Z

Zafirlukast

Acetylsalicylic acid, zafirlukast [2] ---> SmPC of [2] of eMC

Co-administration with acetylsalicylic acid may result in increased plasma levels of zafirlukast, by approximately 45%.

Aminophylline [1], zafirlukast ---> SmPC of [1] of eMC

Zafirlukast may decrease aminophylline clearance resulting in increased plasma theophylline concentrations and the potential for increased toxicity

Astemizole, zafirlukast

The co-administration may decrease the bioavailability of zafirlukast

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

Zafirlukast is excreted in human breast milk. It should not be administered to mothers who are breast-feeding.

Chlorpromazine, zafirlukast

The strong CYP1A2 inhibition may increase the plasma levels of chlorpromazine (small therapeutic range)

Cisapride, zafirlukast

The co-administration may decrease the bioavailability of zafirlukast

Cyclosporine, zafirlukast

The co-administration may decrease the bioavailability of zafirlukast

Dihydropyridines, zafirlukast

The co-administration may decrease the bioavailability of zafirlukast

Erythromycin, zafirlukast [2] ---> SmPC of [2] of eMC

Co-administration with erythromycin will result in decreased plasma levels of zafirlukast, by approximately 40%.

Fluconazole, zafirlukast [2] ---> SmPC of [2] of eMC

Co-administration with fluconazole, a moderate CYP2C9 inhibitor, resulted in increased plasma levels of zafirlukast, by approximately 60%.

Itraconazol, zafirlukast [2] ---> SmPC of [2] of eMC

Co-administration with itraconazole, a strong CYP3A4 inhibitor, caused no change in plasma levels of zafirlukast.

Nicotine, zafirlukast [2] ---> SmPC of [2] of eMC

The clearance of zafirlukast in smokers may be increased by approximately 20%.

Oral anticoagulants, zafirlukast

The co-administration of zafirlukast with oral anticoagulants is contraindicated

Oral contraceptives, zafirlukast [2] ---> SmPC of [2] of eMC

Zafirlukast may be administered with oral contraceptives without adverse interaction.

Pregnancy, zafirlukast [2] ---> SmPC of [2] of eMC

The potential risks should be weighed against the benefits of continuing therapy during pregnancy and zafirlukast should be used during pregnancy only if clearly needed.

Strong CYP2C9 inhibitors, zafirlukast

The strong CYP2C9 inhibition may increase plasma concentrations of zafirlukast

Terfenadine, zafirlukast [2] ---> SmPC of [2] of eMC

Co-administration with terfenadine resulted in a 54% decrease in AUC for zafirlukast, but with no effect on plasma terfenadine levels.

Theophylline [1], zafirlukast ---> SmPC of [1] of eMC

In clinical trials co-administration with theophylline resulted in decreased plasma levels of zafirlukast, by ca. 30%. However, during post-marketing surveillance, there have been rare cases of patients experiencing increased theophylline levels

Warfarin, zafirlukast [2] ---> SmPC of [2] of eMC

Co-administration with warfarin results in an increase in maximum prothrombin time by approximately 35%. The interaction is probably due to an inhibition by zafirlukast of the cytochrome P450 2C9 isoenzyme system.

CONTRAINDICATIONS of Zafirlukast

- Accolate should not be given to patients who have previously experienced hypersensitivity to the product or any of its ingredients.

- Accolate is contraindicated in patients with hepatic impairment or cirrhosis; it has not been studied in patients with hepatitis or in long term studies of

patients with cirrhosis.

- Accolate is contraindicated in children under 12 years of age until safety information is available.

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

Zaleplon (Sonata)

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

Sedation, amnesia, impaired concentration and impaired muscular function may adversely affect the ability to drive or to use machines the next day.

Alcohol, zaleplon [2] ---> SmPC of [2] of EMA

Concomitant intake with alcohol is not recommended. The sedative effect may be enhanced when the product is used in combination with alcohol.

Anaesthetics, zaleplon [2] ---> SmPC of [2] of EMA

Combination of zaleplon with other CNS-acting compounds may enhance the central sedation. Concomitant use of zaleplon with these drugs may increase the risk of next day drowsiness

Antidepressants, zaleplon [2] ---> SmPC of [2] of EMA

Combination of zaleplon with other CNS-acting compounds may enhance the central sedation. Concomitant use of zaleplon with these drugs may increase the risk of next day drowsiness

Antiepileptics, zaleplon [2] ---> SmPC of [2] of EMA

Combination of zaleplon with other CNS-acting compounds may enhance the central sedation. Concomitant use of zaleplon with these drugs may increase the risk of next day drowsiness

Anxiolytics, zaleplon [2] ---> SmPC of [2] of EMA

Combination of zaleplon with other CNS-acting compounds may enhance the central sedation. Concomitant use of zaleplon with these drugs may increase the risk of next day drowsiness

Aprepitant, zaleplon

Possible increase of plasma concentrations of benzodiazepines metabolised via CYP3A4. Caution is advised

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

Because zaleplon is excreted in the breast milk, Sonata should not be administered to breast-feeding mothers.

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

Co-administration of zaleplon together with inducers of CYP3A4 may result in a reduction of zaleplon efficacy.

Cimetidine, zaleplon [2] ---> SmPC of [2] of EMA

The inhibition of CYP3A4 and aldehyde oxidase produces an increase in plasma concentrations of zaleplon. Caution is advisable in co-administering

CNS depressants, zaleplon [2] ---> SmPC of [2] of EMA

The co-administration may potentiate the central sedation

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

The moderate CYP3A4 inhibition may increase the plasma concentrations of zaleplon. The sedative effect may be enhanced

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

Sonata did not affect the pharmacokinetic and pharmacodynamic profiles of digoxin and warfarin, two compounds with a narrow therapeutic index.

Diphenhydramine, zaleplon [2] ---> SmPC of [2] of EMA

However, because both of these compounds have CNS effects, an additive pharmacodynamic effect is possible.

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

Erythromycin, a strong, selective CYP3A4 inhibitor, produced a 34% increase in zaleplon plasma concentrations. Patients should be advised that the sedative effects might be enhanced.

Hypnotics, zaleplon [2] ---> SmPC of [2] of EMA

Combination of zaleplon with other CNS-acting compounds may enhance the central sedation. Concomitant use of zaleplon with these drugs may increase the risk of next day drowsiness

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

In addition, ibuprofen, as an example of compounds that alter renal excretion, showed no interaction with Sonata.

Melatonin [1], zaleplon ---> SmPC of [1] of EMA

Melatonin may enhance the sedative properties of benzodiazepines and non-benzodiazepine hypnotics

Narcotics, zaleplon [2] ---> SmPC of [2] of EMA

Combination of zaleplon with other CNS-acting compounds may enhance the central sedation. Concomitant use of zaleplon with these drugs may increase the risk of next day drowsiness

Neuroleptics, zaleplon [2] ---> SmPC of [2] of EMA

Combination of zaleplon with other CNS-acting compounds may enhance the central sedation. Concomitant use of zaleplon with these drugs may increase the risk of next day drowsiness

Opioid analgesics, zaleplon [2] ---> SmPC of [2] of EMA

Enhancement of the central sedation and enhancement of the euphoria may occur leading to an increase in physiological dependence

Phenobarbital, zaleplon [2] ---> SmPC of [2] of EMA

Co-administration of zaleplon together with inducers of CYP3A4 may result in a reduction of zaleplon efficacy.

Pregnancy, zaleplon [2] ---> SmPC of [2] of EMA

Use of Sonata is not recommended during pregnancy.

Rifampicin, zaleplon [2] ---> SmPC of [2] of EMA

In contrast, rifampicin, a strong inducer of several hepatic enzymes, including CYP3A4 resulted in a four fold reduction in zaleplon plasma concentration.

Sedating antihistamines, zaleplon [2] ---> SmPC of [2] of EMA

Combination of zaleplon with other CNS-acting compounds may enhance the central sedation. Concomitant use of zaleplon with these drugs may increase the risk of next day drowsiness

Sedatives, zaleplon [2] ---> SmPC of [2] of EMA

Combination of zaleplon with other CNS-acting compounds may enhance the central sedation. Concomitant use of zaleplon with these drugs may increase the risk of next day drowsiness

Strong CYP3A4 inductors, zaleplon [2] ---> SmPC of [2] of EMA

Co-administration of zaleplon together with inducers of CYP3A4 may result in a reduction of zaleplon efficacy.

Telithromycin, zaleplon

The CYP3A4 inhibition may increase the plasma levels of zaleplon. Oral coadministration should be avoided

Venlafaxine, zaleplon [2] ---> SmPC of [2] of EMA

Additionally, there was no pharmacokinetic interaction between zaleplon and venlafaxine (extended release).

Warfarin, zaleplon [2] ---> SmPC of [2] of EMA

Sonata did not affect the pharmacokinetic and pharmacodynamic profiles of digoxin and warfarin, two compounds with a narrow therapeutic index.

CONTRAINDICATIONS of Zaleplon (Sonata)

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

- Severe hepatic impairment

- Severe renal impairment

- Sleep apnoea syndrome

- Myasthenia gravis

- Severe respiratory insufficiency

- Children and adolescents (under 18 years of age)

https://www.ema.europa.eu/en/documents/product-information/sonata-epar-product-information_en.pdf 21/10/2015

Zalmoxis (Zalmoxis)

Both male and female patients, Zalmoxis [2] ---> SmPC of [2] of EMA

Both male and female patients (to be) treated with Zalmoxis and their partners need to use effective contraception during and up to 6 months after treatment with Zalmoxis.

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

There are no data on the use of Zalmoxis during breast-feeding. Immune cells are excreted in human milk in low amounts. It is recommended not to breast-feed during or after treatment with Zalmoxis therapy.

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

There are no data on the effect of Zalmoxis treatment on fertility. However myeloablative conditioning regimens performed in the context of a haploidentical bone marrow transplantation is associated with sterility.

Pregnancy, Zalmoxis [2] ---> SmPC of [2] of EMA

In the event of pregnancy following Zalmoxis treatment adverse effect on pregnancy and the developing foetus are not expected as lymphocytes do not pass the placenta.

Pregnancy, Zalmoxis [2] ---> SmPC of [2] of EMA

As a precautionary measure, Zalmoxis must not be administered during pregnancy and in women of childbearing potential not using contraception.

Women of childbearing potential, Zalmoxis [2] ---> SmPC of [2] of EMA

Women of childbearing potential have to provide a negative pregnancy test (serum or urine) within 14 days prior to start the treatment.

CONTRAINDICATIONS of Zalmoxis (Zalmoxis)

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

- Immune reconstitution defined as circulating T lymphocytes ≥100 per 無 at the day of planned infusion after haploidentical HSCT.

- GvHD requiring systemic immunosupressive therapy.

https://www.ema.europa.eu/en/documents/product-information/zalmoxis-epar-product-information_en.pdf 14/02/2020 (withdrawn)

Zanubrutinib (Brukinsa)

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

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

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

Narrow therapeutic index medicinal products that are metabolised by CYP3A should be used with caution, as zanubrutinib may decrease the plasma exposures of these medicinal products.

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

BRUKINSA may increase the risk of haemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding.

Aprepitant, 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.

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

Concomitant use with strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin, St. John's wort) and moderate CYP3A inducers (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) should be avoided

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

It is not known whether zanubrutinib or its metabolites are excreted in human milk and no non- clinical studies were conducted. A risk to breast-fed children cannot be excluded. Breast-feeding should be discontinued during treatment with Brukinsa.

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

Ciprofloxacin, 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.

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

If a strong CYP3A inhibitor must be used (e.g., posaconazole, voriconazole, ketoconazole, itraconazole, clarithromycin, indinavir, lopinavir, ritonavir, telaprevir), reduce the BRUKINSA dose to 80 mg (one capsule) for the duration of the inhibitor use.

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

Narrow therapeutic index medicinal products that are metabolised by CYP3A should be used with caution, as zanubrutinib may decrease the plasma exposures of these medicinal products.

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

Simulations using fasted conditions suggested that the mild CYP3A inhibitors (e.g., cyclosporine and fluvoxamine) may increase the AUC of zanubrutinib by <1.5-fold. No dose adjustment is required in combination with mild inhibitors.

CYP2C19 substrates with narrow therapeutic index, zanubrutinib [2] ---> SmPC of [2] of EMA

Narrow therapeutic index medicinal products that are metabolized by CYP2C19 (e.g., S-mephenytoin) should be used with caution, as zanubrutinib may decrease the plasma exposures of these medicinal products.

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

Mild CYP3A inducers may be used with caution during BRUKINSA treatment.

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

Cytopenia, zanubrutinib [2] ---> SmPC of [2] of EMA

Grade 3 or 4 cytopenias including neutropenia, thrombocytopenia, and anaemia based on laboratory measurements were reported in patients treated with BRUKINSA (see section 4.8).

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

The coadministration of oral P-gp substrates with a narrow therapeutic index (e.g., digoxin) should be done with caution as zanubrutinib may increase their concentrations.

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

Narrow therapeutic index medicinal products that are metabolised by CYP3A should be used with caution, as zanubrutinib may decrease the plasma exposures of these medicinal products.

Diltiazem, 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.

Dronedarone, 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.

Drugs primarily metabolised by CYP2C19, zanubrutinib [2] ---> SmPC of [2] of EMA

Zanubrutinib is a mild inducer of CYP3A and CYP2C19. Concomitant use of zanubrutinib can decrease the plasma concentrations of these substrate medicinal products.

Drugs primarily metabolised by CYP2C9, zanubrutinib [2] ---> SmPC of [2] of EMA

No clinically significant differences were observed with S-warfarin (CYP2C9 substrate) pharmacokinetics when co-administered with zanubrutinib.

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

Narrow therapeutic index medicinal products that are metabolised by CYP3A should be used with caution, as zanubrutinib may decrease the plasma exposures of these medicinal products.

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

Zanubrutinib is a mild inducer of CYP3A and CYP2C19. Concomitant use of zanubrutinib can decrease the plasma concentrations of these substrate medicinal products.

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

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

Narrow therapeutic index medicinal products that are metabolised by CYP3A should be used with caution, as zanubrutinib may decrease the plasma exposures of these medicinal products.

Erythromycin, 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.

Etravirine, zanubrutinib [2] ---> SmPC of [2] of EMA

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

Narrow therapeutic index medicinal products that are metabolised by CYP3A should be used with caution, as zanubrutinib may decrease the plasma exposures of these medicinal products.

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

No effect on male or female fertility was noted in rats but morphological abnormalities in sperm and increased post-implantation loss were noted at 300 mg/kg/day

Fibrillation, zanubrutinib [2] ---> SmPC of [2] of EMA

Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.

Fluconazole, 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.

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

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

The hard capsules can be taken with or without food. Patients should be instructed to swallow the capsules whole with water, and not to open, break or chew the capsules.

Grapefruit juice, 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.

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

Grapefruit and Seville oranges should be used with caution during BRUKINSA treatment, as these contain moderate inhibitors of CYP3A

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

No clinically significant differences in zanubrutinib pharmacokinetics were observed when co-administered with gastric acid reducing agents (proton pump inhibitors, H2-receptor antagonists).

Haemorrhage, zanubrutinib [2] ---> SmPC of [2] of EMA

Serious and fatal haemorrhagic events have occurred in patients treated with BRUKINSA.

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

It is currently unknown whether zanubrutinib may reduce the effectiveness of hormonal contraceptives, and therefore women using hormonal contraceptives should add a barrier method.

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.

Indinavir, zanubrutinib [2] ---> SmPC of [2] of EMA

Infection, zanubrutinib [2] ---> SmPC of [2] of EMA

Fatal and non-fatal infections (including bacterial, viral, fungal infections, or sepsis) and opportunistic infections (e.g., herpes viral, cryptococcal, aspergillus and pneumocystis jiroveci infections) have occurred in patients treated with BRUKINSA.

Itraconazol, zanubrutinib [2] ---> SmPC of [2] of EMA

Ketoconazole, zanubrutinib [2] ---> SmPC of [2] of EMA

Lopinavir, zanubrutinib [2] ---> SmPC of [2] of EMA

Mephenytoin, zanubrutinib [2] ---> SmPC of [2] of EMA

Midazolam, zanubrutinib [2] ---> SmPC of [2] of EMA

Narrow therapeutic index medicinal products that are metabolised by CYP3A should be used with caution, as zanubrutinib may decrease the plasma exposures of these medicinal products.

Modafinil, zanubrutinib [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inductors, zanubrutinib [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inhibitors, 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.

Nafcillin, zanubrutinib [2] ---> SmPC of [2] of EMA

Neoplasia, zanubrutinib [2] ---> SmPC of [2] of EMA

Second primary malignancies, including non-skin carcinoma have occurred in patients treated with BRUKINSA.

Omeprazole, zanubrutinib [2] ---> SmPC of [2] of EMA

Co-administration of multiple doses of zanubrutinib decreased omeprazole (CYP2C19 substrate) Cmax by 20% and AUC by 36%

P-glycoprotein substrates with small therapeutic index, zanubrutinib [2] ---> SmPC of [2] of EMA

The coadministration of oral P-gp substrates with a narrow therapeutic index (e.g., digoxin) should be done with caution as zanubrutinib may increase their concentrations.

Phenytoin, zanubrutinib [2] ---> SmPC of [2] of EMA

Pimozide, zanubrutinib [2] ---> SmPC of [2] of EMA

Narrow therapeutic index medicinal products that are metabolised by CYP3A should be used with caution, as zanubrutinib may decrease the plasma exposures of these medicinal products.

Posaconazole, zanubrutinib [2] ---> SmPC of [2] of EMA

Pregnancy, zanubrutinib [2] ---> SmPC of [2] of EMA

BRUKINSA should not be used during pregnancy. There are no data from the use of BRUKINSA in pregnant women. Studies in animals have shown reproductive toxicity

Proton pump inhibitors, zanubrutinib [2] ---> SmPC of [2] of EMA

No clinically significant differences in zanubrutinib pharmacokinetics were observed when co-administered with gastric acid reducing agents (proton pump inhibitors, H2-receptor antagonists).

Quinidine, zanubrutinib [2] ---> SmPC of [2] of EMA

Narrow therapeutic index medicinal products that are metabolised by CYP3A should be used with caution, as zanubrutinib may decrease the plasma exposures of these medicinal products.

Rifabutin, zanubrutinib [2] ---> SmPC of [2] of EMA

Rifampicin, zanubrutinib [2] ---> SmPC of [2] of EMA

Ritonavir, zanubrutinib [2] ---> SmPC of [2] of EMA

Rosuvastatin, zanubrutinib [2] ---> SmPC of [2] of EMA

No clinically significant differences in the pharmacokinetics of rosuvastatin (BCRP substrate) were observed when co-administered with zanubrutinib.

Seville orange, 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.

Sirolimus, zanubrutinib [2] ---> SmPC of [2] of EMA

Narrow therapeutic index medicinal products that are metabolised by CYP3A should be used with caution, as zanubrutinib may decrease the plasma exposures of these medicinal products.

St. John's wort, zanubrutinib [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inductors, zanubrutinib [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors, zanubrutinib [2] ---> SmPC of [2] of EMA

Tacrolimus, zanubrutinib [2] ---> SmPC of [2] of EMA

Narrow therapeutic index medicinal products that are metabolised by CYP3A should be used with caution, as zanubrutinib may decrease the plasma exposures of these medicinal products.

Telaprevir, zanubrutinib [2] ---> SmPC of [2] of EMA

Tumor lysis syndrome, zanubrutinib [2] ---> SmPC of [2] of EMA

Tumour lysis syndrome has been infrequently reported with zanubrutinib monotherapy therapy, particularly in patients who were treated for chronic lymphocytic leukaemia (CLL)

Verapamil, 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.

Vitamin K antagonists, zanubrutinib [2] ---> SmPC of [2] of EMA

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

Voriconazole, zanubrutinib [2] ---> SmPC of [2] of EMA

Warfarin, zanubrutinib [2] ---> SmPC of [2] of EMA

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

Women of childbearing potential, zanubrutinib [2] ---> SmPC of [2] of EMA

Therefore, women of childbearing potential must use highly effective contraceptive measures while taking BRUKINSA and for up to 1 month after stopping treatment.

CONTRAINDICATIONS of Zanubrutinib (Brukinsa)

- 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/brukinsa-epar-product-information_en.pdf 20/09/2024

Zanamivir (Dectova)

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

As experience is limited, the use of zanamivir in breast-feeding mothers should be considered only if the possible benefit to the mother is thought to outweigh any possible risk to the child.

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

Zanamivir is not a substrate, inhibitor or inducer of cytochrome P450 isoenzymes nor a substrate or inhibitor of renal and hepatic transporters at clinically relevant concentrations (see section 5.2).

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

Animal studies indicate no clinically meaningful effects of zanamivir on male or female fertility.

Interactions, zanamivir [2] ---> SmPC of [2] of EMA

The potential for interactions with other medicines is low, based on the known elimination pathway of zanamivir.

Oseltamivir, zanamivir [2] ---> SmPC of [2] of EMA

Cross-resistance between zanamivir and oseltamivir or peramivir has been observed in neuraminidase inhibition assays.

Peramivir, zanamivir [2] ---> SmPC of [2] of EMA

Cross-resistance between zanamivir and oseltamivir or peramivir has been observed in neuraminidase inhibition assays.

Pregnancy, zanamivir [2] ---> SmPC of [2] of EMA

As experience is limited, the use of Dectova in pregnancy should only be considered if the possible benefit to the patient is thought to outweigh any possible risk to the foetus.

CONTRAINDICATIONS of Zanamivir (Dectova)

- 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/dectova-epar-product-information_en.pdf. 10/01/2024

Other trade names: Relenza,

Zanidatamab (Ziihera)

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

Zanidatamab has minor influence on the ability to drive and use machines. Fatigue has been reported with the use of Ziihera. Therefore, patients should be advised to use caution when driving or operating machines.

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

A decision should be made whether to discontinue breast-feeding or to discontinue treatment, taking into account the benefit of breast-feeding for the child and the benefit of Ziihera therapy for the woman. This consideration should also take into account

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

No dedicated clinical studies evaluating the drug interaction potential of zanidatamab have been conducted. Zanidatamab is an antibody that is not expected to impact the cytochrome P450 enzymes.

Embryo-foetal harm, zanidatamab [2] ---> SmPC of [2] of EMA

Based on the mechanism of action, zanidatamab may cause embryo-foetal harm when administered during pregnancy. Female patients should use effective contraception during treatment with Ziihera and for 4 months following the last dose.

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

Fertility studies have not been performed with zanidatamab.

Pneumonitis, zanidatamab [2] ---> SmPC of [2] of EMA

Pneumonitis has been reported with medicinal products that block HER2 activity, including Ziihera. Pneumonitis has been reported in 0.4% of 233 patients treated with Ziihera 20 mg/kg intravenously as a single agent in clinical studies.

Pregnancy, zanidatamab [2] ---> SmPC of [2] of EMA

Ziihera is not recommended for use during pregnancy or in women of childbearing potential not using contraception. Patients should be advised on potential risks to the foetus.

Women of childbearing potential, zanidatamab [2] ---> SmPC of [2] of EMA

To exclude pregnancy, women of childbearing potential should undergo pregnancy testing before initiation of Ziihera.

CONTRAINDICATIONS of Zanidatamab (Ziihera)

- 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/ziihera-epar-product-information_en.pdf 03/07/2025

Zapomeran (Kostaive)

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

Kostaive has no or negligible influence on the ability to drive and use machines. However, some of the adverse reactions mentioned under section 4.8 may temporarily affect the ability to drive or use machines.

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

No effects on the breast-fed newborn/infant are anticipated since the systemic exposure of the breast-feeding woman to Kostaive is negligible. Kostaive can be used during breast-feeding.

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

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

Pregnancy, zapomeran [2] ---> SmPC of [2] of EMA

Administration of Kostaive in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and foetus.

Vaccinations, zapomeran [2] ---> SmPC of [2] of EMA

Concomitant administration of Kostaive with other vaccines has not been studied.

CONTRAINDICATIONS of Zapomeran (Kostaive)

- 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/kostaive-epar-product-information_en.pdf 20/01/2026

Ziconotide (Prialt)

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

Prialt has moderate influence on the ability to drive and use machines. Ziconotide may cause confusion, somnolence and other neurological adverse reactions, therefore patients must be advised not to drive or operate machines if affected.

Baclofen, ziconotide [2] ---> SmPC of [2] of EMA

An increased incidence of somnolence has been observed when ziconotide is administered concomitantly with systemic baclofen, clonidine, bupivacaine or propofol thus for the time being their simultaneous use is discouraged.

Benazepril, ziconotide [2] ---> SmPC of [2] of EMA

Angiotensin converting enzyme inhibitors (e.g., benazepril, lisinopril and moexipril) and HIV protease inhibitors (e.g., ritonavir, saquinavir, indinavir), have no readily apparent effect on plasma ziconotide exposure.

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

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

Bupivacaine, ziconotide [2] ---> SmPC of [2] of EMA

Buprenorphine, ziconotide [2] ---> SmPC of [2] of EMA

No data are available regarding the concomitant use of partial opioid agonists (e.g. buprenorphine) with ziconotide.

Antineoplastics, ziconotide [2] ---> SmPC of [2] of EMA

No clinical data are available on the interaction between IT chemotherapy and IT ziconotide. Ziconotide is contraindicated in combination with IT chemotherapy (see section 4.3).

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

Only a small number of patients have received systemic chemotherapy and IT ziconotide. Caution should be exercised when ziconotide is administered to patients who are receiving systemic chemotherapy (see section 4.4).

Clonidine, ziconotide [2] ---> SmPC of [2] of EMA

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

In a study on male and female fertility in rats no effects in males while reductions in corpora lutea; implantation sites and number of live embryos were observed in females (see section 5.3).

Indinavir, ziconotide [2] ---> SmPC of [2] of EMA

Lisinopril, ziconotide [2] ---> SmPC of [2] of EMA

Moexipril, ziconotide [2] ---> SmPC of [2] of EMA

Morphine, ziconotide [2] ---> SmPC of [2] of EMA

Adding IT ziconotide to stable doses of IT morphine is possible but requires special attention, as a high rate of neuropsychiatric adverse reactions, some of them serious, was observed in Study 202 despite a low dose of ziconotide.

Opiates, ziconotide [2] ---> SmPC of [2] of EMA

Ziconotide does not interact with opiate receptors. If discontinuing opiates when initiating ziconotide therapy, opiate withdrawal should be gradual.

Pregnancy, ziconotide [2] ---> SmPC of [2] of EMA

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

Propofol, ziconotide [2] ---> SmPC of [2] of EMA

Ritonavir, ziconotide [2] ---> SmPC of [2] of EMA

Saquinavir, ziconotide [2] ---> SmPC of [2] of EMA

CONTRAINDICATIONS of Ziconotide (Prialt)

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

- Combination with IT chemotherapy (see section 4.5).

- Pre-existing history of psychosis with ziconotide.

- History of suicidal attempt or suicidal ideation with ziconotide.(see Section 4.2, 4.4 and 4.8).

Infection at the microinfusion injection site, uncontrolled bleeding diathesis, and spinal canal obstruction that impairs circulation of cerebrospinal fluid (CSF).

https://www.ema.europa.eu/en/documents/product-information/prialt-epar-product-information_en.pdf 12/12/2025

Zidovudine

Abacavir [1], zidovudine ---> SmPC of [1] of EMA

Nucleoside and nucleotide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

Abacavir/lamivudine [1], zidovudine ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Ability to drive, zidovudine

The ability to drive and use machines may be impaired

Aceclofenac [1], zidovudine ---> SmPC of [1] of eMC

Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There are indications of an increased risk of haemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen

Acetylsalicylic acid, zidovudine

The acetylsalicylic acid may increase the zidovudine plasma levels by inhibition of glucuronidation or microsomal hepatic metabolism

Aciclovir, zidovudine

The combination may cause neuropathies, convulsions and lethargy.

Amphotericin, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Amprenavir [1], zidovudine ---> SmPC of [1] of EMA

No dose adjustment is necessary for either medicinal product when zidovudine is administered in combination with amprenavir.

Atovaquone [1], zidovudine ---> SmPC of [1] of eMC

Pharmacokinetic data have shown that atovaquone appears to decrease the rate of metabolism of zidovudine to its glucuronide metabolite

Azithromycin [1], zidovudine ---> SmPC of [1] of eMC

Administration of azithromycin increased the concentrations of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of this finding is unclear, but it may be of benefit to patients.

Benzodiazepines, zidovudine ---> SmPC of [oxazepam] of

Concurrent use of zidovudine with benzodiazepines may decrease zidovudine clearance.

Breast-feeding, zidovudine

Zidovudine and the virus pass into breast milk. It is recommended that women who are taking zidovudine not breast-feed their infants

Clarithromycin [1], zidovudine ---> SmPC of [1] of eMC

Simultaneous oral use of clarithromycin tablets and zidovudine may result in decreased steady-state zidovudine concentrations. This interaction can be largely avoided by staggering the doses to allow for a 4-hour interval between each medication.

Cotrimoxazole, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Cyclophosphamide, zidovudine

The co-administration may increase the hematotoxicity and/or immunosuppression

Daclatasvir [1], zidovudine ---> SmPC of [1] of EMA

No dose adjustment of Daklinza or the NRTI is required.

Dapsone, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Darunavir/cobicistat [1], zidovudine ---> SmPC of [1] of EMA

Based on the different elimination pathways, no interactions are expected with darunavir/cobicistat. The can be used without dose adjustment.

Darunavir/ritonavir, zidovudine ---> SmPC of [darunavir] of EMA

Darunavir co-administered with low dose ritonavir can be used with zidovudine without dose adjustment.

Dexibuprofen, zidovudine

Increased risk of haematological toxicity. Caution is recommended

Dexketoprofen [1], zidovudine ---> SmPC of [1] of eMC

Risk of increased red cell line toxicity via action on reticulocytes, with severe anaemia occurring one week after the NSAID is started

Diazepam [1], zidovudine ---> SmPC of [1] of eMC

Increased zidovudine clearance by diazepam

Diclofenac [1], zidovudine ---> SmPC of [1] of eMC

Increased risk of haematological toxicity when NSAIDs are given with zidovudine.

Didanosine [1], zidovudine ---> SmPC of [1] of eMC

No dosage adjustment necessary.

Doxorubicine, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Efavirenz [1], zidovudine ---> SmPC of [1] of EMA

No clinically significant pharmacokinetic interaction. No dosage adjustment necessary.

Elvitegravir [1], zidovudine ---> SmPC of [1] of EMA

No dose adjustment is required when elvitegravir is co-administered with zidovudine.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], zidovudine ---> SmPC of [1] of EMA

Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

Emtricitabine [1], zidovudine ---> SmPC of [1] of EMA

Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine

Emtricitabine/rilpivirine/tenofovir disoproxil [1], zidovudine ---> SmPC of [1] of EMA

Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

Emtricitabine/tenofovir disoproxil [1], zidovudine ---> SmPC of [1] of EMA

Nucleoside and nucleotide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

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

Fluconazole increases Cmax and AUC of zidovudine by 84% and 74%, respectively, due to an approx. 45% decrease in oral zidovudine clearance.

Flucytosine, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Flurbiprofen [1], zidovudine ---> SmPC of [1] of eMC

Increased risk of haematological toxicity when NSAIDs are given with zidovudine

Fosamprenavir/ritonavir, zidovudine ---> SmPC of [fosamprenavir] of EMA

No clinically significant interaction is observed. No dosage adjustment necessary.

Foscarnet [1], zidovudine ---> SmPC of [1] of eMC

There is no pharmacokinetic interaction between foscarnet and zidovudine (AZT)

Ganciclovir, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Glucuronidation inductors, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Zidovudine is primarily metabolised by UGT enzymes; co-administration of inducers or inhibitors of UGT enzymes could alter zidovudine exposure.

Glucuronidation inhibitors, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Zidovudine is primarily metabolised by UGT enzymes; co-administration of inducers or inhibitors of UGT enzymes could alter zidovudine exposure.

Hepatitis, zidovudine ---> SmPC of [abacavir/lamivudine/zidovudine] of EMA

Caution should be exercised when administering zidovudine to any patient (particularly obese women) with hepatomegaly, hepatitis or other known risk factors for liver disease and hepatic steatosis (including certain medicinal products and alcohol).

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

Increased risk of haematological toxicity when NSAIDs are given with zidovudine

Indinavir [1], zidovudine ---> SmPC of [1] of EMA

Indinavir and NRTIs can be co-administered without dose adjustment.

Interferon beta-1b, zidovudine

The interferon increases the effect and toxicity of zidovudine

Interferon, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Ketoprofen [1], zidovudine ---> SmPC of [1] of eMC

Increased risk of haematological toxicity when NSAIDs are given with zidovudine.

Lamivudine [1], zidovudine ---> SmPC of [1] of EMA

A modest increase in Cmax (28 %) was observed for zidovudine when administered with lamivudine, however overall exposure (AUC) was not significantly altered. Zidovudine had no effect on the pharmacokinetics of lamivudine

Laropiprant, zidovudine

The UGT inhibition may increase the zidovudine exposition. Monitor closely

Laropiprant/nicotinic acid [1], zidovudine ---> SmPC of [1] of EMA

Laropiprant is a mild to moderate inhibitor of UGT2B4/UGT2B7. Caution should be used when Pelzont is co-administered with medicinal products metabolised predominantly by UGT2B4 or UGT2B7, for instance zidovudine.

Leflunomide [1], zidovudine ---> SmPC of [1] of EMA

A771726 is an inhibitor of OAT3 in vivo .Therefore, when co-administered leflunomide with substrates of OAT3 caution is recommended.

Levocarnitine, zidovudine

Possible Levocarnitine deficiency

Lopinavir/ritonavir [1], zidovudine ---> SmPC of [1] of EMA

The induction of the glucuronidation by lopinavir/ritonavir may decrease the plasma concentrations of zidovudine

Lorazepam [1], zidovudine ---> SmPC of [1] of eMC

Increased zidovudine clearance by lorazepam

Maraviroc [1], zidovudine ---> SmPC of [1] of EMA

No significant interaction seen/expected. Maraviroc and NRTIs can be co-administered without dose adjustment.

Methadone [1], zidovudine ---> SmPC of [1] of eMC

Methadone may increase the plasma concentrations of zidovudine.

Mitochondrial function, zidovudine ---> SmPC of [abacavir/lamivudine/zidovudine] of EMA

Nucleoside and nucleotide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

Myelosuppressive agents, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Nabumetone [1], zidovudine ---> SmPC of [1] of eMC

Increased risk of haematological toxicity when NSAIDs are given with zidovudine.

Nephrotoxic substances, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Netupitant/palonosetron [1], zidovudine ---> SmPC of [1] of EMA

In vitro data shows that netupitant inhibits UGT2B7, the magnitude of such an effect in the clinical setting is not established. Caution is recommended when netupitant is combined with an oral substrate of this enzyme

Nevirapine [1], zidovudine ---> SmPC of [1] of EMA

Zidovudine and nevirapine can be co-administered without dose adjustments. Granulocytopenia is commonly associated with zidovudine.

Nimodipine [1], zidovudine ---> SmPC of [1] of eMC

Animal studies have shown that when nimodipine and zidovudine are administered concomitantly, the AUC for zidovudine was increased, and the volume of distribution and clearance rate decreased.

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

Increased risk of haematological toxicity when NSAIDs are given with zidovudine

Oxazepam [1], zidovudine ---> SmPC of [1] of eMC

Concurrent use of zidovudine with benzodiazepines may decrease zidovudine clearance.

P-gp inhibitors, zidovudine

The inhibition of P-glycoprotein may increase the exposure to zidovudine

Paracetamol, zidovudine

The co-administration may enhance the tendency to neutropenia

Peginterferon alfa-2a/ribavirin, zidovudine ---> SmPC of [peginterferon alfa-2a] of EMA

Exacerbation of anaemia due to ribavirin has been reported when zidovudine is part of the regimen used to treat HIV although the exact mechanism remains to be elucidated. The concomitant use of ribavirin with zidovudine is not recommended

Peginterferon alfa-2b [1], zidovudine ---> SmPC of [1] of EMA

When administered in combination with other interferon preparations, suppressive effect on bone marrow function may be strengthened and aggravation of blood cell reduction such as white blood cells decreased may occur.

Peginterferon alfa-2b/ribavirin, zidovudine ---> SmPC of [peginterferon alfa-2b] of EMA

Exacerbation of anaemia due to ribavirin has been reported when zidovudine is part of the regimen used to treat HIV. The concomitant use of ribavirin with zidovudine is not recommended due to an increased risk of anaemia

Peginterferon, zidovudine ---> SmPC of [peginterferon alfa-2b] of EMA

Pentamidine, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Phenobarbital, zidovudine

The glucuronidation induction may decrease the plasma concentrations of zidovudine

Phenytoin, zidovudine

Increased/decreased AUC of phenytoin. Monitor phenytoin concentrations

Pramipexole [1], zidovudine ---> SmPC of [1] of EMA

Medicines that are inhibitors of the cationic secretory transport system of renal tubules/are eliminated by this pathway may interact with pramipexole resulting in reduced clearance of pramipexole. Reduction of the pramipexole dose should be considered

Pregnancy, zidovudine

There is a risk of mutagen/carcinogen effect

Probenecide, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

The UGT inhibition may increase the AUC of zidovudine. Monitor for signs of zidovudine toxicity

Pyrazinamide, zidovudine

Decrease of pyrazinamide plasma levels. Die co-administration should be avoided

Pyrimethamine, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Ribavirin [1], zidovudine ---> SmPC of [1] of EMA

Patients treated with ribavirin and zidovudine are at increased risk of developing anaemia; therefore, the concomitant use of ribavirin with zidovudine is not recommended

Rifampicin, zidovudine

The UGT induction may decrease the plasma concentration of zidovudine. The concomitant use should be avoided

Rilpivirine [1], zidovudine ---> SmPC of [1] of EMA

No clinically relevant drug-drug interactions are expected. No dose adjustment is required.

Ritonavir [1], zidovudine ---> SmPC of [1] of EMA

Ritonavir may induce the glucuronidation of zidovudine, resulting in slightly decreased levels of zidovudine. Dose alterations should not be necessary.

Saquinavir/ritonavir, zidovudine ---> SmPC of [saquinavir] of EMA

For zidovudine (200 mg every 8 hours) a 25 % decrease in AUC was reported when combined with ritonavir (300 mg every 6 hours). No dose adjustment required.

Simeprevir [1], zidovudine ---> SmPC of [1] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Sodium valproate [1], zidovudine ---> SmPC of [1] of eMC

Valproic acid may raise zidovudine plasma concentration leading to increased zidovudine toxicity.

Sonidegib [1], zidovudine ---> SmPC of [1] of EMA

Patients should be closely monitored for muscle-related symptoms if Odomzo is used in combination with certain medicinal products that may increase the potential risk of developing muscle toxicity

Stavudine, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

In vitro antagonism of anti-HIV activity between stavudine and zidovudine could result in decreased efficacy of both drugs. Combination not recommended

Strong glucuronidation inductors, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Zidovudine is primarily metabolised by UGT enzymes; co-administration of inducers or inhibitors of UGT enzymes could alter zidovudine exposure.

Tafamidis [1], zidovudine ---> SmPC of [1] of EMA

Tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters

Telaprevir [1], zidovudine ---> SmPC of [1] of EMA

An effect of telaprevir on UDP-glucuronyltransferases cannot be ruled out and may affect the plasma concentrations of zidovudine.

Tenofovir disoproxil [1], zidovudine ---> SmPC of [1] of EMA

Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

Terbinafine [1], zidovudine ---> SmPC of [1] of eMC

There was no clinically relevant interaction between terbinafine and the potential comedications zidovudine

Teriflunomide [1], zidovudine ---> SmPC of [1] of EMA

When teriflunomide (OAT3 inhibitor) is coadministered with substrates of OAT3 caution is recommended.

Tiaprofenic acid, zidovudine [2] ---> SmPC of [2] of eMC

Increased risk of haematological toxicity when NSAIDs are given with zidovudine.

Tipranavir/ritonavir, zidovudine ---> SmPC of [tipranavir] of EMA

The concomitant use of tipranavir, co-administered with low dose ritonavir, with zidovudine or abacavir, results in a significant decrease in plasma concentration of these nucleoside reverse transcriptase inhibitors

Trifluridine/tipiracil [1], zidovudine ---> SmPC of [1] of EMA

Caution is required when using medicinal products that are human thymidine kinase substrates, e.g., zidovudine.

Trimethoprim, zidovudine

The co-administration may increase the plasma levels of zidovudine

Trimethoprim/sulfamethoxazol, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Valganciclovir [1], zidovudine ---> SmPC of [1] of eMC

When zidovudine was given in the presence of oral ganciclovir there was a small (17 %), but statistically significant increase in the AUC of zidovudine. Zidovudine and ganciclovir have the potential to cause neutropenia and anaemia

Valproic acid [1], zidovudine ---> SmPC of [1] of eMC

Valproic acid may raise zidovudine plasma concentration leading to increased zidovudine toxicity.

Vinblastine, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Vincristine, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Zilucoplan (Zilbrysq)

Breast-feeding [1], zilucoplan ---> SmPC of [1] of EMA

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

Cytochrome P450 [1], zilucoplan ---> SmPC of [1] of EMA

Based on results from in vitro testing, zilucoplan will not inhibit or induce drug metabolising enzymes (CYPs and UGTs) and common transporters in a clinically relevant manner.

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

The effect of zilucoplan on human fertility has not been evaluated. In some non-human primate fertility and repeat-dose toxicity studies, findings of uncertain clinical relevance were observed in male and female reproductive organs (see section 5.3).

Pregnancy [1], zilucoplan ---> SmPC of [1] of EMA

Treatment of pregnant women with Zilbrysq should only be considered if the clinical benefit outweighs the risks.

Rituximab [1], zilucoplan ---> SmPC of [1] of EMA

Based on the potential inhibitory effect of zilucoplan on complement-dependent cytotoxicity of rituximab, zilucoplan may reduce the expected pharmacodynamic effects of rituximab.

CONTRAINDICATIONS of Zilucoplan (Zilbrysq)

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

Patients who are not currently vaccinated against Neisseria meningitidis (see section 4.4).

Patients with unresolved Neisseria meningitidis infection.

https://www.ema.europa.eu/en/documents/product-information/zilbrysq-epar-product-information_en.pdf 29/04/2025

Zinc (Wilzin)

Baloxavir [1], zinc ---> SmPC of [1] of EMA

Products that contain polyvalent cations may decrease plasma concentrations of baloxavir. Xofluza should not be taken with products that contain polyvalent cations

Bread, zinc [2] ---> SmPC of [2] of EMA

Studies of the co-administration of zinc with food performed in healthy volunteers showed that the absorption of zinc was significantly delayed by many foods (including bread, hard boiled eggs, coffee and milk).

Breast-feeding, cinchocaine

Strict indication

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

Zinc is excreted in human breast milk and zinc-induced copper deficiency in the breast-fed baby may occur. Therefore, breast-feeding should be avoided during zinc therapy.

Calcium carbonate/cholecalciferol, zinc

Calcium salts may reduce the absorption of zinc. It is advisable to allow a minimum period of 2 hours before taking the calcium.

Calcium, zinc [2] ---> SmPC of [2] of EMA

The absorption of zinc may be reduced by iron and calcium supplements, tetracyclines and phosphorus-containing compounds, while zinc may reduce the absorption of iron, tetracyclines, fluoroquinolones.

Chelating agents, zinc [2] ---> SmPC of [2] of EMA

Complexation. Decreased absorption of both active substances. The administration should be separated by at least 1 hour.

Cinchocaine, latex

Decreased breaking strength

Cinchocaine, pregnancy

Strict indication

Cinchophen, lymecycline

The co-administration of tetracyclines with other potentially hepatotoxic medicinal products should be avoided

Coffee, zinc [2] ---> SmPC of [2] of EMA

Delafloxacin [1], zinc ---> SmPC of [1] of EMA

Oral dosing of delafloxacin with this agent may substantially interfere with the absorption of delafloxacin, resulting in systemic levels considerably lower than desired. Delafloxacin should be taken at least 2 hours before or 6 hours after this agent.

Eggs, zinc [2] ---> SmPC of [2] of EMA

Eltrombopag [1], zinc ---> SmPC of [1] of EMA

Eltrombopag chelates with polyvalent cations. Eltrombopag should be taken at least 2 hours before or 4 hours after any products such as antacids, dairy products or mineral supplements containing polyvalent cations

Folic acid, zinc

Drugs that may adversely affect the absorption or metabolism of folic acid may cause statuses of folate deficiency

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

Substances in food, especially phytates and fibres, bind zinc and prevent it from entering the intestinal cells. However, protein appears to interfere the least.

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

Hyaluronidase, zinc

Inhibition of hyaluronidase

Iron, zinc [2] ---> SmPC of [2] of EMA

Milk, zinc [2] ---> SmPC of [2] of EMA

Penicillamine, zinc [2] ---> SmPC of [2] of EMA

Complexation. Decreased absorption of both active substances. The administration should be separated by at least 1 hour.

Pentetic acid, zinc

Mutual abolishment of effects

Phosphates, zinc [2] ---> SmPC of [2] of EMA

Phytic acid, zinc

Decreased zinc absorption. It is recommended to avoid phytic acid after taking zinc

Pregnancy, zinc [2] ---> SmPC of [2] of EMA

It is extremely important that pregnants continue their therapy during pregnancy

Quinolones, zinc [2] ---> SmPC of [2] of EMA

Tetracyclines, zinc [2] ---> SmPC of [2] of EMA

Tilactase, zinc

The co-administration may decrease the effect of tilactase

Trientine, zinc

The combination of trientine with zinc is not recommended.

Trientine, zinc [2] ---> SmPC of [2] of EMA

Complexation. Decreased absorption of both active substances. The administration should be separated by at least 1 hour.

CONTRAINDICATIONS of Zinc (Wilzin)

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

https://www.ema.europa.eu/en/documents/product-information/wilzin-epar-product-information_en.pdf 18/12/2024

Ziprasidone

Ability to drive, ziprasidone

Somnolence may occur

Alcohol, ziprasidone

The possibility of an additive or potentiating effect with CNS depressants should be considered.

Antacids, ziprasidone

Repeated administration of magnesium and aluminium containing antacids or cimetidine after eating had no significant effect on ziprasidone pharmacokinetics

Arsenic trioxide, ziprasidone

Additive QT-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Azithromycin, ziprasidone

Additive QT-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Breast-feeding, ziprasidone

Contraindicated

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

Carbamazepine may lower the plasma level of ziprasidone

Cimetidine, ziprasidone

Repeated administration of magnesium and aluminium containing antacids or cimetidine after eating had no significant effect on ziprasidone pharmacokinetics

Cisapride, ziprasidone

The co-administration may prolong the QT interval and/or induce torsades de pointes and is contraindicated

Class IA antiarrhythmic agents, ziprasidone

Additive QT-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Class III antiarrhythmic agents, ziprasidone

Additive QT-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

CNS depressants, ziprasidone

The possibility of an additive or potentiating effect with CNS depressants should be considered.

Dolasetron, ziprasidone

Additive QT-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Drugs primarily metabolised by CYP2D6, ziprasidone

Ziprasidone could be a moderate CYP2D6 and CYP3A4 inhibitor. But it is not likely that ziprasidone affect the pharmacokinetics of drugs which are metabolized by these isoenzymes to a clinically relevant extent

Drugs primarily metabolised by CYP3A4, ziprasidone

Drugs with high protein binding, ziprasidone

The probability of interactions of ziprasidone with other drugs by displacement from plasma protein binding sites is unlikely

Estrogens, ziprasidone

The co-administration of ziprasidone didn't cause any significant changes in the pharmacokinetic of estrogens

Ethinyl estradiol, ziprasidone

The co-administration of ziprasidone didn't cause any significant changes in the pharmacokinetic of estrogens

Gatifloxacin, ziprasidone

Additive QT-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Gestagens, ziprasidone

The co-administration of ziprasidone didn't cause any significant changes in the pharmacokinetic of progestagens

Halofantrine, ziprasidone

Additive QT-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Itraconazol, ziprasidone

The co-administration of ziprasidone with P glycoprotein inhibitors may increase the plasma concentrations of ziprasidone

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.

Ketoconazole, ziprasidone

It is unlikely that changes in pharmacokinetics (with the concomitant use of strong CYP3A4 inhibitors) be of clinical relevance. No dose adjustment is required

Lithium, ziprasidone

Both principle actives are associated with changes in the heart conduction

Mefloquine, ziprasidone

Additive QT-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Mesoridazine, ziprasidone

Additive QT-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Moxifloxacin, ziprasidone

Additive QT-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Oral contraceptives, ziprasidone

Oral contraceptives - The use of ziprasidone caused no significant changes of estrogen pharmacokinetics (ethinylestradiol, CYP3A4 substrate) or progesterone derivates

Pimozide, ziprasidone

Additive QT-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Pregnancy, ziprasidone

Is not recommended during pregnancy unless the benefit outweighs the potential risk

QT interval prolonging drugs, ziprasidone

Additive QT-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Quinidine, ziprasidone

The co-administration of ziprasidone with P glycoprotein inhibitors may increase the plasma concentrations of ziprasidone

Rifampicin, ziprasidone

The co-administration of ziprasidone with P glycoprotein inductors may decrease the plasma concentrations of ziprasidone

Ritonavir, ziprasidone

The co-administration of ziprasidone with P glycoprotein inhibitors may increase the plasma concentrations of ziprasidone

Saquinavir/ritonavir, ziprasidone ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Serotonergic medicines, ziprasidone

Risk of serotonin syndrome

Sertindole, ziprasidone

Additive QT-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Sparfloxacin, ziprasidone

Additive QT-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

SSRI, ziprasidone

Risk of serotonin syndrome

St. John's wort, ziprasidone

The co-administration of ziprasidone with P glycoprotein inductors may decrease the plasma concentrations of ziprasidone

Strong CYP3A4 inhibitors, ziprasidone

It is unlikely that changes in pharmacokinetics (with the concomitant use of strong CYP3A4 inhibitors) be of clinical relevance. No dose adjustment is required

Strong P-gp inductors, ziprasidone

The co-administration of ziprasidone with P glycoprotein inductors may decrease the plasma concentrations of ziprasidone

Strong P-gp inhibitors, ziprasidone

The co-administration of ziprasidone with P glycoprotein inhibitors may increase the plasma concentrations of ziprasidone

Thioridazine, ziprasidone

Additive QT-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Verapamil, ziprasidone

The co-administration of ziprasidone with P glycoprotein inhibitors may increase the plasma concentrations of ziprasidone

Zofenopril

Ability to drive, zofenopril

Debility, dizziness or fatigue may occur

ACE inhibitors, haemodialysis with high-flux dialysis membranes ---> SmPC of [zofenopril] of eMC

Increased risk of anaphylactoid reactions when ACE inhibitors are used concurrently.

AIIRA, zofenopril

Dual blockade of the RAAS through the combined use of ACE-inhibitors, AIIRAs or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure)

Alfa-adrenergic receptor blockers, zofenopril

Additive or enhanced hypotension may occur

Aliskiren, zofenopril

Allopurinol, zofenopril

Increased risk of hypersensitivity reactions when ACE inhibitors are used concurrently. Data from other ACE inhibitors indicate an increased risk of leucopenia when used concurrently.

Amiloride, zofenopril

Potassium sparing diuretics, potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium. Combination is not recommended

Anaesthetics, zofenopril

ACE inhibitors may enhance the hypotensive effects of certain anaesthetic medicinal products.

Antacids, zofenopril

Antacids reduce the bioavailability of ACE inhibitors.

Antihypertensives, zofenopril

Additive or enhanced hypotension may occur

Aurothiomalate, zofenopril

Nitritoid reactions following injectable gold (for example, sodium aurothiomalate) have been reported more frequently in patients receiving ACE inhibitor therapy.

Barbiturates, zofenopril

Postural hypotension may occur

Betablockers, zofenopril

Additive or enhanced hypotension may occur

Breast-feeding, zofenopril

The use of zofenopril during breast-feeding is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

Calcium antagonists, zofenopril

Additive or enhanced hypotension may occur

Cimetidine, zofenopril

Cimetidine may increase the risk of acute hypotension

Corticosteroids, zofenopril

Concomitant administration of systemic corticosteroids with ACE inhibitors may lead to an increased risk for leucopenia.

Cyclosporine, zofenopril

Increased risk of renal dysfunction when ACE inhibitors are used concurrently with cyclosporin

Cytostatics, zofenopril

Increased risk of hypersensitivity reactions when ACE inhibitors are used concurrently. Data from other ACE inhibitors indicate an increased risk of leucopenia when used concurrently.

Foods, zofenopril

Foods may reduce the rate but not the extent of absorption of zofenopril calcium.

Gold, zofenopril

Nitritoid reactions following injectable gold (for example, sodium aurothiomalate) have been reported more frequently in patients receiving ACE inhibitor therapy.

Haemodialysis with high-flux dialysis membranes, zofenopril

Increased risk of anaphylactoid reactions when ACE inhibitors are used concurrently.

Immunosuppressives, zofenopril

Increased risk of hypersensitivity reactions when ACE inhibitors are used concurrently. Data from other ACE inhibitors indicate an increased risk of leucopenia when used concurrently.

Insulin, zofenopril

Rarely ACE inhibitors can potentiate the blood glucose-reducing effects of insulin and oral antidiabetics like sulphonylurea, in diabetics.

Lithium, zofenopril

Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors.

Loop diuretics, zofenopril

Prior treatment with high dose diuretics may result in volume depletion and a risk of hypotension when initiating therapy with zofenopril

Metabolized by cytochrome P450, zofenopril

In vitro metabolic studies with zofenopril demonstrated no potential interaction with drug that are metabolised by CYP enzymes.

Narcotics, zofenopril

Postural hypotension may occur

Neuroleptics, zofenopril

Postural hypotension may occur

NSAID, zofenopril

The administration of NSAIDS may reduce the antihypertensive effect of an ACE inhibitor. Furthermore, it has been described that NSAIDS and ACE inhibitors exert an additive effect on the increase in serum potassium whereas renal function may decrease.

Oral antidiabetics, zofenopril

Rarely ACE inhibitors can potentiate the blood glucose-reducing effects of insulin and oral antidiabetics like sulphonylurea, in diabetics.

Organic nitrates, zofenopril

Additive or enhanced hypotension may occur. Caution is recommended when coadministering zofenopril with nitroglycerin and other nitrates or with vasodilatators

Potassium, zofenopril

Potassium sparing diuretics, potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium. Combination is not recommended

Potassium-sparing diuretics, zofenopril

Potassium sparing diuretics, potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium. Combination is not recommended

Pregnancy, zofenopril

The use of ACE inhibitors is not recommended during the 1st trimester of pregnancy and are contraindicated during the 2nd and 3rd trimester of pregnancy.

Procainamide, zofenopril

Increased risk of hypersensitivity reactions when ACE inhibitors are used concurrently. Data from other ACE inhibitors indicate an increased risk of leucopenia when used concurrently.

Spironolactone, zofenopril

Potassium sparing diuretics, potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium. Combination is not recommended

Sulfonylureas, zofenopril

Rarely ACE inhibitors can potentiate the blood glucose-reducing effects of insulin and oral antidiabetics like sulphonylurea, in diabetics.

Sympathomimetics, zofenopril

Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors; patients should be carefully monitored to confirm that the desired effect is being obtained.

Thiazides, zofenopril

Prior treatment with high dose diuretics may result in volume depletion and a risk of hypotension when initiating therapy with zofenopril

Triamterene, zofenopril

Potassium sparing diuretics, potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium. Combination is not recommended

Tricyclic antidepressant, zofenopril

Postural hypotension may occur

Vasodilators, zofenopril

Additive or enhanced hypotension may occur. Caution is recommended when coadministering zofenopril with nitroglycerin and other nitrates or with vasodilatators

Zoledronic acid (Zoledronic acid Actavis)

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

Adverse reactions, such as dizziness and somnolence, may have influence on the ability to drive or use machines, therefore caution should be exercised with the use of Zoledronic acid Actavis along with driving and operating of machinery.

Aminoglycoside antibiotics, zoledronic acid [2] ---> SmPC of [2] of EMA

Caution is advised when bisphosphonates are administered with aminoglycosides, since both agents may have an additive effect, resulting in a lower serum calcium level for longer periods than required.

Analgesics, zoledronic acid [2] ---> SmPC of [2] of EMA

In clinical studies, zoledronic acid, used as indicated in sections 4.1 and 4.2, has been administered concomitantly with commonly used anticancer agents, diuretics, antibiotics and analgesics without clinically apparent interactions occurring.

Antiangiogenic medicine, zoledronic acid [2] ---> SmPC of [2] of EMA

Caution is advised when Zoledronic acid Actavis is administered with anti-angiogenic medicinal products, as an increase in the incidence of ONJ has been observed in patients treated concomitantly with these medicinal products.

Antibiotics, zoledronic acid [2] ---> SmPC of [2] of EMA

Antineoplastics, zoledronic acid [2] ---> SmPC of [2] of EMA

Antineovascularisation agents, zoledronic acid [2] ---> SmPC of [2] of EMA

Reports of osteonecrosis of the jaw have been received in patients treated with zoledronic acid and concomitant anti-angiogenic medicinal products

Biphosphonates, loop diuretics ---> SmPC of [zoledronic acid] of EMA

Caution is advised when bisphosphonates are administered with loop diuretics, since these agents may have an additive effect, resulting in a lower serum calcium level for longer periods than required

Biphosphonates, osteonecrosis of the external auditory ---> SmPC of [zoledronic acid] of EMA

Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in association with long-term therapy.

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

It is not known whether zoledronic acid is excreted into human milk. Zoledronic acid Actavis is contraindicated in breast-feeding women (see section 4.3).

Calcitonin, zoledronic acid [2] ---> SmPC of [2] of EMA

Caution is advised when bisphosphonates are administered with calcitonin, since it may have an additive effect, resulting in a lower serum calcium level for longer periods than required

Chemotherapy, zoledronic acid [2] ---> SmPC of [2] of EMA

Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in association with long-term therapy.

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

Zoledronic acid shows no appreciable binding to plasma proteins and does not inhibit human P450 enzymes in vitro (see section 5.2), but no formal clinical interaction studies have been performed.

Diuretics, zoledronic acid [2] ---> SmPC of [2] of EMA

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

Thus these results precluded determining a definitive effect of zoledronic acid on fertility in humans.

Hypomagnesemia, zoledronic acid [2] ---> SmPC of [2] of EMA

Attention should be paid to the possibility of hypomagnesaemia developing during treatment.

Loop diuretics, zoledronic acid [2] ---> SmPC of [2] of EMA

Caution is advised when bisphosphonates are administered with loop diuretics, since these agents may have an additive effect, resulting in a lower serum calcium level for longer periods than required

Nephrotoxic substances, zoledronic acid [2] ---> SmPC of [2] of EMA

Caution is indicated when Zoledronic acid Actavis is used with other potentially nephrotoxic medicinal products. Attention should also be paid to the possibility of hypomagnesaemia developing during treatment.

Osteonecrosis of the external auditory, zoledronic acid [2] ---> SmPC of [2] of EMA

Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in association with long-term therapy.

Osteonecrosis of the jaw, zoledronic acid [2] ---> SmPC of [2] of EMA

Osteonecrosis of the jaw (ONJ) has been reported uncommonly in clinical trials and in the post-marketing setting in patients receiving zoledronic acid.

Pregnancy, zoledronic acid [2] ---> SmPC of [2] of EMA

Zoledronic acid Actavis should not be used during pregnancy. Women of childbearing potential should be advised to avoid becoming pregnant.

Steroids, zoledronic acid [2] ---> SmPC of [2] of EMA

Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in association with long-term therapy.

Thalidomide, zoledronic acid [2] ---> SmPC of [2] of EMA

In multiple myeloma patients, the risk of renal dysfunction may be increased when Zoledronic acid Actavis is used in combination with thalidomide.

Women of childbearing potential, zoledronic acid [2] ---> SmPC of [2] of EMA

Women of childbearing potential should be advised to avoid becoming pregnant.

CONTRAINDICATIONS of Zoledronic acid Zoledronic acid Actavis

- Hypersensitivity to the active substance, to other bisphosphonates or to any of the excipients listed in section 6.1

- Breast-feeding

https://www.ema.europa.eu/en/documents/product-information/zoledronic-acid-actavis-epar-product-information_en.pdf 01/06/2023

Other trade names: Aclasta, Zoledronic Acid Accord, Zoledronic Acid Hospira, Zoledronic acid medac, Zoledronic acid Mylan, Zoledronic acid Teva, Zoledronic acid Teva Generics, Zoledronic acid Teva Pharma, Zometa,

Zolbetuximab (Vyloy)

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

Since it is known that antibodies can be excreted in human milk, and because of the potential for serious adverse reactions in a breast-fed child, breast-feeding is not recommended during treatment with zolbetuximab.

Catabolism, zolbetuximab [2] ---> SmPC of [2] of EMA

Since zolbetuximab is cleared from the circulation through catabolism, no metabolic drug-drug interactions are expected.

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

Studies to evaluate the effect of zolbetuximab on fertility have not been performed. Thus, the effect of zolbetuximab on male and female fertility is unknown.

Pregnancy, zolbetuximab [2] ---> SmPC of [2] of EMA

Zolbetuximab should only be given to a pregnant woman if the benefit outweighs the potential risk.

Women of childbearing potential, zolbetuximab [2] ---> SmPC of [2] of EMA

As a precautionary measure, women of childbearing potential should be advised to use effective contraception to prevent pregnancy during treatment.

CONTRAINDICATIONS of Zolbetuximab (Vyloy)

- 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/vyloy-epar-product-information_en.pdf 23/09/2024

Zolmitriptan

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

Caution is recommended in patients performing skilled tasks (e.g. driving or operating machinery) as drowsiness and other symptoms may occur during a migraine attack.

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

Caution should be exercised when administering Zolmitriptan to women who are breast-feeding. Infant exposure should be minimised by avoiding breast feeding for 24 hours after treatment.

Bromocriptine, zolmitriptan

Additive vasoconstrictive effects. The combination increases the risk of serotonin syndrome.

Cimetidine, zolmitriptan [2] ---> SmPC of [2] of eMC

Following the administration of cimetidine, a general P450 inhibitor, the half-life of zolmitriptan was increased by 44% and the AUC increased by 48%.

Ciprofloxacin, zolmitriptan [2] ---> SmPC of [2] of eMC

Based on the overall interaction profile, an interaction of zolmitriptan with inhibitors of the cytochrome P450 isoenzyme CYP1A2 cannot be excluded.

CYP1A2 inhibitors, zolmitriptan [2] ---> SmPC of [2] of eMC

Based on the overall interaction profile, an interaction of zolmitriptan with inhibitors of the cytochrome P450 isoenzyme CYP1A2 cannot be excluded.

Dihydroergotamine, zolmitriptan [2] ---> SmPC of [2] of eMC

Increased risk of coronary vasospasm is a theoretical possibility. Concomitant use is contraindicated.

Ergot derivatives, zolmitriptan [2] ---> SmPC of [2] of eMC

Increased risk of coronary vasospasm is a theoretical possibility. Concomitant use is contraindicated.

Ergotamine, zolmitriptan [2] ---> SmPC of [2] of eMC

Increased risk of coronary vasospasm is a theoretical possibility. Concomitant use is contraindicated.

Fluvoxamine, zolmitriptan [2] ---> SmPC of [2] of eMC

Based on the overall interaction profile, an interaction of zolmitriptan with inhibitors of the cytochrome P450 isoenzyme CYP1A2 cannot be excluded.

IMAOs A, zolmitriptan [2] ---> SmPC of [2] of eMC

The MAO inhibition may increase the serum concentration of zolmitriptan.

Methysergide, zolmitriptan [2] ---> SmPC of [2] of eMC

Increased risk of coronary vasospasm is a theoretical possibility. Concomitant use is contraindicated.

Moclobemide, zolmitriptan [2] ---> SmPC of [2] of eMC

The MAO inhibition may increase the serum concentration of zolmitriptan.

Naratriptan, zolmitriptan [2] ---> SmPC of [2] of eMC

Increased risk of coronary vasospasm is a theoretical possibility. Concomitant use is contraindicated.

Pregnancy, zolmitriptan [2] ---> SmPC of [2] of eMC

Administration of zolmitriptan should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.

Procarbazine, zolmitriptan [2] ---> SmPC of [2] of eMC

The MAO inhibition may increase the serum concentration of zolmitriptan.

Quinolones, zolmitriptan [2] ---> SmPC of [2] of eMC

Based on the overall interaction profile, an interaction of zolmitriptan with inhibitors of the cytochrome P450 isoenzyme CYP1A2 cannot be excluded.

Rasagiline, zolmitriptan [2] ---> SmPC of [2] of eMC

The MAO inhibition may increase the serum concentration of zolmitriptan.

Rizatriptan [1], zolmitriptan ---> SmPC of [1] of eMC

Due to an additive effect, the concomitant use increases the risk of coronary artery vasoconstriction and hypertensive effects. This combination is contraindicated

SNRIs, zolmitriptan [2] ---> SmPC of [2] of eMC

There have been isolated reports describing patients with symptoms compatible with serotonin syndrome following the use serotonin norepinephrine reuptake inhibitors (SNRIs) and triptans

SSRI, zolmitriptan [2] ---> SmPC of [2] of eMC

There have been isolated reports describing patients with symptoms compatible with serotonin syndrome following the use of selective serotonin reuptake inhibitors (SSRIs) and triptans

St. John's wort, triptans ---> SmPC of [zolmitriptan] of eMC

Undesirable effects may be more common during concomitant use of triptans and herbal preparations containing St John's wort (Hypericum perforatum).

St. John's wort, zolmitriptan [2] ---> SmPC of [2] of eMC

Undesirable effects may be more common during concomitant use of triptans and herbal preparations containing St John's wort (Hypericum perforatum).

Strong CYP1A2 inhibitors, zolmitriptan [2] ---> SmPC of [2] of eMC

Based on the overall interaction profile, an interaction of zolmitriptan with inhibitors of the cytochrome P450 isoenzyme CYP1A2 cannot be excluded.

Sumatriptan, zolmitriptan [2] ---> SmPC of [2] of eMC

Increased risk of coronary vasospasm is a theoretical possibility. Concomitant use is contraindicated.

Triptans, zolmitriptan [2] ---> SmPC of [2] of eMC

Increased risk of coronary vasospasm is a theoretical possibility. Concomitant use is contraindicated.

CONTRAINDICATIONS of Zolmitriptan

Zolmitriptan is contraindicated in patients with:

- Hypersensitivity to zolmitriptan or to any of the excipients

- Moderate or severe hypertension, and mild uncontrolled hypertension.

- A history of myocardial infarction or ischaemic heart disease.

- Coronary vasospasm/Prinzmetal's angina.

- Peripheral vascular disease

- A history of cerebrovascular accident (CVA) or transient ischaemic attack (TIA).

- Concomitant administration of zolmitriptan with ergotamine or ergotamine derivatives (including methysergide) or other 5-HT1 receptor agonists (e.g. sumatriptan, naratriptan).

- Symptomatic Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathways.

- Creatinine clearance lower than 15 ml/min.

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

Zolpidem

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

Vehicle drivers and machine operators should be warned that, as with other hypnotics, there may be a possible risk of drowsiness the morning after therapy.

Alcohol, zolpidem [2] ---> SmPC of [2] of eMC

The sedative effect may be enhanced when the product is used in combination with alcohol.

Anaesthetics, zolpidem [2] ---> SmPC of [2] of eMC

Enhancement of the central depressive effect may occur in case of concomitant use of zolpidem with other central nervous system depressants

Antidepressants, zolpidem [2] ---> SmPC of [2] of eMC

Enhancement of the central depressive effect may occur in case of concomitant use of zolpidem with other central nervous system depressants

Antiepileptics, zolpidem [2] ---> SmPC of [2] of eMC

Enhancement of the central depressive effect may occur in case of concomitant use of zolpidem with other central nervous system depressants

Anxiolytics, zolpidem [2] ---> SmPC of [2] of eMC

Enhancement of the central depressive effect may occur in case of concomitant use of zolpidem with other central nervous system depressants

Aprepitant, zolpidem

Possible increase of plasma concentrations of benzodiazepines metabolised via CYP3A4. Caution is advised

Atazanavir/cobicistat [1], zolpidem ---> SmPC of [1] of EMA

Concentrations of the sedative/hypnotic may be increased when co-administered with EVOTAZ. The mechanism is inhibition of CYP3A4 by cobicistat. For the sedative/hypnotic, dose reduction may be necessary and concentration monitoring is recommended.

Azole antifungals, zolpidem

CYP3A4 inhibitors may increase the effect of zolpidem

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

Small quantities of zolpidem tartrate appear in breast milk. The use of zolpidem tartrate in nursing mothers is therefore not recommended.

Carbamazepine, zolpidem

The strong CYP3A4 induction may reduce plasma concentrations and de hypnotic effects of zolpidem

Ciprofloxacin, zolpidem

Concomitant use of ciprofloxacin may increase plasma concentrations of zolpidem. Concomitant use is not recommended

CNS depressants, zolpidem [2] ---> SmPC of [2] of eMC

Enhancement of the central depressive effect may occur in case of concomitant use of zolpidem with other central nervous system depressants

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

Concentrations of this sedative/hypnotic may be increased when co-administered with cobicistat.

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

REZOLSTA is expected to increase the sedative/hypnotic plasma concentrations. (CYP3A inhibition). Clinical monitoring is recommended when co-administering REZOLSTA with this sedative/hypnotic and a lower dose of the sedative/hypnotic should be considered

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], zolpidem ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this sedative/hypnotic plasma concentrations. CYP3A inhibition

Darunavir/ritonavir, zolpidem ---> SmPC of [darunavir] of EMA

Sedative/hypnotics are extensively metabolised by CYP3A. Co-administration with boosted darunavir may cause a large increase in the concentration of these medicines.

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

Zolpidem is metabolized by CYP3A, drug interaction studies indicate that no dose adjustment is needed when co-administering zolpidem with ombitasvir/paritaprevir/ritonavir with or without dasabuvir

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], zolpidem ---> SmPC of [1] of EMA

Concentrations of other benzodiazepines, including diazepam, may be increased when administered with Genvoya. With other sedatives/hypnotics, dose reduction may be necessary and concentration monitoring is recommended.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], zolpidem ---> SmPC of [1] of EMA

The co-administration may increase the plasma concentrations of sedative. Dose reduction may be necessary and concentration monitoring is recommended.

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

Enzalutamide, enzymatic inductor, may increase the metabolism of zolpidem and decrease its plasma levels and effect

Fluvoxamine, zolpidem

Concomitant use of fluvoxamine may increase plasma concentrations of zolpidem. Concomitant use is not recommended

Foods, zolpidem

Should not be administered with or immediately after a meal.

Grapefruit juice, zolpidem

CYP3A4 inhibitors may increase the effect of zolpidem

Hypnotics, zolpidem [2] ---> SmPC of [2] of eMC

Enhancement of the central depressive effect may occur in case of concomitant use of zolpidem with other central nervous system depressants

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.

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.

Ketoconazole, zolpidem [2] ---> SmPC of [2] of eMC

Co-administration with ketoconazole increased total AUC, and decreased apparent oral clearance of zolpidem. A routine dosage adjustment of zolpidem is not considered necessary. The use of zolpidem with ketoconazole may enhance the sedative effects.

Macrolide antibiotics, zolpidem

CYP3A4 inhibitors may increase the effect of zolpidem

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

Melatonin may enhance the sedative properties of benzodiazepines and non-benzodiazepine hypnotics

Muscle relaxants, zolpidem

The co-administration of zolpidem with muscle relaxants may potentiate the muscle-relaxant effect

Neuroleptics, zolpidem [2] ---> SmPC of [2] of eMC

Enhancement of the central depressive effect may occur in case of concomitant use of zolpidem with other central nervous system depressants

Ombitasvir/paritaprevir/ritonavir [1], zolpidem ---> SmPC of [1] of EMA

Zolpidem is metabolized by CYP3A, drug interaction studies indicate that no dose adjustment is needed when co-administering zolpidem with ombitasvir/paritaprevir/ritonavir with or without dasabuvir

Opioid analgesics, zolpidem [2] ---> SmPC of [2] of eMC

The co-administration may enhance the depressive effect on the CNS and an enhancement of the euphoria, leading to an increase in psychic dependence

Phenytoin, zolpidem

The strong CYP3A4 induction may reduce plasma concentrations and de hypnotic effects of zolpidem

Pregnancy, zolpidem [2] ---> SmPC of [2] of eMC

As with all drugs zolpidem tartrate should be avoided in pregnancy particularly during the first trimester.

Rifampicin, zolpidem [2] ---> SmPC of [2] of eMC

The pharmacodynamic effect of zolpidem tartrate is decreased when it is administered with rifampicin (a CYP3A4 inducer).

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

Zolpidem and ritonavir may be co-administered with careful monitoring for excessive sedative effects.

Sedating antihistamines, zolpidem [2] ---> SmPC of [2] of eMC

Enhancement of the central depressive effect may occur in case of concomitant use of zolpidem with other central nervous system depressants

Sedatives, zolpidem [2] ---> SmPC of [2] of eMC

Enhancement of the central depressive effect may occur in case of concomitant use of zolpidem with other central nervous system depressants

Strong CYP3A4 inductors, zolpidem

The strong CYP3A4 induction may reduce plasma concentrations and de hypnotic effects of zolpidem

Strong CYP3A4 inhibitors, zolpidem

CYP3A4 inhibitors may increase the effect of zolpidem

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

Decreased AUC and Cmax of zolpidem. Increased dose of zolpidem may be required to maintain efficacy.

Telithromycin, zolpidem

The CYP3A4 inhibition may increase the plasma levels of zolpidem. Oral coadministration should be avoided

CONTRAINDICATIONS of Zolpidem

- Zolpidem tartrate is contraindicated in patients with a hypersensitivity to zolpidem tartrate or any of the inactive ingredients,

- obstructive sleep apnoea,

- myasthenia gravis,

- severe hepatic insufficiency,

- acute and/or severe respiratory depression.

In the absence of data, zolpidem tartrate should not be prescribed for children or patients with psychotic illness.

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

Zonisamide (Zonegran)

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

Some patients may experience drowsiness or difficulty with concentration, particularly early in treatment or after a dose increase

Acetazolamide, zonisamide [2] ---> SmPC of [2] of EMA

Zonegran should be used with caution in adult patients treated concomitantly with carbonic anhydrase inhibitors such as topiramate and acetazolamide, as there are insufficient data to rule out a possible pharmacodynamic interaction

Anticholinergics, zonisamide [2] ---> SmPC of [2] of EMA

Caution should be used in adults when Zonegran is prescribed with other medicinal products that predispose patients to heat related disorders; these include carbonic anhydrase inhibitors and medicinal products with anticholinergic activity

Antiepileptics, zonisamide [2] ---> SmPC of [2] of EMA

In epileptic patients, steady-state dosing with Zonegran resulted in no clinically relevant pharmacokinetic effects on carbamazepine, lamotrigine, phenytoin, or sodium valproate

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

Due to the long retention time of zonisamide in the body, breast-feeding must not be resumed until one month after Zonegran therapy is completed.

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

Zonisamide is excreted in human milk; the concentration in breast milk is similar to maternal plasma. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Zonegran therapy.

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

In epileptic patients, steady-state dosing with Zonegran resulted in no clinically relevant pharmacokinetic effects on carbamazepine, lamotrigine, phenytoin, or sodium valproate.

Carbonic anhydrase inhibitors, zonisamide [2] ---> SmPC of [2] of EMA

Cimetidine, zonisamide [2] ---> SmPC of [2] of EMA

Steady-state dosing of either ketoconazole (400 mg/day) or cimetidine (1200 mg/day) had no clinically relevant effects on the single-dose pharmacokinetics of zonisamide given to healthy subjects.

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

Zonegran is not expected to affect the pharmacokinetics of other medicinal products via cytochrome P450-mediated mechanisms, as demonstrated for carbamazepine, phenytoin, ethinylestradiol and desipramine in vivo.

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

Caution is advised when starting or stopping zonisamide treatment or changing the zonisamide dose in patients who are also receiving medicinal products which are P-gp substrates (e.g. digoxin, quinidine).

Ethinylestradiol/norethisterone, zonisamide [2] ---> SmPC of [2] of EMA

In clinical studies in healthy subjects, steady-state dosing with Zonegran did not affect serum concentrations of ethinylestradiol or norethisterone in a combined oral contraceptive.

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

There are no clinical data available on the effects of zonisamide on human fertility. Studies in animals have shown changes in fertility parameters (see section 5.3).

Hepatic event, zonisamide [2] ---> SmPC of [2] of EMA

Nevertheless, if a hepatic event is suspected, liver function should be evaluated and discontinuation of Zonegran should be considered.

Insolation, zonisamide [2] ---> SmPC of [2] of EMA

Interruption, zonisamide [2] ---> SmPC of [2] of EMA

As with all antiepileptic medicines, sudden discontinuation of zonisamide should be avoided as this may lead to breakthrough seizures that could have serious consequences for the woman and the unborn child.

Ketoconazole, zonisamide [2] ---> SmPC of [2] of EMA

Steady-state dosing of either ketoconazole (400 mg/day) or cimetidine (1200 mg/day) had no clinically relevant effects on the single-dose pharmacokinetics of zonisamide given to healthy subjects.

Lamotrigine, zonisamide [2] ---> SmPC of [2] of EMA

In epileptic patients, steady-state dosing with Zonegran resulted in no clinically relevant pharmacokinetic effects on carbamazepine, lamotrigine, phenytoin, or sodium valproate.

Moderate CYP3A4 inhibitors, zonisamide [2] ---> SmPC of [2] of EMA

Therefore, modification of Zonegran dosing should not be necessary when co-administered with known CYP3A4 inhibitors.

N-acetyltransferase inductors, zonisamide [2] ---> SmPC of [2] of EMA

Zonisamide is metabolised partly by CYP3A4 (reductive cleavage), and also by N-acetyl-transferases and conjugation with glucuronic acid; therefore, substances that can induce or inhibit these enzymes may affect the pharmacokinetics of zonisamide

Oral contraceptives, zonisamide [2] ---> SmPC of [2] of EMA

In clinical studies in healthy subjects, steady-state dosing with Zonegran did not affect serum concentrations of ethinylestradiol or norethisterone in a combined oral contraceptive.

P-glycoprotein substrates, zonisamide [2] ---> SmPC of [2] of EMA

Pediatrics, zonisamide [2] ---> SmPC of [2] of EMA

Zonegran should not be used as co-medication in paediatric patients with other carbonic anhydrase inhibitors such as topiramate and acetazolamide

Perampanel [1], zonisamide ---> SmPC of [1] of EMA

Clonazepam, levetiracetam, phenobarbital, topiramate, zonisamide, clobazam, lamotrigine and valproic acid did not affect to a clinically relevant manner the clearance of Fycompa.

Phenobarbital, zonisamide [2] ---> SmPC of [2] of EMA

The strong CYP3A4 induction decreases the zonisamide exposition. This effect is unlikely to be of clinical significance when zonisamide is added to existing therapy

Phenytoin, zonisamide [2] ---> SmPC of [2] of EMA

In epileptic patients, steady-state dosing with Zonegran resulted in no clinically relevant pharmacokinetic effects on carbamazepine, lamotrigine, phenytoin, or sodium valproate.

Pregnancy, zonisamide [2] ---> SmPC of [2] of EMA

If Zonegran is prescribed during pregnancy, patients should be fully informed of the potential harm to the foetus and use of the minimal effective dose is advised along with careful monitoring.

Pregnancy, zonisamide [2] ---> SmPC of [2] of EMA

Zonegran must not be used during pregnancy unless clearly necessary and only if the potential benefit is considered to justify the risk to the foetus.

Primidone, zonisamide

Primidone, enzymatic inductor, may accelerate the metabolism of zonisamide and decrease its plasma levels and effect

Quinidine, zonisamide [2] ---> SmPC of [2] of EMA

Retigabine [1], zonisamide ---> SmPC of [1] of EMA

Based on these pooled data, retigabine did not cause clinically significant effects on the plasma trough concentrations of this antiepileptic medicinal product

Rifampicin, zonisamide [2] ---> SmPC of [2] of EMA

Rifampicin is a potent CYP3A4 inducer. If co-administration is necessary, the patient should be closely monitored and the dose of Zonegran and other CYP3A4 substrates adjusted as needed.

Strong CYP3A4 inductors, zonisamide [2] ---> SmPC of [2] of EMA

The strong CYP3A4 induction decreases the zonisamide exposition. This effect is unlikely to be of clinical significance when zonisamide is added to existing therapy

Strong CYP3A4 inhibitors, zonisamide [2] ---> SmPC of [2] of EMA

Therefore, modification of Zonegran dosing should not be necessary when co-administered with known CYP3A4 inhibitors.

Topiramate, zonisamide [2] ---> SmPC of [2] of EMA

Urolithiasis, zonisamide [2] ---> SmPC of [2] of EMA

The combination of Zonegran with other medicinal products that may lead to urolithiasis may enhance the risk of developing kidney stones; therefore the concomitant administration of such medicinal products should be avoided.

Valproate, zonisamide [2] ---> SmPC of [2] of EMA

In epileptic patients, steady-state dosing with Zonegran resulted in no clinically relevant pharmacokinetic effects on carbamazepine, lamotrigine, phenytoin, or sodium valproate.

Women of childbearing potential, zonisamide [2] ---> SmPC of [2] of EMA

Women planning a pregnancy should meet with their specialists to reassess treatment with zonisamide and to consider other therapeutic options prior to conception and before contraception is discontinued.

Women of childbearing potential, zonisamide [2] ---> SmPC of [2] of EMA

Women of childbearing potential must use effective contraception during treatment with Zonegran, and for one month after discontinuation.

CONTRAINDICATIONS of Zonisamide (Zonegran)

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

- Zonegran contains Hydrogenated vegetable oil (from soyabean). Patients must not take this medicinal product if they are allergic to peanut or soya.

https://www.ema.europa.eu/en/documents/product-information/zonegran-epar-product-information_en.pdf 18/09/2025

Other trade names: Zonisamide Mylan, Zonisamide Viatris (previously Zonisamide Mylan),

Zopiclone

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

Although residual effects are rare and generally of minor significance, patients should be advised not to drive or operate machinery the day after treatment

Alcohol, zopiclone [2] ---> SmPC of [2] of eMC

The sedative effect of zopiclone may be enhanced when used in combination with alcohol, concomitant use is therefore not recommended.

Anaesthetics, zopiclone [2] ---> SmPC of [2] of eMC

The combination with CNS depressants an enhancement of the central depressive effect may occur.

Antidepressants, zopiclone [2] ---> SmPC of [2] of eMC

The combination with CNS depressants an enhancement of the central depressive effect may occur.

Antiepileptics, zopiclone [2] ---> SmPC of [2] of eMC

The combination with CNS depressants an enhancement of the central depressive effect may occur.

Anxiolytics, zopiclone [2] ---> SmPC of [2] of eMC

The combination with CNS depressants an enhancement of the central depressive effect may occur.

Aprepitant, zopiclone

Possible increase of plasma concentrations of benzodiazepines metabolised via CYP3A4. Caution is advised

Azole antifungals, 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

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

Zopiclone is excreted in breast milk, although the concentration of zopiclone in the breast milk is low, use in nursing mothers must be avoided.

Carbamazepine, zopiclone [2] ---> SmPC of [2] of eMC

Plasma levels of zopiclone may be decreased when co-administered with CYP3A4 inducers

Cimetidine, 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

Clarithromycin, 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

CNS depressants, zopiclone [2] ---> SmPC of [2] of eMC

The combination with CNS depressants an enhancement of the central depressive effect may occur.

CYP3A4 inhibitors, 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

Erythromycin, 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

Hypnotics, zopiclone [2] ---> SmPC of [2] of eMC

The combination with CNS depressants an enhancement of the central depressive effect may occur.

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

Ketoconazole, 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

Macrolide antibiotics, 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

Melatonin [1], zopiclone ---> SmPC of [1] of EMA

Melatonin may enhance the sedative properties of benzodiazepines and non-benzodiazepine hypnotics

Moderate CYP3A4 inhibitors, 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

Muscle relaxants, zopiclone

The co-administration may enhance the muscle-relaxant effect

Neuroleptics, zopiclone [2] ---> SmPC of [2] of eMC

The combination with CNS depressants an enhancement of the central depressive effect may occur.

Opioid analgesics, zopiclone [2] ---> SmPC of [2] of eMC

The co-administration may enhance the depressive effect on the CNS and an enhancement of the euphoria, leading to an increase in psychic dependence

Phenobarbital, zopiclone [2] ---> SmPC of [2] of eMC

Plasma levels of zopiclone may be decreased when co-administered with CYP3A4 inducers

Phenytoin, zopiclone [2] ---> SmPC of [2] of eMC

Plasma levels of zopiclone may be decreased when co-administered with CYP3A4 inducers

Pregnancy, zopiclone [2] ---> SmPC of [2] of eMC

Use in pregnancy is not recommended.

Protease inhibitors, 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

Rifampicin, zopiclone [2] ---> SmPC of [2] of eMC

Plasma levels of zopiclone may be decreased when co-administered with CYP3A4 inducers

Ritonavir, 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

Sedating antihistamines, zopiclone [2] ---> SmPC of [2] of eMC

The combination with CNS depressants an enhancement of the central depressive effect may occur.

Sedatives, zopiclone [2] ---> SmPC of [2] of eMC

The combination with CNS depressants an enhancement of the central depressive effect may occur.

St. John's wort, zopiclone [2] ---> SmPC of [2] of eMC

Plasma levels of zopiclone may be decreased when co-administered with CYP3A4 inducers

Strong CYP3A4 inductors, zopiclone [2] ---> SmPC of [2] of eMC

Plasma levels of zopiclone may be decreased when co-administered with CYP3A4 inducers

Strong CYP3A4 inhibitors, 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

Telithromycin, 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 Zopiclone

Zimovane is contraindicated in patients with:

- Myasthenia gravis

- Respiratory failure

- Severe sleep apnoea syndrome

- Severe hepatic insufficiency

- Hypersensitivity to zopiclone or to any of the excipients.

As with all hypnotics Zimovane should not be used in children.

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

Zuclopenthixol

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

Alertness may be impaired, especially at the start of treatment, or following the consumption of alcohol

Adrenergics, zuclopenthixol [2] ---> SmPC of [2] of eMC

Antipsychotics may impair the effect of adrenergic drugs

Alcohol, zuclopenthixol [2] ---> SmPC of [2] of eMC

Zuclopenthixol enhances the response to alcohol

Alpha-methyldopa, zuclopenthixol [2] ---> SmPC of [2] of eMC

Antipsychotics may reverse the antihypertensive effects of guanethidine and similar adrenergic-blocking agents.

Amiodarone, zuclopenthixol [2] ---> SmPC of [2] of eMC

Increases in the QT interval related to antipsychotic treatment may be exacerbated by the co-administration of other drugs known to significantly increase the QT interval. Co-administration of such drugs should be avoided.

Anticholinergics, zuclopenthixol [2] ---> SmPC of [2] of eMC

The anticholinergic effects of other drugs with anticholinergic properties may be increased.

Anticoagulants, zuclopenthixol [2] ---> SmPC of [2] of eMC

Zuclopenthixol may potentiate the effects of anticoagulants

Antidiabetics, zuclopenthixol [2] ---> SmPC of [2] of eMC

As described for other psychotropics zuclopenthixol may modify insulin and glucose responses calling for adjustment of the antidiabetic therapy in diabetic patients.

Antihypertensives, zuclopenthixol

Zuclopenthixol may increase or decrease the effect of antihypertensive agent

Astemizole, zuclopenthixol [2] ---> SmPC of [2] of eMC

Barbiturates, zuclopenthixol [2] ---> SmPC of [2] of eMC

Zuclopenthixol enhances the effects of barbiturates

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

As zuclopenthixol is found in breast milk in low concentrations it is not likely to affect the infant when therapeutic doses are used.

Chlorpromazine, lithium ---> SmPC of [zuclopenthixol] of eMC

Combined use of antipsychotics and lithium has been associated with an increased risk of neurotoxicity.

Chlorpromazine, zuclopenthixol [2] ---> SmPC of [2] of eMC

Since zuclopenthixol is partly metabolised by CYP2D6 concomitant use of drugs known to inhibit this enzyme may lead to higher than expected plasma concentrations of zuclopenthixol, increasing the risk of adverse effects and cardiotoxicity.

Cisapride, zuclopenthixol [2] ---> SmPC of [2] of eMC

Class IA antiarrhythmic agents, zuclopenthixol [2] ---> SmPC of [2] of eMC

Class III antiarrhythmic agents, zuclopenthixol [2] ---> SmPC of [2] of eMC

Clonidine, zuclopenthixol [2] ---> SmPC of [2] of eMC

Antipsychotics may reverse the antihypertensive effects of guanethidine and similar adrenergic-blocking agents.

CNS depressants, zuclopenthixol [2] ---> SmPC of [2] of eMC

Zuclopenthixol enhances the effects of other CNS depressants.

CYP2D6 inhibitors, zuclopenthixol [2] ---> SmPC of [2] of eMC

Dofetilide, zuclopenthixol [2] ---> SmPC of [2] of eMC

The co-administration of zuclopenthixol with drugs that can prolong the QT interval should be avoided

Dopamine agonists, zuclopenthixol

Antipsychotics may impair the effect of dopamine agonist

Electrolyte imbalance, zuclopenthixol [2] ---> SmPC of [2] of eMC

Drugs known to cause electrolyte disturbances such as thiazide diuretics (hypokalemia) should be used with caution as they may increase the risk of QT prolongation and malignant arrhythmias

Erythromycin, zuclopenthixol [2] ---> SmPC of [2] of eMC

Gatifloxacin, zuclopenthixol [2] ---> SmPC of [2] of eMC

General anesthetics, zuclopenthixol [2] ---> SmPC of [2] of eMC

Zuclopenthixol may potentiate the effects of general anaesthetics

Gonadorelin, zuclopenthixol

Decrease of the reaction to gonadorelin due to increase of the prolactin

Guanethidine, zuclopenthixol [2] ---> SmPC of [2] of eMC

Antipsychotics may reverse the antihypertensive effects of guanethidine and similar adrenergic-blocking agents.

Hypokalemia, zuclopenthixol [2] ---> SmPC of [2] of eMC

Drugs known to cause electrolyte disturbances such as thiazide diuretics (hypokalemia) should be used with caution as they may increase the risk of QT prolongation and malignant arrhythmias

Levodopa, zuclopenthixol [2] ---> SmPC of [2] of eMC

Antipsychotics may impair the effect of levodopa

Lithium carbonate, neuroleptics ---> SmPC of [zuclopenthixol] of eMC

Combined use of antipsychotics and lithium has been associated with an increased risk of neurotoxicity.

Lithium, neuroleptics ---> SmPC of [zuclopenthixol] of eMC

Combined use of antipsychotics and lithium or sibutramine has been associated with an increased risk of neurotoxicity.

Lithium, prothipendyl ---> SmPC of [zuclopenthixol] of eMC

Co-administration of antipsychotics and lithium may increase the risk of neuroleptic malignant syndrome, which may be fatal.

Lithium, zuclopenthixol [2] ---> SmPC of [2] of eMC

Combined use of antipsychotics and lithium or sibutramine has been associated with an increased risk of neurotoxicity.

Metoclopramide, zuclopenthixol [2] ---> SmPC of [2] of eMC

Concomitant use of zuclopenthixol and metoclopramide may increase the risk of extrapyramidal effects such as tardive dyskinesia.

Moxifloxacin, zuclopenthixol [2] ---> SmPC of [2] of eMC

Muscle relaxants, zuclopenthixol [2] ---> SmPC of [2] of eMC

Zuclopenthixol may prolong the action of neuromuscular blocking agents.

Neuroleptics, zuclopenthixol [2] ---> SmPC of [2] of eMC

Concomitant treatment of zuclopenthixol with other antipsychotics should be avoided

Non-potassium-sparing diuretics, zuclopenthixol [2] ---> SmPC of [2] of eMC

Drugs known to cause electrolyte disturbances such as thiazide diuretics (hypokalemia) should be used with caution as they may increase the risk of QT prolongation and malignant arrhythmias

Pentetrazol, zuclopenthixol

The co-administration of zuclopenthixol and pentetrazol may cause cerebral seizures

Piperazine, zuclopenthixol [2] ---> SmPC of [2] of eMC

Concomitant use of zuclopenthixol and piperazine may increase the risk of extrapyramidal effects such as tardive dyskinesia.

Polypeptide antibiotics, zuclopenthixol

Thioxanthenes combined with peptide antibiotics (e. g. capreomycin, colistin, polymyxin B) may enhance a central respiratory depression

Pregnancy, zuclopenthixol [2] ---> SmPC of [2] of eMC

Zuclopenthixol should not be administered during pregnancy unless the expected benefit to the patient outweighs the theoretical risk to the foetus.

QT interval prolonging drugs, zuclopenthixol [2] ---> SmPC of [2] of eMC

Quinidine, zuclopenthixol [2] ---> SmPC of [2] of eMC

Sotalol, zuclopenthixol [2] ---> SmPC of [2] of eMC

Strong CYP2D6 inhibitors, zuclopenthixol [2] ---> SmPC of [2] of eMC

Sympathomimetics, zuclopenthixol [2] ---> SmPC of [2] of eMC

Antipsychotics may antagonise the effects of sympathomimetic agents

Terfenadine, zuclopenthixol [2] ---> SmPC of [2] of eMC

Thiazides, zuclopenthixol [2] ---> SmPC of [2] of eMC

Drugs known to cause electrolyte disturbances such as thiazide diuretics (hypokalemia) should be used with caution as they may increase the risk of QT prolongation and malignant arrhythmias

Thioridazine, zuclopenthixol [2] ---> SmPC of [2] of eMC

Tiapride, zuclopenthixol

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

Tricyclic antidepressant, zuclopenthixol [2] ---> SmPC of [2] of eMC

The metabolism of tricyclic antidepressants may be inhibited

Vandetanib [1], zuclopenthixol ---> SmPC of [1] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

CONTRAINDICATIONS of Zuclopenthixol

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

- Circulatory collapse, depressed level of consciousness due to any cause (e.g. intoxication with alcohol, barbiturates or opiates), coma.

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

Zynteglo (Zynteglo)

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

The effect of the mobilisation agents and the myeloablative conditioning agent on the ability to drive or use machines must be considered.

Antiretrovirals, Zynteglo [2] ---> SmPC of [2] of EMA

Patients should not take anti-retroviral medicinal products or hydroxyurea from at least one month prior to mobilisation until at least 7 days after Zynteglo infusion

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

Zynteglo must not be administered to women who are breast-feeding.

CYP3A4 substrates, Zynteglo [2] ---> SmPC of [2] of EMA

The Summary of Product Characteristics (SmPC) for the iron chelator and the myeloablative conditioning agent must be consulted for the recommendations regarding co-administration with CYP3A substrates.

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

No formal drug interaction studies have been performed. Zynteglo is not expected to interact with the hepatic cytochrome P-450 family of enzymes or drug transporters.

Erythropoiesis, Zynteglo [2] ---> SmPC of [2] of EMA

There is no clinical experience with the use of erythropoiesis-stimulating agents in patients treated with Zynteglo.

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

Data are available on the risk of infertility with myeloablative conditioning. It is therefore advised to cryopreserve semen or ova before treatment if possible.

Hydroxyurea, Zynteglo [2] ---> SmPC of [2] of EMA

Patients should not take anti-retroviral medicinal products or hydroxyurea from at least one month prior to mobilisation until at least 7 days after Zynteglo infusion

Iron chelators, myeloablative conditioning agent ---> SmPC of [Zynteglo] of EMA

Drug-drug interactions between iron chelators and the myeloablative conditioning agent must be considered.

Iron chelators, Zynteglo [2] ---> SmPC of [2] of EMA

Some iron chelators are myelosuppressive. After Zynteglo infusion, avoid use of these iron chelators for 6 months. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators (see sections 4.2 and 5.1).

Iron chelators, Zynteglo [2] ---> SmPC of [2] of EMA

Iron chelators should be discontinued 7 days prior to initiation of conditioning.

Men, Zynteglo [2] ---> SmPC of [2] of EMA

Men capable of fathering a child must use a reliable method of contraception from start of mobilisation through at least 6 months after administration of Zynteglo.

Myelosuppressive agents, Zynteglo [2] ---> SmPC of [2] of EMA

Pregnancy, Zynteglo [2] ---> SmPC of [2] of EMA

Zynteglo must not be used during pregnancy because of myeloablative conditioning (see section 4.3). It is unknown whether Zynteglo transduced cells have the potential to be transferred in utero to a foetus.

Vaccinations with live organism vaccines, Zynteglo [2] ---> SmPC of [2] of EMA

The safety of immunisation with live viral vaccines during or following Zynteglo treatment has not been studied.

Women of childbearing potential, Zynteglo [2] ---> SmPC of [2] of EMA

Women of childbearing potential must use a reliable method of contraception (intra-uterine device or combination of hormonal and barrier contraception) from start of mobilisation through at least 6 months after administration of Zynteglo.

CONTRAINDICATIONS of Zynteglo (Zynteglo)

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

- Pregnancy and breast-feeding (see section 4.6).

- Previous treatment with HSC gene therapy.

- Contraindications to the mobilisation agents and the myeloablative conditioning agent must be considered.

https://www.ema.europa.eu/en/documents/product-information/zynteglo-epar-product-information_en.pdf 20/01/2022 (withdrawn)

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