O

Obecabtagene autoleucel (Aucatzyl)

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

Due to the potential for neurological events, including altered mental status or seizures, patients should refrain from driving or operating heavy or potentially dangerous machines until at least 8 weeks after infusion or until resolution of the neurological

Breast-feeding, obecabtagene autoleucel [2] ---> SmPC of [2] of EMA

A risk to the breast-fed infant cannot be excluded. Breast-feeding women must be advised by the treating physician of the potential risk to the breast-fed child.

Contraceptives, obecabtagene autoleucel [2] ---> SmPC of [2] of EMA

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

Corticosteroids, obecabtagene autoleucel [2] ---> SmPC of [2] of EMA

Prophylactic use of systemic corticosteroids may interfere with the activity of Aucatzyl. Prophylactic use of systemic corticosteroids is therefore not recommended before infusion (see section 4.2).

Fertility, obecabtagene autoleucel [2] ---> SmPC of [2] of EMA

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

Obecabtagene autoleucel [1], pregnancy ---> SmPC of [1] of EMA

Therefore, Aucatzyl is not recommended for women who are pregnant. Pregnant women must be advised on the potential risks to the foetus. Pregnancy after Aucatzyl therapy must be discussed with the treating physician

Obecabtagene autoleucel [1], tocilizumab ---> SmPC of [1] of EMA

Administration of tocilizumab or corticosteroids for the treatment of CRS and ICANS did not affect the rate or extent of expansion and persistency.

Obecabtagene autoleucel [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

As a precautionary measure, vaccination with live vaccines is not recommended for at least 6 weeks prior to the start of lymphodepletion chemotherapy, during Aucatzyl treatment, and until immune recovery following treatment.

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

The pregnancy status of women of childbearing potential must be verified before starting Aucatzyl treatment. Aucatzyl is not recommended for women of childbearing potential who are not using contraception.

CONTRAINDICATIONS of Obecabtagene autoleucel (Aucatzyl)

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

- Contraindications of the lymphodepleting chemotherapy must be considered.

https://www.ema.europa.eu/en/documents/product-information/aucatzyl-epar-product-information_en.pdf 19/08/2025

Obeticholic acid (Ocaliva)

Bile-acid sequestrants, obeticholic acid [2] ---> SmPC of [2] of EMA

Bile acid binding resins such as cholestyramine reduce bile acid absorption and may reduce efficacy of obeticholic acid. When co-administered, obeticholic acid should be taken at least 4-6 hours before or 4-6 hours after taking a bile acid binding resin

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

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

Cholestyramine, obeticholic acid [2] ---> SmPC of [2] of EMA

Colesevelam, obeticholic acid [2] ---> SmPC of [2] of EMA

Colestipol, obeticholic acid [2] ---> SmPC of [2] of EMA

CYP1A2 substrates with narrow therapeutic index, obeticholic acid [2] ---> SmPC of [2] of EMA

Therapeutic monitoring of CYP1A2 substrates with narrow therapeutic index (e.g. theophylline and tizanidine) is recommended.

Drugs primarily metabolised by CYP1A2, obeticholic acid [2] ---> SmPC of [2] of EMA

Obeticholic acid may increase the exposure to concomitant medicinal products that are CYP1A2 substrates.

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

No fertility data is available in humans. Animal studies do not indicate any direct or indirect effects on fertility or reproduction (see section 5.3).

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

Obeticholic acid may increase the exposure to concomitant medicinal products that are CYP1A2 substrates. Therapeutic monitoring of CYP1A2 substrates with narrow therapeutic index (e.g., theophylline and tizanidine) is recommended.

Obeticholic acid [1], theophylline ---> SmPC of [1] of EMA

Therapeutic monitoring of CYP1A2 substrates with narrow therapeutic index (e.g. theophylline and tizanidine) is recommended.

Obeticholic acid [1], tizanidine ---> SmPC of [1] of EMA

Therapeutic monitoring of CYP1A2 substrates with narrow therapeutic index (e.g. theophylline and tizanidine) is recommended.

Obeticholic acid [1], warfarin ---> SmPC of [1] of EMA

When concomitant bile acid binding resins are administered, obeticholic acid should be taken at least 4 to 6 hours before or 4 to 6 hours after taking a bile acid binding resin, or at as great an interval as possible.

CONTRAINDICATIONS of Obeticholic acid (Ocaliva)

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

- Patients with decompensated cirrhosis (e.g., Child-Pugh Class B or C) or a prior decompensation event (see section 4.4).

- Patients with complete biliary obstruction.

https://www.ema.europa.eu/en/documents/product-information/ocaliva-epar-product-information_en.pdf 20/01/2025 (revoked)

Obiltoxaximab (Nyxthracis)

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

Obiltoxaximab may have a minor influence on the ability to drive and use machines since headache, dizziness, fatigue and vomiting may occur following administration of NYXTHRACIS

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

Human IgG is known to be excreted in breast milk during the first days after birth and is decreasing to low concentrations soon afterwards. Afterwards, use of obiltoxaximab could be considered during breast-feading, only if clinically needed.

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

Fertility studies have not been conducted with obiltoxaximab.

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

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

CONTRAINDICATIONS of Obiltoxaximab (Nyxthracis)

- 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/nyxthracis-epar-product-information_en.pdf 09/09/2024 (withdrawn)

Other trade names: previously Obiltoxaximab SFL,

Obinutuzumab (Gazyvaro)

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

Infusion-related reactions are very common during the first infusion of obinutuzumab, and patients experiencing infusion related symptoms should be advised not to drive or use machines until symptoms abate.

Bendamustine, obinutuzumab [2] ---> SmPC of [2] of EMA

The combination of obinutuzumab with chlorambucil, bendamustine, CHOP or CVP may increase the risk of neutropenia (see section 4.4).

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

Women should be advised to discontinue breast-feeding during Gazyvaro therapy and for 18 months after the last dose of Gazyvaro.

Chlorambucil, obinutuzumab [2] ---> SmPC of [2] of EMA

The combination of obinutuzumab with chlorambucil, bendamustine, CHOP or CVP may increase the risk of neutropenia (see section 4.4).

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

Obinutuzumab is not a substrate, inhibitor, or inducer of cytochrome P450 (CYP450), uridine diphosphate glucuronyltransferase (UGT) enzymes and transporters such as P-glycoprotein.

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

No adverse effects on male and female reproductive organs were observed in repeat-dose toxicity studies in cynomolgus monkeys (see section 5.3).

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

In patients with underlying cardiac disease, arrhythmias (such as atrial fibrillation and tachyarrhythmia), angina pectoris, acute coronary syndrome, myocardial infarction and heart failure have occurred when treated with Gazyvaro (see section 4.8).

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

Serious bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of Gazyvaro therapy. Fatal infections have been reported.

Neutropenia, obinutuzumab [2] ---> SmPC of [2] of EMA

Severe and life-threatening neutropenia including febrile neutropenia has been reported during treatment with Gazyvaro.

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

Co-administration with Gazyvaro had no effect on the PK of bendamustine, FC, chlorambucil or the individual components of CHOP. In addition, there were no apparent effects of bendamustine, FC, chlorambucil or CHOP on the PK of Gazyvaro.

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

Gazyvaro should not be administered to pregnant women unless the possible benefit outweighs the potential risk.

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

Postponing vaccination with live vaccines should be considered for infants born to mothers who have been exposed to Gazyvaro during pregnancy until the infant's B-cell levels are within normal ranges (see section 4.4).

Obinutuzumab [1], progressive multifocal leukoencephalopathy ---> SmPC of [1] of EMA

Progressive multifocal leukoencephalopathy (PML) has been reported in patients treated with Gazyvaro (see section 4.8).

Obinutuzumab [1], thrombocytopenia ---> SmPC of [1] of EMA

Severe and life-threatening thrombocytopenia including acute thrombocytopenia (occurring within 24 hours after the infusion) has been observed during treatment with Gazyvaro.

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

Vaccination with live virus vaccines is not recommended during treatment and until B-cell recovery because of the immunosuppressive effect of obinutuzumab (see section 4.4).

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

Women of childbearing potential must use effective contraception during and for 18 months after treatment with Gazyvaro.

Obinutuzumab, viral reactivation [2] ---> SmPC of [2] of EMA

Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients treated with anti-CD20 antibodies including Gazyvaro (see section 4.8).

CONTRAINDICATIONS of Obinutuzumab (Gazyvaro)

- 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/gazyvaro-epar-product-information_en.pdf 07/01/2026

Ocrelizumab (Ocrevus)

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

A risk to neonates and infants cannot be excluded. Women should be advised to discontinue breast-feeding during therapy.

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

No interaction studies have been performed, as no interactions are expected via cytochrome P450 enzymes, other metabolising enzymes or transporters.

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

Preclinical data reveal no special hazards for humans based on studies of male and female fertility in cynomolgus monkeys.

Immunosuppressives, ocrelizumab [2] ---> SmPC of [2] of EMA

It is not recommended to use other immunosuppressive therapies concomitantly with ocrelizumab except corticosteroids for symptomatic treatment of relapses (see section 4.4).

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

Ocrevus should be avoided during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus.

Ocrelizumab [1], vaccinations ---> SmPC of [1] of EMA

The safety of immunisation with live or live-attenuated vaccines, following ocrelizumab therapy has not been studied.

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

Women of childbearing potential should use contraception while receiving ocrelizumab and for 12 months after the last administered dose of ocrelizumab.

CONTRAINDICATIONS of Ocrelizumab (Ocrevus)

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

- Current active infection (see section 4.4)

- Patients in a severely immunocompromised state (see section 4.4).

- Known active malignancies (see section 4.4)

https://www.ema.europa.eu/en/documents/product-information/ocrevus-epar-product-information_en.pdf 24/06/2024

Ocriplasmin (Jetrea)

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

The intravitreal injection of JETREA may be followed by temporary visual disturbances

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

JETREA should be used during breast-feeding only if the clinical benefit outweighs the potential risks.

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

JETREA should be used during pregnancy only if the clinical benefit outweighs the potential risks.

Ocriplasmin [1], VEGF inhibitors ---> SmPC of [1] of EMA

There are no clinical data on concomitant use of ocriplasmin with VEGF-inhibitors (vascular endothelial growth factor).

CONTRAINDICATIONS of Ocriplasmin (Jetrea)

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

- Active or suspected ocular or periocular infections.

https://www.ema.europa.eu/en/documents/product-information/jetrea-epar-product-information_en.pdf 19/06/2025 (withdrawn)

Octocog alfa (Helixate NexGen)

Breast-feeding, octocog alfa [2] ---> SmPC of [2] of EMA

Helixate NexGen should be used during pregnancy and breast-feeding only if clearly indicated.

Octocog alfa [1], pregnancy ---> SmPC of [1] of EMA

Helixate NexGen should be used during pregnancy and breast-feeding only if clearly indicated.

CONTRAINDICATIONS of Octocog alfa (Helixate NexGen)

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

- Known allergic reactions to mouse or hamster protein

https://www.ema.europa.eu/en/documents/product-information/helixate-nexgen-epar-product-information_en.pdf. 02/06/2020 (withdrawn)

Other trade names: Advate, Iblias, Kogenate Bayer, Kovaltry,

Octreotide (Mycapssa)

Alendronate, octreotide [2] ---> SmPC of [2] of EMA

No interaction studies with other drugs that are transported via the paracellular route (e.g. alendronate or desmopressin) were conducted.

Antacids, octreotide [2] ---> SmPC of [2] of EMA

Medicinal products that alter the pH of the upper gastrointestinal tract (e.g. other proton pump inhibitors, H2-receptor antagonists, and antacids) may alter the absorption of Mycapssa and lead to a reduction in bioavailability.

Antidiabetics, octreotide

Dose adjustments of insulin and antidiabetic medicinal products may be required when Mycapssa is administered concomitantly

Betablockers, octreotide

Dose adjustment of medicinal products such as beta blockers, calcium channel blockers, or agents to control fluid and electrolyte balance may be necessary when Mycapssa is administered concomitantly

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

A risk to the newborns cannot be excluded. Mycapssa should not be used during breast-feeding.

Bromocriptine [1], octreotide ---> SmPC of [1] of EMA

Concomitant administration of octreotide injections and bromocriptine increases the bioavailability of bromocriptine. Dose adjustments of bromocriptine may be necessary.

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

Dose adjustment of medicinal products such as beta blockers, calcium channel blockers, or agents to control fluid and electrolyte balance may be necessary when Mycapssa is administered concomitantly

Carbamazepine, octreotide [2] ---> SmPC of [2] of eMC

Drugs mainly metabolised by CYP3A4 and which have a low therapeutic index should be only used with octreotide with caution.

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

Octreotide injections have been found to delay the intestinal absorption of cimetidine. Dose adjustment of cimetidine may be necessary.

Cyclosporine [1], octreotide ---> SmPC of [1] of EMA

Octreotide has been found to reduce the intestinal absorption of ciclosporin (71% decrease in Cmax and 63% decrease in AUC(inf)). Dose adjustment of ciclosporin may be necessary.

Desmopressin, octreotide [2] ---> SmPC of [2] of EMA

No interaction studies with other drugs that are transported via the paracellular route (e.g. alendronate or desmopressin) were conducted.

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

Concomitant administration of digoxin and Mycapssa has been found to decrease the rate of digoxin absorption.

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

Drugs mainly metabolised by CYP3A4 and which have a low therapeutic index should be only used with octreotide with caution.

Drugs with a narrow therapeutic window, octreotide [2] ---> SmPC of [2] of EMA

Therefore, drug-drug interactions may vary between medicinal products. As a consequence, other medicinal products which have a narrow therapeutic index should therefore be used with caution and doses adjusted as necessary.

Esomeprazole, octreotide [2] ---> SmPC of [2] of EMA

Concomitant administration of Mycapssa with esomeprazole has been found to decrease the bioavailability of Mycapssa.

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

Co-administration of everolimus and depot octreotide increased octreotide Cmin with a geometric mean ratio (everolimus/placebo) of 1.47.

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

Mycapssa capsules should be swallowed whole with a glass of water, at least 1 hour before or at least 2 hours after eating any food.

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

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

Human insulin [1], octreotide ---> SmPC of [1] of EMA

Octreotide may either increase or decrease the insulin requirement.

Hydrochlorothiazide, octreotide [2] ---> SmPC of [2] of EMA

Concomitant administration of hydrochlorothiazide (HCTZ) and Mycapssa resulted in a 9% decrease in Cmax and 19% decrease in AUC(0-5) of HCTZ. Dose adjustment of HCTZ may be necessary.

Insulin aspart [1], octreotide ---> SmPC of [1] of EMA

Octreotide may either increase or decrease the insulin requirement.

Insulin degludec [1], octreotide ---> SmPC of [1] of EMA

Octreotide may either increase or decrease the insulin requirement.

Insulin degludec/insulin aspart [1], octreotide ---> SmPC of [1] of EMA

Octreotide/lanreotide may either increase or decrease the insulin requirement.

Insulin degludec/liraglutide [1], octreotide ---> SmPC of [1] of EMA

Octreotide may either increase or decrease the Xultophy requirement.

Insulin detemir [1], octreotide ---> SmPC of [1] of EMA

Octreotide may either increase or decrease the insulin requirement.

Insulin lispro [1], octreotide ---> SmPC of [1] of EMA

Insulin requirements may be reduced in the presence of medicinal products with hypoglycaemic activity

Insulin, octreotide

Dose adjustments of insulin and antidiabetic medicinal products may be required when Mycapssa is administered concomitantly

Levonorgestrel, octreotide [2] ---> SmPC of [2] of EMA

Concomitant administration of levonorgestrel and Mycapssa decreases the bioavailability of levonorgestrel (38% decrease in Cmax and 24% decrease in AUC(0-5)), which may diminish the effectiveness of oral contraceptives containing progestogens

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

Concomitant administration of lisinopril and Mycapssa increases the bioavailability of lisinopril (50% increase in Cmax and 40% increase in AUC(0-12)). Dose adjustment of lisinopril may be necessary when Mycapssa is administered concomitantly.

Loperamide, octreotide [2] ---> SmPC of [2] of EMA

Concomitant administration of Mycapssa with loperamide reduced the Cmax and AUC of octreotide by an average of approximately 9% and 3%, respectively. Mycapssa should be titrated as indicated to clinical/biochemical effect.

Metformin, octreotide [2] ---> SmPC of [2] of EMA

Concomitant administration of metformin and Mycapssa resulted in no significant changes in the early exposure to metformin.

Methadone, octreotide

Octreotide may decrease the analgetic effect of methadone and morphine

Metoclopramide, octreotide [2] ---> SmPC of [2] of EMA

Concomitant administration of Mycapssa with metoclopramide reduced the Cmax and AUC of octreotide by an average of approximately 5% and 11%, respectively. Mycapssa should be titrated as indicated to clinical/biochemical effect.

Morphine, octreotide ---> SmPC of [methadone] of eMC

Octreotide may decrease the analgetic effect of methadone and morphine

Nateglinide [1], octreotide ---> SmPC of [1] of EMA

Somatostatin analogues may reduce the hypoglycaemic effect of nateglinide

Nutrition, octreotide [2] ---> SmPC of [2] of EMA

Octreotide may alter absorption of dietary fats in some patients.

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

Women should be counselled to use an alternative non-hormonal method of contraception or a back-up method when Mycapssa is used with oral contraceptives.

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

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

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

Octreotide [1], quinidine ---> SmPC of [1] of eMC

Drugs mainly metabolised by CYP3A4 and which have a low therapeutic index should be only used with octreotide with caution.

Octreotide [1], terfenadine ---> SmPC of [1] of eMC

Drugs mainly metabolised by CYP3A4 and which have a low therapeutic index should be only used with octreotide with caution.

Octreotide [1], transient permeability enhancer ---> SmPC of [1] of EMA

Transient permeability enhancer (TPEŽ) excipients in the formulation increase the intestinal absorption of octreotide via paracellular transport, using the lactulose to mannitol ratio test

Octreotide [1], vitamin B12 ---> SmPC of [1] of EMA

Depressed vitamin B12 levels and abnormal Schilling's tests have been observed in some patients receiving octreotide therapy.

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

Concomitant administration of warfarin and Mycapssa resulted in no significant changes in the early exposure to warfarin.

Octreotide, repaglinide [2] ---> SmPC of [2] of EMA

Octreotide may enhance and/or prolong the hypoglycaemic effect of repaglinide

Octreotide, telotristat ethyl [2] ---> SmPC of [2] of EMA

Concomitant administration of short-acting octreotide with Xermelo significantly decreased the systemic exposure of telotristat ethyl and telotristat, the active metabolite

Octreotide, tolbutamide [2] ---> SmPC of [2] of eMC

Increased hypoglycaemic effects have occurred or might be expected

CONTRAINDICATIONS of (Mycapssa)

- Hypersensitivity to octreotide or to any of the excipients

https://www.ema.europa.eu/en/documents/product-information/mycapssa-epar-product-information_en.pdf 21/03/2025 (withdrawn)

Other trade names: Octreotida GP PHARMA, Octreótida Hospira, Oktidel, Sandostatin, Treoject,

Odevixibat (Bylvay)

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

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

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

In adult healthy subjects, concomitant use of odevixibat decreased the area under the curve (AUC) of oral midazolam (a CYP3A4 substrate) by 30% and 1-OH-midazolam exposure by less than 20%, which is not considered clinically relevant.

Fat-soluble vitamins, odevixibat [2] ---> SmPC of [2] of EMA

In clinical trials, decreased levels of fat-soluble vitamins were observed in some patients receiving odevixibat. Levels of fat-soluble vitamins should be monitored

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

No fertility data are available in humans. Animal studies do not indicate any direct or indirect effects on fertility or reproduction (see section 5.3).

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

In adult healthy subjects, co- administration of the strong P-gp inhibitor itraconazole increased the plasma exposure of a single dose of odevixibat 7 200 mcg by approximately 50-60%. This increase is not considered clinically relevant.

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

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

Concomitant use of odevixibat had no impact on the AUC of LVN and decreased the AUC of EE by 17%, which is not considered clinically relevant. Interaction studies with other lipophilic medicinal products have not been performed

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

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

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

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

Women of childbearing potential should use an effective method of contraception when treated with Bylvay.

CONTRAINDICATIONS of Odevixibat (Bylvay)

- 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/bylvay-epar-product-information_en.pdf 06/06/2025

Other trade names: Kayfanda,

Odronextamab (Ordspono)

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

Patients who experience CRS (or other adverse reactions that impair consciousness) should be evaluated and advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.

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

Women should be advised not to breastfeed during treatment with Ordspono and for at least 6 months after the last dose due to the potential risk for serious adverse reactions in the breastfed child.

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

The highest risk is during Cycle 1 in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index (e.g., warfarin, cyclosporine, or theophylline).

CYP450 substrates with narrow therapeutic index, odronextamab [2] ---> SmPC of [2] of EMA

The highest risk is during Cycle 1 in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index (e.g., warfarin, cyclosporine, or theophylline).

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

Initiation of treatment with Ordspono causes a transient elevation of cytokines, which may suppress CYP450 enzyme activities.

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

No human data on the effect of odronextamab on fertility are available. Animal studies do not indicate harmful effects on male or female reproductive organs or fertility parameters (see section 5.3).

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

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

Odronextamab [1], theophylline ---> SmPC of [1] of EMA

The highest risk is during Cycle 1 in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index (e.g., warfarin, cyclosporine, or theophylline).

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

The highest risk is during Cycle 1 in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index (e.g., warfarin, cyclosporine, or theophylline).

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

Females of reproductive potential should use effective contraception during treatment with Ordspono and for at least 6 months after the last dose.

CONTRAINDICATIONS of Odronextamab (Ordspono)

- 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/ordspono-epar-product-information_en.pdf 19/11/2024

Ofatumumab (Kesimpta)

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

Kesimpta has no or negligible influence on the ability to drive and use machines.

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

Consequently, a risk to the breast-fed child cannot be excluded during this short period. Afterwards, ofatumumab could be used during breast-feeding if clinically needed.

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

No interaction studies have been performed, as no interactions are expected via cytochrome P450 enzymes, other metabolising enzymes or transporters.

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

There are no data on the effect of ofatumumab on human fertility. Non-clinical data did not indicate potential hazards for humans based on male and female fertility parameters assessed in monkeys.

Immunosuppressives, ofatumumab [2] ---> SmPC of [2] of EMA

The duration and mode of action of these medicinal products should be taken into account because of potential additive immunosuppressive effects (see section 5.1).

Immunosuppressives, ofatumumab [2] ---> SmPC of [2] of EMA

The risk of additive immune system effects should be considered when co-administering immunosuppressive therapies with ofatumumab.

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

Treatment with ofatumumab should be avoided during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus.

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

In addition, all adverse pregnancy events should be reported via the national reporting system listed in Appendix V.

Ofatumumab [1], response to vaccination ---> SmPC of [1] of EMA

The response to vaccination could be impaired when B cells are depleted. It is recommended that patients complete immunisations prior to the start of ofatumumab therapy (see section 4.4).

Ofatumumab [1], vaccinations ---> SmPC of [1] of EMA

The safety of and the ability to generate a primary or anamnestic (recall) response to immunisation with live, live-attenuated or inactivated vaccines during ofatumumab treatment has not been investigated

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

Women of childbearing potential should use effective contraception (methods that result in less than 1% pregnancy rates) while receiving Kesimpta and for 6 months after the last administration of Kesimpta.

CONTRAINDICATIONS of Ofatumumab (Kesimpta)

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

- Patients in a severely immunocompromised state (see section 4.4).

- Severe active infection until resolution (see section 4.4).

- Known active malignancy.

https://www.ema.europa.eu/en/documents/product-information/kesimpta-epar-product-information_en.pdf 19/03/2024

Other trade names: Arzerra (Withdrawn)

Ofloxacin

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

There have been occasional reports of somnolence, impairment of skills, dizziness and visual disturbances

Aluminium hydroxide, ofloxacin [2] ---> SmPC of [2] of eMC

The co-administration may decrease the absorption of ofloxacin. Separate administration by at least 2 hours

Aluminium, ofloxacin [2] ---> SmPC of [2] of eMC

The co-administration may decrease the absorption of ofloxacin. Separate administration by at least 2 hours

Antacids, ofloxacin [2] ---> SmPC of [2] of eMC

The co-administration may decrease the absorption of ofloxacin. Separate administration by at least 2 hours

Antihypertensives, ofloxacin

The co-administration of ofloxacin i.v. with hypotensive agents may cause a sudden fall in blood pressure

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

Because of the potential for arthropathy and other serious toxicity in the nursing infant, breast feeding should be discontinued during treatment with ofloxacin.

Calcium, ofloxacin [2] ---> SmPC of [2] of eMC

The co-administration may decrease the absorption of ofloxacin. Separate administration by at least 2 hours

Carbaldrate, ofloxacin [2] ---> SmPC of [2] of eMC

The co-administration may decrease the absorption of ofloxacin. Separate administration by at least 2 hours

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

With high doses of quinolones, impairment of excretion and an increase in serum levels may occur when co-administered with other drugs that undergo renal tubular secretion

Cimetidine, quinolones ---> SmPC of [ofloxacin] of eMC

With high doses of quinolones, impairment of excretion and an increase in serum levels may occur when co-administered with other drugs that undergo renal tubular secretion

Class IA antiarrhythmic agents, ofloxacin [2] ---> SmPC of [2] of eMC

The fluoroquinolones should be used with caution in patients receiving drugs known to prolong the QT interval

Class III antiarrhythmic agents, ofloxacin [2] ---> SmPC of [2] of eMC

The fluoroquinolones should be used with caution in patients receiving drugs known to prolong the QT interval

Coumarin anticoagulants, ofloxacin [2] ---> SmPC of [2] of eMC

The co-administration may enhance the effect of coumarin derivative

Coumarin anticoagulants, quinolones ---> SmPC of [ofloxacin] of eMC

The co-administration may enhance the effect of coumarin derivative

Electrolyte imbalance, ofloxacin [2] ---> SmPC of [2] of eMC

Caution should be taken when using fluoroquinolones, including ofloxacin, in patients with known risk factors for prolongation of the QT interval such as, for example uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia)

Fenbufen, lomefloxacin ---> SmPC of [ofloxacin] of eMC

There may be a further lowering of the cerebral seizure threshold when quinolones are given concurrently with other drugs which lower the seizure threshold

Fenbufen, ofloxacin [2] ---> SmPC of [2] of eMC

There may be a further lowering of the cerebral seizure threshold when quinolones are given concurrently with other drugs which lower the seizure threshold

Fenbufen, prulifloxacin ---> SmPC of [ofloxacin] of eMC

There may be a further lowering of the cerebral seizure threshold when quinolones are given concurrently with other drugs which lower the seizure threshold

Ferric maltol [1], ofloxacin ---> SmPC of [1] of EMA

Oral iron is known to reduce the absorption of ofloxacin. This medicinal product should be given at least 2 hours apart from Feraccru.

Furosemide, ofloxacin [2] ---> SmPC of [2] of eMC

With high doses of quinolones, impairment of excretion and an increase in serum levels may occur when co-administered with other drugs that undergo renal tubular secretion

Furosemide, quinolones ---> SmPC of [ofloxacin] of eMC

With high doses of quinolones, impairment of excretion and an increase in serum levels may occur when co-administered with other drugs that undergo renal tubular secretion

Glibenclamide, ofloxacin [2] ---> SmPC of [2] of eMC

Ofloxacin may cause a slight increase in serum concentrations of glibenclamide administered concurrently; patients treated with this combination should be closely monitored.

Hydrotalcite, ofloxacin

The co-administration of hydrotalcite with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 1-2 hours

Hypokalemia, ofloxacin [2] ---> SmPC of [2] of eMC

Hypokalemia, quinolones ---> SmPC of [ofloxacin] of eMC

Hypomagnesemia, ofloxacin [2] ---> SmPC of [2] of eMC

Hypomagnesemia, quinolones ---> SmPC of [ofloxacin] of eMC

Iron, ofloxacin [2] ---> SmPC of [2] of eMC

The co-administration may decrease the absorption of ofloxacin. Separate administration by at least 2 hours

Macrolide antibiotics, ofloxacin [2] ---> SmPC of [2] of eMC

The fluoroquinolones should be used with caution in patients receiving drugs known to prolong the QT interval

Magnesium hydroxide, ofloxacin [2] ---> SmPC of [2] of eMC

The co-administration may decrease the absorption of ofloxacin. Separate administration by at least 2 hours

Magnesium, ofloxacin [2] ---> SmPC of [2] of eMC

The co-administration may decrease the absorption of ofloxacin. Separate administration by at least 2 hours

Methotrexate, ofloxacin [2] ---> SmPC of [2] of eMC

With high doses of quinolones, impairment of excretion and an increase in serum levels may occur when co-administered with other drugs that undergo renal tubular secretion

Methotrexate, quinolones ---> SmPC of [ofloxacin] of eMC

With high doses of quinolones, impairment of excretion and an increase in serum levels may occur when co-administered with other drugs that undergo renal tubular secretion

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

The fluoroquinolones should be used with caution in patients receiving drugs known to prolong the QT interval

NSAID, ofloxacin [2] ---> SmPC of [2] of eMC

There may be a further lowering of the cerebral seizure threshold when quinolones are given concurrently with other drugs which lower the seizure threshold

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

Ofloxacin should not be used during pregnancy.

Ofloxacin [1], probenecide ---> SmPC of [1] of eMC

With high doses of quinolones, impairment of excretion and an increase in serum levels may occur when co-administered with other drugs that undergo renal tubular secretion

Ofloxacin [1], QT interval prolonging drugs ---> SmPC of [1] of eMC

The fluoroquinolones should be used with caution in patients receiving drugs known to prolong the QT interval

Ofloxacin [1], seizure-threshold lowering drugs ---> SmPC of [1] of eMC

There may be a further lowering of the cerebral seizure threshold when quinolones are given concurrently with other drugs which lower the seizure threshold

Ofloxacin [1], sucralfate ---> SmPC of [1] of eMC

The co-administration may decrease the absorption of ofloxacin. Separate administration by at least 2 hours

Ofloxacin [1], sun ---> SmPC of [1] of eMC

Patients being treated with ofloxacin should not expose themselves unnecessarily to strong sunlight and should avoid UV rays (sun lamps, solaria).

Ofloxacin [1], theophylline ---> SmPC of [1] of eMC

There may be a further lowering of the cerebral seizure threshold when quinolones are given concurrently with other drugs which lower the seizure threshold

Ofloxacin [1], tricyclic antidepressant ---> SmPC of [1] of eMC

The fluoroquinolones should be used with caution in patients receiving drugs known to prolong the QT interval

Ofloxacin [1], tubular secretion ---> SmPC of [1] of eMC

With high doses of quinolones, impairment of excretion and an increase in serum levels may occur when co-administered with other drugs that undergo renal tubular secretion

Ofloxacin [1], vitamin K antagonists ---> SmPC of [1] of eMC

The co-administration may enhance the effect of coumarin derivative

Ofloxacin, warfarin

The enzymatic inhibitor may decrease the metabolism of warfarin and increase its plasma levels, the anticoagulant effect and the bleeding risk

Probenecide, quinolones ---> SmPC of [ofloxacin] of eMC

With high doses of quinolones, impairment of excretion and an increase in serum levels may occur when co-administered with other drugs that undergo renal tubular secretion

Quinolones, tubular secretion ---> SmPC of [ofloxacin] of eMC

With high doses of quinolones, impairment of excretion and an increase in serum levels may occur when co-administered with other drugs that undergo renal tubular secretion

Quinolones, vitamin K antagonists ---> SmPC of [ofloxacin] of eMC

The co-administration may enhance the effect of coumarin derivative

CONTRAINDICATIONS of Ofloxacin

- Ofloxacin should not be used in patients with known hypersensitivity to 4-quinolone antibacterials or any of the excipients.

- Ofloxacin should not be used in patients with a past history of tendinitis.

- Ofloxacin, like other 4-quinolones, is contra-indicated in patients with a history of epilepsy or with a lowered seizure threshold.

- Ofloxacin is contra-indicated in children or growing adolescents, and in pregnant or breast-feeding women, since animal experiments do not entirely exclude the risk of damage to the cartilage of joints in the growing subject.

- Patients with latent or actual defects in glucose-6-phosphate dehydrogenase activity may be prone to haemolytic reactions when treated with quinolone antibacterial agents.

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

Olanzapine (Olanzapine Apotex)

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

Because olanzapine may cause somnolence and dizziness, patients should be cautioned about operating machinery, including motor vehicles.

Activated charcoal, olanzapine [2] ---> SmPC of [2] of EMA

Activated charcoal reduces the bioavailability of oral olanzapine and should be taken at least 2 hours before or after olanzapine.

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

Caution should be exercised in patients who consume alcohol or receive medicinal products that can cause central nervous system depression.

Antacids, olanzapine [2] ---> SmPC of [2] of EMA

Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have not been found to significantly affect the pharmacokinetics of olanzapine.

Antiparkinsonian agents, olanzapine [2] ---> SmPC of [2] of EMA

The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with Parkinson's disease and dementia is not recommended (see section 4.4).

Biperiden, olanzapine [2] ---> SmPC of [2] of EMA

Olanzapine showed no interaction when co-administered with lithium or biperiden

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

Patients should be advised not to breast-feed an infant if they are taking olanzapine.

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

The metabolism of olanzapine may be induced by carbamazepine, which may lead to reduced olanzapine concentrations.

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

Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have not been found to significantly affect the pharmacokinetics of olanzapine.

Ciprofloxacin [1], olanzapine ---> SmPC of [1] of eMC

Ciprofloxacin inhibits CYP1A2 and thus may cause increased serum concentration of concomitantly administered substances metabolised by this enzyme

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

Caution should be exercised in patients who consume alcohol or receive medicinal products that can cause central nervous system depression.

CYP1A2 inductors, olanzapine [2] ---> SmPC of [2] of EMA

Since olanzapine is metabolised by CYP1A2, substances that can specifically induce this isoenzyme may decrease olanzapine concentration

CYP1A2 inhibitors, olanzapine [2] ---> SmPC of [2] of EMA

Since olanzapine is metabolised by CYP1A2, substances that can specifically inhibit this isoenzyme may increase olanzapine concentration

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

Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e.g. 1A2, 2D6, 2C9, 2C19, 3A4). Thus no particular interaction is expected as verified through in vivo studies where no inhibition of metabolism was found

Dopamine agonists, olanzapine [2] ---> SmPC of [2] of EMA

Olanzapine may antagonise the effects of direct and indirect dopamine agonists.

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

Effects on fertility are unknown (see section 5.3 for preclinical information).

Fesoterodine, olanzapine

Caution should be exercised. The combination may lead to more pronounced therapeutic and side effects

Fluoxetine, olanzapine [2] ---> SmPC of [2] of EMA

Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have not been found to significantly affect the pharmacokinetics of olanzapine.

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

Fluvoxamine, a specific CYP1A2 inhibitor, has been shown to significantly inhibit the metabolism of olanzapine.

Futibatinib [1], olanzapine ---> SmPC of [1] of EMA

Co-administration of futibatinib with CYP1A2 sensitive substrates (e.g, olanzapine, theophylline) may decrease their exposure and therefore may affect their activity.

Galantamine, olanzapine

Possible antagonism of action

Insulin glargin [1], olanzapine ---> SmPC of [1] of EMA

Reduced blood-glucose-lowering effect

Insulin glargine/lixisenatide [1], olanzapine ---> SmPC of [1] of EMA

This substance may reduce the blood-glucose-lowering effect.

Insulin glulisin [1], olanzapine ---> SmPC of [1] of EMA

Possible decrease in blood-glucose-lowering activity

Lamotrigine [1], olanzapine ---> SmPC of [1] of eMC

In a study in healthy adult volunteers, 15 mg olanzapine reduced the AUC and Cmax of lamotrigine by an average of 24% and 20%, respectively.

Lithium, olanzapine [2] ---> SmPC of [2] of EMA

Olanzapine showed no interaction when co-administered with lithium or biperiden

New-born child, olanzapine [2] ---> SmPC of [2] of EMA

Newborn infants exposed to antipsychotics (including olanzapine) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery.

Nicotine, olanzapine [2] ---> SmPC of [2] of EMA

The metabolism of olanzapine may be induced by smoking, which may lead to reduced olanzapine concentrations.

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

Olanzapine should be used in pregnancy only if the potential benefit justifies the potential risk to the foetus.

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

Caution should be used if olanzapine is being administered concomitantly with medicinal products known to increase QTc interval

Olanzapine [1], strong CYP1A2 inductors ---> SmPC of [1] of EMA

Since olanzapine is metabolised by CYP1A2, substances that can specifically induce this isoenzyme may decrease olanzapine concentration

Olanzapine [1], strong CYP1A2 inhibitors ---> SmPC of [1] of EMA

Since olanzapine is metabolised by CYP1A2, substances that can specifically inhibit this isoenzyme may increase olanzapine concentration

Olanzapine [1], theophylline ---> SmPC of [1] of EMA

Olanzapine [1], tricyclic antidepressant ---> SmPC of [1] of EMA

Olanzapine [1], valproate ---> SmPC of [1] of EMA

Therapeutic monitoring of valproate plasma levels did not indicate that valproate dosage adjustment is required after the introduction of concomitant olanzapine.

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

Olanzapine, probenecide

Probenecid increases the absorption rate and the plasma levels of olanzapine

Olanzapine, ranolazine

The CYP2D6 inhibition may increase the plasma concentrations of olanzapine

Olanzapine, ritonavir

Decrease of the olanzapine effect

Olanzapine, rufinamide [2] ---> SmPC of [2] of EMA

A specific interaction study in healthy subjects revealed no influence of rufinamide at a dose of 400 mg twice daily on the pharmacokinetics of olanzapine, a CYP1A2 substrate.

CONTRAINDICATIONS of Olanzapine (Olanzapine Apotex)

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

- Patients with known risk of narrow-angle glaucoma.

https://www.ema.europa.eu/en/documents/product-information/olanzapine-apotex-epar-product-information_en.pdf 09/03/2023 (withdrawn)

Other trade names: Arenbil,Olazax, Onezyp, Zalasta, Zapris, Zolafren, Zypadhera, Zyprexa, Olanzapina: Actavis, Almus, Alter, Amger, Aurobindo, Benel, Bluefish, Cantabria, Cinfa, Comadrol, Combix, Germed, Kern Pharma, KRKA, Mabo, Mylan, Mylangen, Normon, Pensa, Pharmagenus

Olaparib (Lynparza)

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

During treatment with Lynparza, asthenia, fatigue, and dizziness have been reported and those patients who experience these symptoms should observe caution when driving or using machines.

Anastrozole, olaparib [2] ---> SmPC of [2] of EMA

A clinical study has been performed to assess the combination of olaparib with anastrozole, letrozole or tamoxifen. No clinically relevant interactions were observed.

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

The recommended Lynparza monotherapy dose is not suitable for combination with myelosuppressive anticancer medicinal products.

BCRP substrates, olaparib [2] ---> SmPC of [2] of EMA

Olaparib is an inhibitor of OAT3. It cannot be excluded that olaparib may increase the exposure to substrates of OAT3

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

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

Boosted protease-inhibitors, olaparib [2] ---> SmPC of [2] of EMA

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

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

Olaparib is an inhibitor of OATP1B1. It cannot be excluded that olaparib may increase the exposure to substrates of OATP1B1

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

Lynparza is contraindicated during breast-feeding and for 1 month after receiving the last dose, given the pharmacologic property of the product

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

Known strong inducers of this isozyme (CYP3A) are not recommended with Lynparza, as it is possible that the efficacy of Lynparza could be substantially reduced.

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

Olaparib inhibits CYP3A4 in vitro and is predicted to be a mild CYP3A inhibitor in vivo. Therefore, caution should be exercised when sensitive CYP3A substrates or substrates with a narrow therapeutic margin are combined with olaparib.

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

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

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

In vitro, olaparib inhibits the efflux transporter P-gp (IC50 = 76 然), therefore it cannot be excluded that olaparib may cause clinically relevant drug interactions with substrates of P-gp

Contraceptives, olaparib [2] ---> SmPC of [2] of EMA

The efficacy of hormonal contraceptives may be reduced if co-administered with olaparib. Therefore, an additional non-hormonal contraceptive method should be considered during treatment (see section 4.5).

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

CYP1A2 inductors [1], olaparib ---> SmPC of [1] of EMA

Induction of CYP1A2, 2B6 and 3A4 has been shown in vitro with CYP2B6 being most likely to be induced to a clinically relevant extent.

CYP2B6 inductors [1], olaparib ---> SmPC of [1] of EMA

Induction of CYP1A2, 2B6 and 3A4 has been shown in vitro with CYP2B6 being most likely to be induced to a clinically relevant extent.

CYP2C19 inductors [1], olaparib ---> SmPC of [1] of EMA

The potential for olaparib to induce CYP2C9, CYP2C19 and P-gp can also not be excluded.

CYP2C9 inductors [1], olaparib ---> SmPC of [1] of EMA

The potential for olaparib to induce CYP2C9, CYP2C19 and P-gp can also not be excluded.

CYP3A4 inductors [1], olaparib ---> SmPC of [1] of EMA

Induction of CYP1A2, 2B6 and 3A4 has been shown in vitro with CYP2B6 being most likely to be induced to a clinically relevant extent.

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

In vitro, olaparib inhibits the efflux transporter P-gp (IC50 = 76 然), therefore it cannot be excluded that olaparib may cause clinically relevant drug interactions with substrates of P-gp

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

In vitro, olaparib inhibits the efflux transporter P-gp (IC50 = 76 然), therefore it cannot be excluded that olaparib may cause clinically relevant drug interactions with substrates of P-gp

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

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

Donate sperm, olaparib [2] ---> SmPC of [2] of EMA

Male patients should not donate sperm during therapy and for 3 months after receiving the last dose of Lynparza.

Drugs primarily metabolised by CYP1A2, olaparib [2] ---> SmPC of [2] of EMA

The potential for olaparib to induce CYP3A, CYP1A2, CYP2B6, CYP2C9, CYP2C19 and P-gp is unknown and it cannot be excluded that olaparib upon co-administration may reduce the exposure to substrates of these metabolic enzymes and transport protein.

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

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

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

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

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

Olaparib may inhibit CYP3A4 in vitro and it cannot be excluded that olaparib may increase the exposures to substrates of this enzyme in vivo. Therefore, caution should be exercised when substrates of CYP3A4 are combined with olaparib

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

The magnitude of the effect of moderate to strong inducers (e.g. efavirenz, rifabutin) on olaparib exposure is not established, therefore the co-administration of Lynparza with these medicinal products is also not recommended (see section 4.4).

Empagliflozin/metformin, olaparib [2] ---> SmPC of [2] of EMA

Olaparib is an inhibitor of OCT1. It cannot be excluded that olaparib may increase the exposure to substrates of OCT1

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

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

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

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

Fertility [1], olaparib ---> SmPC of [1] of EMA

There are no clinical data on fertility. In animal studies, no effect on conception was observed but there are adverse effects on embryofoetal survival (see section 5.3).

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

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

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

It is recommended that patients take Lynparza at least 1 hour after food, and refrain from eating preferably for up to 2 hours afterwards

Furosemide, olaparib [2] ---> SmPC of [2] of EMA

Olaparib is an inhibitor of BCRP. It cannot be excluded that olaparib may increase the exposure to substrates of BCRP

Glibenclamide, olaparib [2] ---> SmPC of [2] of EMA

Olaparib is an inhibitor of OATP1B1. It cannot be excluded that olaparib may increase the exposure to substrates of OATP1B1

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

It is also not recommended to consume grapefruit juice while on Lynparza therapy as it is a CYP3A inhibitor.

Immunosuppressives, olaparib [2] ---> SmPC of [2] of EMA

Combination of olaparib with immunosuppressant agents has not been studied. Therefore, caution should be taken if these drugs are co-administered with olaparib and patients should be closely monitored.

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

CYP3A4/5 are the isozymes predominantly responsible for the metabolic clearance of olaparib. It is recommended that known strong inhibitors of these isozymes should be avoided with olaparib

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

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

Letrozole, olaparib [2] ---> SmPC of [2] of EMA

A clinical study has been performed to assess the combination of olaparib with anastrozole, letrozole or tamoxifen. No clinically relevant interactions were observed.

Men, olaparib [2] ---> SmPC of [2] of EMA

Male patients must use a condom during therapy and for 3 months after receiving the last dose of Lynparza when having sexual intercourse with a pregnant woman or with a woman of childbearing potential.

Metformin, olaparib [2] ---> SmPC of [2] of EMA

Olaparib is an inhibitor of OCT1. It cannot be excluded that olaparib may increase the exposure to substrates of OCT1

Metformin/saxagliptin/dapagliflozin [1], olaparib ---> SmPC of [1] of EMA

Co-administration of metformin with inhibitors of both OCT1 and OCT2 (such as crizotinib, olaparib) may alter efficacy and renal elimination of metformin and may increase metformin plasma concentration

Methotrexate, olaparib [2] ---> SmPC of [2] of EMA

Olaparib is an inhibitor of OAT3. It cannot be excluded that olaparib may increase the exposure to substrates of OAT3

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

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

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

Nelfinavir, olaparib [2] ---> SmPC of [2] of EMA

CYP3A4/5 are the isozymes predominantly responsible for the metabolic clearance of olaparib. It is recommended that known strong inhibitors of these isozymes should be avoided with olaparib

Nevirapine, olaparib [2] ---> SmPC of [2] of EMA

Known strong inducers of this isozyme (CYP3A) are not recommended with Lynparza, as it is possible that the efficacy of Lynparza could be substantially reduced.

OATP1B1 substrates, olaparib [2] ---> SmPC of [2] of EMA

Olaparib is an inhibitor of OATP1B1. It cannot be excluded that olaparib may increase the exposure to substrates of OATP1B1

OCT1 substrates, olaparib [2] ---> SmPC of [2] of EMA

Olaparib is an inhibitor of OCT1. It cannot be excluded that olaparib may increase the exposure to substrates of OCT1

OCT2 substrates, olaparib [2] ---> SmPC of [2] of EMA

Olaparib is an inhibitor of OCT2. It cannot be excluded that olaparib may increase the exposure to substrates of OCT2

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

In vitro, olaparib inhibits the efflux transporter P-gp (IC50 = 76 然), therefore it cannot be excluded that olaparib may cause clinically relevant drug interactions with substrates of P-gp

Olaparib [1], phenobarbital ---> SmPC of [1] of EMA

Known strong inducers of this isozyme (CYP3A) are not recommended with Lynparza, as it is possible that the efficacy of Lynparza could be substantially reduced.

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

Known strong inducers of this isozyme (CYP3A) are not recommended with Lynparza, as it is possible that the efficacy of Lynparza could be substantially reduced.

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

Olaparib [1], pravastatine ---> SmPC of [1] of EMA

In vitro, olaparib inhibits the efflux transporter P-gp (IC50 = 76 然), therefore it cannot be excluded that olaparib may cause clinically relevant drug interactions with substrates of P-gp

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

Based on the mode of action of olaparib, Lynparza should not be used during pregnancy and in women of childbearing potential not using reliable contraception during therapy and for 1 month after receiving the last dose of Lynparza.

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

Olaparib [1], repaglinide ---> SmPC of [1] of EMA

Olaparib is an inhibitor of OATP1B1. It cannot be excluded that olaparib may increase the exposure to substrates of OATP1B1

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

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

Known strong inducers of this isozyme (CYP3A) are not recommended with Lynparza, as it is possible that the efficacy of Lynparza could be substantially reduced.

Olaparib [1], rifapentine ---> SmPC of [1] of EMA

Known strong inducers of this isozyme (CYP3A) are not recommended with Lynparza, as it is possible that the efficacy of Lynparza could be substantially reduced.

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

Olaparib is an inhibitor of BCRP. It cannot be excluded that olaparib may increase the exposure to substrates of BCRP

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

CYP3A4/5 are the isozymes predominantly responsible for the metabolic clearance of olaparib. It is recommended that known strong inhibitors of these isozymes should be avoided with olaparib

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

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

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

Known strong inducers of this isozyme (CYP3A) are not recommended with Lynparza, as it is possible that the efficacy of Lynparza could be substantially reduced.

Olaparib [1], statins ---> SmPC of [1] of EMA

It cannot be excluded that olaparib may increase the exposure to substrates of OATP1B1. In particular, caution should be exercised if olaparib is administered in combination with any statin.

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

Known strong inducers of this isozyme (CYP3A) are not recommended with Lynparza, as it is possible that the efficacy of Lynparza could be substantially reduced.

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

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

Olaparib [1], strong P-gp inductors ---> SmPC of [1] of EMA

In vitro olaparib is a substrate for the efflux transporter P-gp. Clinical studies to evaluate the impact of known P-gp inhibitors and inducers have not been conducted.

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

In vitro olaparib is a substrate for the efflux transporter P-gp and therefore P-gp inhibitors may increase exposure to olaparib

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

Olaparib [1], tamoxifen ---> SmPC of [1] of EMA

A clinical study has been performed to assess the combination of olaparib with anastrozole, letrozole or tamoxifen. No clinically relevant interactions were observed.

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

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

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

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

Olaparib [1], vaccinations ---> SmPC of [1] of EMA

Combination of olaparib with vaccines or immunosuppressant agents has not been studied. Therefore, caution should be taken if these medicinal products are co-administered with Lynparza and patients should be closely monitored.

Olaparib [1], valsartan ---> SmPC of [1] of EMA

Olaparib is an inhibitor of OATP1B1. It cannot be excluded that olaparib may increase the exposure to substrates of OATP1B1

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

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

P-gp inductors [1], olaparib ---> SmPC of [1] of EMA

The potential for olaparib to induce CYP2C9, CYP2C19 and P-gp can also not be excluded.

Women of childbearing potential [1], olaparib ---> SmPC of [1] of EMA

Women of childbearing potential must use two forms of reliable contraception before starting Lynparza therapy, during therapy and for 6 months after receiving the last dose of Lynparza, unless abstinence is the chosen method of contraception (see section

CONTRAINDICATIONS of Olaparib (Lynparza)

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

- Breast-feeding during treatment and 1 month after the last dose (see section 4.6).

https://www.ema.europa.eu/en/documents/product-information/lynparza-epar-product-information_en.pdf 04/12/2025

Olaratumab (Lartruvo)

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

Due to frequent occurrence of fatigue, patients should be advised to use caution when driving or operating machinery.

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

Human IgG is excreted in human milk, therefore breast-feeding is not recommended during treatment with olaratumab and for at least 3 months following the last dose.

Cancer, olaratumab [2] ---> SmPC of [2] of EMA

No other formal DDI studies with olaratumab and medicinal products commonly used in cancer patients, including those with STS (e.g. antiemetics, analgesics, anti-diarrheal drugs, oral contraceptives, etc.), have been performed.

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

Monoclonal antibodies are not metabolised by cytochrome P450 (CYP) enzymes or other drug metabolising enzymes

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

There are no data on the effect of olaratumab on human fertility.

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

Olaratumab is not recommended during pregnancy and in women of childbearing potential not using contraception, unless the potential benefit justifies the potential risk to the foetus.

Olaratumab [1], vaccinations ---> SmPC of [1] of EMA

Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic agents including doxorubicin may result in serious or fatal infections.

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

Vaccination with a live vaccine should be avoided in patients receiving olaratumab in combination with doxorubicin.

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

Women of childbearing potential should be advised to use effective contraception during treatment and for at least 3 months following the last dose of olaratumab.

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

Women of childbearing potential should be advised to avoid becoming pregnant while on olaratumab and should be informed of the potential hazard to the pregnancy and foetus.

CONTRAINDICATIONS of Olaratumab (Lartruvo)

- 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/lartruvo-epar-product-information_en.pdf 02/09/2019 (revoked)

Olipudase alfa (Xenpozyme)

Ability to drive, olipudase alfa [2] –––> SmPC of [2] of EMA

Because hypotension has been reported in clinical studies, Xenpozyme may have minor influence on the ability to drive and use machines (see section 4.8).

Breast–feeding, olipudase alfa [2] ---> SmPC of [2] of EMA

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

Cytochrome P450, olipudase alfa [2] ---> SmPC of [2] of EMA

Because olipudase alfa is a recombinant human protein, no cytochrome P450 mediated drug-drug interactions are expected.

Fertility, olipudase alfa [2] ---> SmPC of [2] of EMA

Animal data do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).

Olipudase alfa [1], pregnancy ---> SmPC of [1] of EMA

Xenpozyme is not recommended during pregnancy and in women of childbearing potential not using effective contraception, unless the potential benefits to the mother outweigh the potential risks, including those to the foetus.

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

Women of childbearing potential are advised to use effective contraception during treatment and for 14 days after the last dose if Xenpozyme is discontinued.

CONTRAINDICATIONS of Olipudase alfa (Xenpozyme)

- Life-threatening hypersensitivity (anaphylactic reaction) to olipudase alfa or to any of the excipients listed in section 6.1 (see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/xenpozyme-epar-product-information_en.pdf 19/01/2026

Olmesartan medoxomil

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

Dizziness or fatigue may occasionally occur in patients taking antihypertensive therapy, which may impair the ability to react.

ACE inhibitors, olmesartan medoxomil

Hypotension, hyperkalaemia, and changes in renal function have been reported in susceptible individuals. Dual blockade of the RAA system by combining an ACE inhibitor with an AIIRA or aliskiren is therefore not recommended.

Acetylsalicylic acid, olmesartan ---> SmPC of [olmesartan medoxomil] of eMC

NSAIDs (including ASA at doses > 3 g/day and also COX-2 inhibitors) and AIIRAs may act synergistically by decreasing glomerular filtration (risk of acute renal failure). Additionally, concomitant treatment can reduce the antihypertensive effect of AIIRAs

Acetylsalicylic acid, olmesartan medoxomil [2] ---> SmPC of [2] of eMC

Alfa-adrenergic receptor blockers, olmesartan medoxomil [2] ---> SmPC of [2] of eMC

The blood pressure lowering effect of olmesartan medoxomil can be increased by concomitant use of other antihypertensive medications.

Aliskiren, olmesartan medoxomil

The concomitant use of ARBs with aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m²) and is not recommended in other patients

Antacids, olmesartan medoxomil [2] ---> SmPC of [2] of eMC

After treatment with antacid (aluminium magnesium hydroxide), a modest reduction in bioavailability of olmesartan was observed.

Antihypertensives, olmesartan medoxomil [2] ---> SmPC of [2] of eMC

The blood pressure lowering effect of olmesartan medoxomil can be increased by concomitant use of other antihypertensive medications.

Breast-feeding, olmesartan ---> SmPC of [olmesartan medoxomil] of eMC

The use of olmesartan 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.

Breast-feeding, olmesartan medoxomil [2] ---> SmPC of [2] of eMC

Colesevelam, olmesartan medoxomil [2] ---> SmPC of [2] of EMA

Co-administration of colesevelam and olmesartan decreases the exposure of olmesartan. Olmesartan should be administered at least 4 hours prior to colesevelam.

Coxibs, olmesartan medoxomil [2] ---> SmPC of [2] of eMC

Cyclosporine, olmesartan medoxomil [2] ---> SmPC of [2] of eMC

Ciclosporin may provoke a hyperkalaemia

Digoxin, olmesartan medoxomil [2] ---> SmPC of [2] of eMC

Olmesartan medoxomil had no significant effect on the pharmacokinetics of digoxin.

Diuretics, olmesartan medoxomil [2] ---> SmPC of [2] of eMC

The blood pressure lowering effect of olmesartan medoxomil can be increased by concomitant use of other antihypertensive medications.

Heparin, olmesartan medoxomil [2] ---> SmPC of [2] of eMC

Concomitant use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium or other drugs that may increase serum potassium levels (e.g. heparin) may lead to increases in serum potassium.

Hyperkalemia, olmesartan medoxomil [2] ---> SmPC of [2] of eMC

Lithium, olmesartan medoxomil [2] ---> SmPC of [2] of eMC

Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors and angiotensin II antagonists

NSAID, olmesartan ---> SmPC of [olmesartan medoxomil] of eMC

NSAID, olmesartan medoxomil [2] ---> SmPC of [2] of eMC

Olmesartan medoxomil [1], potassium ---> SmPC of [1] of eMC

Olmesartan medoxomil [1], potassium-sparing diuretics ---> SmPC of [1] of eMC

Olmesartan medoxomil [1], pravastatine ---> SmPC of [1] of eMC

Coadministration of olmesartan medoxomil with pravastatin had no clinically relevant effects on the pharmacokinetics of either component in healthy subjects.

Olmesartan medoxomil [1], pregnancy ---> SmPC of [1] of eMC

The use of angiotensin II antagonists is not recommended during the first trimester of pregnancy. The use of angiotensin II antagonists is contra-indicated during the 2nd and 3rd trimester of pregnancy

Olmesartan medoxomil [1], tacrolimus ---> SmPC of [1] of eMC

Tacrolimus may provoke a hyperkalaemia

Olmesartan medoxomil [1], trimethoprim ---> SmPC of [1] of eMC

Trimethoprim may provoke a hyperkalaemia

Olmesartan medoxomil [1], warfarin ---> SmPC of [1] of eMC

Olmesartan medoxomil had no significant effect on the pharmacokinetics or pharmacodynamics of warfarin

Olmesartan, pregnancy ---> SmPC of [olmesartan medoxomil] of eMC

CONTRAINDICATIONS of Olmesartan medoxomil

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

- Second and third trimesters of pregnancy

- Biliary obstruction

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

Olmesartan medoxomil/amlodipine

Ability to drive, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Dizziness, headache, nausea or fatigue may occasionally occur in patients taking antihypertensive therapy, which may impair the ability to react. Caution is recommended especially at the start of treatment.

ACE inhibitors, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Alfa-adrenergic receptor blockers, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

The blood pressure lowering effect of olmesartan medoxomil/amlodipine can be increased by concomitant use of other antihypertensive medicinal products

Aliskiren, olmesartan medoxomil/amlodipine

The concomitant use of ARBs with aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m²) and is not recommended in other patients

Antacids, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

After treatment with antacid, a modest reduction in bioavailability of olmesartan was observed.

Antihypertensives, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

The blood pressure lowering effects of amlodipine adds to the blood pressure-lowering effects of other antihypertensive agents.

Azole antifungals, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.

Breast-feeding, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Clarithromycin, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.

Colesevelam, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of EMA

Co-administration of colesevelam and olmesartan decreases the exposure of olmesartan. Olmesartan should be administered at least 4 hours prior to colesevelam.

Coxibs, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

When AIIRA are coadministered with NSAIDs, attenuation of the antihypertensive effect may occur. Moreover, this combination may increase the risk of worsening of renal function and may lead to an increase in serum potassium

CYP3A4 inductors, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

The concomitant use of amlodipine and CYP3A4 inducers may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.

Dantrolene, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Due to risk of hyperkalaemia, it is recommended that the co-administration of calcium channel blockers be avoided in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia.

Digoxin, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Olmesartan medoxomil had no significant effect on the pharmacokinetics of digoxin.

Diltiazem, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.

Diuretics, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

The blood pressure lowering effect of olmesartan medoxomil/amlodipine can be increased by concomitant use of other antihypertensive medicinal products

Erythromycin, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.

Grapefruit juice, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Administration of amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability may be increased in some patients resulting in increased blood pressure lowering effects.

Grapefruit, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Administration of amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability may be increased in some patients resulting in increased blood pressure lowering effects.

Heparin, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Hyperkalemia, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Lithium, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Macrolide antibiotics, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.

Moderate CYP3A4 inhibitors, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.

NSAID, olmesartan medoxomil/amlodipine [2] ---> SmPC of [2] of eMC

Olmesartan medoxomil/amlodipine [1], potassium ---> SmPC of [1] of eMC

Olmesartan medoxomil/amlodipine [1], potassium-sparing diuretics ---> SmPC of [1] of eMC

Olmesartan medoxomil/amlodipine [1], pravastatine ---> SmPC of [1] of eMC

Coadministration of olmesartan medoxomil with pravastatin had no clinically relevant effects on the pharmacokinetics of either component in healthy subjects.

Olmesartan medoxomil/amlodipine [1], pregnancy ---> SmPC of [1] of eMC

Olmesartan medoxomil/amlodipine [1], protease inhibitors ---> SmPC of [1] of eMC

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.

Olmesartan medoxomil/amlodipine [1], rifampicin ---> SmPC of [1] of eMC

The concomitant use of amlodipine and CYP3A4 inducers may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.

Olmesartan medoxomil/amlodipine [1], simvastatine ---> SmPC of [1] of eMC

Co-administration of multiple doses of amlodipine with simvastatin resulted in increase in exposure to simvastatin compared to simvastatin alone.

Olmesartan medoxomil/amlodipine [1], St. John's wort ---> SmPC of [1] of eMC

The concomitant use of amlodipine and CYP3A4 inducers may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.

Olmesartan medoxomil/amlodipine [1], strong CYP3A4 inductors ---> SmPC of [1] of eMC

The concomitant use of amlodipine and CYP3A4 inducers may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.

Olmesartan medoxomil/amlodipine [1], strong CYP3A4 inhibitors ---> SmPC of [1] of eMC

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.

Olmesartan medoxomil/amlodipine [1], verapamil ---> SmPC of [1] of eMC

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.

Olmesartan medoxomil/amlodipine [1], warfarin ---> SmPC of [1] of eMC

Olmesartan medoxomil had no significant effect on the pharmacokinetics or pharmacodynamics of warfarin

CONTRAINDICATIONS of Olmesartan medoxomil/amlodipine

- Hypersensitivity to the active substances, to dihydropyridine derivatives or to any of the excipients

- Second and third trimesters of pregnancy

- Severe hepatic insufficiency and biliary obstruction

Due to the component amlodipine Sevikar is also contraindicated in patients with:

- severe hypotension

- shock (including cardiogenic shock).

- obstruction of the outflow tract of the left ventricle (e.g. high grade aortic stenosis).

- haemodynamically unstable heart failure after acute myocardial infarction

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

Olopatadine (Opatanol)

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

As with any eye drop, temporary blurred vision or other visual disturbances may affect the ability to drive or use machines.

Active substance, olopatadine [2] ---> SmPC of [2] of EMA

These results indicate that olopatadine is unlikely to result in metabolic interactions with other concomitantly administered active substances.

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

A risk to the newborn/infants cannot be excluded. Opatanol should not be used during breast-feeding.

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

Studies have not been performed to evaluate the effect of topical ocular administration of olopatadine on human fertility.

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

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

CONTRAINDICATIONS of Olopatadine (Opatanol)

- 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/opatanol-epar-product-information_en.pdf 22/01/2026

Omalizumab (Xolair)

Anthelmintics, omalizumab [2] ---> SmPC of [2] of EMA

Omalizumab may indirectly reduce the efficacy of medicinal products for the treatment of helminthic or other parasitic infections

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

Consequently, if clinically needed, the use of omalizumab may be considered during breast-feeding.

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

Cytochrome P450 enzymes, efflux pumps and protein-binding mechanisms are not involved in the clearance of omalizumab; thus, there is little potential for drug-drug interactions.

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

In specifically-designed non-clinical fertility studies, in non-human primates including mating studies, no impairment of male or female fertility was observed following repeated dosing with omalizumab at dose levels up to 75 mg/kg.

Immunotherapy, omalizumab [2] ---> SmPC of [2] of EMA

In a clinical trial where Xolair was co-administered with immunotherapy, the safety and efficacy of Xolair in combination with specific immunotherapy were found to be no different to that of Xolair alone.

Medicinal products, omalizumab [2] ---> SmPC of [2] of EMA

Other commonly used concomitant medicinal products included other intranasal corticosteroids, bronchodilators, antihistamines, leukotriene receptor antagonists, adrenergics/sympathomimetics and local nasal anaesthetics.

Mometasone, omalizumab [2] ---> SmPC of [2] of EMA

In clinical studies omalizumab was used in conjunction with intranasal mometasone spray as per protocol.

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

If clinically needed, the use of omalizumab may be considered during pregnancy.

Omalizumab [1], safety ---> SmPC of [1] of EMA

There was no indication that the safety of omalizumab was altered by the concomitant use of these other commonly used medicinal products.

CONTRAINDICATIONS of Omalizumab (Xolair)

- 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/xolair-epar-product-information_en.pdf 21/05/2025

Other trade names: Omlyclo,

Omaveloxolone (Skyclarys)

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

Omaveloxolone may have a minor influence on the ability to drive and use machines. Fatigue may occur following administration of omaveloxolone (see section 4.8).

BCRP substrates, omaveloxolone [2] ---> SmPC of [2] of EMA

Omaveloxolone is a weak inducer of BCRP and can reduce the exposure of BCRP substrates.

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

Omaveloxolone is present in the milk of lactating rats and resulted in treatment-related effects in offspring (see section 5.3). A risk to the newborn infant cannot be excluded. Skyclarys should not be used during breast-feeding.

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

Omaveloxolone is a CYP3A4 substrate. Concomitant use of Skyclarys with strong or moderate CYP3A4 inducers may significantly decrease the exposure of omaveloxolone, which may reduce the effectiveness of Skyclarys.

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

Omaveloxolone is primarily metabolised by CYP3A4 (see section 5.2). Concomitant use of strong or moderate CYP3A4 inhibitors may significantly increase the systemic exposure of omaveloxolone (see section 4.5).

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

CYP2C8 substrates, omaveloxolone [2] ---> SmPC of [2] of EMA

Omaveloxolone is a weak inducer of CYP2C8 and can reduce the exposure of CYP2C8 substrates.

CYP3A4 substrates, omaveloxolone [2] ---> SmPC of [2] of EMA

Omaveloxolone is a weak inducer of CYP3A4 and can reduce the exposure of CYP3A4 substrates.

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

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

There are no data on the effects of Skyclarys on human fertility. Animal data did not indicate impairment of parent male or female fertility (see section 5.3).

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

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

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

As grapefruit and grapefruit juice are inhibitors of CYP3A4, patients should be warned to avoid these while taking Skyclarys (see section 4.4).

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

As grapefruit and grapefruit juice are inhibitors of CYP3A4, patients should be warned to avoid these while taking Skyclarys (see section 4.4).

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

Concomitant use with Skyclarys may reduce the efficacy of hormonal contraceptives. Advise patients to avoid concomitant use with combined hormonal contraceptives (e.g., pill, patch, ring), implants, and progestin only pills (see section 4.6).

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

In a clinical study, co-administration of Skyclarys with itraconazole, a strong CYP3A4 inhibitor, increased the area under the curve (AUC0-inf) and maximal plasma concentration (Cmax) by approximately 4-fold and 3-fold, respectively.

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

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

The AUC of midazolam, a CYP3A4 substrate, was reduced by approximately 45% when co-administered with omaveloxolone, indicating that omaveloxolone is a weak inducer of CYP3A4 and can reduce the exposure of CYP3A4 substrates.

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

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

Omaveloxolone [1], phenobarbital ---> SmPC of [1] of EMA

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

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

Skyclarys should not be used during pregnancy or in women of childbearing potential not using contraception.

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

Patients should use effective contraception prior to starting treatment with Skyclarys, during treatment, and for 28 days following discontinuation of treatment.

Omaveloxolone [1], primidone ---> SmPC of [1] of EMA

Omaveloxolone [1], repaglinide ---> SmPC of [1] of EMA

The AUC of repaglinide, a CYP2C8 substrate, was reduced by approximately 35% when co-administered with omaveloxolone, indicating that omaveloxolone is a weak inducer of CYP2C8 and can reduce the exposure of CYP2C8 substrates.

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

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

The AUC of rosuvastatin, a BCRP and OATP1B1 substrate, was reduced by approximately 30% when co-administered with omaveloxolone, indicating that omaveloxolone is a weak inducer of BCRP and can reduce the exposure of BCRP substrates.

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

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

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

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

In a clinical study with healthy subjects, coadministration of verapamil (120 mg once daily) increased the AUC and Cmax by 1.24-fold and 1.28fold, respectively. Verapamil is a known moderate CYP3A4 inhibitor and inhibitor of the P-gp transporter.

CONTRAINDICATIONS of Omaveloxolone (Skyclarys)

- 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/skyclarys-epar-product-information_en.pdf 26/02/2024

Ombitasvir/paritaprevir/ritonavir (Viekirax)

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

No dose adjustment needed for abacavir/lamivudine when administered with Viekirax with or without dasabuvir.

Ability to drive, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Patients should be informed that fatigue has been reported during treatment with Viekirax in combination with dasabuvir and ribavirin

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

CYP3A4 and/or OATP1B inhibition by paritaprevir. Clinical monitoring and dose reduction is recommended for angiotensin receptor blockers when co-administered with Viekirax with or without dasabuvir.

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

CYP3A4 and/or OATP1B inhibition by paritaprevir. Clinical monitoring and dose reduction is recommended for angiotensin receptor blockers when co-administered with Viekirax with or without dasabuvir.

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

Ritonavir is a strong inhibitor of CYP3A. Medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma levels are associated with serious events are contraindicated

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

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

CYP3A4 substrates may require dose adjustment and/or clinical monitoring

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

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

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

CYP3A4 inhibition by ritonavir. Decrease amlodipine dose by 50% and monitor patients for clinical effects.

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

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

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

The combination carries an increased risk for hyperbilirubinemia (including ocular icterus), in particular when ribavirin is part of the hepatitis C regimen.

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

The combination carries an increased risk for hyperbilirubinemia (including ocular icterus), in particular when ribavirin is part of the hepatitis C regimen.

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

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

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

Co-administration of ombitasvir/paritaprevir/ritonavir with or without dasabuvir with medicinal products that are substrates of BCRP may increase plasma concentrations of these transporter substrates

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

Because of the potential for adverse reactions from the medicinal product in breastfed infants, a decision must be made whether to discontinue breast-feeding or discontinue treatment with Viekirax

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

CYP3A4 inhibition by ritonavir and UGT inhibition by paritaprevir, ombitasvir and dasabuvir. No dose adjustment is necessary for buprenorphine/naloxone and Viekirax with or without dasabuvir.

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

Viekirax administered with or without dasabuvir. Exposures of cyclobenzaprine, a CYP1A2 substrate, were decreased. Clinical monitoring and dose adjustment may be needed for other CYP1A2 substrates (e.g. ciprofloxacin, theophylline and caffeine).

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

Calcium antagonists, dasabuvir with ombitasvir/paritaprevir/ritonavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

Dose decrease and clinical monitoring of calcium channel blockers is recommended when coadministered with Viekirax with and without dasabuvir.

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

Dose decrease and clinical monitoring of calcium channel blockers is recommended when coadministered with Viekirax with and without dasabuvir.

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

CYP3A4 and/or OATP1B inhibition by paritaprevir. Clinical monitoring and dose reduction is recommended for angiotensin receptor blockers when co-administered with Viekirax with or without dasabuvir.

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

CYP3A4 and/or OATP1B inhibition by paritaprevir. Clinical monitoring and dose reduction is recommended for angiotensin receptor blockers when co-administered with Viekirax with or without dasabuvir.

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

Coadministration of Viekirax with/without dasabuvir with drugs that are strong or moderate enzyme inducers is expected to decrease ombitasvir, paritaprevir, and ritonavir plasma levels and reduce their therapeutic effect. Concomitant use contraindicated

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

CYP2C19 induction by ritonavir. No dose adjustment required for carisoprodol; increase dose if clinically indicated

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

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

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

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

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

Co-administration of ombitasvir/paritaprevir/ritonavir with or without dasabuvir with medicinal products that are strong inhibitors of CYP3A4 is expected to increase paritaprevir plasma concentrations. The coadministration is contraindicated

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

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

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

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

The strong CYP3A inhibition by ritonavir may increase the plasma levels of colchicine. Concomitant use is contraindicated in patients with renal or hepatic impairment

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

The strong CYP3A inhibition by ritonavir may increase the plasma levels of colchicine. Concomitant use is contraindicated in patients with renal or hepatic impairment

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

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

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

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

CYP3A4 substrates may require dose adjustment and/or clinical monitoring

CYP3A4 and P-glycoprotein-inhibitors, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Caution is advised if co-administering Viekirax with medicinal products that are both moderate inhibitors of CYP3A4 and inhibitors of multiple transporters. These medicinal products may show clinically relevant increases in exposures of paritaprevir

CYP3A4, P-gp, and BCRP inhibitors, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

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

Viekirax may increase the plasma exposure to medicinal products that are sensitive for changed intestinal P-gp activity (such as dabigatran etexilate).

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

No dose adjustment is required

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

Viekirax administered with or without dasabuvir. CYP2D6 substrates (e.g. desipramine, metoprolol and dextromethorphan) are not expected to require dose adjustments.

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

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

CYP3A4/P-gp inhibition. Caution is advised due to the expected increase in paritaprevir exposures. Dose decrease and clinical monitoring of calcium channel blockers is recommended when coadministered with Viekirax with and without dasabuvir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, drugs primarily metabolised by CYP1A2 ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

Dasabuvir with ombitasvir/paritaprevir/ritonavir, drugs primarily metabolised by CYP2D6 ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

Viekirax administered with or without dasabuvir. CYP2D6 substrates (e.g. desipramine, metoprolol and dextromethorphan) are not expected to require dose adjustments.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, drugs primarily metabolised by UGT1A1 ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

Paritaprevir, ombitasvir and dasabuvir are inhibitors of UGT1A1. Co-administration of Viekirax with or without dasabuvir with medicinal products that are primarily metabolized by UGT1A1 result in increased plasma concentrations of such medicinal products

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

Viekirax administered with or without dasabuvir did not affect the exposures of the CYP2D6/CYP1A2 substrate, duloxetine.

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

No dose adjustment is necessary for emtricitabine/tenofovir and Viekirax with or without dasabuvir.

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

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

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

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

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

Mechanism: possibly due to UGT inhibition by paritaprevir, ombitasvir and dasabuvir Ethinylestradiol-containing oral contraceptives are contraindicated

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

Co-administration of ombitasvir/paritaprevir/ritonavir with or without dasabuvir with medicinal products that are substrates of OATP1B1, OATP1B3, OATP2B1 or OCT1 may increase plasma concentrations of these transporter substrates

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

Concomitant use of fluticasone can increase systemic exposures of fluticasone. CYP3A4 inhibition by ritonavir.

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

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

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

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

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

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

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

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

Co-administration of Viekirax with medicinal products that are primarily metabolized by UGT1A1 increased plasma concentrations of such medicinal products, routine clinical monitoring is recommended for narrow therapeutic index medicinal products

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

CYP3A4 and/or OATP1B inhibition by paritaprevir. Clinical monitoring and dose reduction is recommended for angiotensin receptor blockers when co-administered with Viekirax with or without dasabuvir.

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

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

No dose adjustment needed for methadone when administered with Viekirax with or without dasabuvir.

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

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

Viekirax administered with or without dasabuvir. CYP2D6 substrates (e.g. desipramine, metoprolol and dextromethorphan) are not expected to require dose adjustments.

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

The strong CYP3A inhibition by ritonavir may increase the plasma levels of midazolam. Concomitant use with oral midazolam is contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, moderate CYP3A4 inductors ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

Co-administration of Viekirax and dasabuvir with medicinal products that are moderate or strong enzyme inducers is expected to decrease ombitasvir, paritaprevir, ritonavir and dasabuvir plasma concentrations and reduce their therapeutic effect.

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

CYP3A4 inhibition. Dose decrease and clinical monitoring of calcium channel blockers is recommended when coadministered with Viekirax with and without dasabuvir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, OATP1B1 substrates ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

Dasabuvir with ombitasvir/paritaprevir/ritonavir, OATP1B3 substrates ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

Dasabuvir with ombitasvir/paritaprevir/ritonavir, OATP2B1 substrates ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

Dasabuvir with ombitasvir/paritaprevir/ritonavir, OCT1 substrates ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

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

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

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

OATP1B1 inhibition by paritaprevir may increase the plasma concentrations of pravastatin. Reduce pravastatin dose by 50%.

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

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

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

OATP1B1 inhibition by paritaprevir. Caution should be used and dose decrease maybe needed for repaglinide when administered with Viekirax with or without dasabuvir.

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

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

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

The strong CYP3A inhibition by ritonavir may increase the plasma levels of sildenafil. Concomitant use is contraindicated when sildenafil used for the treatment of pulmonary arterial hypertension

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

Dasabuvir with ombitasvir/paritaprevir/ritonavir, strong CYP3A4 inductors ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

Dasabuvir with ombitasvir/paritaprevir/ritonavir, strong CYP3A4 inhibitors ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

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

BCRP inhibition by paritaprevir, ritonavir and dasabuvir. Caution should be used when sulfasalazine is coadministered with Viekirax with or without dasabuvir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, telithromycin ---> SmPC of [ombitasvir/paritaprevir/ritonavir] o

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

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

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

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

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

Dasabuvir with ombitasvir/paritaprevir/ritonavir, UGT1A1 substrates with narrow therapeutic index ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

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

CYP3A4 and/or OATP1B inhibition by paritaprevir. Clinical monitoring and dose reduction is recommended for angiotensin receptor blockers when co-administered with Viekirax with or without dasabuvir.

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

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

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

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

Dasabuvir, ombitasvir/paritaprevir/ritonavir

As liver function may change during treatment with Exviera administered with ombitasvir/paritaprevir/ritonavir, a close monitoring of International Normalised Ratio (INR) values is recommended.

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

Viekirax may be administered with or without dasabuvir. When co-administered, they exert mutual effects on each other (see section 5.2). Therefore, the interaction profile of the compounds must be considered as a combination.

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

Viekirax administered with or without dasabuvir. CYP2D6 substrates (e.g. desipramine, metoprolol and dextromethorphan) are not expected to require dose adjustments.

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

Viekirax administered with or without dasabuvir. CYP2D6 substrates (e.g. desipramine, metoprolol and dextromethorphan) are not expected to require dose adjustments.

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

CYP2C19 induction by ritonavir. No dose adjustment required for diazepam; increase dose if clinically indicated.

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

P-gp inhibition by paritaprevir, ritonavir and dasabuvir. Decrease digoxin dose by 30-50%. Appropriate monitoring of serum digoxin levels is recommended.

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

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

Direct acting antivirals, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Co-administration of Viekirax with other antivirals has not been studied and therefore cannot be recommended.

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

No dose adjustment needed for dolutegravir when administered with Viekirax with or without dasabuvir.

Drugs primarily metabolised by CYP1A2, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP2C19, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Co-administration of Viekirax with or without dasabuvir can decrease exposures of medicinal products that are metabolized by CYP2C19 (e.g. lansoprazole, esomeprazole, S-mephenytoin), which may require dose adjustment/clinical monitoring.

Drugs primarily metabolised by CYP2C9, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP2D6, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Viekirax administered with or without dasabuvir. CYP2D6 substrates (e.g. desipramine, metoprolol and dextromethorphan) are not expected to require dose adjustments.

Drugs primarily metabolised by CYP3A4, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir is a strong inhibitor of CYP3A. Co-administration of Viekirax with or without dasabuvir with medicinal products primarily metabolized by CYP3A may result in increased plasma concentrations of these medicinal products.

Drugs primarily metabolised by UGT1A1, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

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

Viekirax administered with or without dasabuvir did not affect the exposures of the CYP2D6/CYP1A2 substrate, duloxetine.

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

Emtricitabine/tenofovir disoproxil, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

No dose adjustment is necessary for emtricitabine/tenofovir and Viekirax with or without dasabuvir.

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

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

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

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

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

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

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

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

Coadministration of ombitasvir/paritaprevir/ritonavir with ethinylestradiol may increase the risk of ALT elevations und is contraindicated

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

Mechanism: possibly due to UGT inhibition by paritaprevir, ombitasvir and dasabuvir Ethinylestradiol-containing oral contraceptives are contraindicated

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

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

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

Concomitant use of fluticasone can increase systemic exposures of fluticasone. CYP3A4 inhibition by ritonavir.

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

OATP1B/BCRP inhibition by paritaprevir. A temporary suspension of fluvastatin and pitavastatin is recommended for the duration of treatment with Viekirax.

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

To maximise absorption, Viekirax tablets should be taken with food, without regard to fat and calorie content

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

Co-administration of paritaprevir and fosamprenavir/ritonavir is contraindicated due to the expected increase of paritaprevir exposure and the lack of clinical data assessing the magnitude of this increase

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

Possibly increased furosemide plasma concentrations due to UGT1A1 inhibition by paritaprevir, ombitasvir and dasabuvir. Monitor patients for clinical effects; a decrease in furosemide dose of up to 50% may be required.

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

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

No interaction expected when gemfibrozil is used in combination with ombitasvir/paritaprevir/ritonavir without dasabuvir. No dose adjustment is necessary.

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

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

Glucocorticoids metabolized by CYP3A4, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Caution should be used when administering ombitasvir/paritaprevir/ritonavir with fluticasone or other glucocorticoids that are metabolised by CYP3A4. Concomitant use can increase systemic exposures of the glucocorticoids

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

Hydrocodone (as given in a fixed-dose hydrocodone/paracetamol). CYP3A4 inhibition by ritonavir. A reduction of hydrocodone dose by 50% and/or clinical monitoring should be considered when administered with Viekirax with or without dasabuvir .

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

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

Co-administration of ombitasvir/paritaprevir/ritonavir with or without dasabuvir with medicinal products that are substrates of BCRP may increase plasma concentrations of these transporter substrates

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

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

CYP3A4/P-gp inhibition by itraconazol and paritaprevir/ ritonavir/ ombitasvir. Concomitant use is contraindicated

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

CYP3A4/P-gp inhibition by ketoconazole and paritaprevir/ ritonavir/ ombitasvir. Concomitant use is contraindicated

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

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

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

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

CYP3A4 and/or OATP1B inhibition by paritaprevir. Clinical monitoring and dose reduction is recommended for angiotensin receptor blockers when co-administered with Viekirax with or without dasabuvir.

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

MATE1 substrates, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

In vitro studies show that ombitasvir, paritaprevir, and ritonavir are not inhibitors of toxin extrusion proteins (MATE1 and MATE2K) at clinically relevant concentrations.

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

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

No dose adjustment needed for metformin when co-administered with Viekirax with and without dasabuvir.

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

No dose adjustment needed for methadone when administered with Viekirax with or without dasabuvir.

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

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

Viekirax administered with or without dasabuvir. CYP2D6 substrates (e.g. desipramine, metoprolol and dextromethorphan) are not expected to require dose adjustments.

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

The strong CYP3A inhibition by ritonavir may increase the plasma levels of midazolam. Concomitant use with oral midazolam is contraindicated

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

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

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

CYP3A4 inhibition. Dose decrease and clinical monitoring of calcium channel blockers is recommended when coadministered with Viekirax with and without dasabuvir.

Non-nucleoside reverse transcriptase inhibitors, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

NNRTIs other than rilpivirine (efavirenz, etravirine and nevirapine) are contraindicated

NS3/4A inhibitors, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

The efficacy of Viekirax in patients previously exposed to Viekirax, or to medicinal products of the same classes as those of Viekirax (NS3/4A- or NS5A inhibitors), has not been demonstrated.

NS5A inhibitors, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

The efficacy of Viekirax in patients previously exposed to Viekirax, or to medicinal products of the same classes as those of Viekirax (NS3/4A- or NS5A inhibitors), has not been demonstrated.

OAT1 substrates, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Ombitasvir, paritaprevir, and ritonavir do not inhibit organic anion transporter (OAT1) in vivo as shown by the lack of interaction with tenofovir (OAT1 substrate).

OAT3 substrates, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

In vitro studies show that ombitasvir, paritaprevir, and ritonavir are not inhibitors of organic cation transporters (OCT2), organic anion transporters (OAT3) at clinically relevant concentrations.

OATP1B1 substrates, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

OATP1B3 substrates, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

OATP2B1 substrates, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

OCT1 substrates, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

OCT2 substrates, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

In vitro studies show that ombitasvir, paritaprevir, and ritonavir are not inhibitors of organic cation transporters (OCT2), organic anion transporters (OAT3) at clinically relevant concentrations.

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

Ombitasvir/paritaprevir/ritonavir [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Ombitasvir/paritaprevir/ritonavir may increase the plasma exposure to medicinal products that are sensitive for changed intestinal P-gp activity (such as dabigatran etexilate).

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

Paracetamol (as given in a fixed-dose hydrocodone/paracetamol). No dose adjustment needed for paracetamol when administered with Viekirax with or without dasabuvir.

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

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

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

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

OATP1B inhibition by paritaprevir. A temporary suspension of fluvastatin and pitavastatin is recommended for the duration of treatment with Viekirax.

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

CYP3A4/P-gp inhibition by posaconazole and paritaprevir/ ritonavir/ ombitasvir. Concomitant use is contraindicated

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

OATP1B1 inhibition by paritaprevir. Reduce pravastatin dose by 50%. No dose adjustment needed for Viekirax with or without dasabuvir.

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

Viekirax should not be used during pregnancy or in women of childbearing potential not using effective contraception.

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

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

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

UGT1A1 inhibition by paritaprevir, ombitasvir and dasabuvir. No dose adjustment is necessary

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

OATP1B1 inhibition by paritaprevir. Caution should be used and dose decrease maybe needed for repaglinide when administered with Viekirax with or without dasabuvir.

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

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

CYP3A4 inhibition by ritonavir. Co-administration of Viekirax with rilpivirine once daily should only be considered in patients without known QT prolongation, and without other QT-prolongation comedications.

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

OATP1B inhibition by paritaprevir and BCRP inhibition by paritaprevir, ritonavir or dasabuvir. The maximum daily dose of rosuvastatin should be 10 mg. No dose adjustment needed for Viekirax.

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

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

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

The strong CYP3A inhibition by ritonavir may increase the plasma levels of sildenafil. Concomitant use is contraindicated when sildenafil used for the treatment of pulmonary arterial hypertension

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

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

BCRP and P-gp inhibition by paritaprevir, ritonavir and dasabuvir. No dose adjustment needed for sofosbuvir when administered with Viekirax with or without dasabuvir.

Ombitasvir/paritaprevir/ritonavir [1], St. John's wort ---> SmPC of [1] of EMA

Ombitasvir/paritaprevir/ritonavir [1], strong BCRP inhibitors ---> SmPC of [1] of EMA

Potent inhibitors of P-gp, BCRP, OATP1B1 and/or OATP1B3 have the potential to increase the exposure to paritaprevir.

Ombitasvir/paritaprevir/ritonavir [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Ombitasvir/paritaprevir/ritonavir [1], strong OATP1B1 inhibitors ---> SmPC of [1] of EMA

Potent inhibitors of P-gp, BCRP, OATP1B1 and/or OATP1B3 have the potential to increase the exposure to paritaprevir.

Ombitasvir/paritaprevir/ritonavir [1], strong OATP1B3 inhibitors ---> SmPC of [1] of EMA

Potent inhibitors of P-gp, BCRP, OATP1B1 and/or OATP1B3 have the potential to increase the exposure to paritaprevir.

Ombitasvir/paritaprevir/ritonavir [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Potent inhibitors of P-gp, BCRP, OATP1B1 and/or OATP1B3 have the potential to increase the exposure to paritaprevir.

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

Increase in dasabuvir possibly due to CYP2C8 inhibition by trimethoprim. No dose adjustment needed for Viekirax with or without dasabuvir.

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

BCRP inhibition by paritaprevir, ritonavir and dasabuvir. Caution should be used when sulfasalazine is coadministered with Viekirax with or without dasabuvir.

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

CYP3A4 substrates may require dose adjustment and/or clinical monitoring

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

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

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

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

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

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

CYP3A4 substrates may require dose adjustment and/or clinical monitoring

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

Ombitasvir/paritaprevir/ritonavir [1], UGT1A1 substrates with narrow therapeutic index ---> SmPC of [1] of EMA

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

CYP3A4 and/or OATP1B inhibition by paritaprevir. Clinical monitoring and dose reduction is recommended for angiotensin receptor blockers when co-administered with Viekirax with or without dasabuvir.

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

Ombitasvir/paritaprevir/ritonavir [1], vitamin K antagonists ---> SmPC of [1] of EMA

As liver function may change during treatment with Viekirax administered with or without dasabuvir, a close monitoring of International Normalised Ratio (INR) values is recommended.

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

CYP2C19 induction and CYP3A4 inhibition by ritonavir. Concomitant use is contraindicated

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

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

CONTRAINDICATIONS of Ombitasvir/paritaprevir/ritonavir (Viekirax)

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

- Patients with severe hepatic impairment (Child-Pugh C) (see section 5.2).

- Use of ethinylestradiol-containing medicinal products such as those contained in most combined oral contraceptives or contraceptive vaginal rings (see section 4.4 and 4.5).

- Medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma levels are associated with serious events must not be co-administered with Viekirax (see section 4.5). Examples are provided below.

CYP3A4 substrates:

- alfuzosin hydrochloride

- amiodarone

- astemizole, terfenadine

- cisapride

- colchicine in patients with renal or hepatic impairment

- ergotamine, dihydroergotamine, ergonovine, methylergometrine. Dronedarone Lurasidone. Ranolazine

- fusidic acid

- lovastatin, simvastatin, atorvastatin

- oral midazolam, triazolam

- pimozide

- quetiapine

- quinidine

- salmeterol

- sildenafil (when used for the treatment of pulmonary arterial hypertension)

- ticagrelor

- Co-administration of Viekirax with or without dasabuvir with medicinal products that are strong or moderate enzyme inducers is expected to decrease ombitasvir,

paritaprevir, and ritonavir plasma concentrations and reduce their therapeutic effect and must not be co-administered (see section 4.5). Examples of contraindicated strong or moderate enzyme inducers are provided below.

Enzyme inducers:

- carbamazepine, phenytoin, phenobarbital

- efavirenz, nevirapine, etravirine

- enzalutamide

- mitotane

- rifampicin

- St. John's Wort (Hypericum perforatum)

- Co-administration of Viekirax with or without dasabuvir with medicinal products that are strong inhibitors of CYP3A4 is expected to increase paritaprevir plasma concentrations and must not be co-administered with Viekirax (see section 4.5). Examples of contraindicated strong CYP3A4 inhibitors are provided below.

CYP3A4 inhibitors:

- cobicistat

- indinavir, lopinavir/ritonavir, saquinavir, tipranavir,

- itraconazole, ketoconazole, posaconazole, voriconazole

- clarithromycin, telithromycin

- conivaptan

https://www.ema.europa.eu/es/documents/product-information/viekirax-epar-product-information_es.pdf 02/10/2024 (withdrawn)

Omeprazole

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

If side effects such as dizziness and light headedness are experienced the ability to drive and use machines may be affected

Acenocoumarol, omeprazole

The co-administration may enhance the anticoagulant effect of acenocoumarol and increase the bleeding risk

Amprenavir/ritonavir, omeprazole ---> SmPC of [esomeprazole] of EMA

Treatment with omeprazole had no effect on the exposure of darunavir (with concomitant ritonavir) and amprenavir (with concomitant ritonavir).

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

When aripiprazole was administered concomitantly with omeprazol, there was no clinically important change in concentrations of omeprazol. Thus, no dosage adjustment is required

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

The mechanism of interaction is decreased solubility of atazanavir as intra-gastric pH increases with proton pump inhibitors. Co-administration of EVOTAZ with proton pump inhibitors is not recommended.

Atazanavir/ritonavir, omeprazole ---> SmPC of [esomeprazole] of EMA

For atazanavir, decreased serum levels have been reported when given together with omeprazole and concomitant administration is not recommended.

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

Further clinical studies using omeprazole, rosiglitazone and desipramine did not reveal clinically relevant interactions with CYPs 2C19, 2C8/9 and 2D6.

Benzodiazepines, omeprazole ---> SmPC of [lorazepam] of eMC

Inhibitors reduce clearance and may potentiate the action of benzodiazepines.

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

No dosage adjustment necessary.

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

In a drug-drug interaction study assessing the effect of omeprazole, a potent CYP2C19 inhibitor, on the pharmacokinetics of bortezomib (injected intravenously), there was no significant effect on the pharmacokinetics of bortezomib

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

Omeprazole is excreted into breast milk but is unlikely to influence the child when used in therapeutic doses.

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

Brivaracetam may increase plasma concentrations of medicinal products metabolised by CYP2C19 (e.g. lansoprazole, omeprazole, diazepam).

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

The plasma concentrations of carbamazepine may be increased

Chlordiazepoxide [1], omeprazole ---> SmPC of [1] of eMC

Enzymatic inhibitors reduce clearance and may potentiate the action of benzodiazepines.

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

The overall pharmacological activity of cilostazol increases by 47% when co-administered with omeprazole.

Ciprofloxacin [1], omeprazole ---> SmPC of [1] of eMC

Concomitant administration of ciprofloxacin and omeprazole containing medicinal products results in a slight reduction of Cmax and AUC of ciprofloxacin.

Clarithromycin, omeprazole

Concomitant administration of omeprazole and a CYP2C19 and CYP3A4 inhibitor, increased the omeprazole exposure.

Clobazam [1], omeprazole ---> SmPC of [1] of eMC

The moderate CYP2C19 inhibition may increase the exposure to the active metabolite of clobazam. Dosage adjustment of clobazam may be necessary

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

Since clopidogrel is metabolised to its active metabolite partly by CYP2C19, use of medicinal products that inhibit the activity of this enzyme would be expected to result in reduced drug levels of the active metabolite of clopidogrel.

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

Omeprazole 80 mg once daily administered either at the same time as clopidogrel or with 12 hours between the administrations of the two drugs decreased the exposure of the active metabolite by 45% (loading dose) and 40% (maintenance dose).

Clozapine [1], omeprazole ---> SmPC of [1] of eMC

Concomitant administration of substances known to inhibit the activity of some cytochrome P450 isozymes (CYP1A2) may increase the levels of clozapine, and the dose of clozapine may need to be reduced to prevent undesirable effects.

Cyanocobalamin, omeprazole [2] ---> SmPC of [2] of eMC

The inhibition of acid secretion may decrease the absorption of cyanocobalamin (vitamin B12) due to hypochlorhydria or achlorhydria

Cyanocobalamin, proton pump inhibitors ---> SmPC of [omeprazole] of eMC

The inhibition of acid secretion may decrease the absorption of cyanocobalamin (vitamin B12) due to hypochlorhydria or achlorhydria

CYP2C19 inhibitors, omeprazole [2] ---> SmPC of [2] of eMC

Concomitant administration of omeprazole and a CYP2C19 inhibitor, increased the omeprazole exposure.

CYP3A4 and CYP2C19 inductors, omeprazole

Principle actives known to induce CYP2C19 and CYP3A4 may increase the omeprazole metabolism and decrease its plasma levels

CYP3A4 and CYP2C19 inhibitors, omeprazole

Concomitant administration of omeprazole and a CYP2C19 and CYP3A4 inhibitor, increased the omeprazole exposure.

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

Co-administration of the proton pump inhibitor omeprazole and PROCYSBI in vivo showed no effects on cysteamine bitartrate exposure

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

No dose adjustment is required

Dapsone, omeprazole

Omeprazol may decrease the clearance of dapsone

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

Based on theoretical considerations, no mechanistic interaction is expected. REZOLSTA can be co-administered with proton pump inhibitors without dose adjustments.

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

Based on theoretical considerations, no mechanistic interaction is expected. Symtuza can be co-administered with proton pump inhibitors without dose adjustments.

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

Darunavir co-administered with low dose ritonavir can be co-administered with proton pump inhibitors without dose adjustments.

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

Co-administration of dasabuvir with ombitasvir/paritaprevir/ritonavir can decrease exposures of medicinal products that are metabolized by CYP2C19, which may require dose adjustment/clinical monitoring.

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

Long-term suppression of gastric acid secretion by H2 antagonists or proton pump inhibitors (e.g. famotidine and omeprazole) is likely to reduce dasatinib exposure.

Diazepam, omeprazole [2] ---> SmPC of [2] of eMC

As omeprazole is metabolised in the liver through cytochrome P450, it can prolong the elimination of diazepam

Digoxin, omeprazole [2] ---> SmPC of [2] of eMC

Simultaneous treatment with omeprazole and digoxin in healthy subjects lead to a 10% increase in the bioavailability of digoxin as a consequence of the increased intragastric pH.

Dipotassium clorazepate, omeprazole

The co-administration may enhance and prolong the clorazepate effect

Dolutegravir/rilpivirine [1], omeprazole ---> SmPC of [1] of EMA

Co-administration may significantly decrease rilpivirine plasma concentration. This may result in loss of therapeutic effect of Juluca. Co-administration of Juluca with proton pump inhibitors is contraindicated

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

Dronedarone does not affect the pharmacokinetics of omeprazole, a CYP 2C19 substrate.

Drugs metabolised by CYP2C19, omeprazole [2] ---> SmPC of [2] of eMC

Omeprazol, moderate CYP2C19 inhibitor, may increase the plasma concentrations of medicinal products metabolized by CYP2C19

Drugs primarily metabolised by CYP2C19, omeprazole [2] ---> SmPC of [2] of eMC

Omeprazol, moderate CYP2C19 inhibitor, may increase the plasma concentrations of medicinal products mainly metabolized by CYP2C19

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

No dose adjustment is required when Vitekta is co-administered with omeprazol.

Emtricitabine/rilpivirine/tenofovir alafenamide [1], omeprazole ---> SmPC of [1] of EMA

Reduced absorption, increase in gastric pH. Co-administration is contraindicated.

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

Co-administration of proton pump inhibitors has been observed to decrease the plasma concentrations of rilpivirine (due to an increase in gastric pH) which could potentially lead to loss of therapeutic effect. Concomitant use contraindicated

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

Enzalutamide, CYP2C19 inductor, may decrease the AUC of omeprazol

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

Co-administration of erlotinib with omeprazole, a proton pump inhibitor (PPI), decreased the erlotinib exposure [AUC] and maximum concentration [Cmax] by 46% and 61%, respectively.

Erlotinib, omeprazole

Significant decrease of absorption and of maximum concentrations of erlotinib. The concomitant use should be avoided

Erythromycin, omeprazole

The co-administration increases the bioavailability of erythromycin and omeprazol and potentiates the effects and adverse reactions

Escitalopram [1], omeprazole ---> SmPC of [1] of eMC

Caution should be exercised when used escitalopram concomitantly with CYP2C19 inhibitors. A reduction in the dose of escitalopram may be necessary based on monitoring of side-effects during concomitant treatment.

Ethinylestradiol/norgestimate, omeprazole

Combination hormonal contraceptives with omeprazol may increase plasma levels (due to CYP inhibition) of omeprazol

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

Etravirine can be co-administered with proton pump inhibitors without dose adjustments.

Fluvastatin [1], omeprazole ---> SmPC of [1] of eMC

Concomitant administration of fluvastatin with omeprazole results in an increase in the bioavailability of fluvastatin, which, however, is of no clinical relevance.

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

The increase in gastric pH decreases the fosamprenavir absorption. No dosage adjustment necessary

Fosphenytoin [1], omeprazole ---> SmPC of [1] of eMC

Omeprazole may increase plasma phenytoin concentrations

Glecaprevir/pibrentasvir [1], omeprazole ---> SmPC of [1] of EMA

Increase gastric pH value. Co-administration of Maviret with omeprazole 40 mg once daily may lead to reduced therapeutic effect and is not recommended.

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

No CRESEMBA dose adjustment necessary. Omeprazole: no dose adjustment required.

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

Acid secretion suppressors impair the absorption of itraconazole. It is recommended that itraconazole be administered with an acidic beverage (such as non-diet cola)

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

Specific drug-drug interaction studies have shown no clinically significant effect of the proton pump inhibitors on pharmacokinetics and pharmacodynamics of ivabradine

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

Due to the decreased intragastric acidity the absorption of ketoconazole may be reduced during omeprazole treatment

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

The CYP2C19 inhibitor omeprazole (40 mg q.d.) did not give rise to a clinically significant change in lacosamide exposure. Thus moderate inhibitors of CYP2C19 are unlikely to affect systemic lacosamide exposure to a clinically relevant extent.

Lamivudine/raltegravir [1], omeprazole ---> SmPC of [1] of EMA

Co-administration of lamivudine/raltegravir with other agents that increase gastric pH may increase the rate of raltegravir absorption and result in increased plasma levels of raltegravir. No dose adjustment is required

Ledipasvir/sofosbuvir [1], omeprazole ---> SmPC of [1] of EMA

Proton pump inhibitor doses comparable to omeprazole 20 mg can be administered simultaneously with ledipasvir/sofosbuvir. Proton pump inhibitors should not be taken before ledipasvir/sofosbuvir.

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

Letermovir has the potential to decrease the exposure of CYP2C9 and/or CYP2C19 substrates potentially resulting in subtherapeutic levels.

Lopinavir/ritonavir, omeprazole ---> SmPC of [esomeprazole] of EMA

Treatment with omeprazole had no effect on the exposure of lopinavir (with concomitant ritonavir).

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

Inhibitors reduce clearance and may potentiate the action of benzodiazepines.

Lumacaftor/ivacaftor [1], omeprazole ---> SmPC of [1] of EMA

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

Medazepam, omeprazole

The co-administration of omeprazol may enhance and prolong the effect of medazepam

Mephenytoin, omeprazole

Increased hydantoin plasma levels

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

Co-administration of proton-pump inhibitors such as omeprazole or pantoprazole can lead to interactions: concomitant administration of methotrexate and omeprazole has led to a delay in the renal elimination of methotrexate.

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

Cimetidine, ranitidine and omeprazole have been shown to reduce the clearance of midazolam and other benzodiazepines and may potentiate their actions.

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

Medicinal products with a narrow therapeutic range that are substrates of CYP2C19 (e.g. omeprazole) should be used with caution when administered concomitantly with midostaurin and may need dose adjustment to maintain optimal exposure

Modafinil [1], omeprazole ---> SmPC of [1] of eMC

Substances that are largely eliminated via CYP2C19 metabolism may have reduced clearance upon co-administration of modafinil and may thus require dosage reduction.

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

Concomitant administration with a UGT inducer may potentially lead to subtherapeutic nalmefene plasma concentrations.

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

Nelfinavir should not be co-administered with omeprazole due to a reduction in exposure to nelfinavir and its active metabolite M8 (Tert-butyl hydroxy nelfinavir). This may lead to a loss of virologic response and possible resistance to nelfinavir

Nitrazepam, omeprazole

Known inhibitors of hepatic enzymes, particularly cytochrome P450 have been shown to reduce the clearance of benzodiazepines and may potentiate their action

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

Omeprazole [1], phenytoin ---> SmPC of [1] of eMC

As omeprazole is metabolised in the liver through cytochrome P450, it can prolong the elimination of phenytoin

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

Omeprazole can be used during pregnancy.

Omeprazole [1], strong CYP2C19 inhibitors ---> SmPC of [1] of eMC

Concomitant administration of omeprazole and a CYP2C19 inhibitor, increased the omeprazole exposure.

Omeprazole [1], strong CYP3A4 inhibitors ---> SmPC of [1] of eMC

Concomitant administration of omeprazole and a CYP3A4 inhibitor, increased the omeprazole exposure.

Omeprazole [1], tacrolimus ---> SmPC of [1] of eMC

Concomitant administration of omeprazole and tacrolimus may increase the serum levels of tacrolimus.

Omeprazole [1], warfarin ---> SmPC of [1] of eMC

As omeprazole is metabolised in the liver through cytochrome P450, it can prolong the elimination of warfarin

Omeprazole, oral contraceptives

Combination hormonal contraceptives with omeprazol may increase plasma levels (due to CYP inhibition) of omeprazol

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

Co-administration of omeprazole did not result in clinically relevant changes in osimertinib exposures. Gastric pH modifying agents can be concomitantly used with TAGRISSO without any restrictions.

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

Ospemifene did not cause a clinically meaningful change in the exposure to the CYP3A4 substrates, indicating that ospemifene does not affect those enzyme activities in vivo to a clinically significant extent.

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

Caution should be observed when administering parecoxib with medicinal products known to be substrates of CYP2C19

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

Pazopanib does not have a clinically relevant effect on the pharmacokinetics of caffeine (CYP1A2 probe substrate), warfarin (CYP2C9 probe substrate), or omeprazole (CYP2C19 probe substrate) in cancer patients.

Omeprazole, phenprocoumon

Omeprazol, moderate CYP2C19 inhibitor, may increase the plasma concentrations of phenprocoumon and increase the bleeding risk

Omeprazole, piperaquine/artenimol [2] ---> SmPC of [2] of EMA

Piperaquine, CYP2C19 inhibitor, may increase the plasma concentrations of omeprazol

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

In the case of moderate inducers of CYP1A2 (e.g. omeprazole), concomitant use may theoretically result in a lowering of pirfenidone plasma levels.

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

Co-administration of posaconazole with H2 receptor antagonists or with proton pump inhibitors should be avoided if possible.

Omeprazole, prazepam

The strong CYP2C19 inhibition may increase the plasma concentrations of prazepam. Caution should be exercised

Omeprazole, primidone

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

Omeprazole, protease inhibitors ---> SmPC of [esomeprazole] of EMA

Increased gastric pH during omeprazole treatment may change the absorption of the protease inhibitors.

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

The co-administration may increase the rate of raltegravir absorption. No dosage adjustment necessary.

Omeprazole, rifampicin

Principle actives known to induce CYP2C19 and CYP3A4 may increase the omeprazole metabolism and decrease its plasma levels

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

The increase of the gastric pH decreases the absorption, plasma level and therapeutic effect of rilpivirine. Rilpivirine must not be used with proton pump inhibitors

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

In vitro studies suggest that CYP1A2 is the principal isozyme involved in the initial oxidative metabolism of riluzole. Inducers of CYP1A2 could increase the rate of riluzole elimination.

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

Concurrent administration of omeprazole or ranitidine does not significantly modify ritonavir efficacy as a pharmacokinetic enhancer despite a slight change of exposure (about 6 - 18%).

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

Co-administration of omeprazole (inhibitor of CYP2C19), in doses of 40 mg/day, had no effect on the pharmacokinetics and metabolism of rotigotine in healthy volunteers.

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

No dose adjustment is considered necessary for co-administered medicinal products that are CYP2C19 substrates.

Omeprazole, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Concomitant use may increase the plasma concentrations of saquinavir. Combination not recommended.

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

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

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

Concomitant administration of sitaxentan with omeprazole increased the omeprazole AUC0-24 by 30%; Cmax was unchanged. The change in AUC was not considered clinically significant.

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

The co-administration of omeprazole has no clinically significant effect on the pharmacokinetics of sodium oxybate.

Omeprazole, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

If it is considered necessary to co-administer, then Epclusa should be administered with food and taken 4 hours before proton pump inhibitor at max doses comparable to omeprazole 20 mg.

Omeprazole, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Increase in gastric pH decreases velpatasvir solubility. Proton pump inhibitors may be administered with Vosevi at a dose that does not exceed doses comparable with omeprazole 20 mg.

Omeprazole, St. John's wort

Principle actives known to induce CYP2C19 and CYP3A4 may increase the omeprazole metabolism and decrease its plasma levels

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

Stiripentol is an inhibitor of the enzymes CYP2C19 and may markedly increase the plasma concentrations of substances metabolised by these enzymes and increase the risk of adverse reactions

Omeprazole, strong CYP2C19 inductors

Principle actives known to induce CYP2C19 may increase the omeprazole metabolism and decrease its plasma levels

Omeprazole, strong CYP3A4 inductors

Principle actives known to induce CYP3A4 may increase the omeprazole metabolism and decrease its plasma levels

Omeprazole, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

Drug-drug interaction studies have been conducted in healthy subjects with losartan, furosemide, digoxin, warfarin, and omeprazole. Co-administration of Velphoro did not affect the bioavailability of these products as measured by the AUC.

Omeprazole, sultiame

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

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

Caution should be used when administering tasimelteon in combination with strong CYP2C19 inhibitors such as omeprazole because there is uncertainty regarding the involvement of CYP2C19 and the effect of coadministration has not been studied.

Omeprazole, tetracosactide

Decreased release of cortisol

Omeprazole, tetrazepam

The co-administration may enhance and prolong the effect of tetrazepam

Omeprazole, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The CYP2C19 induction by tipranavir/ritonavir may decrease the plasma concentrations of esomeprazole. Concomitant use is not recommended

Omeprazole, topiramate [2] ---> SmPC of [2] of eMC

Topiramate inhibits the enzyme CYP 2C19 and may interfere with other substances metabolized via this enzyme

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

Valdecoxib, CYP2C19 inhibitor, may increase the plasma concentrations of omeprazol

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

No change in dose of vandetanib is required when vandetanib is given with either omeprazole

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

Proton pump inhibitors that are CYP2C19 substrates may be inhibited by voriconazole and may result in increased plasma concentrations of these medicinal products.

CONTRAINDICATIONS of Omeprazole

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

- When gastric ulcer is suspected, the possibility of malignancy should be excluded before treatment with omeprazole is commenced, as treatment may alleviate symptoms and delay diagnosis.

- Omeprazole like other proton pump inhibitors should not be administered with atazanavir

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

Onasemnogene abeparvovec (Zolgensma)

Breast-feeding, onasemnogene abeparvovec [2] ---> SmPC of [2] of EMA

Human data on use during pregnancy or lactation are not available and animal fertility or reproduction studies have not been performed.

Hepatotoxic drugs, onasemnogene abeparvovec [2] ---> SmPC of [2] of EMA

Experience with use of onasemnogene abeparvovec in patients receiving hepatotoxic medicinal products or using hepatotoxic substances is limited. Safety of onasemnogene abeparvovec in these patients have not been established.

Onasemnogene abeparvovec [1], pregnancy ---> SmPC of [1] of EMA

Human data on use during pregnancy or lactation are not available and animal fertility or reproduction studies have not been performed.

Onasemnogene abeparvovec [1], spinal muscular atrophy ---> SmPC of [1] of EMA

Experience with use of concomitant 5q SMA targeting agents is limited.

Onasemnogene abeparvovec [1], vaccinations ---> SmPC of [1] of EMA

Where feasible, the patient's vaccination schedule should be adjusted to accommodate concomitant corticosteroid administration prior to and following onasemnogene abeparvovec infusion

Onasemnogene abeparvovec [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Live vaccines, such as MMR and varicella, should not be administered to patients on an immunosuppressive steroid dose

CONTRAINDICATIONS of Onasemnogene abeparvovec (Zolgensma)

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/zolgensma-epar-product-information_en.pdf 26/03/2024

Ondansetron

Anthracyclines, ondansetron [2] ---> SmPC of [2] of eMC

Concomitant use of ondansetron with cardiotoxic drugs (e.g. anthracyclines) may increase the risk of arrhythmias.

Apomorphine, ondansetron [2] ---> SmPC of [2] of eMC

Based on reports of profound hypotension and loss of consciousness when ondansetron was administered with apomorphine hydrochloride, concomitant use with apomorphine is contraindicated.

Aprepitant [1], ondansetron ---> SmPC of [1] of EMA

In clinical interaction studies, aprepitant did not have clinically important effects on the pharmacokinetics of ondansetron

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

It is recommended that mothers receiving ondansetron should not breast-feed their babies.

Carbamazepine, ondansetron [2] ---> SmPC of [2] of eMC

In patients treated with potent inducers of CYP3A4, the oral clearance of ondansetron was increased and ondansetron blood concentrations were decreased.

Cyclophosphamide, ondansetron

The co-administration may decrease the AUC of cyclophosphamide

Electrolyte imbalance, ondansetron [2] ---> SmPC of [2] of eMC

Caution should be exercised when ondansetron is coadministered with drugs that cause electrolyte abnormalities.

Medicines with cardiotoxic effects, ondansetron [2] ---> SmPC of [2] of eMC

Concomitant use of ondansetron with cardiotoxic drugs (e.g. anthracyclines) may increase the risk of arrhythmias.

Ondansetron [1], phenytoin ---> SmPC of [1] of eMC

In patients treated with potent inducers of CYP3A4, the oral clearance of ondansetron was increased and ondansetron blood concentrations were decreased.

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

The use of ondansetron in pregnancy is not recommended.

Ondansetron [1], QT interval prolonging drugs ---> SmPC of [1] of eMC

Use of ondansetron with QT prolonging drugs may result in additional QT prolongation.

Ondansetron [1], rifampicin ---> SmPC of [1] of eMC

In patients treated with potent inducers of CYP3A4, the oral clearance of ondansetron was increased and ondansetron blood concentrations were decreased.

Ondansetron [1], serotonergic medicines ---> SmPC of [1] of eMC

There have been post-marketing reports describing patients with serotonin syndrome following the concomitant use of ondansetron and other serotonergic drugs

Ondansetron [1], SSRI ---> SmPC of [1] of eMC

There have been post-marketing reports describing patients with serotonin syndrome following the concomitant use of ondansetron and other serotonergic drugs

Ondansetron [1], strong CYP3A4 inductors ---> SmPC of [1] of eMC

In patients treated with potent inducers of CYP3A4, the oral clearance of ondansetron was increased and ondansetron blood concentrations were decreased.

Ondansetron [1], tramadol ---> SmPC of [1] of eMC

Data from small studies indicate that ondansetron may reduce the analgesic effect of tramadol.

Ondansetron, panobinostat [2] ---> SmPC of [2] of EMA

Based on preclinical and clinical data, panobinostat has the potential to prolong the QT interval. Concomitant use of panobinostat and other substances that are known to prolong the QT interval is not recommended.

Ondansetron, pixantrone [2] ---> SmPC of [2] of EMA

Ondansetron is metabolised by CYP1A2, and therefore, a theoretical concern exists that co-administration of pixantrone may increase blood levels of this medicinal product.

Ondansetron, rolapitant [2] ---> SmPC of [2] of EMA

Rolapitant had no significant effects on the pharmacokinetics of intravenous ondansetron when concomitantly administered with a single 180 mg dose of rolapitant on the same day

Ondansetron, SSNRI

There have been post-marketing reports describing patients with serotonin syndrome following the concomitant use of ondansetron and other serotonergic drugs

Ondansetron, vandetanib [2] ---> SmPC of [2] 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 Ondansetron

- Concomitant use with apomorphine

- Hypersensitivity to any component of the preparation.

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

Opicapone (Ongentys)

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

Opicapone in association with levodopa may have major influence on the ability to drive and use machines. Opicapone may, together with levodopa, cause dizziness, symptomatic orthostatism and somnolence.

Adrenaline [1], opicapone ---> SmPC of [1] of EMA

The effects of adrenaline may be potentiated

Adrenaline, opicapone [2] ---> SmPC of [2] of EMA

Opicapone may interfere with the metabolism of medicinal products containing a catechol group that are metabolised by COMT, e.g. rimiterole, isoprenaline, adrenaline, dopamine, dopexamine or dobutamine, leading to potentiated effects of these medicines.

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

It is unknown whether opicapone or its metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Ongentys.

Desipramine, opicapone [2] ---> SmPC of [2] of EMA

There is limited experience with opicapone when used concomitantly with tricyclic antidepressants and noradrenaline re-uptake inhibitors. Thus, their concomitant use should be considered with appropriate caution.

Dopamine, opicapone [2] ---> SmPC of [2] of EMA

Dopexamine, opicapone [2] ---> SmPC of [2] of EMA

Doubutamine, opicapone [2] ---> SmPC of [2] of EMA

Drugs metabolised by catechol-O-methyltransferase, opicapone [2] ---> SmPC of [2] of EMA

Opicapone may interfere with the metabolism of medicinal products containing a catechol group that are metabolised by COMT, e.g. rimiterole, isoprenaline, adrenaline, noradrenaline, dopamine, dopexamine or dobutamine, leading to potentiated effects of these medicinal products.

Drugs with high protein binding, opicapone [2] ---> SmPC of [2] of EMA

The binding of 14C-opicapone to plasma proteins was unaffected by the presence of warfarin, diazepam, digoxin and tolbutamide, and the binding of 14C-warfarin, 2-14C-diazepam, 3H-digoxin and 14C-tolbutamide was unaffected by the presence of opicapone

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

The effects of opicapone on fertility in humans have not been studied. Animal studies with opicapone do not indicate harmful effects with respect to fertility (see section 5.3).

IMAOs, opicapone [2] ---> SmPC of [2] of EMA

Concomitant use of opicapone and MAO inhibitors for the treatment of Parkinson's disease, e.g. rasagiline (up to 1 mg/day) and selegiline (up to 10 mg/day in oral formulation or 1.25 mg/day in buccal absorption formulation), is permissible

IMAOs, opicapone [2] ---> SmPC of [2] of EMA

Concomitant use of opicapone with MAO inhibitors (e.g. phenelzine, tranylcypromine and moclobemide) other than those for the treatment of Parkinson's disease is contraindicated.

Isoprenaline, opicapone [2] ---> SmPC of [2] of EMA

Levodopa, opicapone [2] ---> SmPC of [2] of EMA

In patients taking levodopa and a peripheral DOPA decarboxylase inhibitor (DDCI), such as carbidopa or benserazide, opicapone increases levodopa plasma levels thereby improving the clinical response to levodopa.

Maprotiline, opicapone [2] ---> SmPC of [2] of EMA

Moclobemide, opicapone [2] ---> SmPC of [2] of EMA

Concomitant use of opicapone with MAO inhibitors (e.g. phenelzine, tranylcypromine and moclobemide) other than those for the treatment of Parkinson's disease is contraindicated.

Noradrenaline, opicapone [2] ---> SmPC of [2] of EMA

Norepinephrine reuptake inhibitors, opicapone [2] ---> SmPC of [2] of EMA

Opicapone [1], phenelzine ---> SmPC of [1] of EMA

Concomitant use of opicapone with MAO inhibitors (e.g. phenelzine, tranylcypromine and moclobemide) other than those for the treatment of Parkinson's disease is contraindicated.

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

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

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

Thus, particular consideration should be given to cases where quinidine needs to be administered together with opicapone as their co-administration should be avoided.

Opicapone [1], rasagiline ---> SmPC of [1] of EMA

Opicapone [1], repaglinide ---> SmPC of [1] of EMA

A study conducted in healthy subjects showed that there were no changes in repaglinide's exposure when repaglinide was administered following multiple once-daily administration of opicapone 50 mg.

Opicapone [1], safinamide ---> SmPC of [1] of EMA

There is no experience with opicapone when used concomitantly with the MAO-B inhibitor safinamide. Therefore, their concomitant use should be considered with appropriate caution.

Opicapone [1], selegiline ---> SmPC of [1] of EMA

Opicapone [1], tranylcypromine ---> SmPC of [1] of EMA

Concomitant use of opicapone with MAO inhibitors (e.g. phenelzine, tranylcypromine and moclobemide) other than those for the treatment of Parkinson's disease is contraindicated.

Opicapone [1], tricyclic antidepressant ---> SmPC of [1] of EMA

Opicapone [1], venlafaxine ---> SmPC of [1] of EMA

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

Clinical interaction studies conducted with warfarin showed no effect of opicapone on the pharmacodynamics of warfarin, a substrate of CYP2C9.

CONTRAINDICATIONS of Opicapone (Ongentys)

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

- Phaeochromocytoma, paraganglioma, or other catecholamine secreting neoplasms.

- History of neuroleptic malignant syndrome and/or non-traumatic rhabdomyolysis.

- Concomitant use with monoamine oxidase (MAO-A and MAO-B) inhibitors (e.g. phenelzine, tranylcypromine and moclobemide) other than those for the treatment of Parkinson's disease

https://www.ema.europa.eu/en/documents/product-information/ongentys-epar-product-information_en.pdf 18/09/2024

Other trade names: Ontilyv,

Oritavancin (Tenkasi)

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

Tenkasi has a minor influence on the ability to drive and use machines. Dizziness may occur and this may have an effect on driving and use of machines (see section 4.8).

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

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

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

Oritavancin is a nonspecific, weak CYP2C9 and CYP2C19 inhibitor. Caution should be used when administering oritavancin concomitantly with medicinal products with a narrow therapeutic window that are predominantly metabolised by one of these isoenzymes

CYP2C9 substrates with narrow therapeutic index, oritavancin [2] ---> SmPC of [2] of EMA

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

Caution should be used when administering oritavancin concomitantly with medicinal products with a narrow therapeutic window that are predominantly metabolised by one of the affected CYP450 enzymes (e.g., warfarin),

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

Oritavancin is a nonspecific, weak CYP3A4 and CYP2D6 inductor. Caution should be used when administering oritavancin concomitantly with medicinal products with a narrow therapeutic window that are predominantly metabolised by one of these isoenzymes

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

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

Animal studies have revealed no evidence of impaired fertility due to oritavancin at the highest concentrations administered. However, there are no data on the effects of oritavancin on human fertility.

Oritavancin [1], phospholipid reagent ---> SmPC of [1] of EMA

Oritavancin binds to and prevents the action of the phospholipid reagents which activate coagulation in commonly used laboratory coagulation tests.

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

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

Oritavancin [1], sodium heparin ---> SmPC of [1] of EMA

Use of intravenous unfractionated heparin sodium is contraindicated for 120 hours (5 days) after oritavancin administration, because the activated partial thromboplastin time (aPTT) test results may remain falsely elevated for up to 120 hours

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

Patients should be monitored for bleeding, if concomitantly receiving oritavancin and warfarin) (see section 4.4).

CONTRAINDICATIONS of Oritavancin (Tenkasi)

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

- Use of intravenous unfractionated heparin sodium is contraindicated for 120 hours (5 days) after oritavancin administration, because the activated partial thromboplastin time (aPTT) test results may remain falsely elevated for up to 120 hours after oritavancin administration (see sections 4.4 and 4.5).

https://www.ema.europa.eu/en/documents/product-information/tenkasi-previously-orbactiv-epar-product-information_en.pdf 20/11/2024

Other trade names: Oritavancina (Tenkasi (previously Orbactiv)), Orbactiv,

Orlistat (Xenical)

Acarbose, orlistat [2] ---> SmPC of [2] of EMA

In the absence of pharmacokinetic interaction studies, the concomitant administration of orlistat with acarbose should be avoided.

Alendronate/colecalciferol [1], orlistat ---> SmPC of [1] of EMA

Olestra, mineral oils, orlistat, and bile acid sequestrants (e.g. cholestyramine, colestipol) may impair the absorption of vitamin D.

Alendronic acid/colecalciferol [1], orlistat ---> SmPC of [1] of EMA

Olestra, mineral oils, orlistat, and bile acid sequestrants (e.g. cholestyramine, colestipol) may impair the absorption of vitamin D.

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

Possible decrease of the amiodarone plasma levels. In patients receiving concomitant amiodarone treatment, reinforcement of clinical and ECG monitoring is warranted.

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

There are some case reports of reduced efficacy of antiretroviral HIV medicines, antidepressants antipsychotics (including lithium) and benzodiazepines coincidental to the initiation of orlistat treatment in previously well-controlled patients.

Antidiabetics, orlistat [2] ---> SmPC of [2] of EMA

In clinical trials, the decrease in bodyweight with orlistat treatment was less in type II diabetic patients than in non-diabetic patients. Antidiabetic medicinal product treatment may have to be closely monitored when taking orlistat.

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

Convulsions have been reported in patients treated concomitantly with orlistat and antiepileptic drugs e.g. valproate, lamotrigine, for which a causal relationship to an interaction cannot be excluded. Therefore, these patients should be monitored

Antiretrovirals, orlistat [2] ---> SmPC of [2] of EMA

Benzodiazepines, orlistat [2] ---> SmPC of [2] of EMA

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

As it is not known whether orlistat is secreted into human milk, orlistat is contra-indicated during breast-feeding.

Calcifediol, orlistat

Medicinal products that reduce calcifediol absorption may reduce its effects. It is recommended to separate the times of administration by at least 2 hours

Cholecalciferol, orlistat ---> SmPC of [alendronic acid/colecalciferol] of EMA

Olestra, mineral oils, orlistat, and bile acid sequestrants (e.g. cholestyramine, colestipol) may impair the absorption of vitamin D.

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

Decrease of the cyclosporine plasma levels. Co-administration of orlistat with ciclosporin is not recommended

Fat-soluble vitamins, orlistat [2] ---> SmPC of [2] of EMA

Treatment with orlistat may potentially impair the absorption of fat-soluble vitamins (A, D, E and K).

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

Orlistat can be taken immediately before, during a meal or up to one hour after a meal. The capsule should be swallowed with water.

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

No interactions with amitriptyline, atorvastatin, biguanides, digoxin, fibrates, fluoxetine, losartan, phenytoin, phentermine, pravastatin, nifedipine Gastrointestinal Therapeutic System (GITS), sibutramine or alcohol have been observed.

Iodine, orlistat [2] ---> SmPC of [2] of EMA

Rare occurrence of hypothyroidism and/or reduced control of hypothyroidism may occur. The mechanism, although not proven, may involve a decreased absorption of iodine salts and/or levothyroxine (see section 4.4).

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

Levothyroxine, orlistat [2] ---> SmPC of [2] of EMA

Lithium, orlistat [2] ---> SmPC of [2] of EMA

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

Oral anticoagulants, orlistat [2] ---> SmPC of [2] of EMA

When warfarin or other anticoagulants are given in combination with orlistat, international normalized ratio (INR) values should be monitored

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

Orlistat may indirectly reduce the availability of oral contraceptives and lead to unexpected pregnancies in some individual cases. An additional contraceptive method is recommended in case of severe diarrhoea

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

Caution should be exercised when prescribing to pregnant women.

Orlistat [1], sodium valproate ---> SmPC of [1] of EMA

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

When warfarin or other anticoagulants are given in combination with orlistat, international normalized ratio (INR) values should be monitored

Orlistat, ospemifene [2] ---> SmPC of [2] of EMA

Due to its lipophilic nature and absorption characteristics, an interaction between ospemifene and medicinal products like orlistat, cannot be ruled out. A clinical monitoring of a decrease in the efficacy of ospemifene should be made.

CONTRAINDICATIONS of Orlistat (Xenical)

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

- Chronic malabsorption syndrome

- Cholestasis

- Breast-feeding

https://www.ema.europa.eu/en/documents/product-information/xenical-epar-product-information_en.pdf. 10/05/2023

Oseltamivir (Tamiflu)

Amoxicillin, oseltamivir [2] ---> SmPC of [2] of EMA

Oseltamivir has no kinetic interaction with amoxicillin, which is eliminated via the same pathway, suggesting that oseltamivir interaction with this pathway is weak.

Ataluren [1], oseltamivir ---> SmPC of [1] of EMA

Caution should be exercised when ataluren is co-administered with medicinal products that are substrates of UGT1A9, OAT1, OAT3, or OATP1B3 because of the risk of increase concentration of these medicinal products

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

Administration of oseltamivir may be considered, where there are clear potential benefits to breastfeeding mothers.

Chlorpropamide, oseltamivir [2] ---> SmPC of [2] of EMA

Care should be taken when prescribing oseltamivir in subjects when taking co-excreted agents with a narrow therapeutic margin

Co-excreted agents with a narrow therapeutic margin, oseltamivir [2] ---> SmPC of [2] of EMA

Care should be taken when prescribing oseltamivir in subjects when taking co-excreted agents with a narrow therapeutic margin

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

Based on preclinical data, there is no evidence that Tamiflu has an effect on male or female fertility (see section 5.3).

Methotrexate, oseltamivir [2] ---> SmPC of [2] of EMA

Care should be taken when prescribing oseltamivir in subjects when taking co-excreted agents with a narrow therapeutic margin

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

Pharmacokinetic properties of oseltamivir, such as low protein binding and metabolism independent of the CYP450 and glucuronidase systems, suggest that clinically significant drug interactions via these mechanisms are unlikely.

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

No pharmacokinetic interactions between oseltamivir with paracetamol, acetylsalicylic acid, cimetidine, antacids, rimantadine or warfarin (in subjects stable on warfarin and without influenza).

Oseltamivir [1], phenylbutazone ---> SmPC of [1] of EMA

Care should be taken when prescribing oseltamivir in subjects when taking co-excreted agents with a narrow therapeutic margin

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

Pregnant women may receive Tamiflu, after considering the available safety information, the pathogenicity of the circulating influenza virus strain and the underlying condition of the pregnant woman.

Oseltamivir [1], probenecide ---> SmPC of [1] of EMA

Co-administration of probenecid, a potent inhibitor of the anionic pathway of renal tubular secretion, results in an approximate 2-fold increase in exposure to the active metabolite of oseltamivir.

Oseltamivir, tafamidis [2] ---> SmPC of [2] 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

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

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

CONTRAINDICATIONS of Oseltamivir (Tamiflu)

- 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/tamiflu-epar-product-information_en.pdf 15/04/2025

Other trade names: Ebilfumin,

Osilodrostat (Isturisa)

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

Patients should be warned about the potential for dizziness and fatigue (see section 4.8) and should be advised not to drive or use machines if these symptoms occur.

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

A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Isturisa and for at least one week after treatment.

Caffeine, osilodrostat [2] ---> SmPC of [2] of EMA

AUC geometric mean ratio of 2.5 for caffeine (CYP1A2 substrate) when dosed with osilodrostat compared to when dosed alone.

CYP1A2 substrates with narrow therapeutic index, osilodrostat [2] ---> SmPC of [2] of EMA

Osilodrostat should be used with caution when co-administered with sensitive CYP1A2 substrates with a narrow therapeutic index such as theophylline and tizanidine.

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

Osilodrostat should be used with caution when co-administered with sensitive CYP2C19 substrates with a narrow therapeutic index.

Dextromethorphan, osilodrostat [2] ---> SmPC of [2] of EMA

AUC geometric mean ratio of 1.5 for dextromethorphan (CYP2D6 substrate) when dosed with osilodrostat compared to when dosed alone.

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

There is no information on the effect of osilodrostat on human fertility. Animal studies have shown effects on the menstrual cycle and reduced female fertility in rats (see section 5.3).

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

If hormonal contraceptives other than the oral combination of ethinylestradiol and levonorgestrel are used, an additional barrier method of contraception is recommended (see section 4.5).

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

A washout period should be considered when switching from other products known to affect the QT interval such as pasireotide or ketoconazole.

Levonorgestrel/ethinylestradiol, osilodrostat [2] ---> SmPC of [2] of EMA

In a healthy volunteer study (n=24), osilodrostat did not have a clinically meaningful effect on the AUC and Cmax of ethinyl estradiol and AUC of levonorgestrel

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

AUC geometric mean ratio of 1.5 for midazolam (CYP3A4 substrate) when dosed with osilodrostat compared to when dosed alone.

Narrow therapeutic window, osilodrostat [2] ---> SmPC of [2] of EMA

Because osilodrostat and its major metabolite M34.5 may inhibit and/or induce multiple enzymes and transporters, general caution is advised when it is co-administered with sensitive enzyme or transporter substrates with a narrow therapeutic index.

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

AUC geometric mean ratio of 1.9 for omeprazole (CYP2C19 substrate) when dosed with osilodrostat compared to when dosed alone.

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

Osilodrostat should be used with caution when co-administered with sensitive CYP2C19 substrates with a narrow therapeutic index.

Osilodrostat [1], pasireotide ---> SmPC of [1] of EMA

A washout period should be considered when switching from other products known to affect the QT interval such as pasireotide or ketoconazole.

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

Isturisa should not be used during pregnancy and in women of childbearing potential not using contraception.

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

Co-administration of osilodrostat with other therapies known to affect the QT interval can lead to QT prolongation in patients with known cardiac rhythm disorders

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

Caution is advised when co-administered medicinal products that strongly induce multiple enzymes (e.g. rifampin) are introduced or discontinued during osilodrostat treatment

Osilodrostat [1], strong inductors ---> SmPC of [1] of EMA

Caution is advised when co-administered medicinal products that strongly induce multiple enzymes (e.g. rifampin) are introduced or discontinued during osilodrostat treatment

Osilodrostat [1], strong inhibitors ---> SmPC of [1] of EMA

Caution is advised when co-administered medicinal products that strongly inhibit multiple enzymes are introduced or discontinued during osilodrostat treatment

Osilodrostat [1], theophylline ---> SmPC of [1] of EMA

Osilodrostat should be used with caution when co-administered with sensitive CYP1A2 substrates with a narrow therapeutic index such as theophylline and tizanidine.

Osilodrostat [1], tizanidine ---> SmPC of [1] of EMA

Osilodrostat should be used with caution when co-administered with sensitive CYP1A2 substrates with a narrow therapeutic index such as theophylline and tizanidine.

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

A pregnancy test before initiating treatment is recommended in women of childbearing potential. Women of childbearing potential have to use effective contraception during and for at least one week after treatment.

CONTRAINDICATIONS of Osilodrostat (Isturisa)

- 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/isturisa-epar-product-information_en.pdf 29/05/2024

Osimertinib (Tagrisso)

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

Patients taking concomitant medications with disposition dependent upon P-gp and with narrow therapeutic index should be closely monitored for signs of changed tolerability as a result of increased exposure of the concomitant medication

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

Patients taking concomitant medications with disposition dependent upon BCRP and with narrow therapeutic index should be closely monitored as a result of increased exposure whilst receiving TAGRISSO

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

Moderate CYP3A4 inducers (e g bosentan, efavirenz, etravirine, modafinil) may also decrease osimertinib exposure and should be used with caution, or avoided when possible.

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

A risk to the suckling child cannot be excluded. Breast-feeding should be discontinued during treatment with TAGRISSO.

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

It is recommended that concomitant use of strong CYP3A inducers (e.g. Phenytoin, rifampicin and carbamazepine) with TAGRISSO should be avoided.

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

Itraconazole (a strong CYP3A4 inhibitor) had no clinically significant effect on the exposure of osimertinib. Therefore, CYP3A4 inhibitors are not likely to affect the exposure of osimertinib.

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

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

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

Moderate CYP3A4 inducers (e g bosentan, efavirenz, etravirine, modafinil) may also decrease osimertinib exposure and should be used with caution, or avoided when possible.

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

Moderate CYP3A4 inducers (e g bosentan, efavirenz, etravirine, modafinil) may also decrease osimertinib exposure and should be used with caution, or avoided when possible.

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

There are no data on the effect of TAGRISSO on human fertility. Results from animal studies have shown that osimertinib has effects on male and female reproductive organs and could impair fertility (see section 5.3).

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

Co-administration of omeprazole did not result in clinically relevant changes in osimertinib exposures. Gastric pH modifying agents can be concomitantly used with TAGRISSO without any restrictions.

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

A risk for decreased exposure of hormonal contraceptives cannot be excluded.

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

Itraconazole (a strong CYP3A4 inhibitor) had no clinically significant effect on the exposure of osimertinib. Therefore, CYP3A4 inhibitors are not likely to affect the exposure of osimertinib.

Men, osimertinib [2] ---> SmPC of [2] of EMA

Patients should be advised to use effective contraception for the following periods after completion of treatment with this medicinal product: at least 2 months for females and 4 months for males.

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

Moderate CYP3A4 inducers (e g bosentan, efavirenz, etravirine, modafinil) may also decrease osimertinib exposure and should be used with caution, or avoided when possible.

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

Moderate CYP3A4 inducers (e g bosentan, efavirenz, etravirine, modafinil) may also decrease osimertinib exposure and should be used with caution, or avoided when possible.

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

Co-administration of omeprazole did not result in clinically relevant changes in osimertinib exposures. Gastric pH modifying agents can be concomitantly used with TAGRISSO without any restrictions.

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

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

It is recommended that concomitant use of strong CYP3A inducers (e.g. Phenytoin, rifampicin and carbamazepine) with TAGRISSO should be avoided.

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

Based on its mechanism of action and preclinical data, osimertinib may cause foetal harm when administered to a pregnant woman. TAGRISSO should not be used during pregnancy unless the clinical condition of the woman requires treatment with osimertinib.

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

QTc interval prolongation occurs in patients treated with TAGRISSO. QTc interval prolongation may lead to an increased risk for ventricular tachyarrhythmias (e.g. torsade de pointes) or sudden death.

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

It is recommended that concomitant use of strong CYP3A inducers (e.g. Phenytoin, rifampicin and carbamazepine) with TAGRISSO should be avoided.

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

In a clinical PK study, co-administration of TAGRISSO with rosuvastatin (sensitive BCRP substrate) increased the AUC and Cmax of rosuvastatin by 35% and 72%, respectively.

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

Co-administration of TAGRISSO with simvastatin (sensitive CYP3A4 substrate) decreased the AUC and Cmax of simvastatin by 9% and 23% respectively. These changes are small and not likely to be of clinical significance.

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

Concomitant use of St. John's Wort is contraindicated.

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

It is recommended that concomitant use of strong CYP3A inducers (e.g. Phenytoin, rifampicin and carbamazepine) with TAGRISSO should be avoided.

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

Itraconazole (a strong CYP3A4 inhibitor) had no clinically significant effect on the exposure of osimertinib. Therefore, CYP3A4 inhibitors are not likely to affect the exposure of osimertinib.

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

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

CONTRAINDICATIONS of Osimertinib (Tagrisso)

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

- St. John’s wort should not be used together with TAGRISSO (see section 4.5).

https://www.ema.europa.eu/en/documents/product-information/tagrisso-epar-product-information_en.pdf 20/03/2024

Ospemifene (Senshio)

Aciclovir, ospemifene [2] ---> SmPC of [2] of EMA

Ospemifene and its major metabolite, 4-hydroxyospemifene, inhibited organic cation transporter (OCT)1 in vitro at clinically relevant concentrations. Therefore, ospemifene may increase concentrations of medicinal products which are substrates of OCT1

Bazedoxifene, ospemifene [2] ---> SmPC of [2] of EMA

The safety of using ospemifene concomitantly with oestrogens or other SERMS has not been studied and its concurrent use is not recommended.

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

It is unknown if ospemifene is a substrate for BCRP in the intestine. Therefore care should be taken if ospemifene is administered with a BCRP inhibitor.

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

Senshio is not indicated during breast-feeding.

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

Ospemifene did not cause a clinically meaningful change in the exposure to the CYP2B6 substrates, indicating that ospemifene does not affect those enzyme activities in vivo to a clinically significant extent.

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

Rifampicin, strong CYP3A/CYP2C9 enzyme inducer, decreased the ospemifene AUC by 58%. Therefore, co-administration of ospemifene with strong enzyme inducers would be expected to decrease the exposure of ospemifene, which may decrease the clinical effect.

CYP2C9 and CYP3A4 inhibitors, ospemifene [2] ---> SmPC of [2] of EMA

Co-administration of ospemifene with any medicinal products that inhibit both CYP3A4 and CYP2C9 activity (e.g. fluconazole) would be expected to increase the exposure of ospemifene.

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

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

Ospemifene did not cause a clinically meaningful change in the exposure to the CYP2C19 substrates, indicating that ospemifene does not affect those enzyme activities in vivo to a clinically significant extent.

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

Ospemifene did not cause a clinically meaningful change in the exposure to the CYP2C9 substrates, indicating that ospemifene does not affect those enzyme activities in vivo to a clinically significant extent.

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

Drugs primarily metabolised by UGT1A3, ospemifene [2] ---> SmPC of [2] of EMA

The pharmacokinetics of drugs that are mainly metabolised by UGT1A3 and UGT1A9 could be affected when administered concomitantly with ospemifene and co-administration should be made with caution.

Drugs primarily metabolised by UGT1A9, ospemifene [2] ---> SmPC of [2] of EMA

The pharmacokinetics of drugs that are mainly metabolised by UGT1A3 and UGT1A9 could be affected when administered concomitantly with ospemifene and co-administration should be made with caution.

Estrogens, ospemifene [2] ---> SmPC of [2] of EMA

The safety of using ospemifene concomitantly with oestrogens or other SERMS has not been studied and its concurrent use is not recommended.

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

Ospemifene is not indicated for fertile women.

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

Co-administration of ospemifene with any medicinal products that inhibit both CYP3A4 and CYP2C9 activity (e.g. fluconazole) would be expected to increase the exposure of ospemifene.

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

One tablet should be swallowed whole once daily with food and should be taken at the same time each day.

Ganciclovir, ospemifene [2] ---> SmPC of [2] of EMA

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

Ketoconazole, a strong CYP3A4 inhibitor and moderate P-glycoprotein inhibitor, increased the AUC of ospemifene by 1.4-fold. This increase is not considered to be clinically significant given the inherent pharmacokinetic variability of ospemifene.

Metformin, ospemifene [2] ---> SmPC of [2] of EMA

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

Moderate CYP3A4 inhibitors in CYP2C9 poor metabolizers, ospemifene [2] ---> SmPC of [2] of EMA

Co-administration of ospemifene with strong/moderate CYP3A4 inhibitors should be avoided in patients who are known, or suspected to be CYP2C9 poor metabolizers

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

Coadministration of ospemifene with strong/moderate CYP3A4 inhibitors should be avoided in patients who are known or suspected to be CYP2C9 poor metabolizers based on genotyping or previous history/experience with other CYP2C9 substrates.

OCT1 substrates, ospemifene [2] ---> SmPC of [2] of EMA

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

In healthy subjects, the absorption of ospemifene is not affected by co-administration of oral omeprazole, a medicinal product that increases gastric pH.

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

Orlistat, ospemifene [2] ---> SmPC of [2] of EMA

Ospemifene [1], oxaliplatin ---> SmPC of [1] of EMA

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

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

Senshio is only for use in postmenopausal women and should not be used in women of child-bearing potential. If pregnancy occurs during treatment with ospemifene, ospemifene should be withdrawn immediately.

Ospemifene [1], raloxifene ---> SmPC of [1] of EMA

The safety of using ospemifene concomitantly with oestrogens or other SERMS has not been studied and its concurrent use is not recommended.

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

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

Ospemifene [1], selective estrogen receptor modulators ---> SmPC of [1] of EMA

The safety of using ospemifene concomitantly with oestrogens or other SERMS has not been studied and its concurrent use is not recommended.

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

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

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

There is therefore no reason to expect that strong CYP3A4 inhibitors would cause a clinically meaningful change in ospemifene exposure.

Ospemifene [1], strong CYP3A4 inhibitors in CYP2C9 poor metabolizers ---> SmPC of [1] of EMA

Co-administration of ospemifene with strong/moderate CYP3A4 inhibitors should be avoided in patients who are known, or suspected to be CYP2C9 poor metabolizers

Ospemifene [1], tamoxifen ---> SmPC of [1] of EMA

The safety of using ospemifene concomitantly with oestrogens or other SERMS has not been studied and its concurrent use is not recommended.

Ospemifene [1], toremifene ---> SmPC of [1] of EMA

The safety of using ospemifene concomitantly with oestrogens or other SERMS has not been studied and its concurrent use is not recommended.

Ospemifene [1], UGT1A3 inhibitors ---> SmPC of [1] of EMA

Inhibition of UGT1A3, UGT2B7, UGT1A1, or UGT1A8 may potentially affect the glucuronidation of ospemifene and/or 4-hydroxyospemifene.

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

CONTRAINDICATIONS of Ospemifene (Senshio)

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

- Active or past history of venous thromboembolic events (VTEs),including deep vein thrombosis, pulmonary embolism and retinal vein thrombosis.

- Unexplained vaginal bleeding.

- Patients with suspected breast cancer or patients undergoing active treatment (including adjuvant therapy) for breast cancer (see section 4.4).

- Suspected or active sex-hormone dependent malignancy (e.g. endometrial cancer).

- Patients with signs or symptoms of endometrial hyperplasia; safety in this patient group has not been studied.

https://www.ema.europa.eu/en/documents/product-information/senshio-epar-product-information_en.pdf 25/11/2024

Oxaliplatin

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

Oxaliplatin treatment resulting in an increased risk of dizziness, nausea and vomiting, and other neurologic symptoms that affect gait and balance

Amikacine [1], oxaliplatin ---> SmPC of [1] of eMC

There is an increased risk of nephrotoxicity and possibly of ototoxicity when aminoglycosides are administered with platinum compounds.

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

Breast-feeding is contra-indicated during oxaliplatin therapy.

Capecitabine [1], oxaliplatin ---> SmPC of [1] of EMA

No clinically significant differences in exposure to capecitabine or its metabolites, free platinum or total platinum occurred when capecitabine was administered in combination with oxaliplatin or in combination with oxaliplatin and bevacizumab.

Cetuximab [1], oxaliplatin ---> SmPC of [1] of EMA

The combination may increase the frequency of severe diarrhoea

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

In vitro, no significant displacement of oxaliplatin binding to plasma proteins has been observed

Granisetron, oxaliplatin [2] ---> SmPC of [2] of eMC

In vitro, no significant displacement of oxaliplatin binding to plasma proteins has been observed

Ospemifene [1], oxaliplatin ---> SmPC of [1] of EMA

Oxaliplatin [1], paclitaxel ---> SmPC of [1] of eMC

In vitro, no significant displacement of oxaliplatin binding to plasma proteins has been observed

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

Oxaliplatin is not recommended during pregnancy and in women of childbearing potential not using contraceptive measures.

Oxaliplatin [1], salicylates ---> SmPC of [1] of eMC

In vitro, no significant displacement of oxaliplatin binding to plasma proteins has been observed

Oxaliplatin [1], sodium valproate ---> SmPC of [1] of eMC

In vitro, no significant displacement of oxaliplatin binding to plasma proteins has been observed

Oxaliplatin, panitumumab [2] ---> SmPC of [2] of EMA

The combination of panitumumab with oxaliplatin-containing chemotherapy is contraindicated for patients with mutant KRAS mCRC or for whom KRAS mCRC status is unknown.

Oxaliplatin, rhabdomyolysis

It is caution recommended, if medicinal products associated with rhabdomyolysis are co-administrated with oxaliplatin

Oxaliplatin, topotecan

May increase the risk of neutropenia and thrombocytopenia.

Oxaliplatin, trastuzumab

Trastuzumab may increase the risk of neutropenia and anemia.

CONTRAINDICATIONS of Oxaliplatin

Oxaliplatin is contraindicated in patients who

- have a known history of hypersensitivity to oxaliplatin.

- are breast feeding.

- have myelosuppression prior to starting first course, as evidenced by baseline neutrophils < 2 x 109/l and/or platelet count of < 100 x 109/l.

- have a peripheral sensitive neuropathy with functional impairment prior to first course.

- have a severely impaired renal function (creatinine clearance less than 30 ml/min)

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

Oxcarbazepine

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

The use of oxcarbazepine has been associated with adverse reactions such as dizziness or somnolence

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

Caution should be exercised if alcohol is taken in combination with oxcarbazepine therapy, due to a possible additive sedative effect.

Benperidol [1], oxcarbazepine ---> SmPC of [1] of eMC

The dosage of anti-convulsants may need to be increased to take account of the lowered seizure threshold.

Bictegravir/emtricitabine/tenofovir alafenamide [1], oxcarbazepine ---> SmPC of [1] of EMA

Co-administration is not recommended.

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

Oxcarbazepine and its active metabolite (MHD) are excreted in human breast milk. Therefore, oxcarbazepine should not be used during breast-feeding.

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

Carbamazepine may decrease the plasma levels of active metabolite of oxcarbazepine (MHD). Oxcarbazepine may decrease the plasma levels of carbamazepine

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

Cimetidine had no effect on the pharmacokinetics of MHD.

Clopidogrel [1], oxcarbazepine ---> SmPC of [1] of EMA

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

Oxcarbazepine and its pharmacologically active metabolite (the monohydroxy derivative, MHD) are weak inducers of the cytochrome P450 enzymes CYP3A4 and CYP3A5, resulting in a lower plasma levels of drug coadministered with oxcarbazepine

Cyproterone/ethinylestradiol [1], oxcarbazepine ---> SmPC of [1] of eMC

Drugs which induce hepatic enzymes (especially cytochrome P450 3A4) increase the metabolism of contraceptive steroids and hence may result in breakthrough bleeding and pregnancy.

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

Daclatasvir is contraindicated in combination with medicinal products that strongly induce CYP3A4 and P-gp, and thus may lead to lower exposure and loss of efficacy of daclatasvir.

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

Co-administration of Symtuza with oxcarbazepine is not recommended. Alternative anticonvulsants should be considered.

Desogestrel [1], oxcarbazepine ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Dextropropoxyphene, oxcarbazepine [2] ---> SmPC of [2] of eMC

Dextropropoxyphene had no effect on the pharmacokinetics of MHD.

Dihydropyridines, oxcarbazepine

Oxcarbazepine, CYP3A4 inductor, may decrease the plasma concentrations of dihydropyridine

Dolutegravir/rilpivirine [1], oxcarbazepine ---> SmPC of [1] of EMA

Metabolic inducers may significantly decrease dolutegravir/rilpivirine plasma concentrations, resulting in loss of therapeutic effect. Co-administration of Juluca with these metabolic inducers is contraindicated

Drugs primarily metabolised by CYP2C19, oxcarbazepine [2] ---> SmPC of [2] of eMC

Oxcarbazepine and MHD, CYP2C19 inhibitors, may increase the plasma concentrations of medicinal products that are mainly metabolised by CYP2C19

Drugs primarily metabolised by CYP3A4, oxcarbazepine [2] ---> SmPC of [2] of eMC

Drugs primarily metabolised by glucuronidation, oxcarbazepine [2] ---> SmPC of [2] of eMC

Oxcarbazepine and MHD may have a small inducing effect on the metabolism of medicinal products which are mainly eliminated by conjugation through the UDP-glucuronyl transferases.

Emtricitabine/rilpivirine/tenofovir alafenamide [1], oxcarbazepine ---> SmPC of [1] of EMA

Co-administration may cause significant decreases in the plasma concentrations of rilpivirine (induction of CYP3A) and tenofovir alafenamide (induction of P-gp). Co-administration is contraindicated.

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

Co-administration of medicinal products that induce CYP3A has been observed to decrease the plasma concentrations of rilpivirine which could potentially lead to loss of therapeutic effect. Concomitant use contraindicated

Emtricitabine/tenofovir alafenamide [1], oxcarbazepine ---> SmPC of [1] of EMA

Co-administration of oxcarbazepine, phenobarbital, or phenytoin, all of which are P-gp inducers, may decrease tenofovir alafenamide plasma concentrations, which may result in loss of therapeutic effect and development of resistance.

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

Erythromycin had no effect on the pharmacokinetics of MHD.

Ethinyl estradiol, oxcarbazepine [2] ---> SmPC of [2] of eMC

Concurrent use of oxcarbazepine with hormonal contraceptives may render these contraceptives ineffective. Another reliable contraceptive method should be used.

Ethinylestradiol/desogestrel [1], oxcarbazepine ---> SmPC of [1] of eMC

Interactions can occur with drugs that induce microsomal enzymes, which can result in increased clearance of sex hormones

Ethinylestradiol/drospirenone [1], oxcarbazepine ---> SmPC of [1] of eMC

Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones

Ethinylestradiol/etonogestrel [1], oxcarbazepine ---> SmPC of [1] of eMC

Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones

Ethinylestradiol/gestodene [1], oxcarbazepine ---> SmPC of [1] of eMC

Drugs which induce hepatic enzymes (especially cytochrome P450 3A4) increase the metabolism of contraceptive steroids and hence may result in breakthrough bleeding and pregnancy.

Ethinylestradiol/norgestimate [1], oxcarbazepine ---> SmPC of [1] of eMC

Drugs or herbal products that induce enzymes, especially CYP3A4, may decrease the plasma concentrations of contraceptive hormones, and may decrease their effectiveness and/or increase breakthrough bleeding.

Fentanyl, oxcarbazepine

Oxcarbazepine, CYP3A4 inductor, may decrease the plasma concentrations of fentanyl

Glecaprevir/pibrentasvir [1], oxcarbazepine ---> SmPC of [1] of EMA

Co-administration of Maviret with medicinal products that are moderate inducers P-gp/CYP3A may decrease glecaprevir and pibrentasvir plasma concentrations. Co-administration of moderate inducers is not recommended

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

There was a significant decrease in the rate and extent of guanfacine exposure when co-administered with rifampin, a CYP3A4 inducer. Other CYP3A4 inducers may have a comparable effect

IMAOs, oxcarbazepine [2] ---> SmPC of [2] of eMC

The interaction between oxcarbazepine and MAOIs is theoretically possible based on a structural relationship of oxcarbazepine to tricyclic antidepressants.

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

The induction of CYP3A4 may significantly decrease the imatinib plasma levels. Concomitant use should be avoided.

Ledipasvir/sofosbuvir [1], oxcarbazepine ---> SmPC of [1] of EMA

Medicinal products that are moderate P-gp inducers in the intestine may decrease ledipasvir/sofosbuvir plasma concentrations leading to reduced therapeutic effect of Harvoni. Co-administration with such medicinal products is not recommended with Harvoni

Levonorgestrel, oxcarbazepine [2] ---> SmPC of [2] of eMC

Concurrent use of oxcarbazepine with hormonal contraceptives may render these contraceptives ineffective. Another reliable contraceptive method should be used.

Levonorgestrel/ethinylestradiol [1], oxcarbazepine ---> SmPC of [1] of eMC

Interactions of enzyme inducers with oral contraceptives may lead to breakthrough bleeding and/or contraceptive failure: Women should temporarily use a barrier method in addition to the COC or choose another method of contraception.

Lithium, oxcarbazepine [2] ---> SmPC of [2] of eMC

The combination of lithium and oxcarbazepine might cause enhanced neurotoxicity.

Nomegestrol/estradiol [1], oxcarbazepine ---> SmPC of [1] of EMA

Interactions between oral contraceptives and enzyme-inducing medicinal products may lead to breakthrough bleeding and even contraceptive failure.

Norelgestromin/ethinylestradiol [1], oxcarbazepine ---> SmPC of [1] of EMA

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Norethisterone, oxcarbazepine

Oxcarbazepine, CYP3A4 inductor, may decrease the plasma concentrations of norethisterone

Norgestimate, oxcarbazepine

Oxcarbazepine, CYP3A4 inductor, may decrease the plasma concentrations of norgestimate

Norgestrel, oxcarbazepine

Oxcarbazepine, CYP3A4 inductor, may decrease the plasma concentrations of norgestrel

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

Concurrent use of oxcarbazepine with hormonal contraceptives may render these contraceptives ineffective. Another reliable contraceptive method should be used.

Oxcarbazepine [1], phenobarbital ---> SmPC of [1] of eMC

Phenobarbital, enzymatic inductor, may decrease the plasma levels of active metabolite of oxcarbazepine (MHD)

Oxcarbazepine [1], phenytoin ---> SmPC of [1] of eMC

Oxcarbazepine, CYP2C19 inhibitor, may increase the phenytoin plasma levels. Phenytoin, enzymatic inductor, may decrease the plasma levels of oxcarbazepine (MHD)

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

During pregnancy, an effective antiepileptic oxcarbazepine treatment must not be interrupted, since the aggravation of the illness is detrimental to both the mother and the foetus.

Oxcarbazepine [1], tacrolimus ---> SmPC of [1] of eMC

Oxcarbazepine [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Patients on tricyclic antidepressant therapy were included in clinical trials and no clinically relevant interactions have been observed.

Oxcarbazepine [1], viloxazine ---> SmPC of [1] of eMC

Viloxazine had no effect on the pharmacokinetics of MHD.

Oxcarbazepine [1], warfarin ---> SmPC of [1] of eMC

Warfarin had no effect on the pharmacokinetics of MHD.

Oxcarbazepine, perampanel [2] ---> SmPC of [2] of EMA

Oxcarbazepine, enzymatic inductor, may decrease the plasma levels of perampanel

Oxcarbazepine, primidone

The enzymatic induction may decrease the plasma levels of primidone and oxcarbazepine and increase the levels of phenobarbital

Oxcarbazepine, retigabine [2] ---> SmPC of [2] of EMA

Based on these pooled data, retigabine did not cause clinically significant effects on the plasma trough concentrations of this antiepileptic medicinal product. The antiepileptic had no clinically significant effects on retigabine pharmacokinetics

Oxcarbazepine, rilpivirine [2] ---> SmPC of [2] of EMA

Significant decreases in rilpivirine plasma concentrations are expected (induction of CYP3A enzymes). The co-administration is contraindicated

Oxcarbazepine, simeprevir [2] ---> SmPC of [2] of EMA

Co-administration of simeprevir with moderate or strong inductors of CYP3A4 may significantly reduce the plasma exposure of simeprevir and lead to loss of efficacy. Co-administration of simeprevir with these inductors is not recommended.

Oxcarbazepine, sofosbuvir [2] ---> SmPC of [2] of EMA

Medicinal products that are moderate P-gp inducers in the intestine may decrease sofosbuvir plasma concentration leading to reduced therapeutic effect of Sovaldi. Co-administration of such medicinal products is not recommended with Sovaldi

Oxcarbazepine, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Induction of P-gp and CYPs. Co-administration of Epclusa with oxcarbazepine is expected to decrease the concentration of sofosbuvir and velpatasvir, leading to reduced therapeutic effect of Epclusa. Co-administration is not recommended

Oxcarbazepine, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Medicinal products that are moderate P-gp or moderate CYP inducers (e.g. oxcarbazepine, rifapentine, modafinil or efavirenz) may decrease sofosbuvir, velpatasvir and/or voxilaprevir plasma concentrations leading to reduced therapeutic effect of Vosevi.

Oxcarbazepine, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration of Vemlidy with inducers of P-glycoprotein (P-gp) may decrease tenofovir alafenamide plasma concentrations and is not recommended.

Oxcarbazepine, ulipristal [2] ---> SmPC of [2] of EMA

Administration of the potent CYP3A4 inducers markedly decreased Cmax and AUC of ulipristal acetate and its active metabolite. Concomitant use of ulipristal acetate and potent CYP3A4 inducers is not recommended

CONTRAINDICATIONS of Oxcarbazepine

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

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

Oxprenolol

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

Patients receiving oxprenolol should be warned that dizziness, fatigue or visual disturbances may occur

Adrenaline, oxprenolol [2] ---> SmPC of [2] of eMC

Non-cardioselective beta-blockers enhance the pressor response to sympathomimetic drugs, resulting in hypertension and bradycardia.

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

Alcohol effects on the central nervous system have been observed to be additive and it is possible that symptoms such as dizziness may be exaggerated if alcohol and oxprenolol are taken together

Alpha-methyldopa, oxprenolol [2] ---> SmPC of [2] of eMC

Catecholamine-depleting drugs may have an additive effect when administered concomitantly with beta-blockers. Patients should be closely observed for hypotension.

Amiodarone, oxprenolol [2] ---> SmPC of [2] of eMC

Amiodarone may increase atrial-conduction time and induce negative inotropic effect when administered concomitantly with beta-blockers.

Antihypertensives, oxprenolol

The co-administration may enhance the hypotensive effect

Atracurium [1], oxprenolol ---> SmPC of [1] of eMC

As with all non-depolarising neuromuscular blocking agents the magnitude and/or duration of a non-depolarising neuromuscular block may be increased as a result of interaction with beta-blockers

Barbiturates, oxprenolol

The co-administration may enhance the hypotensive effect

Betablockers, digital glycosides ---> SmPC of [oxprenolol] of eMC

Beta-blockers and digitalis glycosides may be additive in their depressant effect on myocardial conduction, particularly through the atrioventricular node, resulting in bradycardia or heart block.

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

Oxprenolol is excreted into breast milk. However, although the estimated daily infant dose derived from breast-feeding is likely to be very low, breast feeding is not recommended.

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

Calcium antagonists may enhance bradycardia, myocardial depression and hypotension; particularly after i.v. use of verapamil in patients taking oral betablockers, the possibility of hypotension and cardiac arrhythmias cannot be excluded

Catecholamine depleting drugs, oxprenolol [2] ---> SmPC of [2] of eMC

Catecholamine-depleting drugs may have an additive effect when administered concomitantly with beta-blockers. Patients should be closely observed for hypotension.

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

Cimetidine may reduce the hepatic metabolism of beta-blockers, resulting in increased plasma levels of beta-blocker and prolonged serum half-life. Marked bradycardia may occur.

Class I antiarrhythmic agents, oxprenolol [2] ---> SmPC of [2] of eMC

Class I anti-arrhythmic drugs may increase atrial-conduction time and induce negative inotropic effect when administered concomitantly with beta-blockers.

Class IA antiarrhythmic agents, oxprenolol [2] ---> SmPC of [2] of eMC

Class I anti-arrhythmic drugs may increase atrial-conduction time and induce negative inotropic effect when administered concomitantly with beta-blockers.

Class IB antiarrhythmic agents, oxprenolol [2] ---> SmPC of [2] of eMC

Class I anti-arrhythmic drugs may increase atrial-conduction time and induce negative inotropic effect when administered concomitantly with beta-blockers.

Class IC antiarrhythmic agents, oxprenolol [2] ---> SmPC of [2] of eMC

Class I anti-arrhythmic drugs may increase atrial-conduction time and induce negative inotropic effect when administered concomitantly with beta-blockers.

Class III antiarrhythmic agents, oxprenolol

Class III anti-arrhythmic drugs may increase atrial-conduction time and induce negative inotropic effect when administered concomitantly with oxprenolol.

Clonidine, non-selective betablockers ---> SmPC of [oxprenolol] of eMC

When clonidine is used in conjunction with non-selective beta-blockers, treatment with clonidine should be continued for some time after beta-blocker has been discontinued to reduce the danger of rebound hypertension.

Clonidine, oxprenolol [2] ---> SmPC of [2] of eMC

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

Non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the hypotensive effect of beta-blockade.

Digital glycosides, oxprenolol [2] ---> SmPC of [2] of eMC

Beta-blockers and digitalis glycosides may be additive in their depressant effect on myocardial conduction, particularly through the atrioventricular node, resulting in bradycardia or heart block.

Dihydropyridines, oxprenolol

The co-administration may enhance the hypotensive effect

Diltiazem, oxprenolol [2] ---> SmPC of [2] of eMC

Disopyramide, oxprenolol [2] ---> SmPC of [2] of eMC

Class I anti-arrhythmic drugs may increase atrial-conduction time and induce negative inotropic effect when administered concomitantly with beta-blockers.

Diuretics, oxprenolol

The co-administration may enhance the hypotensive effect

Ephedrine, non-selective betablockers ---> SmPC of [oxprenolol] of eMC

Non-cardioselective beta-blockers enhance the pressor response to sympathomimetic drugs, resulting in hypertension and bradycardia.

Ephedrine, oxprenolol [2] ---> SmPC of [2] of eMC

Non-cardioselective beta-blockers enhance the pressor response to sympathomimetic drugs, resulting in hypertension and bradycardia.

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

Concomitant administration of ergot alkaloids with beta-blockers may enhance the vasoconstrictive action of ergot alkaloids.

Guanethidine, oxprenolol [2] ---> SmPC of [2] of eMC

Catecholamine-depleting drugs may have an additive effect when administered concomitantly with beta-blockers. Patients should be closely observed for hypotension.

Halogenated anaesthetics, oxprenolol [2] ---> SmPC of [2] of eMC

Beta-blockers and certain anaesthetics (e.g. halothane) are additive in their cardiodepressant effect. However, continuation of beta-blockers reduces the risk of arrhythmia during anaesthesia

Halothane, oxprenolol [2] ---> SmPC of [2] of eMC

Beta-blockers and certain anaesthetics (e.g. halothane) are additive in their cardiodepressant effect. However, continuation of beta-blockers reduces the risk of arrhythmia during anaesthesia

Hydralazine, oxprenolol

Hydralazine may induce increased plasma levels of hepatically metabolised beta-blockers.

IMAOs, oxprenolol

The use of MAO inhibitors (except MAO-B inhibitors) with oxprenolol is contraindicated due to the risk of exaggerated hypertension

Indometacin, oxprenolol

Non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the hypotensive effect of beta-blockade.

Insulin, oxprenolol ---> SmPC of [brinzolamide/timolol] of EMA

The beta-blocker may increase the hypoglycaemic effect of antidiabetic agent. Blockade of beta-adrenoreceptors may mask the symptoms of hypoglycaemia

Isoprenaline, non-selective betablockers ---> SmPC of [oxprenolol] of eMC

Non-cardioselective beta-blockers enhance the pressor response to sympathomimetic drugs, resulting in hypertension and bradycardia.

Isoprenaline, oxprenolol [2] ---> SmPC of [2] of eMC

Non-cardioselective beta-blockers enhance the pressor response to sympathomimetic drugs, resulting in hypertension and bradycardia.

Lidocaine, oxprenolol

The betablocker reduces the clearance of lidocaine and may cause toxic plasma concentrations. Concomitant use should be avoided

Nifedipine, oxprenolol

The co-administration may enhance the hypotensive effect

Non-selective betablockers, noradrenaline ---> SmPC of [oxprenolol] of eMC

Non-cardioselective beta-blockers enhance the pressor response to sympathomimetic drugs, resulting in hypertension and bradycardia.

Non-selective betablockers, phenylephrine ---> SmPC of [oxprenolol] of eMC

Non-cardioselective beta-blockers enhance the pressor response to sympathomimetic drugs, resulting in hypertension and bradycardia.

Non-selective betablockers, sympathomimetics ---> SmPC of [oxprenolol] of eMC

Non-cardioselective beta-blockers enhance the pressor response to sympathomimetic drugs, resulting in hypertension and bradycardia.

Noradrenaline, oxprenolol [2] ---> SmPC of [2] of eMC

Non-cardioselective beta-blockers enhance the pressor response to sympathomimetic drugs, resulting in hypertension and bradycardia.

NSAID, oxprenolol [2] ---> SmPC of [2] of eMC

Non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the hypotensive effect of beta-blockade.

Oral antidiabetics, oxprenolol ---> SmPC of [brinzolamide/timolol] of EMA

The beta-blocker may increase the hypoglycaemic effect of antidiabetic agent. Blockade of beta-adrenoreceptors may mask the symptoms of hypoglycaemia

Oxprenolol [1], phenylephrine ---> SmPC of [1] of eMC

Non-cardioselective beta-blockers enhance the pressor response to sympathomimetic drugs, resulting in hypertension and bradycardia.

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

As in the case of any form of drug therapy, oxprenolol should be employed with caution during pregnancy, especially in the first 3 months.

Oxprenolol [1], quinidine ---> SmPC of [1] of eMC

Class I anti-arrhythmic drugs may increase atrial-conduction time and induce negative inotropic effect when administered concomitantly with beta-blockers.

Oxprenolol [1], reserpine ---> SmPC of [1] of eMC

Catecholamine-depleting drugs may have an additive effect when administered concomitantly with beta-blockers. Patients should be closely observed for hypotension.

Oxprenolol [1], sympathomimetics ---> SmPC of [1] of eMC

Non-cardioselective beta-blockers enhance the pressor response to sympathomimetic drugs, resulting in hypertension and bradycardia.

Oxprenolol [1], verapamil ---> SmPC of [1] of eMC

Oxprenolol, peripheral muscle relaxants

The neuromuscular blockade by peripheral muscle relaxants may be potentiate by betablockers

Oxprenolol, phenothiazines

The co-administration may enhance the hypotensive effect

Oxprenolol, suxamethonium

The neuromuscular blockade by peripheral muscle relaxants may be potentiate by betablockers

Oxprenolol, tricyclic antidepressant

The co-administration may enhance the hypotensive effect

Oxprenolol, vasodilators

The co-administration may enhance the hypotensive effect

CONTRAINDICATIONS of Oxprenolol

Trasicor is contraindicated in patients with

- Hypersensitivity to oxprenolol and related derivatives, cross-sensitivity to other beta-blockers or to any of the excipients.

- Cardiogenic shock.

- Second or third degree atrioventricular block.

- Uncontrolled heart failure.

- Sick-sinus syndrome.

- Bradycardia (< 45 - 50 bpm).

- Hypotension.

- Untreated phaeochromocytoma.

- Severe peripheral arterial circulatory disturbances.

- History of bronchospasm and bronchial asthma. (A warning stating "Do not take this medicine if you have a history of wheezing or asthma" will appear on the label)

- Prinzmetal's angina (variant angina pectoris).

- Use of anaesthetics which are known to have a negative inotropic effect.

- Metabolic acidosis.

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

Oxybutynine (Kentera)

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

Because Kentera may produce drowsiness, somnolence, or blurred vision, patients should be advised to exercise caution when driving or using machinery (see section 4.5).

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

Patients should be informed that alcohol may enhance the drowsiness caused by anticholinergic agents such as oxybutynin (see section 4.7).

Amantadine, oxybutynine [2] ---> SmPC of [2] of EMA

The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity

Anticholinergic antiparkinsonian agents, oxybutynine [2] ---> SmPC of [2] of EMA

The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity

Anticholinergics, anticholinergics ---> SmPC of [oxybutynine] of EMA

The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity

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

Anticholinergic agents may potentially alter the absorption of some concomitantly administered medicinal products due to anticholinergic effects on gastrointestinal motility.

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

The concomitant use of oxybutynin with other anticholinergic medicinal products or with other agents that compete for CYP3A4 enzyme metabolism may increase the frequency or severity of dry mouth, constipation, and drowsiness.

Antihistamines, oxybutynine [2] ---> SmPC of [2] of EMA

The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity

Atropine, oxybutynine [2] ---> SmPC of [2] of EMA

The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity

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

As oxybutynin is metabolised by cytochrome P 450 isoenzyme CYP 3A4, interactions with medicinal products that inhibit this isoenzyme cannot be ruled out.

Biperiden, oxybutynine [2] ---> SmPC of [2] of EMA

The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity

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

When oxybutynin is used during breast-feeding, a small amount is excreted in the mother's milk. Use of oxybutynin while breast-feeding is therefore not recommended.

Butyrophenones, oxybutynine [2] ---> SmPC of [2] of EMA

The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity

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

The plasma concentrations of carbamazepine may be increased

Clozapine, oxybutynine [2] ---> SmPC of [2] of EMA

The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity

Darifenacin [1], oxybutynine ---> SmPC of [1] of EMA

As with any other antimuscarinic agents, concomitant use of medicinal products that possess antimuscarinic properties may result in more pronounced therapeutic and side effects.

Dipyridamole, oxybutynine [2] ---> SmPC of [2] of EMA

The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity

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

As oxybutynin is metabolised by cytochrome P 450 isoenzyme CYP 3A4, interactions with medicinal products that inhibit this isoenzyme cannot be ruled out.

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

As oxybutynin is metabolised by cytochrome P 450 isoenzyme CYP 3A4, interactions with medicinal products that inhibit this isoenzyme cannot be ruled out.

Levodopa, oxybutynine [2] ---> SmPC of [2] of EMA

The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity

Macrolide antibiotics, oxybutynine [2] ---> SmPC of [2] of EMA

As oxybutynin is metabolised by cytochrome P 450 isoenzyme CYP 3A4, interactions with medicinal products that inhibit this isoenzyme cannot be ruled out.

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

The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity

Oxybutynine [1], phenothiazines ---> SmPC of [1] of EMA

The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity

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

Kentera should not be used during pregnancy unless clearly necessary.

Oxybutynine [1], prokinetics ---> SmPC of [1] of EMA

Oxybutynin may antagonize prokinetic therapies.

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

The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity

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

As oxybutynin is metabolised by cytochrome P 450 isoenzyme CYP 3A4, interactions with medicinal products that inhibit this isoenzyme cannot be ruled out.

Oxybutynine [1], tricyclic antidepressant ---> SmPC of [1] of EMA

The anticholinergic activity of oxybutynin is increased by concurrent use of other anticholinergics or medicinal products with anticholinergic activity

Oxybutynine, pasireotide [2] ---> SmPC of [2] of EMA

Clinical monitoring of heart rate, notably at the beginning of treatment, is recommended in patients receiving pasireotide concomitantly with bradycardic medicinal products

Oxybutynine, rivastigmine [2] ---> SmPC of [2] of EMA

Rivastigmine might interfere with the activity of anticholinergic medicinal products (e.g oxybutynin, tolterodine).

CONTRAINDICATIONS of Oxybutynine (Kentera)

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

- Kentera is contraindicated in patients with urinary retention, severe gastro-intestinal condition, myasthenia gravis or narrow-angle glaucoma and in patients who are at risk for these conditions.

https://www.ema.europa.eu/en/documents/product-information/kentera-epar-product-information_en.pdf 08/04/2025

Other trade names: Ditropan, Dresplan, Kentera (previously Oxybutynin Nicobrand), Lyrinel, Orodina,

Oxycodone

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

Oxycodone can impair alertness and reactivity to such an extent that the ability to drive and operate machinery is affected or ceases altogether.

Abiraterone [1], oxycodone ---> SmPC of [1] of EMA

Caution is advised when administering abiraterone with medicinal products activated by or metabolised by CYP2D6, particularly with medicinal products that have a narrow therapeutic index.

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

Alcohol may enhance the pharmacodynamic effects of oxycodone; concomitant use should be avoided.

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

Central nervous system depressants can enhance the adverse reactions of oxycodone, in particular respiratory depression.

Anticholinergics, oxycodone [2] ---> SmPC of [2] of eMC

Anticholinergics can enhance the anticholinergic undesirable effects of oxycodone (such as constipation, dry mouth or micturition disorders).

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

Central nervous system depressants can enhance the adverse reactions of oxycodone, in particular respiratory depression.

Antihistamines, oxycodone [2] ---> SmPC of [2] of eMC

Central nervous system depressants can enhance the adverse reactions of oxycodone, in particular respiratory depression.

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

Oxycodone passes into breast milk; it must not be taken during lactation

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

Cimetidine can inhibit the metabolism of oxycodone.

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

Central nervous system depressants can enhance the adverse reactions of oxycodone, in particular respiratory depression.

Coumarin anticoagulants, oxycodone [2] ---> SmPC of [2] of eMC

Clinically relevant changes in International Normalized Ratio (INR) in both directions have been observed in individuals if coumarin anticoagulants are co-applied with oxycodone.

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

Based on theoretical considerations darunavir/cobicistat (CYP2D6 and/or CYP3A inhibition) may increase analgesic plasma concentrations. Clinical monitoring is recommended

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

Based on theoretical considerations DRV/COBI may increase analgesic plasma concentrations. CYP2D6 and/or CYP3A inhibition

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

Central nervous system depressants can enhance the adverse reactions of oxycodone, in particular respiratory depression.

IMAOs, oxycodone [2] ---> SmPC of [2] of eMC

MAO inhibitors are known to interact with narcotic analgesics, producing CNS excitation or depression with hyper- or hypotensive crisis

Indocyanine green, oxycodone

Extinction attenuation

Ketoconazole [1], oxycodone ---> SmPC of [1] of EMA

Increasing in plasma concentrations of oxycodone have been observed. Careful monitoring. The oxycodone dose may be adjusted.

Muscle relaxants, oxycodone [2] ---> SmPC of [2] of eMC

Central nervous system depressants can enhance the adverse reactions of oxycodone, in particular respiratory depression.

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

Central nervous system depressants can enhance the adverse reactions of oxycodone, in particular respiratory depression.

Opiates, oxycodone [2] ---> SmPC of [2] of eMC

Central nervous system depressants can enhance the adverse reactions of oxycodone, in particular respiratory depression.

Opioid agonist/antagonists, oxycodone

Weakening of opioid agonist effect

Oxycodone [1], phenothiazines ---> SmPC of [1] of eMC

Central nervous system depressants can enhance the adverse reactions of oxycodone, in particular respiratory depression.

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

Oxycodone crosses the placenta. Oxycodone crosses the placenta. Prolonged use of oxycodone during pregnancy can cause withdrawal symptoms in newborns.

Oxycodone [1], sedatives ---> SmPC of [1] of eMC

Central nervous system depressants can enhance the adverse reactions of oxycodone, in particular respiratory depression.

Oxycodone [1], strong CYP2D6 inhibitors ---> SmPC of [1] of eMC

Strong CYP2D6 inhibitors may have an effect on the elimination of oxycodone.

Oxycodone, pregabalin [2] ---> SmPC of [2] of EMA

Pregabalin appears to be additive in the impairment of cognitive and gross motor function caused by oxycodone

Oxycodone, saquinavir

The CYP3A4 inhibitors may decrease the oxycodone clearance, which may increase the plasma concentrations of oxycodone. It can be necessary adjust the dose of oxycodone

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

Dose reduction in oxycodone and other long-acting opiates metabolized by CYP3A4 (e.g., hydrocodone) should be considered. Frequent monitoring for opiate-associated adverse reactions may be necessary.

CONTRAINDICATIONS of Oxycodone

- Hypersensitivity to active substance or to any of the excipients

- Severe respiratory depression with hypoxia and/or hypercapnia

- Severe chronic obstructive pulmonary disease

- Cor pulmonale

- Severe bronchial asthma

- Paralytic ileus, chronic constipation

- Pregnancy

- Lactation

- Acute abdomen, delayed gastric emptying.

- Concurrent administration of monoamine oxidase inhibitors or within 2 weeks of discontinuation of their use.

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

Oxymetazoline

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

No adverse effects known.

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

The safety of oxymetazoline during pregnancy and lactation has not been established, but is not thought to constitute a hazard during these periods.

Desloratadine/pseudoephedrine [1], oxymetazoline ---> SmPC of [1] of EMA

Risk of vasoconstriction

Fentanyl [1], oxymetazoline ---> SmPC of [1] of EMA

Decreased plasma concentrations of fentanyl. It is recommended to avoid the concomitant use of nasal decongestants

Hypertensive drugs, oxymetazoline

Concomitant use of oxymetazoline and hypertensive drugs may increase the blood pressure

IMAOs, oxymetazoline [2] ---> SmPC of [2] of eMC

Oxymetazoline should not be given to patients being treated with monoamine oxidase inhibitors or within 14 days of ceasing such treatment.

Levocabastine, oxymetazoline

Decreased absorption of levocabastine

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

The safety of oxymetazoline during pregnancy and lactation has not been established, but is not thought to constitute a hazard during these periods.

Oxymetazoline, sympathomimetics ---> SmPC of [pseudoephedrine] of eMC

Caution should be exercised with patients receiving other sympathomimetic agents (e.g. avoid use with apraclonidine), appetite suppressants or other amphetamine-like psychostimulants, as there is a risk of hypertension.

Oxymetazoline, tricyclic antidepressant

Increased blood pressure or enhancement of vasoconstrictor effect

CONTRAINDICATIONS of Oxymetazoline

- Hypersensitivity to any of the ingredients, patients with cardiovascular disease, hyperthyroidism, angle closure glaucoma or prostatic enlargement.

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

Oxytocin

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

Oxytocin can induce labour, therefore caution should be exercised when driving or operating machines. Women with uterine contractions should not drive or use machines.

Adrenaline [1], oxytocin ---> SmPC of [1] of eMC

The vasoconstrictor and pressor effects of adrenaline, mediated by its alpha-adrenergic action, may be enhanced by concomitant administration of drugs with similar effects, such as ergot alkaloids or oxytocin.

Alprostadil, oxytocin

Prostaglandin potentiates the uterotonic effect of oxytocic drugs. Co-administration is not recommended

Antihypertensives, oxytocin

Increased hypotensive effect

Beclometasone/formoterol/glycopyrronium [1], oxytocin ---> SmPC of [1] of EMA

L-dopa, L-thyroxine, oxytocin and alcohol can impair cardiac tolerance towards beta2-sympathomimetics.

Beta-adrenergic agonists, oxytocin

Oxytocin may enhance the cardiovascular adverse effects of beta-adrenergic agonist

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

Oxytocin may be found in small quantities in mother's breast milk. However, oxytocin is not expected to cause harmful effects in the newborn because it passes into the alimentary tract where it undergoes rapid inactivation.

Budesonide/formoterol [1], oxytocin ---> SmPC of [1] of EMA

Oxytocin can impair cardiac tolerance towards beta2 sympathomimetics.

Corticorelin, oxytocin

The co-administration of corticorelin with medicinal products that can inhibit its effect should be avoided

Desmopressin, oxytocin

The co-administration may increase the antidiuretic effect

Doubutamine [1], oxytocin ---> SmPC of [1] of eMC

There is a possibility of oxytocin enhancing the pressor effects of sympathomimetics with or without hypertension.

Epinephrine [1], oxytocin ---> SmPC of [1] of eMC

Ergot derivatives, oxytocin ---> SmPC of [carbetocin] of eMC

During combination with ergot-alkaloids, such as methylergometrine, oxytocin and carbetocin may enhance the blood pressure enhancing effect of these agents.

Formoterol, oxytocin ---> SmPC of [budesonide/formoterol] of EMA

Oxytocin can impair cardiac tolerance towards beta2 sympathomimetics.

Gemeprost [1], oxytocin ---> SmPC of [1] of eMC

Oxytocin and other labour inducers or accelerators can potentiate the action of Gemeprost.

General anesthetics, oxytocin [2] ---> SmPC of [2] of eMC

Inhalation anaesthetics have a relaxing effect on the uterus and produce a notable inhibition of uterine tone and thereby, may diminish the uterotonic effect of oxytocin.

Methylergometrine, oxytocin

The co-administration may enhance the oxytocic effect and cause hypertensive crisis with cerebral edema and seizures

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

Based on the wide experience with this drug and its chemical structure and pharmacological properties, it is not expected to present a risk of foetal abnormalities when used as indicated.

Oxytocin [1], prostaglandins ---> SmPC of [1] of eMC

Prostaglandins and its analogues facilitate contraction of the myometrium hence oxytocin can potentiate the uterine action of prostaglandins and analogues and vice versa

Oxytocin [1], QT interval prolonging drugs ---> SmPC of [1] of eMC

Oxytocin should be considered as potentially arrhythmogenic, particularly in patients with other risk factors for Torsades de Pointes such as drugs which prolong the QT interval or in patients with history of long QT syndrome

Oxytocin [1], sympathomimetics ---> SmPC of [1] of eMC

Oxytocin may enhance the vasopressor effects of sympathomimetics

Oxytocin [1], vasoconstrictors ---> SmPC of [1] of eMC

Oxytocin may enhance the vasopressor effects of vasoconstrictors

Oxytocin, succinylcholine

The co-administration may enhance the neuromuscular blocking action of suxamethonium

Oxytocin, suxamethonium

The co-administration may enhance the neuromuscular blocking action of suxamethonium

Oxytocin, terbutaline

Oxytocin may enhance the cardiac and circulatory regulator sympathomimetics effects of terbutaline

CONTRAINDICATIONS of Oxytocin

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

- Hypertonic uterine contractions, mechanical obstruction to delivery, foetal distress.

- Any condition in which, for foetal or maternal reasons, spontaneous labour is inadvisable and/or vaginal delivery is contra-indicated: e.g.:

- Significant cephalopelvic disproportion

- Foetal malpresentation

- Placenta praevia and vasa praevia

- Placental abruption

- Cord presentation or prolapse

- Overdistension or impaired resistance of the uterus to rupture as in multiple pregnancy

- Polyhydramnios

- Grand multiparity

- In the presence of a uterine scar resulting from major surgery including classical caesarean section.

- Syntocinon should not be used for prolonged periods in patients with oxytocin-resistant uterine inertia, severe pre-eclamptic toxaemia or severe cardiovascular disorders.

- Syntocinon must not be administered within 6 hours after vaginal prostaglandins have been given

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

Ozanimod (Zeposia)

Antiarrhythmics, ozanimod [2] ---> SmPC of [2] of EMA

Patients on other bradycardic medicinal products and on antiarrhythmic medicinal products (which have been associated with cases of torsades de pointes in patients with bradycardia) have not been studied with ozanimod.

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

Anti-neoplastic, immunomodulatory or non-corticosteroid immunosuppressive therapies should not be coadministered due to the risk of additive immune system effects

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

Caution should be applied when ozanimod is initiated in patients receiving treatment with a betablocker or a calcium-channel blocker (e.g. diltiazem and verapamil) because of the potential for additive effects on lowering HR.

Bradycardic medicinal products, ozanimod [2] ---> SmPC of [2] of EMA

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

Due to the potential for serious adverse reactions to ozanimod/metabolites in nursing infants, women receiving ozanimod should not breastfeed.

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

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

Caution should be exercised for concomitant use of ozanimod with strong CYP2C8 inhibitors (e.g. gemfibrozil, clopidogrel).

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

Coadministration of ozanimod with ciclosporin, a strong BCRP inhibitor, had no effect on the exposure of ozanimod and its major active metabolites (CC112273 and CC1084037).

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

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

No fertility data are available in humans. In animal studies, no adverse effects on fertility were observed (see section 5.3).

Gemfibrozil, ozanimod [2] ---> SmPC of [2] of EMA

Caution should be exercised for concomitant use of ozanimod with strong CYP2C8 inhibitors (e.g. gemfibrozil, clopidogrel).

IMAOs, ozanimod [2] ---> SmPC of [2] of EMA

The coadministration of MAO inhibitors (e.g., selegiline, phenelzine) with ozanimod is not recommended (see section 4.4).

Immunomodulatory agents, ozanimod [2] ---> SmPC of [2] of EMA

Anti-neoplastic, immunomodulatory or non-corticosteroid immunosuppressive therapies should not be coadministered due to the risk of additive immune system effects

Immunosuppressives, ozanimod [2] ---> SmPC of [2] of EMA

Anti-neoplastic, immunomodulatory or non-corticosteroid immunosuppressive therapies should not be coadministered due to the risk of additive immune system effects

MAO-B inhibitors, ozanimod [2] ---> SmPC of [2] of EMA

However, the coadministration with MAO-B inhibitors may decrease exposure of the major active metabolites and may result in reduced clinical response.

Ozanimod [1], phenelzine ---> SmPC of [1] of EMA

The coadministration of MAO inhibitors (e.g., selegiline, phenelzine) with ozanimod is not recommended (see section 4.4).

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

Consequently, Zeposia is contraindicated during pregnancy (see section 4.3). Zeposia should be stopped 3 months before planning a pregnancy (see section 4.4).

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

If a woman becomes pregnant during treatment, Zeposia must be discontinued. Medical advice should be given regarding the risk of harmful effects to the foetus associated with treatment

Ozanimod [1], propranolol ---> SmPC of [1] of EMA

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

The coadministration of CYP2C8 inducers (i.e., rifampin) with ozanimod is not recommended

Ozanimod [1], selegiline ---> SmPC of [1] of EMA

The coadministration of MAO inhibitors (e.g., selegiline, phenelzine) with ozanimod is not recommended (see section 4.4).

Ozanimod [1], strong BCRP inhibitors ---> SmPC of [1] of EMA

Coadministration of ozanimod with ciclosporin, a strong BCRP inhibitor, had no effect on the exposure of ozanimod and its major active metabolites (CC112273 and CC1084037).

Ozanimod [1], strong CYP2C8 inductors ---> SmPC of [1] of EMA

The coadministration of CYP2C8 inducers (i.e., rifampin) with ozanimod is not recommended

Ozanimod [1], strong CYP2C8 inhibitors ---> SmPC of [1] of EMA

Caution should be exercised for concomitant use of ozanimod with strong CYP2C8 inhibitors (e.g. gemfibrozil, clopidogrel).

Ozanimod [1], sun ---> SmPC of [1] of EMA

Since there is a potential risk of malignant skin growths, patients treated with ozanimod should be cautioned against exposure to sunlight without protection. These should not receive concomitant phototherapy with UV-B-radiation or PUVA-photochemotherapy

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

The use of live attenuated vaccines may carry a risk of infections and should, therefore, be avoided during and for up to 3 months after treatment with ozanimod (see section 4.4).

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

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

Zeposia is contraindicated in women of childbearing potential not using effective contraception (see section 4.3).

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

Therefore, before initiation of treatment in women of childbearing potential, a negative pregnancy test result must be available and counselling should be provided regarding the risk to the foetus.

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

Women of childbearing potential must use effective contraception during ozanimod treatment and for 3 months after treatment discontinuation (see section 4.4).

CONTRAINDICATIONS of Ozanimod (Zeposia)

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

- Immunodeficient state (see section 4.4).

- Patients who in the last 6 months experienced myocardial infarction (MI), unstable angina, stroke, transient ischaemic attack (TIA), decompensated heart failure requiring hospitalisation or New York Heart Association (NYHA) Class III/IV heart failure.

- Patients with history or presence of second-degree atrioventricular (AV) block Type II or third-degree AV block or sick sinus syndrome unless the patient has a functioning pacemaker.

- Severe active infections, active chronic infections such as hepatitis and tuberculosis (see section 4.4).

- Active malignancies.

- Severe hepatic impairment (Child-Pugh class C).

- During pregnancy and in women of childbearing potential not using effective contraception (see sections 4.4 and 4.6).

https://www.ema.europa.eu/en/documents/product-information/zeposia-epar-product-information_en.pdf 27/03/2025

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