezacaftor/elexacaftor [1], verapamil ---> SmPC of [1] of EMA

The dose of IVA/TEZ/ELX and ivacaftor should be reduced when co-administered with moderate CYP3A inhibitors (see Table 2 in section 4.2 and section 4.4).

Ivacaftor/tezacaftor/elexacaftor [1], voriconazole ---> SmPC of [1] of EMA

The dose of IVA/TEZ/ELX and ivacaftor should be reduced when co-administered with strong CYP3A inhibitors (see Table 1 in section 4.2 and section 4.4).

Ivacaftor/tezacaftor/elexacaftor [1], warfarin ---> SmPC of [1] of EMA

Ivacaftor may inhibit CYP2C9; therefore, monitoring of the international normalised ratio (INR) during co-administration of warfarin with IVA/TEZ/ELX and ivacaftor is recommended.

CONTRAINDICATIONS of Ivacaftor/tezacaftor/elexacaftor (Kaftrio)

- Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/kaftrio-epar-product-information_en.pdf 15/05/2024

Ivosidenib (Tibsovo)

5-HT3 receptor antagonists, ivosidenib [2] ---> SmPC of [2] of EMA

Concomitant administration of medicinal products known to prolong the QTc interval may increase the risk of QTc interval prolongation and should be avoided whenever possible during treatment with Tibsovo.

Ability to drive, ivosidenib [2] ---> SmPC of [2] of EMA

Fatigue and dizziness have been reported in some patients taking ivosidenib (see section 4.8) and should be considered when assessing a patient's ability to drive or operate machines.

Alfentanyl, ivosidenib [2] ---> SmPC of [2] of EMA

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Antiarrhythmics, ivosidenib [2] ---> SmPC of [2] of EMA

Aprepitant, ivosidenib [2] ---> SmPC of [2] of EMA

Atorvastatin, ivosidenib [2] ---> SmPC of [2] of EMA

Concomitant administration of OAT3 substrates (e.g. benzylpenicillin, furosemide) or sensitive OATP1B1/1B3 substrates (e.g. atorvastatin, pravastatin, rosuvastatin) should be avoided whenever possible during treatment with Tibsovo

Benzylpenicillin, ivosidenib [2] ---> SmPC of [2] of EMA

Breast-feeding, ivosidenib [2] ---> SmPC of [2] of EMA

Breast-feeding should be discontinued during treatment with Tibsovo and for at least 1 month after the last dose.

Carbamazepine, ivosidenib [2] ---> SmPC of [2] of EMA

Co-administration of strong CYP3A4 inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifampicin, St. John's wort) is expected to decrease plasma concentrations of ivosidenib and is contraindicated during treatment with Tibsovo (see section 4.3).

Clarithromycin, ivosidenib [2] ---> SmPC of [2] of EMA

Contraceptives, ivosidenib [2] ---> SmPC of [2] of EMA

Women of childbearing potential and males with female partners of childbearing potential should use effective contraception during treatment with Tibsovo and for at least 1 month after the last dose.

Cyclophosphamide, ivosidenib [2] ---> SmPC of [2] of EMA

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Cyclosporine, ivosidenib [2] ---> SmPC of [2] of EMA

CYP2B6 substrates, ivosidenib [2] ---> SmPC of [2] of EMA

Ivosidenib induces CYP3A4, CYP2B6, CYP2C8, CYP2C9 and may induce CYP2C19. Therefore, it may decrease systemic exposure to substrates of these enzymes.

CYP2C19 substrates, ivosidenib [2] ---> SmPC of [2] of EMA

Ivosidenib induces CYP3A4, CYP2B6, CYP2C8, CYP2C9 and may induce CYP2C19. Therefore, it may decrease systemic exposure to substrates of these enzymes.

CYP2C8 substrates, ivosidenib [2] ---> SmPC of [2] of EMA

Ivosidenib induces CYP3A4, CYP2B6, CYP2C8, CYP2C9 and may induce CYP2C19. Therefore, it may decrease systemic exposure to substrates of these enzymes.

CYP2C9 substrates, ivosidenib [2] ---> SmPC of [2] of EMA

Ivosidenib induces CYP3A4, CYP2B6, CYP2C8, CYP2C9 and may induce CYP2C19. Therefore, it may decrease systemic exposure to substrates of these enzymes.

CYP3A4 inductors, ivosidenib [2] ---> SmPC of [2] of EMA

Ivosidenib induces CYP3A4 and it may, therefore, decrease systemic exposure to CYP3A4 substrates. Patients should be monitored for loss of antifungal efficacy if use of itraconazole or ketoconazole cannot be avoided (see section 4.5).

Dabigatran, ivosidenib [2] ---> SmPC of [2] of EMA

Ivosidenib inhibits P-gp and has the potential to induce P-gp. Therefore, it may alter systemic exposure to active substances that are predominantly transported by P-gp (e.g. dabigatran). Co-administration of dabigatran is contraindicated.

Diltiazem, ivosidenib [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP2B6 with narrow therapeutic index, ivosidenib [2] ---> SmPC of [2] of EMA

Suitable alternatives that are not CYP3A4, CYP2B6, CYP2C8 or CYP2C9 substrates with a narrow therapeutic index, or CYP2C19 substrates should be considered during treatment with Tibsovo.

Drugs primarily metabolised by CYP2C19, ivosidenib [2] ---> SmPC of [2] of EMA

Suitable alternatives that are not CYP3A4, CYP2B6, CYP2C8 or CYP2C9 substrates with a narrow therapeutic index, or CYP2C19 substrates should be considered during treatment with Tibsovo.

Drugs primarily metabolised by CYP2C8 with narrow therapeutic index, ivosidenib [2] ---> SmPC of [2] of EMA

Suitable alternatives that are not CYP3A4, CYP2B6, CYP2C8 or CYP2C9 substrates with a narrow therapeutic index, or CYP2C19 substrates should be considered during treatment with Tibsovo.

Drugs primarily metabolised by CYP2C9 with narrow therapeutic index, ivosidenib [2] ---> SmPC of [2] of EMA

Suitable alternatives that are not CYP3A4, CYP2B6, CYP2C8 or CYP2C9 substrates with a narrow therapeutic index, or CYP2C19 substrates should be considered during treatment with Tibsovo.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, ivosidenib [2] ---> SmPC of [2] of EMA

Suitable alternatives that are not CYP3A4, CYP2B6, CYP2C8 or CYP2C9 substrates with a narrow therapeutic index, or CYP2C19 substrates should be considered during treatment with Tibsovo.

Drugs primarily metabolised by UGT, ivosidenib [2] ---> SmPC of [2] of EMA

Suitable alternatives that are not UGT substrates should be considered during treatment with Tibsovo. Patients should be monitored for loss of UGT substrate efficacy if use of such medicinal products cannot be avoided (see section 5.2).

Erythromycin, ivosidenib [2] ---> SmPC of [2] of EMA

Everolimus, ivosidenib [2] ---> SmPC of [2] of EMA

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Fentanyl, ivosidenib [2] ---> SmPC of [2] of EMA

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Fertility, ivosidenib [2] ---> SmPC of [2] of EMA

Undesirable effects on reproductive organs were observed in a 28-day repeat-dose toxicity study (see section 5.3). The clinical relevance of these effects is unknown.

Fluconazole, ivosidenib [2] ---> SmPC of [2] of EMA

Fluoroquinolones, ivosidenib [2] ---> SmPC of [2] of EMA

Foods, ivosidenib [2] ---> SmPC of [2] of EMA

The tablets are taken once daily at about the same time each day. Patients should not eat anything for 2 hours before and through 1 hour after taking the tablets (see section 5.2). The tablets should be swallowed whole with water.

Furosemide, ivosidenib [2] ---> SmPC of [2] of EMA

If administration of furosemide is clinically indicated to manage signs/symptoms of differentiation syndrome, patients should be closely monitored for electrolyte imbalances and QTc interval prolongation.

Grapefruit juice, ivosidenib [2] ---> SmPC of [2] of EMA

Grapefruit, ivosidenib [2] ---> SmPC of [2] of EMA

Patients should be advised to avoid grapefruit and grapefruit juice during treatment (see section 4.5). Patients should also be advised not to swallow the silica gel desiccant found in the tablet bottle (see section 6.5).

Hormonal contraceptives, ivosidenib [2] ---> SmPC of [2] of EMA

Ivosidenib may decrease the systemic concentrations of hormonal contraceptives and, therefore, concomitant use of a barrier method of contraception is recommended for at least 1 month after the last dose (see sections 4.4 and 4.6).

Ifosfamide, ivosidenib [2] ---> SmPC of [2] of EMA

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Isavuconazole, ivosidenib [2] ---> SmPC of [2] of EMA

Itraconazol [1], ivosidenib ---> SmPC of [1] of EMA

Itraconazol*, ivosidenib [2] ---> SmPC of [2] of EMA

Ivosidenib [1], ketoconazole ---> SmPC of [1] of EMA

Ivosidenib [1], ketoconazole* ---> SmPC of [1] of EMA

Ivosidenib [1], lamotrigine ---> SmPC of [1] of EMA

Ivosidenib [1], methadone ---> SmPC of [1] of EMA

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Ivosidenib [1], moderate CYP3A4 inhibitors ---> SmPC of [1] of EMA

Concomitant administration of medicinal products known to prolong the QTc interval, or moderate or strong CYP3A4 inhibitors may increase the risk of QTc interval prolongation and should be avoided whenever possible during treatment with Tibsovo.

Ivosidenib [1], OAT3 substrates ---> SmPC of [1] of EMA

Ivosidenib inhibits OAT3, organic anion-transporting polypeptide 1B1 (OATP1B1) and organic anion-transporting polypeptide 1B3 (OATP1B3). Therefore, it may increase systemic exposure to OAT3 or OATP1B1/1B3 substrates.

Ivosidenib [1], omeprazole ---> SmPC of [1] of EMA

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Ivosidenib [1], paclitaxel ---> SmPC of [1] of EMA

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Ivosidenib [1], phenobarbital ---> SmPC of [1] of EMA

Ivosidenib [1], phenytoin ---> SmPC of [1] of EMA

Ivosidenib [1], pimozide ---> SmPC of [1] of EMA

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Ivosidenib [1], pioglitazone ---> SmPC of [1] of EMA

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Ivosidenib [1], posaconazole ---> SmPC of [1] of EMA

Ivosidenib [1], pravastatine ---> SmPC of [1] of EMA

Ivosidenib [1], pregnancy ---> SmPC of [1] of EMA

Tibsovo is not recommended for use during pregnancy and in women of childbearing potential not using effective contraception. Patients should be informed of the potential risk to the foetus

Ivosidenib [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

Ivosidenib [1], quinidine ---> SmPC of [1] of EMA

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Ivosidenib [1], raltegravir ---> SmPC of [1] of EMA

Ivosidenib [1], repaglinide ---> SmPC of [1] of EMA

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Ivosidenib [1], rifampicin ---> SmPC of [1] of EMA

Ivosidenib [1], ritonavir ---> SmPC of [1] of EMA

Ivosidenib [1], sirolimus ---> SmPC of [1] of EMA

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Ivosidenib [1], St. John's wort ---> SmPC of [1] of EMA

Ivosidenib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Ivosidenib [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Ivosidenib [1], tacrolimus ---> SmPC of [1] of EMA

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Ivosidenib [1], triazole antifungals ---> SmPC of [1] of EMA

Ivosidenib [1], verapamil ---> SmPC of [1] of EMA

Ivosidenib [1], voriconazole ---> SmPC of [1] of EMA

Ivosidenib [1], warfarin ---> SmPC of [1] of EMA

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Ivosidenib [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should have a pregnancy test prior to starting treatment with Tibsovo and should avoid becoming pregnant during therapy (see section 4.6).

Ivosidenib [1], women of childbearing potential* ---> SmPC of [1] of EMA

Women of childbearing potential and males with female partners of childbearing potential should use effective contraception during treatment with Tibsovo and for at least 1 month after the last dose.

Ivosidenib, OATP1B1 substrates [2] ---> SmPC of [2] of EMA

Ivosidenib, OATP1B3 substrates [2] ---> SmPC of [2] of EMA

Ivosidenib, rosuvastatin [2] ---> SmPC of [2] of EMA

CONTRAINDICATIONS of Ivosidenib (Tibsovo)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Concomitant administration of strong CYP3A4 inducers or dabigatran (see section 4.5).

- Congenital long QT syndrome.

- Familial history of sudden death or polymorphic ventricular arrhythmia.

- QT/QTc interval > 500 msec, regardless of the correction method (see section 4.2 and 4.4).

https://www.ema.europa.eu/en/documents/product-information/tibsovo-epar-product-information_en.pdf 25/02/2026

Ixazomib (Ninlaro)

Ability to drive, ixazomib [2] ---> SmPC of [2] of EMA

Ixazomib has minor influence on the ability to drive or use machines. Fatigue and dizziness have been observed in clinical trials. Patients should be advised not to drive or operate machines if they experience any of these symptoms.

Breast-feeding, ixazomib [2] ---> SmPC of [2] of EMA

A risk to newborns/infants cannot be excluded and therefore breast-feeding should be discontinued. Ixazomib will be given in combination with lenalidomide and breast-feeding should be stopped because of the use of lenalidomide.

Clarithromycin, ixazomib [2] ---> SmPC of [2] of EMA

No dose modification is required for ixazomib with co-administration of strong CYP3A inhibitors.

Dexamethasone, ixazomib [2] ---> SmPC of [2] of EMA

When ixazomib is administered together with dexamethasone, which is known to be a weak to moderate inducer of CYP3A4 as well as other enzymes and transporters, the risk for reduced efficacy of oral contraceptives needs to be considered.

Fertility, ixazomib [2] ---> SmPC of [2] of EMA

Fertility studies have not been conducted with ixazomib (see section 5.3).

Foods, ixazomib [2] ---> SmPC of [2] of EMA

Ixazomib should be taken at approximately the same time on days 1, 8, and 15 of each treatment cycle at least 1 hour before or at least 2 hours after food

Hormonal contraceptives, ixazomib [2] ---> SmPC of [2] of EMA

Women using oral hormonal contraceptives should additionally use a barrier method of contraception.

Ixazomib [1], men ---> SmPC of [1] of EMA

Male and female patients who are able to have children must use effective contraceptive measures during and for 90 days following treatment.

Ixazomib [1], oral contraceptives ---> SmPC of [1] of EMA

When NINLARO is administered together with dexamethasone, which is known to be a weak to moderate inducer of CYP3A4 as well as other enzymes and transporters, the risk for reduced efficacy of oral contraceptives needs to be considered.

Ixazomib [1], oral contraceptives ---> SmPC of [1] of EMA

Women using hormonal contraceptives should additionally use a barrier method of contraception.

Ixazomib [1], P450 ---> SmPC of [1] of EMA

Ixazomib is not expected to produce drug-drug interactions via CYP inhibition or induction.

Ixazomib [1], pregnancy ---> SmPC of [1] of EMA

Ixazomib is not recommended during pregnancy as it can cause foetal harm when administered to a pregnant woman. Therefore, women should avoid becoming pregnant while being treated with ixazomib.

Ixazomib [1], pregnancy ---> SmPC of [1] of EMA

Ixazomib is given in combination with lenalidomide. Lenalidomide is structurally related to thalidomide. Thalidomide is a known human teratogenic active substance that causes severe life-threatening birth defects.

Ixazomib [1], rifampicin ---> SmPC of [1] of EMA

Co-administration of ixazomib with rifampicin decreased ixazomib Cmax by 54% and AUC by 74%. Therefore, co-administration of strong CYP3A inducers with ixazomib is not recommended (see section 4.4).

Ixazomib [1], strong CYP1A2 inhibitors ---> SmPC of [1] of EMA

No dose modification is required for ixazomib with co-administration of strong CYP1A2 inhibitors.

Ixazomib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Co-administration of ixazomib with rifampicin decreased ixazomib Cmax by 54% and AUC by 74%. Therefore, co-administration of strong CYP3A inducers with ixazomib is not recommended (see section 4.4).

Ixazomib [1], transporters ---> SmPC of [1] of EMA

Ixazomib is not expected to cause transporter-mediated drug-drug interactions.

Ixazomib [1], women of childbearing potential ---> SmPC of [1] of EMA

Ixazomib is not recommended in women of childbearing potential not using contraception.

CONTRAINDICATIONS of Ixazomib (Ninlaro)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- As ixazomib is administered in combination with lenalidomide and dexamethasone, refer to the SmPC for these medicinal products for additional contraindications.

https://www.ema.europa.eu/en/documents/product-information/ninlaro-epar-product-information_en.pdf 20/09/2024

Ixekizumab (Taltz)

Breast-feeding, ixekizumab [2] ---> SmPC of [2] of EMA

A decision should be made whether to discontinue breast-feeding or to discontinue Taltz taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility, ixekizumab [2] ---> SmPC of [2] of EMA

The effect of ixekizumab on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).

Immunomodulatory agents, ixekizumab [2] ---> SmPC of [2] of EMA

In plaque psoriasis studies, the safety of Taltz in combination with other immunomodulatory agents or phototherapy has not been evaluated.

Infection, ixekizumab [2] ---> SmPC of [2] of EMA

Treatment with Taltz is associated with an increased rate of infections such as upper respiratory tract infection, oral candidiasis, conjunctivitis, and tinea infections (see section 4.8).

Inflammatory bowel disease, ixekizumab [2] ---> SmPC of [2] of EMA

Cases of new or exacerbations of inflammatory bowel disease have been reported with ixekizumab (see section 4.8). Ixekizumab is not recommended in patients with inflammatory bowel disease.

Ixekizumab [1], pharmacokinetics ---> SmPC of [1] of EMA

In population pharmacokinetic analyses, clearance of ixekizumab was not affected by concomitant administration of oral corticosteroids, NSAIDs, sulfasalazine, or methotrexate.

Ixekizumab [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of Taltz during pregnancy.

Ixekizumab [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Taltz should not be used with live vaccines. No data are available on the response to live vaccines; there are insufficient data on response to inactive vaccines

Ixekizumab [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should use an effective method of contraception during treatment and for at least 10 weeks after treatment.

CONTRAINDICATIONS of Ixekizumab (Taltz)

- Serious hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Clinically important active infections (e.g. active tuberculosis, see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/taltz-epar-product-information_en.pdf 22/07/2025

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