M

Macimorelin (Ghryvelin)

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

In case a patient should be reporting dizziness as side effect, the patient should be instructed to neither drive nor use machines.

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

Medicinal products that directly affect the pituitary secretion of growth hormone. Concomitant use is to be avoided

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

Co-administration of macimorelin with medicinal products with a potential to induce torsades de pointes should be avoided

Antibiotics, macimorelin [2] ---> SmPC of [2] of EMA

Co-administration of macimorelin with medicinal products with a potential to induce torsades de pointes should be avoided

Antithyroid medicines, macimorelin [2] ---> SmPC of [2] of EMA

Medicinal products that may blunt the growth hormone response to macimorelin. Concomitant use is to be avoided

Atropine, macimorelin [2] ---> SmPC of [2] of EMA

Medicinal products that may blunt the growth hormone response to macimorelin. Concomitant use is to be avoided

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

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

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

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

Chlorpromazine, macimorelin [2] ---> SmPC of [2] of EMA

Co-administration of macimorelin with medicinal products with a potential to induce torsades de pointes should be avoided

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

Co-administration of macimorelin with medicinal products with a potential to induce torsades de pointes should be avoided

Class IA antiarrhythmic agents, macimorelin [2] ---> SmPC of [2] of EMA

Co-administration of macimorelin with medicinal products with a potential to induce torsades de pointes should be avoided

Class III antiarrhythmic agents, macimorelin [2] ---> SmPC of [2] of EMA

Co-administration of macimorelin with medicinal products with a potential to induce torsades de pointes should be avoided

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

Medicinal products that may transiently elevate growth hormone concentrations. Concomitant use is to be avoided

Cyclooxygenase inhibitors, macimorelin [2] ---> SmPC of [2] of EMA

Medicinal products that directly affect the pituitary secretion of growth hormone. Concomitant use is to be avoided

Dabrafenib, macimorelin [2] ---> SmPC of [2] of EMA

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

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

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

Enzalutamide, macimorelin [2] ---> SmPC of [2] of EMA

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

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

Co-administration of macimorelin with medicinal products with a potential to induce torsades de pointes should be avoided

Eslicarbazepine, macimorelin [2] ---> SmPC of [2] of EMA

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

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

There are no data available on animal (see section 5.3) or human male and female fertility.

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

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

Glucocorticoids, macimorelin [2] ---> SmPC of [2] of EMA

Medicinal products that directly affect the pituitary secretion of growth hormone. Concomitant use is to be avoided

Growth hormone, macimorelin [2] ---> SmPC of [2] of EMA

Growth hormone medicinal products should be discontinued at least 1 month before administering macimorelin. Sufficient washout time (five elimination half-lives) of medicinal products prior to administration of macimorelin is recommended.

Growth hormone, macimorelin [2] ---> SmPC of [2] of EMA

Medicinal products that may blunt the growth hormone response to macimorelin. Concomitant use is to be avoided

Haloperidol, macimorelin [2] ---> SmPC of [2] of EMA

Co-administration of macimorelin with medicinal products with a potential to induce torsades de pointes should be avoided

Indometacin, macimorelin [2] ---> SmPC of [2] of EMA

Medicinal products that directly affect the pituitary secretion of growth hormone. Concomitant use is to be avoided

Insulin, macimorelin [2] ---> SmPC of [2] of EMA

Medicinal products that directly affect the pituitary secretion of growth hormone. Concomitant use is to be avoided

Levodopa, macimorelin [2] ---> SmPC of [2] of EMA

Medicinal products that may transiently elevate growth hormone concentrations. Concomitant use is to be avoided

Lumacaftor, macimorelin [2] ---> SmPC of [2] of EMA

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

Macimorelin [1], modafinil ---> SmPC of [1] of EMA

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

Macimorelin [1], moxifloxacin ---> SmPC of [1] of EMA

Co-administration of macimorelin with medicinal products with a potential to induce torsades de pointes should be avoided

Macimorelin [1], muscarinic antagonist ---> SmPC of [1] of EMA

Medicinal products that directly affect the pituitary secretion of growth hormone. Concomitant use is to be avoided

Macimorelin [1], neuroleptics ---> SmPC of [1] of EMA

Co-administration of macimorelin with medicinal products with a potential to induce torsades de pointes should be avoided

Macimorelin [1], nevirapine ---> SmPC of [1] of EMA

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

Macimorelin [1], oxcarbazepine ---> SmPC of [1] of EMA

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

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

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

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

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

Macimorelin [1], pioglitazone ---> SmPC of [1] of EMA

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

Macimorelin [1], pitolisant ---> SmPC of [1] of EMA

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

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

Macimorelin is not recommended during pregnancy.

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

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

Macimorelin [1], procainamide ---> SmPC of [1] of EMA

Co-administration of macimorelin with medicinal products with a potential to induce torsades de pointes should be avoided

Macimorelin [1], propylthiouracil ---> SmPC of [1] of EMA

Medicinal products that may blunt the growth hormone response to macimorelin. Concomitant use is to be avoided

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

Co-administration of macimorelin with medicinal products with a potential to induce torsades de pointes should be avoided

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

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

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

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

Macimorelin [1], somatostatin ---> SmPC of [1] of EMA

Medicinal products that directly affect the pituitary secretion of growth hormone. Concomitant use is to be avoided

Macimorelin [1], sotalol ---> SmPC of [1] of EMA

Co-administration of macimorelin with medicinal products with a potential to induce torsades de pointes should be avoided

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

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

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

Co-administration of a CYP3A4 inhibitor may increase the macimorelin plasma concentration, and this, in turn, could yield higher plasma GH levels.

Macimorelin [1], torsades de pointes inducing drugs ---> SmPC of [1] of EMA

Co-administration of macimorelin with medicinal products with a potential to induce torsades de pointes should be avoided

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

Women of childbearing potential must use adequate contraceptive methods at the time when macimorelin will be administered.

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

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

             CONTRAINDICATIONS of Macimorelin (Ghryvelin)      

             - 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/ghryvelin-previously-macimorelin-aeterna-zentaris-epar-product-information_en.pdf  13/05/2024 

Macitentan (Opsumit)

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

No studies on the effects on the ability to drive and use machines have been performed. However, undesirable effects may occur (e.g., headache, hypotension) that may influence the ability to drive and use machines (see section 4.8).

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

Caution should be exercised when macitentan is administered concomitantly with moderate dual inhibitors of CYP3A4 and CYP2C9 (e.g., fluconazole and amiodarone) (see section 4.4).

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

It is unknown whether macitentan is excreted in human milk. In rats, macitentan and its metabolites are excreted into milk during lactation. A risk to the breastfeeding child cannot be excluded. Opsumit is contraindicated during breastfeeding.

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

In the presence of strong CYP3A4 inducers reduced efficacy of macitentan could occur. The combination of macitentan with strong CYP3A4 inducers should be avoided

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

Caution should also be exercised when macitentan is administered concomitantly with both a moderate CYP3A4 inhibitor (e.g., ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil)

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

Caution should be exercised when macitentan (by CYP3A4 metabolized) is administered concomitantly with strong CYP3A4 inhibitors

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

Concomitant treatment with cyclosporine A 100 mg twice daily, a combined CYP3A4 and OATP inhibitor, did not alter the steady-state exposure to macitentan and its active metabolite to a clinically relevant extent.

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

Macitentan and its active metabolite do not have clinically relevant inhibitory or inducing effects on cytochrome P450 enzymes.

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

Caution should also be exercised when macitentan is administered concomitantly with both a moderate CYP3A4 inhibitor (e.g., ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil)

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

Caution should also be exercised when macitentan is administered concomitantly with both a moderate CYP3A4 inhibitor (e.g., ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil)

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

Caution should be exercised when macitentan is administered concomitantly with moderate dual inhibitors of CYP3A4 and CYP2C9 (e.g., fluconazole and amiodarone) (see section 4.4).

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

Caution should be exercised when macitentan (by CYP3A4 metabolized) is administered concomitantly with strong CYP3A4 inhibitors

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

Caution should be exercised when macitentan (by CYP3A4 metabolized) is administered concomitantly with strong CYP3A4 inhibitors

Macitentan [1], male fertility ---> SmPC of [1] of EMA

The development of testicular tubular atrophy in male animals was observed after treatment with macitentan (see section 5.3). Decreases in sperm count have been observed in patients taking ERAs.

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

Decreases in sperm count have been observed in patients taking ERAs. Macitentan, like other ERAs, may have an adverse effect on spermatogenesis in men.

Macitentan [1], metabolized by cytochrome P450 ---> SmPC of [1] of EMA

Macitentan and its active metabolite do not have clinically relevant inhibitory or inducing effects on cytochrome P450 enzymes.

Macitentan [1], miconazole ---> SmPC of [1] of EMA

Caution should also be exercised when macitentan is administered concomitantly with both a moderate CYP2C9 inhibitor (e.g., miconazole, piperine)

Macitentan [1], moderate CYP2C9 inhibitors ---> SmPC of [1] of EMA

Caution should also be exercised when macitentan is administered concomitantly with both a moderate CYP2C9 inhibitor (e.g., miconazole, piperine)

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

Caution should also be exercised when macitentan is administered concomitantly with both a moderate CYP3A4 inhibitor (e.g., ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil)

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

Caution should be exercised when macitentan (by CYP3A4 metabolized) is administered concomitantly with strong CYP3A4 inhibitors

Macitentan [1], OATP1B1 substrates ---> SmPC of [1] of EMA

Macitentan and its active metabolite are not inhibitors of hepatic or renal uptake transporters at clinically relevant concentrations, including the organic anion transporting polypeptides (OATP1B1 and OATP1B3).

Macitentan [1], OATP1B3 inductors ---> SmPC of [1] of EMA

Macitentan and its active metabolite are not relevant substrates of OATP1B1 and OATP1B3, but enter the liver by passive diffusion.

Macitentan [1], OATP1B3 inhibitors ---> SmPC of [1] of EMA

Macitentan and its active metabolite are not relevant substrates of OATP1B1 and OATP1B3, but enter the liver by passive diffusion.

Macitentan [1], OATP1B3 substrates ---> SmPC of [1] of EMA

Macitentan and its active metabolite are not inhibitors of hepatic or renal uptake transporters at clinically relevant concentrations, including the organic anion transporting polypeptides (OATP1B1 and OATP1B3).

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

Macitentan 10 mg once daily did not affect the pharmacokinetics of an oral contraceptive (norethisterone 1 mg and ethinyl estradiol 35 ľg).

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

Macitentan and its active metabolite are not inhibitors of hepatic or renal efflux pumps at clinically relevant concentrations, including the multi-drug resistance protein (P-gp, MDR-1)

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

In the presence of strong CYP3A4 inducers reduced efficacy of macitentan could occur. The combination of macitentan with strong CYP3A4 inducers should be avoided

Macitentan [1], piperine ---> SmPC of [1] of EMA

Caution should also be exercised when macitentan is administered concomitantly with both a moderate CYP2C9 inhibitor (e.g., miconazole, piperine)

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

Opsumit is contraindicated during pregnancy and in women of childbearing potential who are not using reliable contraception

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

In the presence of strong CYP3A4 inducers reduced efficacy of macitentan could occur. The combination of macitentan with strong CYP3A4 inducers should be avoided

Macitentan [1], riociguat ---> SmPC of [1] of EMA

Macitentan 10 mg once daily did not affect the pharmacokinetics of a BCRP substrate drug (riociguat 1 mg; rosuvastatin 10 mg).

Macitentan [1], ritonavir ---> SmPC of [1] of EMA

Caution should be exercised when macitentan (by CYP3A4 metabolized) is administered concomitantly with strong CYP3A4 inhibitors

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

Macitentan 10 mg once daily did not affect the pharmacokinetics of a BCRP substrate drug (riociguat 1 mg; rosuvastatin 10 mg).

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

Caution should be exercised when macitentan (by CYP3A4 metabolized) is administered concomitantly with strong CYP3A4 inhibitors

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

In a placebo-controlled trial in patients with PAH, the efficacy and safety of macitentan in combination with sildenafil were demonstrated.

Macitentan [1], spermatogenesis ---> SmPC of [1] of EMA

Macitentan, like other ERAs, may have an adverse effect on spermatogenesis in men.

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

In the presence of strong CYP3A4 inducers reduced efficacy of macitentan could occur. The combination of macitentan with strong CYP3A4 inducers should be avoided

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

In the presence of strong CYP3A4 inducers reduced efficacy of macitentan could occur. The combination of macitentan with strong CYP3A4 inducers should be avoided

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

Caution should be exercised when macitentan (by CYP3A4 metabolized) is administered concomitantly with strong CYP3A4 inhibitors

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

Caution should be exercised when macitentan (by CYP3A4 metabolized) is administered concomitantly with strong CYP3A4 inhibitors

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

Caution should also be exercised when macitentan is administered concomitantly with both a moderate CYP3A4 inhibitor (e.g., ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil)

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

Caution should be exercised when macitentan (by CYP3A4 metabolized) is administered concomitantly with strong CYP3A4 inhibitors

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

The pharmacodynamic effect of warfarin on International Normalized Ratio (INR) was not affected by macitentan. The pharmacokinetics of macitentan and its active metabolite were not affected by warfarin.

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

Opsumit treatment should only be initiated in women of childbearing potential when the absence of pregnancy has been verified, appropriate advice on contraception provided, and reliable contraception is practiced

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

Women should not become pregnant for 1 month after discontinuation of Opsumit. Monthly pregnancy tests during treatment with Opsumit are recommended to allow the early detection of pregnancy.

Macitentan, moderate dual inhibitor [2] ---> SmPC of [2] of EMA

Caution should be exercised when macitentan is administered concomitantly with moderate dual inhibitors of CYP3A4 and CYP2C9 (e.g., fluconazole and amiodarone) (see section 4.4).

Macitentan, sparsentan [2] ---> SmPC of [2] of EMA

Concomitant use of sparsentan with ERAs such as bosentan, ambrisentan, macitentan, sitaxentan, ARBs such as irbesartan, losartan, valsartan, candesartan, telmisartan, or renin inhibitors such as aliskiren is contraindicated (see section 4.3).

            CONTRAINDICATIONS of Macitentan (Opsumit)  

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

            - Pregnancy     

            - Women of childbearing potential who are not using reliable contraception       

            - Breastfeeding  

            - Patients with severe hepatic impairment (with or without cirrhosis)      

            - Baseline values of hepatic aminotransferases (aspartate aminotransferases (AST) and/or alanine aminotransferases (ALT) > 3 × ULN)       

            https://www.ema.europa.eu/en/documents/product-information/opsumit-epar-product-information_en.pdf 16/12/2025 

Macitentan/tadalafil (Yuvanci)

Ability to drive, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

Yuvanci has minor influence on the ability to drive and use machines. However, undesirable effects may occur (e.g., headache, hypotension) that may influence the ability to drive and use machines (see section 4.8).

Alcohol, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

Patients should be made aware of these potential side effects. The effect of alcohol on cognitive function was not augmented by tadalafil (10 mg).

Alfuzosin, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

In interaction studies performed in a limited number of healthy volunteers, these effects were not reported with alfuzosin or tamsulosin.

Amiodarone, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

Caution should be exercised when Yuvanci is administered concomitantly with moderate dual inhibitors of CYP3A4 and CYP2C9 (e.g., fluconazole and amiodarone).

Amyl nitrate, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

Therefore, administration of Yuvanci to patients who are using any form of organic nitrate, such as nitroglycerin, isosorbide and amyl nitrate, is contraindicated (see section 4.3).

Antihypertensive, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

In patients receiving concomitant antihypertensive medicinal products, tadalafil 20 mg may induce a blood pressure decrease, which (with the exception of doxazosin -see above) is, in general, minor and not likely to be clinically relevant.

BCRP substrates, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

In in vivo studies, macitentan 10 mg once daily did not affect the pharmacokinetics of a BCRP substrate drug (riociguat 1 mg; rosuvastatin 10 mg).

Breast-feeding, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

. A risk to the breastfed child cannot be excluded. Yuvanci is contraindicated during breastfeeding (see section 4.3).

Carbamazepine, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

Potent inducers of CYP3A4 including rifampicin, St. John's wort, carbamazepine, and phenytoin may reduce the efficacy of Yuvanci. The concomitant use of Yuvanci should be avoided.

Ciprofloxacin, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inhibitor (e.g., ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil) and moderate CYP2C9 inhibitor (e.g., miconazole and piperine) should be administered with caution if administered concomitantly with Yuvanci.

Clarithromycin, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

The combination of Yuvanci with strong CYP3A4 inhibitors such as itraconazole, ketoconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir and saquinavir is not recommended.

Cyclosporine, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inhibitor (e.g., ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil) and moderate CYP2C9 inhibitor (e.g., miconazole and piperine) should be administered with caution if administered concomitantly with Yuvanci.

CYP1A2 substrates, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

When tadalafil 10 mg was administered with theophylline (a non-selective phosphodiesterase inhibitor) there was no pharmacokinetic interaction. The only pharmacodynamic effect was a small (3.5 beats per minute) increase in heart rate.

CYP2C9 substrates, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

Macitentan given as multiple doses of 10 mg once daily had no effect on exposure to S-warfarin (CYP2C9 substrate) or R-warfarin (CYP3A4 substrate) after a single dose of 25 mg warfarin.

Digoxin, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

Tadalafil (40 mg once per day) had no clinically significant effect on the pharmacokinetics of digoxin (P-gp substrate).

Diltiazem, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inhibitor (e.g., ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil) and moderate CYP2C9 inhibitor (e.g., miconazole and piperine) should be administered with caution if administered concomitantly with Yuvanci.

Doxazosin, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

The co-administration of doxazosin (4 and 8 mg daily) and tadalafil (5 mg daily dose and 20 mg as a single dose) increases the blood pressure-lowering effect of this alpha-blocker in a significant manner. Therefore, this combination is not recommended.

Epoprostenol, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

The efficacy and safety of Yuvanci co-administered with prostacyclin or its analogues has not been studied in controlled clinical studies. Therefore, caution is recommended in case of co-administration.

Erectile dysfunction, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

The safety and efficacy of combinations of tadalafil and other PDE5 inhibitors or other treatments for erectile dysfunction have not been studied. Patients should be informed not to take Yuvanci with these medicinal products.

Erythromycin, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inhibitor (e.g., ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil) and moderate CYP2C9 inhibitor (e.g., miconazole and piperine) should be administered with caution if administered concomitantly with Yuvanci.

Fluconazole, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

Caution should be exercised when Yuvanci is administered concomitantly with moderate dual inhibitors of CYP3A4 and CYP2C9 (e.g., fluconazole and amiodarone).

Iloprost, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

The efficacy and safety of Yuvanci co-administered with prostacyclin or its analogues has not been studied in controlled clinical studies. Therefore, caution is recommended in case of co-administration.

Isosorbide, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

Therefore, administration of Yuvanci to patients who are using any form of organic nitrate, such as nitroglycerin, isosorbide and amyl nitrate, is contraindicated (see section 4.3).

Itraconazol, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

The combination of Yuvanci with strong CYP3A4 inhibitors such as itraconazole, ketoconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir and saquinavir is not recommended.

Ketoconazole, macitentan/tadalafil [2] ---> SmPC of [2] of EMA

The combination of Yuvanci with strong CYP3A4 inhibitors such as itraconazole, ketoconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir and saquinavir is not recommended.

Macitentan/tadalafil [1], male fertility ---> SmPC of [1] of EMA

The development of testicular tubular atrophy in male animals was observed after treatment with macitentan (see section 5.3). Decreases in sperm count have been observed in patients taking ERAs.

Macitentan/tadalafil [1], men ---> SmPC of [1] of EMA

Two clinical studies with tadalafil suggested no impairment of fertility in humans, although a decrease in sperm concentration was seen in some men.

Macitentan/tadalafil [1], miconazole ---> SmPC of [1] of EMA

Moderate CYP3A4 inhibitor (e.g., ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil) and moderate CYP2C9 inhibitor (e.g., miconazole and piperine) should be administered with caution if administered concomitantly with Yuvanci.

Macitentan/tadalafil [1], moderate dual inducers of CYP3A4 and CYP2C9 ---> SmPC of [1] of EMA

Caution should be exercised when Yuvanci is administered concomitantly with moderate dual inhibitors of CYP3A4 and CYP2C9 (e.g., fluconazole and amiodarone).

Macitentan/tadalafil [1], moderate inducers of CYP3A4 and CYP2C9 ---> SmPC of [1] of EMA

Moderate CYP3A4 inhibitor (e.g., ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil) and moderate CYP2C9 inhibitor (e.g., miconazole and piperine) should be administered with caution if administered concomitantly with Yuvanci.

Macitentan/tadalafil [1], nefazodone ---> SmPC of [1] of EMA

The combination of Yuvanci with strong CYP3A4 inhibitors such as itraconazole, ketoconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir and saquinavir is not recommended.

Macitentan/tadalafil [1], nitroglycerine ---> SmPC of [1] of EMA

Therefore, administration of Yuvanci to patients who are using any form of organic nitrate, such as nitroglycerin, isosorbide and amyl nitrate, is contraindicated (see section 4.3).

Macitentan/tadalafil [1], oral contraceptives ---> SmPC of [1] of EMA

In in vivo studies, macitentan 10 mg once daily did not affect the pharmacokinetics of an oral contraceptive (norethisterone 1 mg and ethinyl estradiol 35 ľg).

Macitentan/tadalafil [1], oral contraceptives ---> SmPC of [1] of EMA

Reliable contraception is mandatory for users of Yuvanci (see section 4.6).

Macitentan/tadalafil [1], organic nitrates ---> SmPC of [1] of EMA

Therefore, administration of Yuvanci to patients who are using any form of organic nitrate, such as nitroglycerin, isosorbide and amyl nitrate, is contraindicated (see section 4.3).

Macitentan/tadalafil [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Tadalafil (40 mg once per day) had no clinically significant effect on the pharmacokinetics of digoxin (P-gp substrate).

Macitentan/tadalafil [1], phenytoin ---> SmPC of [1] of EMA

Potent inducers of CYP3A4 including rifampicin, St. John's wort, carbamazepine, and phenytoin may reduce the efficacy of Yuvanci. The concomitant use of Yuvanci should be avoided.

Macitentan/tadalafil [1], piperine ---> SmPC of [1] of EMA

Moderate CYP3A4 inhibitor (e.g., ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil) and moderate CYP2C9 inhibitor (e.g., miconazole and piperine) should be administered with caution if administered concomitantly with Yuvanci.

Macitentan/tadalafil [1], pregnancy ---> SmPC of [1] of EMA

There are limited data from the use of tadalafil in pregnant women. Yuvanci is contraindicated during pregnancy (see section 4.3).

Macitentan/tadalafil [1], prostacyclin ---> SmPC of [1] of EMA

The efficacy and safety of Yuvanci co-administered with prostacyclin or its analogues has not been studied in controlled clinical studies. Therefore, caution is recommended in case of co-administration.

Macitentan/tadalafil [1], prostacyclin analogues ---> SmPC of [1] of EMA

The efficacy and safety of Yuvanci co-administered with prostacyclin or its analogues has not been studied in controlled clinical studies. Therefore, caution is recommended in case of co-administration.

Macitentan/tadalafil [1], rifampicin ---> SmPC of [1] of EMA

Potent inducers of CYP3A4 including rifampicin, St. John's wort, carbamazepine, and phenytoin may reduce the efficacy of Yuvanci. The concomitant use of Yuvanci should be avoided.

Macitentan/tadalafil [1], riociguat ---> SmPC of [1] of EMA

In in vivo studies, macitentan 10 mg once daily did not affect the pharmacokinetics of a BCRP substrate drug (riociguat 1 mg; rosuvastatin 10 mg).

Macitentan/tadalafil [1], riociguat ---> SmPC of [1] of EMA

In clinical studies, riociguat has been shown to augment the hypotensive effects of PDE5 inhibitors. Concomitant use of riociguat with PDE5 inhibitors, including tadalafil, is contraindicated (see section 4.3).

Macitentan/tadalafil [1], ritonavir ---> SmPC of [1] of EMA

The combination of Yuvanci with strong CYP3A4 inhibitors such as itraconazole, ketoconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir and saquinavir is not recommended.

Macitentan/tadalafil [1], rosuvastatin ---> SmPC of [1] of EMA

In in vivo studies, macitentan 10 mg once daily did not affect the pharmacokinetics of a BCRP substrate drug (riociguat 1 mg; rosuvastatin 10 mg).

Macitentan/tadalafil [1], saquinavir ---> SmPC of [1] of EMA

The combination of Yuvanci with strong CYP3A4 inhibitors such as itraconazole, ketoconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir and saquinavir is not recommended.

Macitentan/tadalafil [1], St. John's wort ---> SmPC of [1] of EMA

Potent inducers of CYP3A4 including rifampicin, St. John's wort, carbamazepine, and phenytoin may reduce the efficacy of Yuvanci. The concomitant use of Yuvanci should be avoided.

Macitentan/tadalafil [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Potent inducers of CYP3A4 including rifampicin, St. John's wort, carbamazepine, and phenytoin may reduce the efficacy of Yuvanci. The concomitant use of Yuvanci should be avoided.

Macitentan/tadalafil [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

The combination of Yuvanci with strong CYP3A4 inhibitors such as itraconazole, ketoconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir and saquinavir is not recommended.

Macitentan/tadalafil [1], telithromycin ---> SmPC of [1] of EMA

The combination of Yuvanci with strong CYP3A4 inhibitors such as itraconazole, ketoconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir and saquinavir is not recommended.

Macitentan/tadalafil [1], terbutaline ---> SmPC of [1] of EMA

A similar increase in AUC and Cmax seen with ethinylestradiol may be expected with oral administration of terbutaline, probably due to inhibition of gut sulphation by tadalafil.

Macitentan/tadalafil [1], theophylline ---> SmPC of [1] of EMA

When tadalafil 10 mg was administered with theophylline (a non-selective phosphodiesterase inhibitor) there was no pharmacokinetic interaction. The only pharmacodynamic effect was a small (3.5 beats per minute) increase in heart rate.

Macitentan/tadalafil [1], verapamil ---> SmPC of [1] of EMA

Moderate CYP3A4 inhibitor (e.g., ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil) and moderate CYP2C9 inhibitor (e.g., miconazole and piperine) should be administered with caution if administered concomitantly with Yuvanci.

Macitentan/tadalafil [1], voriconazole ---> SmPC of [1] of EMA

The combination of Yuvanci with strong CYP3A4 inhibitors such as itraconazole, ketoconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir and saquinavir is not recommended.

Macitentan/tadalafil [1], warfarin ---> SmPC of [1] of EMA

Macitentan given as multiple doses of 10 mg once daily had no effect on exposure to S-warfarin (CYP2C9 substrate) or R-warfarin (CYP3A4 substrate) after a single dose of 25 mg warfarin.

Macitentan/tadalafil [1], women of childbearing potential ---> SmPC of [1] of EMA

Yuvanci treatment should only be initiated in women of childbearing potential when the absence of pregnancy has been verified, appropriate advice on contraception provided, and reliable contraception is practised (see sections 4.3 and 4.4).

Macitentan/tadalafil [1], women of childbearing potential ---> SmPC of [1] of EMA

Monthly pregnancy tests during treatment with Yuvanci are recommended to allow the early detection of pregnancy. Yuvanci is contraindicated in women of childbearing potential who are not using reliable contraception (see section 4.3).

Macitentan/tadalafil [1], women of childbearing potential ---> SmPC of [1] of EMA

Yuvanci is contraindicated in women of childbearing potential who are not using reliable contraception (see section 4.3).

PDE5 inhibitors, riociguat ---> SmPC of [macitentan/tadalafil] of EMA

In clinical studies, riociguat has been shown to augment the hypotensive effects of PDE5 inhibitors. Concomitant use of riociguat with PDE5 inhibitors, including tadalafil, is contraindicated (see section 4.3).

            CONTRAINDICATIONS of Macitentan/tadalafil (Yuvanci)  

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

            - Acute myocardial infarction within the last 90 days.     

            - Pregnancy (see sections 4.4 and 4.6).     

            - Women of childbearing potential who are not using reliable contraception (see sections 4.4 and 4.6).           

            - Patients with severe hepatic impairment, with or without cirrhosis (Child-Pugh Class C) (see sections 4.2 and 4.4).   

            - Baseline values of hepatic aminotransferases (aspartate aminotransferases (AST) and/or alanine aminotransferases (ALT) > 3 × ULN) (see sections 4.2 and 4.4).   

            - Severe hypotension (<90/50 mm Hg).     

            - Co-administration with nitrates or guanylate cyclase stimulators (such as riociguat, see section4.5).     

            - Patients with a history of non-arteritic anterior ischaemic optic neuropathy (NAION).

            https://www.ema.europa.eu/en/documents/product-information/yuvanci-epar-product-information_en.pdf 07/10/2024             

Macrosalb

Antineoplastics, macrosalb

Pharmacological interactions may occur

Bleomycin, macrosalb

Toxicological interactions may occur

Breast-feeding, macrosalb

Before administering a radioactive medicinal product to a mother who is breast-feeding, consideration should be given as to whether the investigation could be reasonably delayed until the mother has ceased breast-feeding

Bronchodilatators, macrosalb

Pharmacological interactions may occur

Busulfan, macrosalb

Toxicological interactions may occur

Cyclophosphamide, macrosalb

Toxicological interactions may occur

Heparin, macrosalb

Pharmacological interactions may occur

Heroin, macrosalb

Toxicological interactions may occur

Macrosalb, magnesium sulfate

Pharmaceutical interactions may occur

Macrosalb, methotrexate

Toxicological interactions may occur

Macrosalb, methysergide

Toxicological interactions may occur

Macrosalb, nitrofurantoin

Toxicological interactions may occur

Macrosalb, pregnancy

Radionuclide procedures carried out on pregnant women also involve radiation doses to the fetus. Only imperative investigations should be carried out during pregnancy, when likely benefit exceeds the risks incurred by mother and fetus.

Magaldrate

Acenocoumarol, magaldrate

Decreased absorption of acenocoumarol. It is recommended to administer the two substances at least 2-3 hours apart.

Ascorbic acid, magaldrate

The concomitant use of aluminium-containing antacids with ascorbic acid may increase the aluminium absorption and cause toxicity. The combination is not recommended

Benzodiazepines, magaldrate

Decreased absorption of benzodiazepine. It is recommended to administer the two substances at least 2-3 hours apart.

Breast-feeding, magaldrate

Aluminium compounds pass into the mother milk

Chenodeoxycholic acid, magaldrate

Decreased absorption of chenodeoxycholic acid. It is recommended to administer the two substances at least 2-3 hours apart.

Cimetidine, magaldrate

Decreased absorption of cimetidine. It is recommended to administer the two substances at least 2-3 hours apart.

Ciprofloxacin, magaldrate

Considerable decrease in the absorption of quinolone. During the treatment with a quinolone is not recommended la administration of magaldrate

Citric acid, magaldrate

The concomitant intake should be avoided due to increased intestinal absorption of aluminium salt

Digoxin, magaldrate

The co-administration may decrease the absorption of digoxin. It is recommended to administer the two substances at least 2 hours apart.

Fluoroquinolones, magaldrate

Considerable decrease in the absorption of quinolone. During the treatment with a quinolone is not recommended la administration of magaldrate

Fruit juice, magaldrate

The intake of acid beverages (e. g. fruit juice, wine) together with antacids containing aluminium increases the intestinal absorption of aluminium

Indometacin, magaldrate

Decreased absorption of indometacin. It is recommended to administer the two substances at least 2-3 hours apart.

Iron, magaldrate

Decreased absorption of iron salt. It is recommended to administer the two substances at least 2-3 hours apart.

Lomefloxacin, magaldrate

Considerable decrease in the absorption of quinolone. During the treatment with a quinolone is not recommended la administration of magaldrate

Magaldrate, norfloxacin

Considerable decrease in the absorption of quinolone. During the treatment with a quinolone is not recommended la administration of magaldrate

Magaldrate, oral anticoagulants

Decreased absorption of oral anticoagulant. It is recommended to administer the two substances at least 2-3 hours apart.

Magaldrate, pregnancy

Only short-term and the lowest possible dose to avoid an aluminium burden for the fetus

Magaldrate, prulifloxacin

Considerable decrease in the absorption of quinolone. During the treatment with a quinolone is not recommended la administration of magaldrate

Magaldrate, tartaric acid

The concomitant intake should be avoided due to increased intestinal absorption of aluminium salt

Magaldrate, tetracyclines

Considerable decrease in the absorption of tetracycline. During the treatment with a tetracycline is not recommended la administration of magaldrate

Magaldrate, ursodeoxycholic acid

The co-administration may decrease the absorption of ursodeoxycholic acid. It is recommended to administer the two substances at least 2 hours apart.

Magaldrate, vitamin C

The concomitant use of aluminium-containing antacids with ascorbic acid may increase the aluminium absorption and cause toxicity. The combination is not recommended

Magaldrate, warfarin

Decreased absorption of warfarin. It is recommended to administer the two substances at least 2-3 hours apart.

Magaldrate, wine

The concomitant intake should be avoided due to increased intestinal absorption of aluminium salt

Magnesium hydroxide

Acenocoumarol, magnesium hydroxide

Antacids may enhance the anticoagulant effect of acenocoumarol

Alendronic acid, magnesium hydroxide

The magnesium hydroxide may decrease the absorption of alendronic acid. Separate administration by 2-3 hours

Ammonium chloride, magnesium hydroxide

The magnesium hydroxide, urinary alkalinizing agent, increases the pH of renal tubular urine and may counteract the effect of the urinary acidifying

Amphetamine, magnesium hydroxide

The magnesium hydroxide, urinary alkalinizing agent, increases the pH of renal tubular urine and decreases the urinary excretion of amphetamine

Anionic drugs, magnesium hydroxide

The magnesium hydroxide, urinary alkalinizing agent, increases the renal elimination of the acidic (anionic) medicinal product

Anticholinergics, magnesium hydroxide

The magnesium hydroxide may decrease the absorption of anticholinergic. Separate administration by 2-3 hours

Antidiabetics, magnesium hydroxide [2] ---> SmPC of [2] of eMC

The co-administration of magnesium hydroxide may increase the absorption of antidiabetic agents. Separate administration by 2-3 hours

Ascorbic acid, magnesium hydroxide

The magnesium hydroxide, urinary alkalinizing agent, increases the pH of renal tubular urine and may counteract the effect of the urinary acidifying

Atenolol, magnesium hydroxide

The co-administration of magnesium hydroxide may decrease the absorption of atenolol. Separate administration by 2-3 hours

Atorvastatin, magnesium hydroxide

Concomitant use decreases atorvastatin AUC

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

There were no significant pharmacokinetic interactions between bazedoxifene and magnesium hydroxide

Breast-feeding, magnesium hydroxide [2] ---> SmPC of [2] of eMC

As with all other medicines, use of this product should be avoided unless recommended by a doctor.

Calcitriol [1], magnesium hydroxide ---> SmPC of [1] of eMC

Magnesium-containing drugs (e.g. antacids) may cause hypermagnesaemia and should therefore not be taken during therapy with calcitriol by patients on chronic renal dialysis.

Capecitabine [1], magnesium hydroxide ---> SmPC of [1] of EMA

Small increase in plasma concentrations of capecitabine

Captopril, magnesium hydroxide

The magnesium hydroxide may decrease the absorption of captopril. Separate administration by 2-3 hours

Cationic drugs, magnesium hydroxide

The magnesium hydroxide, urinary alkalinizing agent, decreases the renal elimination of the basic (cationic) medicinal product

Cefaclor, magnesium hydroxide

Decreased cefaclor absorption rate. Separate administration by at least 2 hours

Chlordiazepoxide, magnesium hydroxide

The magnesium hydroxide may decrease the absorption of chlordiazepoxide. Separate administration by 2-3 hours

Chlorpromazine [1], magnesium hydroxide ---> SmPC of [1] of eMC

The magnesium hydroxide may decrease the absorption of chlorpromazine. Separate administration by at least 2-3 hours

Chlorpropamide, magnesium hydroxide [2] ---> SmPC of [2] of eMC

The co-administration of magnesium hydroxide may increase the absorption of antidiabetic agents. Separate administration by 2-3 hours

Chlortetracycline, magnesium hydroxide

The magnesium hydroxide may decrease the absorption of tetracycline. Separate administration by 2-3 hours

Cimetidine, magnesium hydroxide

The magnesium hydroxide decreases the absorption of the co-administered active principle. Separate administration by at least 2 hours

Ciprofloxacin [1], magnesium hydroxide ---> SmPC of [1] of eMC

The co-administration should be avoided because absorption of ciprofloxacin may be reduced.

Cloprednol, magnesium hydroxide

Decreased bioavailability of cloprednol in chronic liver desease

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

There were no significant pharmacokinetic interactions between bazedoxifene and magnesium hydroxide

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

No mechanistic interaction expected based on theoretical consideration. Darunavir/cobicistat and antacids can be used concomitantly without dose adjustment.

Dasatinib [1], magnesium hydroxide ---> SmPC of [1] of EMA

Non-clinical data demonstrate that the solubility of dasatinib is pH-dependent. Antacids may be administered up to 2 hours prior to or 2 hours following dasatinib

Deflazacort, magnesium hydroxide

Decreased bioavailability of glucocorticoid in chronic liver desease

Dicoumarol, magnesium hydroxide

The magnesium hydroxide may increase the absorption of dicoumarol. Separate administration by 2-3 hours

Digoxin, magnesium hydroxide

The magnesium hydroxide may decrease the absorption of digoxine. Separate administration by 2-3 hours

Dolutegravir [1], magnesium hydroxide ---> SmPC of [1] of EMA

Magnesium/ aluminium-containing antacid should be taken well separated in time from the administration of dolutegravir (minimum 2 hours after or 6 hours before).

Dolutegravir/abacavir/lamivudine [1], magnesium hydroxide ---> SmPC of [1] of EMA

Magnesium/ aluminium-containing antacid should be taken well separated in time from the administration of dolutegravir (minimum 2 hours after or 6 hours before).

Dolutegravir/rilpivirine [1], magnesium hydroxide ---> SmPC of [1] of EMA

The combination of Juluca and antacids should be used with particular caution. Antacids should be taken well separated in time from the administration of Juluca (minimum 6 hours before or 4 hours after).

Doxycycline [1], magnesium hydroxide ---> SmPC of [1] of eMC

Absorption of doxycycline may be impaired by concurrently administered with drugs containing aluminium, calcium, magnesium or other these cations; oral zinc, iron salts or bismuth preparations. Dosages should be maximally separated.

Efavirenz [1], magnesium hydroxide ---> SmPC of [1] of EMA

Co-administration of efavirenz with medicinal products that alter gastric pH would not be expected to affect efavirenz absorption.

Elbasvir/grazoprevir [1], magnesium hydroxide ---> SmPC of [1] of EMA

No dose adjustment is required.

Elvitegravir [1], magnesium hydroxide ---> SmPC of [1] of EMA

Elvitegravir plasma levels are lower with antacids due to local complexation in the gastrointestinal tract. It is recommended to separate administration by at least 4 hours.

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

Elvitegravir plasma concentrations are lower with antacids due to local complexation in the gastrointestinal tract. Separate administration by at least 4 hours

Emtricitabine/rilpivirine/tenofovir alafenamide [1], magnesium hydroxide ---> SmPC of [1] of EMA

Co-administration may cause significant decreases in rilpivirine plasma concentrations (reduced absorption, increase in gastric pH). Antacids should only be administered either at least 2 hours before or at least 4 hours after Odefsey.

Enoxacin, magnesium hydroxide [2] ---> SmPC of [2] of eMC

The co-administration of magnesium hydroxide may decrease the absorption of quinolones due to formation of insoluble complexes. Separate administration by 2-3 hours

Fexofenadine [1], magnesium hydroxide ---> SmPC of [1] of eMC

Decreased bioavailability of fexofenadine. Separate administration by at least 2 hours

Flufenamic acid, magnesium hydroxide

The co-administration may increase the absorption rate of flufenamic acid

Flurbiprofen, magnesium hydroxide

The co-administration may increase the absorption rate of flurbiprofen

Folic acid, magnesium hydroxide

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

Fosinopril [1], magnesium hydroxide ---> SmPC of [1] of eMC

Antacids may impair absorption of fosinopril. Administration of fosinopril sodium and antacids should be separated by at least 2 hours.

Glibenclamide, magnesium hydroxide [2] ---> SmPC of [2] of eMC

The co-administration of magnesium hydroxide may increase the absorption of antidiabetic agents. Separate administration by 2-3 hours

Glipizide, magnesium hydroxide [2] ---> SmPC of [2] of eMC

The co-administration of magnesium hydroxide may increase the absorption of antidiabetic agents. Separate administration by 2-3 hours

Glucocorticoids, magnesium hydroxide

The magnesium hydroxide may decrease the absorption of glucocorticoid. Separate administration by at least 2 hours

H2 antagonists, magnesium hydroxide

The magnesium hydroxide may decrease the absorption of H2 antagonist. Separate administration by 2-3 hours

Ibuprofen, magnesium hydroxide

The co-administration may increase the absorption rate of ibuprofen

Indometacin, magnesium hydroxide

The magnesium hydroxide may decrease the absorption of indometacin. Separate administration by 2-3 hours

Iron, magnesium hydroxide

The magnesium hydroxide may decrease the absorption of iron compound. Separate administration by 2-3 hours

Ketoconazole, magnesium hydroxide

The magnesium hydroxide may decrease the absorption of ketoconazole. Separate administration by 2-3 hours

Ledipasvir/sofosbuvir [1], magnesium hydroxide ---> SmPC of [1] of EMA

Ledipasvir solubility decreases as pH increases. Medicinal products that increase gastric pH are expected to decrease concentration of ledipasvir. It is recommended to separate the administration by 4 hours.

Levodopa, magnesium hydroxide [2] ---> SmPC of [2] of eMC

The co-administration of magnesium hydroxide may increase the absorption of levodopa. Separate administration by 2-3 hours

Levomepromazine, magnesium hydroxide

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

Magnesium hydroxide [1], pefloxacine ---> SmPC of [1] of eMC

The co-administration of magnesium hydroxide may decrease the absorption of quinolones due to formation of insoluble complexes. Separate administration by 2-3 hours

Magnesium hydroxide [1], pregnancy ---> SmPC of [1] of eMC

As with all other medicines, use of this product should be avoided unless recommended by a doctor.

Magnesium hydroxide [1], quinolones ---> SmPC of [1] of eMC

The co-administration of magnesium hydroxide may decrease the absorption of quinolones due to formation of insoluble complexes. Separate administration by 2-3 hours

Magnesium hydroxide [1], sulphamides ---> SmPC of [1] of eMC

The co-administration of magnesium hydroxide may increase the absorption of sulfonamide. Separate administration by 2-3 hours

Magnesium hydroxide [1], sulphonamides ---> SmPC of [1] of eMC

The co-administration of magnesium hydroxide may increase the absorption of sulfonamide. Separate administration by 2-3 hours

Magnesium hydroxide [1], tolbutamide ---> SmPC of [1] of eMC

The co-administration of magnesium hydroxide may increase the absorption of antidiabetic agents. Separate administration by 2-3 hours

Magnesium hydroxide, mecamylamine

The magnesium hydroxide, urinary alkalinizing agent, increases the pH of renal tubular urine and decreases the urinary excretion of mecamylamine

Magnesium hydroxide, mefenamic acid

The co-administration may increase the absorption rate of mefenamic acid

Magnesium hydroxide, methenamine

The co-administration of magnesium hydroxide may decrease the efficacy of methenamine

Magnesium hydroxide, misoprostol

Magnesium-containing antacids should be avoided as this may worsen the misoprostol-induced diarrhoea

Magnesium hydroxide, mycophenolate mofetil [2] ---> SmPC of [2] of EMA

Decreased mycophenolic acid (MPA) exposure has been observed when antacids, such as magnesium and aluminium hydroxides, and PPIs, including lansoprazole and pantoprazole, were administered with mycophenolate mofetil.

Magnesium hydroxide, mycophenolate [2] ---> SmPC of [2] of EMA

Decreased mycophenolic acid (MPA) exposure has been observed when antacids, such as magnesium and aluminium hydroxides, and PPIs, including lansoprazole and pantoprazole, were administered with mycophenolate mofetil.

Magnesium hydroxide, mycophenolic acid [2] ---> SmPC of [2] of eMC

The chronic, daily use of magnesium-aluminium containing antacids with mycophenolic acid is not recommended due to the potential for decreased mycophenolic acid exposure and reduced efficacy.

Magnesium hydroxide, nilotinib [2] ---> SmPC of [2] of EMA

If necessary, an antacid may be administered approximately 2 hours before or approximately 2 hours after the dose of Tasigna.

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 hydroxide, penicillamine

The magnesium hydroxide may decrease the absorption of penicillamine. Separate administration by 2-3 hours

Magnesium hydroxide, phenothiazines

The magnesium hydroxide may decrease the absorption of phenothiazine. Separate administration by 2-3 hours

Magnesium hydroxide, phenytoin

The magnesium hydroxide may decrease the absorption of phenytoin. Separate administration by 2-3 hours

Magnesium hydroxide, phosphates

Magnesium may bind the phosphat and prevent its absorption. Separate administration by 2-3 hours

Magnesium hydroxide, quinidine

The magnesium hydroxide, urinary alkalinizing agent, increases the pH of renal tubular urine and decreases the urinary excretion of quinidine

Magnesium hydroxide, raltegravir [2] ---> SmPC of [2] of EMA

Co-administration of raltegravir with magnesium containing antacids is not recommended.

Magnesium hydroxide, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of gastric pH decreases absorption, plasma level and effect of rilpivirine. The antacid should be administered at least 2 h before or 4 h after rilpivirine

Magnesium hydroxide, riociguat [2] ---> SmPC of [2] of EMA

Riociguat exhibits a reduced solubility at neutral pH vs. acidic medium. Co-medication of drugs increasing the upper GI pH may decrease oral riociguat bioavailability. Antacids should be taken at least 2 hours before, or 1 hour after riociguat.

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

The simultaneous dosing of rosuvastatin with an antacid suspension containing magnesium hydroxide resulted in a decrease in rosuvastatin plasma concentration of approximately 50%.

Magnesium hydroxide, salicylates

The magnesium hydroxide may increase the salicylate excretion by alkalinization of urine

Magnesium hydroxide, simeprevir [2] ---> SmPC of [2] of EMA

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

Magnesium hydroxide, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Increase in gastric pH. It is recommended to separate antacid and Epclusa administration by 4 hours.

Magnesium hydroxide, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Increase in gastric pH decreases velpatasvir solubility. It is recommended to separate antacid and Vosevi administration by 4 hours.

Magnesium hydroxide, sucralfate

The co-administration may decrease the effect of sucralfate. It is recommended to administer the two substances at least 2-4 hours apart.

Magnesium hydroxide, tacrolimus [2] ---> SmPC of [2] of EMA

The combination may increase systemic exposure of tacrolimus

Magnesium hydroxide, tetracyclines

The magnesium hydroxide may decrease the absorption of tetracycline. Separate administration by 2-3 hours

Magnesium hydroxide, tiludronic acid

The magnesium hydroxide may decrease the absorption of tiludronic acid. Separate administration by 2-3 hours

Magnesium hydroxide, urinary acidifying agents

The magnesium hydroxide, urinary alkalinizing agent, increases the pH of renal tubular urine and may counteract the effect of the urinary acidifying

Magnesium hydroxide, vitamin D

Magnesium compounds should not be administered to patients with renal insufficiency because they can cause hypermagnesemia

           CONTRAINDICATIONS of Magnesium hydroxide

           - Contraindicated in severe renal failure,

           - acute gastrointestinal conditions and in

           - hypersensitivity to magnesium salts or any of the other ingredients.

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

Mangafodipir (Teslascan)

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

Breast-feeding should be discontinued from the time of administration and should not be recommenced until 14 days after administration of Mangafodipir.

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

Mangafodipir must not be used during pregnancy

            CONTRAINDICATIONS of Mangafodipir (Teslascan)        

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

            - Pregnancy and lactation.

            - Phaeochromocytoma.

            - Severely reduced liver function (Child - Pugh class C), especially severe obstructive hepatobiliary disease.

            - Severely reduced renal function

https://www.ema.europa.eu/en/documents/product-information/teslascan-epar-product-information_en.pdf 02/08/2012 (withdrawn)

Manidipine

Ability to drive, manidipine

Dizziness may occur

Alcohol, manidipine

Like with all vasodilatator, antihypertensive agents, caution is recommended with alcohol is taken concomitant because alcohol may enhance their effects

Amiodarone, manidipine

Caution is recommend when manidipine is co-administrated with other CYP3A4 substrates

Antihypertensives, manidipine

The antihypertensive effect of manidipine can be enhanced by the co-administration of other antihypertensive drugs

Astemizole, manidipine

Caution is recommend when manidipine is co-administrated with other CYP3A4 substrates

Betablockers, manidipine

The antihypertensive effect of manidipine can be enhanced by the co-administration of betablockers

Breast-feeding, manidipine

Manidipine should be avoided during breastfeeding. If breast-feeding is necessary the treatment should be discontinued

Carbamazepine, manidipine

Manidipine should not be administered with CYP3A4 inductors

Cimetidine, manidipine

Manidipine should not be administered with CYP3A4 inhibitors

Clarithromycin, manidipine

Manidipine should not be administered with CYP3A4 inhibitors

CYP3A4 inductors, manidipine

Manidipine should not be administered with CYP3A4 inductors

CYP3A4 inhibitors, manidipine

Manidipine should not be administered with CYP3A4 inhibitors

Digoxin [1], manidipine ---> SmPC of [1] of eMC

Serum levels of digoxin may be increased by concomitant administration of calcium antagonists

Diuretics, manidipine

The antihypertensive effect of manidipine can be enhanced by the co-administration of diuretics

Drugs primarily metabolised by CYP3A4, manidipine

Caution is recommend when manidipine is co-administrated with other CYP3A4 substrates

Erythromycin, manidipine

Manidipine should not be administered with CYP3A4 inhibitors

Foods, manidipine

The absorption of manidipine increases in the presence of food in the gastrointestinal tract

Grapefruit juice, manidipine [2] ---> SmPC of [2] of eMC

Dihydropyridines are sensitive to inhibition of metabolism by grapefruit juice, with a consequent rise in their systemic availability and increased hypotensive effect. Dihydropyridines should not be taken with grapefruit juice.

Itraconazol, manidipine

Manidipine should not be administered with CYP3A4 inhibitors

Ketoconazole, manidipine

Manidipine should not be administered with CYP3A4 inhibitors

Manidipine, oral antidiabetics

No interactions were observed with oral hypoglycemic drugs

Manidipine, phenobarbital

Manidipine should not be administered with CYP3A4 inductors

Manidipine, phenytoin

Manidipine should not be administered with CYP3A4 inductors

Manidipine, pregnancy

For security reasons, manidipine should not be used during pregnancy

Manidipine, protease inhibitors

Manidipine should not be administered with CYP3A4 inhibitors

Manidipine, quinidine

Caution is recommend when manidipine is co-administrated with other CYP3A4 substrates

Manidipine, rifampicin

Manidipine should not be administered with CYP3A4 inductors

Manidipine, strong CYP3A4 inductors

Manidipine should not be administered with CYP3A4 inductors

Manidipine, strong CYP3A4 inhibitors

Manidipine should not be administered with CYP3A4 inhibitors

Manidipine, terfenadine

Caution is recommend when manidipine is co-administrated with other CYP3A4 substrates

 Mannitol (Bronchitol)

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

When possible, avoid chronic coadministration of Kivexa with medicinal products containing sorbitol or other osmotic acting poly-alcohols or monosaccharide alcohols (e.g. xylitol, mannitol, lactitol, maltitol).

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

When possible, avoid chronic coadministration of Trizivir with medicinal products containing sorbitol or other osmotic acting poly-alcohols or monosaccharide alcohols (e.g. xylitol, mannitol, lactitol, maltitol).

Acetazolamide, mannitol

The co-administration can enhance the effect of acetazolamide

Atracurium [1], mannitol ---> 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 diuretics

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

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

Cisatracurium [1], mannitol ---> SmPC of [1] of eMC

Diuretics increase the magnitude and/or duration of action of non-depolarising neuromuscular blocking agents

Dolutegravir/abacavir/lamivudine [1], mannitol ---> SmPC of [1] of EMA

When possible, avoid chronic coadministration of Triumeq with medicinal products containing sorbitol or other osmotic acting poly-alcohols or monosaccharide alcohols (eg: xylitol, mannitol, lactitol, maltitol).

Dolutegravir/lamivudine [1], mannitol ---> SmPC of [1] of EMA

When possible, avoid chronic coadministration of Dovato with medicinal products containing sorbitol or other osmotic acting poly-alcohols or monosaccharide alcohols (eg: xylitol, mannitol, lactitol, maltitol).

Doravirine/lamivudine/tenofovir disoproxil [1], mannitol ---> SmPC of [1] of EMA

When possible, avoid chronic co-administration of doravirine/lamivudine/tenofovir disoproxil with medicinal products containing sorbitol or other osmotic acting polyalcohols (eg: xylitol, mannitol, lactitol, maltitol).

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

For mannitol no clinical data on fertility is available. Animal reproduction studies have not been carried out with inhaled mannitol. However, studies with orally administered mannitol indicate no fertility effects (see section 5.3).

Hypertonic saline solution, mannitol [2] ---> SmPC of [2] of EMA

There are no data on concomitant use of hypertonic saline with Bronchitol as it was excluded from the Phase 3 studies.

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

Caution should be exercised when prescribing Bronchitol to pregnant women. As a precautionary measure, it is preferable to avoid the use of Bronchitol during pregnancy

Mannitol, mivacurium [2] ---> SmPC of [2] of eMC

As all non-depolarising neuromuscular blocking agents, the magnitude and/or duration of non-depolarising neuromuscular block may be increased and infusion requirements may be reduced as a result of interaction with diuretics

Mannitol, muscle relaxants (non-depolarizing) ---> SmPC of [atracurium] 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 diuretics

Mannitol, porfimer [2] ---> SmPC of [2] of EMA

Compounds that quench active oxygen species or scavenge radicals would be expected to decrease PDT activity.

Mannitol, tobramycin [2] ---> SmPC of [2] of EMA

Concomitant use of tobramycin with diuretic compounds is not recommended. Such compounds can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.

Mannitol, verteporfin [2] ---> SmPC of [2] of EMA

Possible quenching of the activated oxygen species generated by verteporfin, resulting in decreased verteporfin activity.

             CONTRAINDICATIONS of Mannitol (Bronchitol)           

             - Hypersensitivity to the active substance

             - Bronchial hyperresponsiveness to inhaled mannitol

             https://www.ema.europa.eu/en/documents/product-information/bronchitol-epar-product-information_en.pdf. 27/06/2022

Other trade names: Manitol Mein, Osmofundina,

Maralixibat (Livmarli)

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

No effects on the breastfed newborn/infant are anticipated since the systemic exposure of the breast-feeding woman to maralixibat is negligible. It is preferable to avoid the use of Livmarli during breastfeeding.

CYP450 inductors, maralixibat [2] ---> SmPC of [2] of EMA

Maralixibat is not known to inhibit or induce other cytochrome P450 in patients; therefore, maralixibat is not predicted to affect the disposition of concomitant medicinal products through those mechanisms.

CYP450 inhibitors, maralixibat [2] ---> SmPC of [2] of EMA

Maralixibat is not known to inhibit or induce other cytochrome P450 in patients; therefore, maralixibat is not predicted to affect the disposition of concomitant medicinal products through those mechanisms.

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

Maralixibat is also an inhibitor of CYP3A4 based on in-vitro studies. An increase of plasma levels of CYP3A4 substrates (e.g., midazolam, simvastatin) can therefore not be excluded and caution is advised when administering such compounds concomitantly.

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

There are no clinical data on the effect of maralixibat on fertility. Animal studies do not indicate any direct or indirect effects on fertility or reproduction

Fluvastatin, maralixibat [2] ---> SmPC of [2] of EMA

Maralixibat is an OATP2B1 inhibitor based on in vitro studies. A decrease in the oral absorption of OATP2B1 substrates (e.g. fluvastatin or rosuvastatin) due to OATP2B1 inhibition in the GI tract cannot be ruled out.

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

Maralixibat absorption is relatively higher when administered in the fasted state, but no dose adjustment for food effects is necessary. Maralixibat can be taken before (up to 30 minutes) or with a meal, in the morning.

Maralixibat [1], metabolism ---> SmPC of [1] of EMA

Maralixibat is minimally absorbed, is not significantly metabolised, and is not a substrate of active substance transporters; therefore, other concomitant medicinal products are not known to effect the disposition of maralixibat.

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

Maralixibat is also an inhibitor of CYP3A4 based on in-vitro studies. An increase of plasma levels of CYP3A4 substrates (e.g., midazolam, simvastatin) can therefore not be excluded and caution is advised when administering such compounds concomitantly.

Maralixibat [1], OATP2B1 substrates ---> SmPC of [1] of EMA

Maralixibat is an OATP2B1 inhibitor based on in vitro studies. A decrease in the oral absorption of OATP2B1 substrates (e.g. fluvastatin or rosuvastatin) due to OATP2B1 inhibition in the GI tract cannot be ruled out.

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

No effects on the foetus during pregnancy are anticipated, since systemic exposure to maralixibat is negligible. As a precautionary measure, it is preferable to avoid the use of Livmarli during pregnancy.

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

Maralixibat is an OATP2B1 inhibitor based on in vitro studies. A decrease in the oral absorption of OATP2B1 substrates (e.g. fluvastatin or rosuvastatin) due to OATP2B1 inhibition in the GI tract cannot be ruled out.

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

Maralixibat is also an inhibitor of CYP3A4 based on in-vitro studies. An increase of plasma levels of CYP3A4 substrates (e.g., midazolam, simvastatin) can therefore not be excluded and caution is advised when administering such compounds concomitantly.

Maralixibat [1], ursodeoxycholic acid ---> SmPC of [1] of EMA

Maralixibat, being an inhibitor of bile acid absorption, has not been fully evaluated with regard to the interaction potential with the bile acid Ursodeoxycholic acid (UDCA).

            CONTRAINDICATIONS of Maralixibat (Livmarli)     

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

            - Patients with PFIC who have severe hepatic and/or renal impairment due to the potential risk of toxicity from the excipient propylene glycol (see section 4.4).  

            https://www.ema.europa.eu/en/documents/product-information/livmarli-epar-product-information_en.pdf 12/09/2025 

Maraviroc (Celsentri)

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

The clinical status of the patient and the adverse reaction profile of maraviroc should be borne in mind when considering the patient's ability to drive, cycle or operate machinery.

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

The CYP3A4 inhibition may increase the AUC of maraviroc. Dose adjustment of maraviroc is recommended

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

Maraviroc is a substrate of CYP3A and its plasma concentration increases when coadministered with potent CYP3A inhibitors. The mechanism of interaction is CYP3A4 inhibition by atazanavir and cobicistat.

Atazanavir/ritonavir, maraviroc [2] ---> SmPC of [2] of EMA

The CYP3A4 inhibition may increase the AUC of maraviroc. Dose adjustment of maraviroc is recommended

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

Boceprevir concentrations are not likely to be affected by maraviroc co-administration

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

A risk to the newborn/infants cannot be excluded. It is recommended that women living with HIV do not breast-feed their infants in order to avoid transmission of HIV.

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

CELSENTRI 300 mg twice daily and buprenorphine can be co-administered without dose adjustment.

Cabozantinib [1], maraviroc ---> SmPC of [1] of EMA

Cabozantinib may have the potential to increase plasma concentrations of co-administered substrates of P-gp. Subjects should be cautioned regarding taking a P-gp substrate while receiving cabozantinib.

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

Not studied, but these are potent CYP3A4 inducers and would be expected to decrease maraviroc concentrations.

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

The strong CYP3A4 inhibition by clarithromycin may increase the plasma concentrations of maraviroc. Dose adjustment of maraviroc is recommended

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

The strong CYP3A4 inhibition by cobicistat may increase the plasma concentrations of maraviroc. Dose adjustment of maraviroc is recommended

Cotrimoxazole, maraviroc [2] ---> SmPC of [2] of EMA

Additionally, co-administration of maraviroc with tenofovir (substrate for renal elimination) and cotrimoxazole (contains trimethoprim, a renal cation transport inhibitor), showed no effect on the pharmacokinetics of maraviroc.

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

It may not be excluded that maraviroc can increase the exposure to the P-glycoprotein substrate dabigatran etexilate.

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

No dose adjustment is required

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

Darunavir/cobicistat (CYP3A inhibition) is expected to increase maraviroc plasma concentrations.

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

Darunavir, ritonavir concentrations were consistent with historical data. The maraviroc dose should be 150 mg twice daily when co-administered with darunavir with low dose ritonavir.

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

CELSENTRI 300 mg twice daily and digoxin can be co-administered without dose adjustment.

Doravirine [1], maraviroc ---> SmPC of [1] of EMA

No dose adjustment is required.

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

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

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

Efavirenz may decrease the plasma concentrations of maraviroc. Maraviroc dose should be increased to 600 mg twice daily when co-administered with efavirenz in the absence of a potent CYP3A4 inhibitor.

Efavirenz/atazanavir/ritonavir, maraviroc

Increased AUC y Cmax of maraviroc

Efavirenz/darunavir/ritonavir, maraviroc

Increased AUC y Cmax of maraviroc

Efavirenz/lopinavir/ritonavir, maraviroc

Increased AUC y Cmax of maraviroc

Efavirenz/rifampicin, maraviroc

There may be a risk of suboptimal levels with risk of loss of virologic response and resistance development. The combination is not recommended.

Efavirenz/saquinavir/ritonavir, maraviroc

Increased AUC y Cmax of maraviroc

Elvitegravir, maraviroc [2] ---> SmPC of [2] of EMA

Elvitegravir per se is not expected to affect maraviroc exposure to a clinically relevant degree. Elvitegravir as a single agent is indicated only in combination with certain ritonavir boosted PIs.

Elvitegravir/ritonavir, maraviroc [2] ---> SmPC of [2] of EMA

Elvitegravir per se is not expected to affect maraviroc exposure to a clinically relevant degree and the observed effect is attributed to ritonavir.

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

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

Emtricitabine/tenofovir alafenamide [1], maraviroc ---> SmPC of [1] of EMA

Tenofovir alafenamide exposure is not expected to be affected by maraviroc, nevirapine or raltegravir, nor is it expected to affect the metabolic and excretion pathways relevant to maraviroc, nevirapine or raltegravir.

Ethinyl estradiol, maraviroc [2] ---> SmPC of [2] of EMA

Maraviroc had no clinically relevant effect on the pharmacokinetics of midazolam, the oral contraceptives ethinylestradiol and levonorgestrel, or urinary 6?-hydroxycortisol/cortisol ratio, suggesting no inhibition or induction of CYP3A4 in vivo.

Etravirina/atazanavir/ritonavir, maraviroc

Increased AUC y Cmax of maraviroc

Etravirina/darunavir/ritonavir, maraviroc

Increased AUC y Cmax of maraviroc

Etravirina/lopinavir/ritonavir, maraviroc

Increased AUC y Cmax of maraviroc

Etravirina/saquinavir/ritonavir, maraviroc

Increased AUC y Cmax of maraviroc

Etravirine [1], maraviroc/darunavir/ritonavir ---> SmPC of [1] of EMA

The recommended dose for maraviroc when combined with INTELENCE and a PI is 150 mg twice daily, except for fosamprenavir/ritonavir which is not recommended with maraviroc. No dose adjustment for INTELENCE is necessary.

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

Etravirine may decrease the plasma concentrations of maraviroc. Etravirine is only approved for use with boosted protease inhibitors.

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

There is no data on the effects of maraviroc on human fertility. In rats, there were no adverse effects on male or female fertility (see section 5.3).

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

Fluconazole is considered to be a moderate CYP3A4 inhibitor. Population PK studies suggest that a dose adjustment of maraviroc is not required

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

Concomitant use is not recommended. Significant reductions in amprenavir Cmin observed may result in virological failure in patients.

Fostemsavir [1], maraviroc ---> SmPC of [1] of EMA

No dose adjustment of either medicinal product is necessary.

Ganciclovir, maraviroc ---> SmPC of [valganciclovir] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

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

Indinavir is a potent CYP3A4 inhibitor. Population PK analysis in phase 3 studies suggests dose reduction of maraviroc when co-administered with indinavir gives appropriate maraviroc exposure.

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

Itraconazole is a potent CYP3A4 inhibitor and would be expected to increase the exposure of maraviroc.

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

Maraviroc dose should be decreased when co-administered with ketoconazole.

Lamivudine, maraviroc [2] ---> SmPC of [2] of EMA

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

Lamivudine/zidovudine, maraviroc [2] ---> SmPC of [2] of EMA

In addition, co-administration of maraviroc with lamivudine/zidovudine showed no effect of maraviroc on lamivudine (primarily renally cleared) or zidovudine (non-P450 metabolism and renal clearance) pharmacokinetics.

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

Maraviroc had no clinically relevant effect on the pharmacokinetics of midazolam, the oral contraceptives ethinylestradiol and levonorgestrel, or urinary 6?-hydroxycortisol/cortisol ratio, suggesting no inhibition or induction of CYP3A4 in vivo.

Lomitapide [1], maraviroc ---> SmPC of [1] of EMA

Coadministration of Lojuxta with P gp may increase the absorption of P gp substrates. Dose reduction of the P gp substrate should be considered when used concomitantly with Lojuxta.

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

Due to CYP3A inhibition by lopinavir/ritonavir. The dose of maraviroc should be decreased to 150 mg twice daily during co-administration with Kaletra 400/100 mg twice daily.

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

Maraviroc and methadone can be co-administered without dose adjustments

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

Maraviroc had no clinically relevant effect on the pharmacokinetics of midazolam, the oral contraceptives ethinylestradiol and levonorgestrel, or urinary 6?-hydroxycortisol/cortisol ratio, suggesting no inhibition or induction of CYP3A4 in vivo.

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

Nelfinavir is a potent CYP3A4 inhibitor and would be expected to increase maraviroc concentrations.

Maraviroc [1], nucleoside and nucleotide reverse transcriptase inhibitors ---> SmPC of [1] of EMA

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

Maraviroc [1], pegylated interferon ---> SmPC of [1] of EMA

CELSENTRI 300 mg twice daily and pegylated interferon can be co-administered without dose adjustment.

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

Not studied, but these are potent CYP3A4 inducers and would be expected to decrease maraviroc concentrations.

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

Not studied, but these are potent CYP3A4 inducers and would be expected to decrease maraviroc concentrations.

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

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

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

CELSENTRI 300 mg twice daily and ribavirin can be co-administered without dose adjustment.

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

When combining rifabutin with protease inhibitors that are potent inhibitors of CYP3A4 a net inhibitory effect on maraviroc is expected.

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

Maraviroc is a substrate of cytochrome P450 CYP3A4. Co-administration of maraviroc with medicinal products that induce CYP3A4 may decrease maraviroc concentrations and reduce its therapeutic effects.

Maraviroc [1], rifampicin/efavirenz ---> SmPC of [1] of EMA

There may be a risk of suboptimal levels with risk of loss of virologic response and resistance development. The combination is not recommended.

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

Co-administration of maraviroc with St. John's Wort is expected to substantially decrease maraviroc concentrations and may result in suboptimal levels and lead to loss of virologic response and possible resistance to maraviroc.

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

Maraviroc and statins can be co-administered without dose adjustments

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

Maraviroc is a substrate of cytochrome P450 CYP3A4. Co-administration of maraviroc with medicinal products that induce CYP3A4 may decrease maraviroc concentrations and reduce its therapeutic effects.

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

Maraviroc is a substrate of cytochrome P450 CYP3A4. Co-administration of maraviroc with medicinal products that inhibit CYP3A4 may increase maraviroc plasma concentrations. Dose adjustment of maraviroc is recommended

Maraviroc [1], sulfamethoxazol/trimethoprim ---> SmPC of [1] of EMA

CELSENTRI 300 mg twice daily and sulphamethoxazole/ trimethoprim can be co-administered without dose adjustment.

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

Telaprevir concentrations are not likely to be affected by maraviroc co-administration

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

The strong CYP3A4 inhibition by telithromycin may increase the plasma concentrations of maraviroc. Dose adjustment of maraviroc is recommended

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

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

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

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

Maraviroc, moderate CYP3A4 inhibitors

The moderate CYP3A4 inhibition may increase the plasma concentrations of maraviroc. Caution is recommended

Maraviroc, nevirapine [2] ---> SmPC of [2] of EMA

Maraviroc and nevirapine can be co-administered without dose adjustments

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

Ritonavir increases the serum levels of maraviroc as a result of CYP3A inhibition. Maraviroc may be given with ritonavir to increase the maraviroc exposure. For further information, refer to the Summary of Product Characteristics for maraviroc.

Maraviroc, P-glycoprotein substrates

Maraviroc, P-glycoprotein inhibitor, may affect the bioavailibility of the P-glycoprotein substrates

Maraviroc, raltegravir [2] ---> SmPC of [2] of EMA

No clinically significant interaction seen. No dosage adjustment necessary.

Maraviroc, reverse transcriptase inhibitors

No significant interaction expected. NRTIs can be co-administered with maraviroc without dose adjustment.

Maraviroc, rilpivirine [2] ---> SmPC of [2] of EMA

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

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

Ritonavir increases the serum levels of maraviroc as a result of CYP3A inhibition. Maraviroc may be given with ritonavir to increase the maraviroc exposure.

Maraviroc, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

No dose adjustment of saquinavir/ritonavir is required. Dose of maraviroc should be decreased to 150 mg bid with monitoring.

Maraviroc, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug drug-interaction is expected. No dose adjustment is required for either drug when OLYSIO is co-administered with maraviroc.

Maraviroc, tecovirimat [2] ---> SmPC of [2] of EMA

A risk for decreases in maraviroc plasma concentrations cannot be excluded (CYP3A4 substrate). The combination of tecovirimat and maraviroc should be used with caution.

Maraviroc, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or maraviroc is required.

Maraviroc, valganciclovir [2] ---> SmPC of [2] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Maraviroc, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Maraviroc, voriconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of maraviroc. Dose adjustment of maraviroc is recommended

             CONTRAINDICATIONS of Maraviroc (Celsentri)                         

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

             https://www.ema.europa.eu/en/documents/product-information/celsentri-epar-product-information_en.pdf 02/10/2024      

Maribavir (Livtencity)

Abacavir, maribavir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Aluminium and magnesium hydroxide oral suspension, maribavir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

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

No dose adjustment is required.

Atazanavir-boosted protease inhibitors, maribavir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

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

No dose adjustment is required.

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

Co-administration of maribavir with sensitive BCRP substrates such as rosuvastatin, is expected to increase their exposure and lead to undesirable effects.

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

Maribavir inhibited BCRP transporter in vitro at clinically relevant concentrations. Therefore, co-administration of maribavir with sensitive BCRP substrates such as rosuvastatin, is expected to increase their exposure and lead to undesirable effects.

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

A risk to the suckling child cannot be excluded. Breast-feeding should be discontinued during treatment with LIVTENCITY.

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

If co-administration of LIVTENCITY with other strong or moderate CYP3A inducers (e,g., carbamazepine, efavirenz, phenobarbital and phenytoin) cannot be avoided, the LIVTENCITY dose should be increased to 1 200 mg twice daily

Cilastatin, maribavir [2] ---> SmPC of [2] of EMA

In vitro, maribavir inhibits OAT3, therefore, plasma concentrations of medicinal products transported by OAT3 may be increased (e.g.: ciprofloxacin, imipenem, and cilastin).

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

In vitro, maribavir inhibits OAT3, therefore, plasma concentrations of medicinal products transported by OAT3 may be increased (e.g.: ciprofloxacin, imipenem, and cilastin).

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

No dose adjustment is required.

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

Frequently monitor cyclosporine, everolimus and sirolimus levels, especially following initiation and after discontinuation of maribavir and adjust dose, as needed.

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

The concomitant administration of maribavir and medicinal products that are sensitive substrates of CYP1A2 with a narrow therapeutic window (e.g., tizanidine and theophylline) should be avoided due to the risk for lack of efficacy of CYP1A2 substrates.

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

Maribavir is primarily metabolised by CYP3A. Co-administration of maribavir and medicinal products that are inhibitors of CYP3A may result in increased plasma concentrations of maribavir. No dose adjustment is needed

CYP3A4 substrates with narrow therapeutic index, maribavir [2] ---> SmPC of [2] of EMA

LIVTENCITY has the potential to increase the concentrations of immunosuppressants that are cytochrome P450 (CYP)3A/P-gp substrates with narrow therapeutic margins (including tacrolimus, cyclosporine, sirolimus and everolimus).

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

Caution should be exercised when maribavir and sensitive P-gp substrates (e.g., digoxin, dabigatran) are co-administered. Serum digoxin concentrations should be monitored, and dose of digoxin may need to be reduced, as needed

Darunavir-boosted protease inhibitors, maribavir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Dextromethorphan, maribavir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

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

Caution should be exercised when maribavir and sensitive P-gp substrates (e.g., digoxin, dabigatran) are co-administered. Serum digoxin concentrations should be monitored, and dose of digoxin may need to be reduced, as needed

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

No dose adjustment is required.

Dolutegravir, maribavir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

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

If co-administration of LIVTENCITY with other strong or moderate CYP3A inducers (e,g., carbamazepine, efavirenz, phenobarbital and phenytoin) cannot be avoided, the LIVTENCITY dose should be increased to 1 200 mg twice daily

Emtricitabine, maribavir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

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

A dose adjustment of maribavir to 1 200 mg twice daily is recommended when co-administration with these a non-nucleoside reverse transcriptase inhibitors.

Everolimus, maribavir [2] ---> SmPC of [2] of EMA

Frequently monitor cyclosporine, everolimus and sirolimus levels, especially following initiation and after discontinuation of maribavir and adjust dose, as needed.

Famotidine, maribavir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

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

There were no effects on reproductive organs in either males or females in nonclinical studies in rats and monkeys (see section 5.3).

Fluvastatin, maribavir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Ganciclovir, maribavir [2] ---> SmPC of [2] of EMA

Coadministration is contraindicated. LIVTENCITY may antagonise the antiviral effect of ganciclovir and valganciclovir by inhibiting human CMV UL97 serine/threonine kinase, which is required for activation/phosphorylation of ganciclovir and valganciclovir

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

No dose adjustment is required.

Lamivudine, maribavir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Lopinavir-boosted protease inhibitors, maribavir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Maribavir [1], MATE1 inhibitors ---> SmPC of [1] of EMA

In vitro, maribavir inhibits MATE1. There are no clinical data available whether the co-administration of maribavir with sensitive MATE1 substrates (e.g., metformin) could potentially lead to clinically relevant interactions.

Maribavir [1], metformin ---> SmPC of [1] of EMA

In vitro, maribavir inhibits MATE1. There are no clinical data available whether the co-administration of maribavir with sensitive MATE1 substrates (e.g., metformin) could potentially lead to clinically relevant interactions.

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

No dose adjustment is required.

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

If co-administration of LIVTENCITY with other strong or moderate CYP3A inducers (e,g., carbamazepine, efavirenz, phenobarbital and phenytoin) cannot be avoided, the LIVTENCITY dose should be increased to 1 200 mg twice daily

Maribavir [1], nevirapine ---> SmPC of [1] of EMA

A dose adjustment of maribavir to 1 200 mg twice daily is recommended when co-administration with these a non-nucleoside reverse transcriptase inhibitors.

Maribavir [1], OAT3 substrates ---> SmPC of [1] of EMA

In vitro, maribavir inhibits OAT3, therefore, plasma concentrations of medicinal products transported by OAT3 may be increased (e.g.: ciprofloxacin, imipenem, and cilastin).

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

No dose adjustment is required.

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

No dose adjustment is required. Maribavir is not expected to affect the plasma concentrations of systemically acting oral contraceptive steroids

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

Caution should be exercised when maribavir and sensitive P-gp substrates (e.g., digoxin, dabigatran) are co-administered. Serum digoxin concentrations should be monitored, and dose of digoxin may need to be reduced, as needed

Maribavir [1], pantoprazole ---> SmPC of [1] of EMA

No dose adjustment is required.

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

If co-administration of LIVTENCITY with other strong or moderate CYP3A inducers (e,g., carbamazepine, efavirenz, phenobarbital and phenytoin) cannot be avoided, the LIVTENCITY dose should be increased to 1 200 mg twice daily

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

If co-administration of LIVTENCITY with other strong or moderate CYP3A inducers (e,g., carbamazepine, efavirenz, phenobarbital and phenytoin) cannot be avoided, the LIVTENCITY dose should be increased to 1 200 mg twice daily

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

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

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

Co-administration of LIVTENCITY with the strong cytochrome P450 3A (CYP3A) inducers rifampicin, rifabutin or St. John's wort is not recommended due to potential for a decrease in efficacy of maribavir.

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

Co-administration of LIVTENCITY with the strong cytochrome P450 3A (CYP3A) inducers rifampicin, rifabutin or St. John's wort is not recommended due to potential for a decrease in efficacy of maribavir.

Maribavir [1], ritonavir-boosted protease inhibitors ---> SmPC of [1] of EMA

No dose adjustment is required.

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

The patient should be closely monitored for rosuvastatin-related events, especially the occurrence of myopathy and rhabdomyolysis.

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

No dose adjustment is required.

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

Frequently monitor cyclosporine, everolimus and sirolimus levels, especially following initiation and after discontinuation of maribavir and adjust dose, as needed.

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

Co-administration of LIVTENCITY with the strong cytochrome P450 3A (CYP3A) inducers rifampicin, rifabutin or St. John's wort is not recommended due to potential for a decrease in efficacy of maribavir.

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

Co-administration of LIVTENCITY with the strong cytochrome P450 3A (CYP3A) inducers rifampicin, rifabutin or St. John's wort is not recommended due to potential for a decrease in efficacy of maribavir.

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

Frequently monitor tacrolimus levels, especially following initiation and after discontinuation of maribavir and adjust dose, as needed.

Maribavir [1], tenofovir alafenamide ---> SmPC of [1] of EMA

No dose adjustment is required.

Maribavir [1], tenofovir disoproxil ---> SmPC of [1] of EMA

No dose adjustment is required.

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

The concomitant administration of maribavir and medicinal products that are sensitive substrates of CYP1A2 with a narrow therapeutic window (e.g., tizanidine and theophylline) should be avoided due to the risk for lack of efficacy of CYP1A2 substrates.

Maribavir [1], tizanidine ---> SmPC of [1] of EMA

The concomitant administration of maribavir and medicinal products that are sensitive substrates of CYP1A2 with a narrow therapeutic window (e.g., tizanidine and theophylline) should be avoided due to the risk for lack of efficacy of CYP1A2 substrates.

Maribavir [1], valganciclovir ---> SmPC of [1] of EMA

Coadministration is contraindicated. LIVTENCITY may antagonise the antiviral effect of ganciclovir and valganciclovir by inhibiting human CMV UL97 serine/threonine kinase, which is required for activation/phosphorylation of ganciclovir and valganciclovir

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

No dose adjustment is required.

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

No dose adjustment is required.

            CONTRAINDICATIONS of Maribavir (Livtencity)     

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

            - Co-administration with ganciclovir or valganciclovir (see section 4.5).  

            https://www.ema.europa.eu/en/documents/product-information/livtencity-epar-product-information_en.pdf 05/02/2024             

Marstacimab (Hympavzi)

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

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

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

Indirect effect of a biologic such as marstacimab on the expression of cytochrome P450 enzymes is also not expected.

Elimination, marstacimab [2] ---> SmPC of [2] of EMA

Thus an impact on its clearance via an interaction with concomitant medicinal products cleared via non-catabolic pathways is unlikely.

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

Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3). No fertility data are available in humans. Thus, the effect of marstacimab on male and female fertility is unknown.

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

Hympavzi should be used during pregnancy only if the potential benefit for the mother outweighs the risk to the foetus taking into account that, during pregnancy and after parturition, the risk for thrombosis is increased and that several

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

Women of childbearing potential receiving Hympavzi should use effective contraception during, and for at least 1 month after cessation of Hympavzi treatment.

            CONTRAINDICATIONS of Marstacimab (Hympavzi)         

            - 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/hympavzi-epar-product-information_en.pdf 25/11/2025 

Mebeverine

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

Mebeverine should not be used during breast-feeding.

Foods, mebeverine

Take mebeverine approximately 20 minutes before meals.

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

Mebeverine is not recommended during pregnancy.

           CONTRAINDICATIONS of Mebeverine

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

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

Mecasermin (Increlex)

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

INCRELEX may have a major influence on the ability to drive or use machines in case of a hypoglycaemic episode. Hypoglycaemia is a very common adverse reaction.

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

Breast-feeding while taking INCRELEX is not recommended, because there is insufficient information on the excretion of mecasermin in human milk.

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

Mecasermin has no effects on fertility in rats using intravenous doses 0.25, 1, and 4 mg/day (up to 4 times the clinical exposure with the MRHD based on AUC).

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

INCRELEX should be administered by subcutaneous injection shortly before or after a meal or snack.

Hypoglycemic drugs, mecasermin [2] ---> SmPC of [2] of EMA

Doses of insulin and/or other hypoglycaemic medicinal products may need to be reduced (see section 4.4).

Insulin, mecasermin [2] ---> SmPC of [2] of EMA

Doses of insulin and/or other hypoglycaemic medicinal products may need to be reduced (see section 4.4).

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

This medicinal product should not be used during pregnancy unless clearly necessary.

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

A negative pregnancy test is recommended for all women of child bearing potential prior to treatment with mecasermin. It is also recommended that all women of childbearing potential use adequate contraception during treatment.

             CONTRAINDICATIONS of Mecasermin (Increlex)                      

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

             - INCRELEX is contraindicated in children and adolescents with active or suspected neoplasia, or any condition or medical history which increases the risk of benign or malignant neoplasia.      

             - Therapy should be discontinued if evidence of neoplasia develops.    

             - As INCRELEX contains benzyl alcohol, it must not be given to premature babies or neonates.             

             https://www.ema.europa.eu/en/documents/product-information/increlex-epar-product-information_en.pdf 18/09/2025 

Medroxyprogesterone

Alprazolam, medroxyprogesterone

The co-administration increases the alprazolam plasma levels and therefore the toxicity risk (central nervous system depression and hypotension)

Aminoglutethimide, medroxyprogesterone [2] ---> SmPC of [2] of eMC

Aminoglutethimide has been reported to decrease plasma levels of some progestogens.

Anticoagulants, gestagens

It is possible a decrease in anticoagulant efficacy due to progestagens may affect the clotting factors

Anticoagulants, medroxyprogesterone

It is possible a decrease in anticoagulant efficacy due to progestagens may affect the clotting factors

Barbiturates, medroxyprogesterone ---> SmPC of [estradiol] of eMC

The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes.

Bosentan, medroxyprogesterone

The co-administration decreases the plasma levels of medroxyprogesterone

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

Medroxyprogesterone acetate and/or its metabolites are secreted in breast milk. Therefore, the use of medroxyprogesterone whilst breast-feeding is not recommended.

Carbamazepine, medroxyprogesterone ---> SmPC of [estradiol] of eMC

The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes.

Coagulation factor IX, medroxyprogesterone

The coagulation factor IX levels may increase and therefore it is possible a loss of anticoagulant efficacy

Coagulation factor VII, medroxyprogesterone

The coagulation factor VII levels may increase and therefore it is possible a loss of anticoagulant efficacy

Coagulation factor VIII, medroxyprogesterone

The coagulation factor VIII levels may increase and therefore it is possible a loss of anticoagulant efficacy

Coagulation factor VIII/von Willebrand factor, medroxyprogesterone

The coagulation factor VIII levels may increase and therefore it is possible a loss of anticoagulant efficacy

Coagulation factor X, medroxyprogesterone

The coagulation factor X levels may increase and therefore it is possible a loss of anticoagulant efficacy

Cyclosporine, medroxyprogesterone

Concurrent administration of ciclosporin and medroxyprogesterone has been reported to lead to increased plasma ciclosporin levels and/or decreased plasma medroxyprogesterone levels.

Efavirenz, medroxyprogesterone ---> SmPC of [estradiol] of eMC

The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes.

Enzyme inductors, medroxyprogesterone ---> SmPC of [estradiol] of eMC

The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes.

Hypoglycemic drugs, medroxyprogesterone

Decreased glucose tolerance and may be necessary to adjust the dosage of hypoglycaemic agent

Medicines with cardiotoxic effects, medroxyprogesterone

The co-administration of medroxyprogesterone (fluid retention) with cardiotoxic substances may cause complications due to cardiac volume load

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

Medroxyprogesterone acetate is contraindicated in women who are pregnant.

Medroxyprogesterone [1], rifampicin ---> SmPC of [1] of eMC

The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes.

Medroxyprogesterone [1], vasodilators ---> SmPC of [1] of eMC

Special care should be taken when progestogens are administered with other drugs which also cause fluid retention, such as NSAIDs and vasodilators.

Medroxyprogesterone, meprobamate ---> SmPC of [estradiol] of eMC

The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes.

Medroxyprogesterone, nelfinavir ---> SmPC of [estradiol/norethisterone] of eMC

Nelfinavir, although known as strong inhibitor, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Medroxyprogesterone, nevirapine [2] ---> SmPC of [2] of EMA

Medroxyprogesterone and nevirapine can be co-administered without dose adjustments

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

Special care should be taken when progestogens are administered with other drugs which also cause fluid retention, such as NSAIDs and vasodilators.

Medroxyprogesterone, oral antidiabetics

Decreased glucose tolerance and may be necessary to adjust the dosage of hypoglycaemic agent

Medroxyprogesterone, phenobarbital ---> SmPC of [estradiol] of eMC

The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes.

Medroxyprogesterone, phenylbutazone ---> SmPC of [estradiol] of eMC

The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes.

Medroxyprogesterone, phenytoin ---> SmPC of [estradiol] of eMC

The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes.

Medroxyprogesterone, rifabutin ---> SmPC of [estradiol] of eMC

The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes.

Medroxyprogesterone, ritonavir ---> SmPC of [estradiol/norethisterone] of eMC

Ritonavir, although known as strong inhibitor, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Medroxyprogesterone, St. John's wort ---> SmPC of [estradiol] of eMC

Herbal preparations containing Hypericum perforatum may induce the metabolism of estrogens and progestagens. Clinically, an increased metabolism of estrogens and progestagens may lead to decreased effects and changes in the uterine bleeding profile.

Medroxyprogesterone, succinylcholine

The co-administration may cause a prolongation of neuromuscular block

Medroxyprogesterone, suxamethonium

The co-administration may cause a prolongation of neuromuscular block

           CONTRAINDICATIONS of Medroxyprogesterone

           Medroxyprogesterone acetate is contraindicated in the following conditions:

           - thrombophlebitis, thrombo-embolic disorders, and where there is a high risk of developing such manifestations [presence or history of atrial fibrillation, valvular disorders, endocarditis, heart failure, pulmonary embolism; thromboembolic ischaemic attack (TIA), cerebral infarction; atherosclerosis; immediate post surgery period]

           - hypercalcaemia in patients with osseous metastases

           - known sensitivity to medroxyprogesterone acetate or any component of the drug.

           - impaired liver function or active liver disease.

           - missed abortion, metrorrhagia, known or suspected pregnancy.

           - undiagnosed vaginal bleeding.

           - previous idiopathic or current venous thromboembolism (deep vein thrombosis, pulmonary embolism).

           - active or recent arterial thromboembolic disease (e.g., angina, myocardial infarction).

           - suspected or early breast carcinoma

           Progestogens are known to be porphyrogenic. Patients with a history of attacks or aged under 30 are at greatest risk of an acute attack while on progesterone treatment. A careful assessment of potential benefit should be made where this risk is present.

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

Megestrol

Aminoglutethimide, megestrol

The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes.

Barbexaclone, megestrol

Accelerated metabolism of barbexaclone

Barbiturates, megestrol

Accelerated metabolism of barbiturates

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

Megestrol is not recommended for women who are breast feeding. Because of the potential for adverse effects, nursing should be discontinued during treatment

Broad-spectrum antibiotics, megestrol

Decreased effect of gestagen (the antibiotic agent affects the gut flora)

Carbamazepine, megestrol

Accelerated metabolism of carbamazepine

Dofetilide [1], megestrol ---> SmPC of [1] of EMA

Drugs that inhibit the renal cation transport system are contraindicated with dofetilide

Enzyme inductors, megestrol

The enzymatic induction may accelerate the metabolism of steroid hormones and decrease their plasma levels and effect.

Insulin, megestrol

Change of tolerance to glucose and possible decrease of antidiabetic effect

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

Megestrol is not recommended for women who are pregnant

Megestrol, oral antidiabetics

Change of tolerance to glucose and possible decrease of antidiabetic effect

Megestrol, phenytoin

Accelerated metabolism of phenytoin

Megestrol, primidone

Accelerated metabolism of primidone

Megestrol, rifampicin

Accelerated metabolism of rifampicin

Megestrol, tetracyclines

Decreased effect of gestagen (the antibiotic agent affects the gut flora)

           CONTRAINDICATIONS of Megestrol

           - Megace is contra-indicated in patients who have demonstrated hypersensitivity to any of the components of the formulation.

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

Melatonin (Circadin)

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

Circadin may cause drowsiness, therefore the product should be used with caution if the effects of drowsiness are likely to be associated with a risk to safety.

Adrenergic agonists, melatonin [2] ---> SmPC of [2] of EMA

Whether or not these active substances interfere with the dynamic or kinetic effects of Circadin or vice versa has not been studied.

Adrenoceptor antagonists, melatonin [2] ---> SmPC of [2] of EMA

Whether or not these active substances interfere with the dynamic or kinetic effects of Circadin or vice versa has not been studied.

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

Alcohol should not be taken with melatonin, because it reduces the effectiveness of melatonin on sleep

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

Whether or not these active substances interfere with the dynamic or kinetic effects of Circadin or vice versa has not been studied.

Benzodiazepine analogues, melatonin [2] ---> SmPC of [2] of EMA

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

Benzodiazepines, melatonin [2] ---> SmPC of [2] of EMA

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

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

Breast-feeding is not recommended in women under treatment with melatonin.

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

CYP1A2 inducers such as carbamazepine and rifampicin may give rise to reduced plasma concentrations of melatonin.

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

Caution should be exercised in patients on cimetidine a CYP2D inhibitor, which increases plasma melatonin levels, by inhibiting its metabolism.

CYP1A1 inhibitors, melatonin

The CYP1A1 inhibition may increase plasma concentrations of melatonin

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

CYP1A2 inducers such as carbamazepine and rifampicin may give rise to reduced plasma concentrations of melatonin.

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

CYP1A2 inhibitors such as quinolones may give rise to increased melatonin exposure.

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

Melatonin has been observed to induce CYP3A in vitro at supra-therapeutic concentrations. If induction occurs, this can give rise to reduced plasma concentrations of concomitantly administered medicinal products.

Estrogens, melatonin [2] ---> SmPC of [2] of EMA

Caution should be exercised in patients on oestrogens (e.g. contraceptive or hormone replacement therapy), which increase melatonin levels by inhibiting its metabolism by CYP1A1 and CYP1A2.

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

Caution should be exercised in patients on fluvoxamine, which increases melatonin levels by inhibiting its metabolism by hepatic cytochrome P450 (CYP) isozymes CYP1A2 and CYP2C19. The combination should be avoided.

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

The presence of food delayed the absorption of the melatonin resulting in a later and lower peak plasma concentration in the fed state

Imipramine, melatonin [2] ---> SmPC of [2] of EMA

Melatonin co-administration resulted in increased feelings of tranquility and difficulty in performing tasks compared to imipramine alone

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

Caution should be exercised in patients on 5- or 8-methoxypsoralen (5 and 8-MOP), which increases melatonin levels by inhibiting its metabolism.

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

Cigarette smoking may decrease melatonin levels due to induction of CYP1A2.

Melatonin [1], opiate agonists ---> SmPC of [1] of EMA

Whether or not these active substances interfere with the dynamic or kinetic effects of Circadin or vice versa has not been studied.

Melatonin [1], opiate antagonists ---> SmPC of [1] of EMA

Whether or not these active substances interfere with the dynamic or kinetic effects of Circadin or vice versa has not been studied.

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

In view of the lack of clinical data, use in pregnant women and by women intending to become pregnant is not recommended.

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

CYP1A2 inhibitors such as quinolones may give rise to increased melatonin exposure.

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

CYP1A2 inducers such as carbamazepine and rifampicin may give rise to reduced plasma concentrations of melatonin.

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

CYP1A2 inhibitors such as quinolones may give rise to increased melatonin exposure.

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

Melatonin co-administration resulted in increased feelings of "muzzy-headedness" compared to thioridazine alone.

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

Whether or not these active substances interfere with the dynamic or kinetic effects of Circadin or vice versa has not been studied.

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

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

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

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

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

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

Melatonin, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib may increase the plasma exposure of substances predominantly metabolised by CYP1A2 and dose adjustments may be considered, if clinically indicated.

             CONTRAINDICATIONS of Melatonin (Circadin)  

             - 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/circadin-epar-product-information_en.pdf 07/07/2025 

Other trade names: Slenyto,

Meloxicam

Ability to drive, meloxicam

Dizziness, drowsiness, fatigue and visual disturbances may occur

ACE inhibitors, meloxicam

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

Acetylsalicylic acid, meloxicam

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

AIIRA, meloxicam

The combination of AIIRAs and AIIRAs (selective COX-2 inhibitors, ASA (> 3 g/day) and non-selective NSAIDs) may decrease the antihypertensive effect, increase the renal failure risk and cause hypercaliemia

Antihypertensives, meloxicam

The co-administration may weaken the hypotensive effect

Betablockers, meloxicam

The NSAID can reduce the anti-hypertensive effect of beta-blocker

Breast-feeding, meloxicam

Meloxicam should be avoided by women who breast-feed

Calcineurin inhibitors, meloxicam

Nephrotoxicity of calcineurin inhibitor may be enhanced by meloxicam via renal prostaglandin-mediated effects.

Cholestyramine, meloxicam

Cholestyramine accelerates the elimination of meloxicam by interrupting the enterohepatic circulation

Corticosteroids, meloxicam

Increased risk of gastrointestinal ulceration or bleeding.

Coxibs, meloxicam

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

Cyclosporine [1], meloxicam ---> SmPC of [1] of eMC

Care should be taken when using ciclosporin together with other active substances that exhibit nephrotoxic synergy

Diuretics, meloxicam

The treatment of diuretic agents with meloxicam is associated with a risk of acute renal failure especially by dehydrated patients

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

Fluconazole has the potential to increase the systemic exposure of NSAIDs that are metabolized by CYP2C9. Frequent monitoring for adverse events and toxicity related to NSAIDs is recommended. Adjustment of dose of NSAIDs may be needed.

Heparin, meloxicam

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system.

Lithium, meloxicam

The inhibition of the renal excretion of lithium may increase plasma concentrations and toxicity of lithium. Co-administration is not recommended

Meloxicam, methotrexate

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

Meloxicam, NSAID

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

Meloxicam, oral anticoagulants

Increased risk of bleeding due to inhibition of the platelet function. The combination of NSAID with oral anticoagulants is not recommended

Meloxicam, platelet aggregation inhibitors

Increased risk of bleeding due to inhibition of the platelet function.

Meloxicam, pregnancy

Strict indication in first and second trimester. Contraindicated in third trimester

Meloxicam, salicylates

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

Meloxicam, SSRI

The co-administration may increase the risk of gastrointestinal haemorrhage

Meloxicam, tacrolimus

Nephrotoxicity of calcineurin inhibitor may be enhanced by meloxicam via renal prostaglandin-mediated effects.

Meloxicam, thrombolytics

Increased risk of bleeding due to inhibition of the platelet function.

NSAID, parecoxib

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

Melphalan (Phelinun)

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

It is likely that certain adverse reactions of melphalan, like nausea and vomiting, could affect this ability. This medicinal product also contains alcohol, which is likely to affect children and adolescents

Bortezomib [1], melphalan/prednisone ---> SmPC of [1] of EMA

A drug-drug interaction study assessing the effect of melphalan-prednisone on the pharmacokinetics of bortezomib (injected intravenously), showed a mean bortezomib AUC increase of 17% based on data from 21 patients. This is not considered clinically relevant

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

It is unknown whether melphalan or its metabolites are excreted in human milk. Due to its mutagenic properties, melphalan is contraindicated during breast-feeding (see section 4.3).

Busulfan, melphalan [2] ---> SmPC of [2] of EMA

In the paediatric population, for the busulfan-melphalan regimen it has been reported that the administration of melphalan less than 24 hours after the last oral busulfan administration may influence the development of toxicities.

Carmustine [1], melphalan ---> SmPC of [1] of EMA

Concomitant use with melphalan leads to increased risk of pulmonary toxicity.

Cimetidine, melphalan

Cimetidine may decrease the bioavailability and plasma half-life of oral melphalan

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

Impaired renal function has been described in bone marrow transplant patients who were pre-conditioned with high-dose intravenous melphalan and subsequently received cyclosporin to prevent graft versus host disease.

Extravasation, melphalan [2] ---> SmPC of [2] of EMA

of extravasation could be observed when PHELINUN is administered via peripheral intravenous route. In case of extravasation, the administration should be interrupted immediately and a central venous line route should be used.

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

Melphalan causes suppression of ovarian function in pre-menopausal women resulting in amenorrhoea in a significant number of patients. It is possible that melphalan may cause temporary or permanent sterility in male patients.

Glucose, melphalan [2] ---> SmPC of [2] of EMA

PHELINUN is not compatible with infusion solutions containing glucose. Only sodium chloride 9 mg/ml (0.9%) solution for injection is recommended to be used.

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

As with all cytotoxic treatments, male and female patients that receive melphalan should use effective reliable contraceptive methods up until six months after cessation of treatment.

Melphalan [1], nalidixic acid ---> SmPC of [1] of EMA

The administration of high-dose intravenous PHELINUN together with nalidixic acid in children has caused haemorrhagic enterocolitis with fatal outcome.

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

HSCT is contraindicated in pregnant women. Therefore melphalan is contraindicated during pregnancy for this indication

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

A risk of general illness which may lead to fatal outcome has described. This risk is increased in patients who are already immunosuppressed by their underlying disease. An inactivated vaccines should be used when such a vaccine exists (poliomyelitis).

Melphalan [1], women ---> SmPC of [1] of EMA

As with all cytotoxic treatments, male and female patients that receive melphalan should use effective reliable contraceptive methods up until six months after cessation of treatment.

Melphalan, thiotepa [2] ---> SmPC of [2] of EMA

The concomitant use of thiotepa and other myelosuppressive or myelotoxic agents may potentiate the risk of haematologic adverse reactions due to overlapping toxicity profiles of these medicinal products.

            CONTRAINDICATIONS of Melphalan (Phelinun)

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

            - Pregnancy (only with respect to the treatment prior to HSCT) and breast-feeding (see section 4.6).

            https://www.ema.europa.eu/en/documents/product-information/phelinun-epar-product-information_en.pdf 15/03/2024

Other trade names: Melfalan Aspen Inyectable

Melphalan flufenamide (Pepaxti)

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

Pepaxti has moderate influence on the ability to drive and use machines. It is possible that certain adverse reactions of melphalan flufenamide, such as dizziness and nausea, may affect this ability.

Blood-platelet count, melphalan flufenamide [2] ---> SmPC of [2] of EMA

Platelet counts should be monitored at baseline, during treatment, and as clinically indicated. Patients should be monitored more frequently during the first two months of treatment.

Breast-feeding, melphalan flufenamide [2] ---> SmPC of [2] of EMA

It is unknown whether melphalan flufenamide or its metabolites are excreted in human milk. Due to its genotoxic properties, melphalan flufenamide is contraindicated during breast-feeding (see section 4.3).

Extravasation, melphalan flufenamide [2] ---> SmPC of [2] of EMA

Melphalan flufenamide can cause local tissue damage. Should extravasation occur, it should not be administered by direct infusion into a peripheral vein (see section 4.2).

Fertility, melphalan flufenamide [2] ---> SmPC of [2] of EMA

Melphalan flufenamide, as other agents with alkylating properties, is expected to suppress ovary function in premenopausal women, resulting in amenorrhea in a large number of patients.

Interactions, melphalan flufenamide [2] ---> SmPC of [2] of EMA

No interaction studies have been performed with melphalan flufenamide. Based on available in vitro and clinical data, there is a low risk of pharmacokinetic or pharmacodynamic drug interactions for melphalan flufenamide (see section 5.2).

Lenalidomide, melphalan flufenamide [2] ---> SmPC of [2] of EMA

Melphalan flufenamide is not indicated in combination with lenalidomide or thalidomide.

Live attenuated vaccines, melphalan flufenamide [2] ---> SmPC of [2] of EMA

A risk of severe illness that may lead to fatal outcome has been described with the metabolite melphalan in patients receiving attenuated live vaccines. An inactivated or mRNA based vaccine should be used when such a vaccine exists.

Melphalan flufenamide [1], men ---> SmPC of [1] of EMA

Studies in animals have shown melphalan flufenamide can have adverse effects on spermatogenesis (see section 5.3). Therefore it is possible that melphalan flufenamide may cause temporary or permanent adverse effects on male fertility.

Melphalan flufenamide [1], pregnancy ---> SmPC of [1] of EMA

Melphalan flufenamide should not be used during pregnancy unless the clinical condition of the woman requires treatment with melphalan flufenamide.

Melphalan flufenamide [1], thalidomide ---> SmPC of [1] of EMA

Melphalan flufenamide is not indicated in combination with lenalidomide or thalidomide.

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

As with all cytotoxic treatments, male and female patients who use melphalan flufenamide should use effective and reliable contraceptive methods until six months after cessation of treatment.

             CONTRAINDICATIONS of Melphalan flufenamide (Pepaxti)

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

             - Breast-feeding (see section 4.6).       

             https://www.ema.europa.eu/en/documents/product-information/pepaxti-epar-product-information_en.pdf 9/03/2024        

Memantin (Memantine Accord)

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

Memantine has minor to moderate influence on the ability to drive and use machines such that outpatients should be warned to take special care.

Acetazolamide, memantin

Possible increased levels of memantine

Alkalisation of urine, memantin [2] ---> SmPC of [2] of EMA

Possible increased levels of memantine. Alkalisation of urine may result from drastic changes in diet, e.g. from a carnivore to a vegetarian diet, or from the massive ingestion of alkalising gastric buffers.

Amantadine, memantin [2] ---> SmPC of [2] of EMA

Concomitant use should be avoided, owing to the risk of pharmacotoxic psychosis

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

The mode of action suggests that the effects of L-dopa, dopaminergic agonists, and anticholinergics may be enhanced by concomitant treatment with NMDA-antagonists such as memantine.

Anticholinergics, N-methyl-D-aspartate antagonists ---> SmPC of [memantin] of EMA

The mode of action suggests that the effects of L-dopa, dopaminergic agonists, and anticholinergics may be enhanced by concomitant treatment with NMDA-antagonists such as memantine.

Antispasmodic agents, memantin [2] ---> SmPC of [2] of EMA

Concomitant administration of memantine with the antispasmodic agents, dantrolene or baclofen, can modify their effects and a dose adjustment may be necessary.

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

Concomitant administration of memantine with the antispasmodic agents, dantrolene or baclofen, can modify their effects and a dose adjustment may be necessary.

Barbiturates, memantin [2] ---> SmPC of [2] of EMA

The effects of barbiturates and neuroleptics may be reduced.

Benperidol, memantin

The effects of antipsychotics may be reduced by concomitant treatment with memantine.

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

Women taking memantine should not breast-feed.

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

Active substances that use the same renal cationic transport system as amantadine may possibly interact with memantine leading to a potential risk of increased plasma levels.

Dantrolene, memantin [2] ---> SmPC of [2] of EMA

Concomitant administration of memantine with the antispasmodic agents, dantrolene or baclofen, can modify their effects and a dose adjustment may be necessary.

Dextromethorphan, memantin [2] ---> SmPC of [2] of EMA

Concomitant use should be avoided, owing to the risk of pharmacotoxic psychosis

Dextromethorphan/quinidine [1], memantin ---> SmPC of [1] of EMA

Dextromethorphan and memantine are antagonists of the N-D-aspartate (NMDA) receptor which could theoretically result in an additive effect at NMDA receptors and potentially an increased incidence of adverse reactions.

Dichlorphenamide, memantin

Possible increased levels of dichlorphenamide

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

The mode of action suggests that the effects of L-dopa, dopaminergic agonists, and anticholinergics may be enhanced by concomitant treatment with NMDA-antagonists such as memantine.

Dopamine agonists, N-methyl-D-aspartate antagonists ---> SmPC of [memantin] of EMA

The mode of action suggests that the effects of L-dopa, dopaminergic agonists, and anticholinergics may be enhanced by concomitant treatment with NMDA-antagonists such as memantine.

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

No adverse effects of memantine were noted on non-clinical male and female fertility studies.

Galantamine, memantin [2] ---> SmPC of [2] of EMA

In a clinical study in young healthy subjects, no relevant effect of memantine on the pharmacokinetics of galantamine was observed.

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

There may be a possibility of reduced serum level of hydrochlorothiazide (HCT) when memantine is co-administered with HCT or any combination with HCT.

Ketamine, memantin [2] ---> SmPC of [2] of EMA

Concomitant use should be avoided, owing to the risk of pharmacotoxic psychosis

Levodopa, memantin [2] ---> SmPC of [2] of EMA

The mode of action suggests that the effects of L-dopa, dopaminergic agonists, and anticholinergics may be enhanced by concomitant treatment with NMDA-antagonists such as memantine.

Levodopa, N-methyl-D-aspartate antagonists ---> SmPC of [memantin] of EMA

The mode of action suggests that the effects of L-dopa, dopaminergic agonists, and anticholinergics may be enhanced by concomitant treatment with NMDA-antagonists such as memantine.

Memantin [1], N-methyl-D-aspartate antagonists ---> SmPC of [1] of EMA

Concomitant use of N-methyl-D-aspartate antagonists should be avoided, owing to the risk of pharmacotoxic psychosis

Memantin [1], neuroleptics ---> SmPC of [1] of EMA

The effects of barbiturates and neuroleptics may be reduced.

Memantin [1], nicotine ---> SmPC of [1] of EMA

Active substances that use the same renal cationic transport system as amantadine may possibly interact with memantine leading to a potential risk of increased plasma levels.

Memantin [1], OCT2 substrates ---> SmPC of [1] of EMA

Active substances that use the same renal cationic transport system as amantadine may possibly interact with memantine leading to a potential risk of increased plasma levels.

Memantin [1], oral anticoagulants ---> SmPC of [1] of EMA

Close monitoring of prothrombin time or INR is advisable for patients concomitantly treated with oral anticoagulants.

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

In single-dose pharmacokinetic (PK) studies in young healthy subjects, no relevant active substance-active substance interaction of memantine with glyburide/metformin or donepezil was observed.

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

There is one published case report on a possible risk also for the combination of memantine and phenytoin.

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

Memantine should not be used during pregnancy unless clearly necessary.

Memantin [1], procainamide ---> SmPC of [1] of EMA

Active substances that use the same renal cationic transport system as amantadine may possibly interact with memantine leading to a potential risk of increased plasma levels.

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

Active substances that use the same renal cationic transport system as amantadine may possibly interact with memantine leading to a potential risk of increased plasma levels.

Memantin [1], quinine ---> SmPC of [1] of EMA

Active substances that use the same renal cationic transport system as amantadine may possibly interact with memantine leading to a potential risk of increased plasma levels.

Memantin [1], ranitidine ---> SmPC of [1] of EMA

Active substances that use the same renal cationic transport system as amantadine may possibly interact with memantine leading to a potential risk of increased plasma levels.

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

Close monitoring of prothrombin time or INR is advisable for patients concomitantly treated with oral anticoagulants.

Memantin, methazolamide

Possible increased levels of memantine

Memantin, perphenazine

Memantine may reduce the effects of perphenazine

Memantin, procyclidine [2] ---> SmPC of [2] of eMC

Drugs with anticholinergic properties may increase the anticholinergic action

Memantin, promazine

The effects of antipsychotic drugs may be reduced by memantine.

             CONTRAINDICATIONS of Memantin (Memantine Accord)       

             - 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/memantine-accord-epar-product-information_en.pdf 09/10/2025 

Other trade names: Axura, Ebixa, Mantinex, Marixino (previously Maruxa), Memabix, Nemdatine, Protalon. Memantina: Actavis, Alter, Apotex, Aristo, Aurobindo, Cinfa, Davur, Gobens, Kern Pharma, Mabo, Macleods, Normon, Pensa, Ranbaxy, Sandoz, Stada, Tarbis, Teva, Zentiva,

Meningococcal group A, C, W-135 and Y conjugate vaccine (Nimenrix)

Ability to drive, meningococcal group A; C; W-135 and Y conjugate vaccine [2] ---> SmPC of [2] of EMA

Some of the effects mentioned under section 4.8 "Undesirable effects" may affect the ability to drive or use machines.

Breast-feeding, meningococcal group A; C; W-135 and Y conjugate vaccine [2] ---> SmPC of [2] of EMA

Nimenrix should only be used during breast-feeding when the possible advantages outweigh the potential risks

Fertility, meningococcal group A; C; W-135 and Y conjugate vaccine [2] ---> SmPC of [2] of EMA

Animal studies do not indicate direct or indirect harmful effects with respect to fertility.

Immunosuppressives, meningococcal group A; C; W-135 and Y conjugate vaccine [2] ---> SmPC of [2] of EMA

It may be expected that in patients receiving immunosuppressive treatment an adequate response may not be elicited

Meningococcal group A, C, W-135 and Y conjugate vaccine [1], vaccine ---> SmPC of [1] of EMA

 inactivated poliovirus or Haemophilus influenzae type b (HBV, IPV or Hib) such as DTaP-HBV-IPV/Hib vaccine, and 13-valent pneumococcal conjugate vaccine.

Meningococcal group A, C, W-135 and Y conjugate vaccine [1], vaccine ---> SmPC of [1] of EMA

In individuals aged 9 to 25 years, Nimenrix can be given concomitantly with human papillomavirus bivalent [Type 16 and 18] vaccine, recombinant (HPV2).

Meningococcal group A, C, W-135 and Y conjugate vaccine [1], vaccine ---> SmPC of [1] of EMA

Whenever possible, Nimenrix and a TT containing vaccine, such as DTaP-HBV-IPV/Hib vaccine, should be co-administered or Nimenrix should be administered at least one month before the TT containing vaccine.

Meningococcal group A; C; W-135 and Y conjugate vaccine [1], pregnancy ---> SmPC of [1] of EMA

Nimenrix should be used during pregnancy only when clearly needed, and the possible advantages outweigh the potential risks for the foetus.

             CONTRAINDICATIONS of Meningococcal group A, C, W-135 and Y conjugate vaccine (Nimenrix)          

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

             https://www.ema.europa.eu/en/documents/product-information/nimenrix-epar-product-information_en.pdf 13/02/2025

Other trade names: Menveo, MenQuadfi,

Meningococcal group B vaccine (Bexsero)

Ability to drive, meningococcal group B vaccine [2] ---> SmPC of [2] of EMA

However, some of the effects mentioned under section 4.8 "Undesirable effects" may temporarily affect the ability to drive or use machines.

Breast-feeding, meningococcal group B vaccine [2] ---> SmPC of [2] of EMA

The benefit-risk ratio must be examined before making the decision to immunize during breast-feeding

Fertility, meningococcal group B vaccine [2] ---> SmPC of [2] of EMA

There are no data on fertility in humans. There were no effects on female fertility in animal studies.

Immune response, meningococcal group B vaccine [2] ---> SmPC of [2] of EMA

Clinical studies demonstrated that the immune responses of the co-administered routine vaccines were unaffected by concomitant administration of Bexsero,

Meningococcal group B vaccine [1], paracetamol ---> SmPC of [1] of EMA

Prophylactic use of paracetamol reduces the incidence and severity of fever without affecting the immunogenicity of either Bexsero or routine vaccines.

Meningococcal group B vaccine [1], pregnancy ---> SmPC of [1] of EMA

Vaccination should not be withheld when there is a clear risk of exposure to meningococcal infection

Meningococcal group B vaccine [1], vaccine antigens ---> SmPC of [1] of EMA

Bexsero can be given concomitantly with any of the following vaccine antigens, either as monovalent or as combination vaccines: diphtheria, tetanus, acellular pertussis, Haemophilus influenzae type b, inactivated poliomyelitis, hepatitis B, heptavalent pneumococcal conjugate, measles, mumps, rubella, varicella, and meningococcal groups A, C, W, Y conjugate.

             CONTRAINDICATIONS of Meningococcal group B vaccine (Bexsero)

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

             https://www.ema.europa.eu/en/documents/product-information/bexsero-epar-product-information_en.pdf 13/05/2024 

Other trade names: Trumenba,

Menotropin

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

Menotropin should not be given to lactating mothers.

Clomiphene, menotropin [2] ---> SmPC of [2] of eMC

Although there is no controlled clinical experience, it is expected that the concomitant use of menotropin and clomiphene citrate may enhance the follicular response.

GnRH agonists, menotropin [2] ---> SmPC of [2] of eMC

When using GnRH agonist for pituitary desensitization, a higher dose of menotropin may be necessary to achieve adequate follicular response.

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

Menotropin should not be given during pregnancy

           CONTRAINDICATIONS of Menotropin

           MEN and WOMEN

           - Tumours of the pituitary or hypothalamic glands

           - Hypersensitivity to the active substance or any of the excipients used in the formulation

           MEN

           - Tumours in the testes

           WOMEN

           - Ovarian, uterine or mammary carcinoma

           - Pregnancy and lactation

           - Gynaecological haemorrhage of unknown aetiology

           - Ovarian cysts or enlarged ovaries not due to polycystic ovarian disease.

           In the following situations treatment outcome is unlikely to be favourable, and therefore MENOPUR should not be administrated:

           - Primary ovarian failure

           - Malformation of sexual organs incompatible with pregnancy

           - Fibroid tumours of the uterus incompatible with pregnancy

           - Structural abnormalities in which a satisfactory outcome cannot be expected, for example, tubal occlusion (unless superovulation is to be induced for IVF), ovarian dysgenesis, absent uterus or premature menopause.

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

Mepivacaine

Ability to drive, mepivacaine

Transient decrease of the ability to react

Alcohol, mepivacaine

Excessive alcohol intake may decrease the sensitivity to local anaesthetics

Antiarrhythmics, mepivacaine

The co-administration of mepivacaine with structurally related compounds (e. g. antiarrhythmics like aprindine, mexiletine) should be done with great care due to the adverse effects in these cases are additive

Antiepileptics, mepivacaine

Long-term or permanent therapy with anticonvulsants may decrease the sensitivity to local anaesthetics

Betablockers, mepivacaine

The co-administration may have an additive inhibitory effect on AV conduction, intraventricular impulse spreading and contraction force

Breast-feeding, mepivacaine

It is recommended that breast feeding is not initiated within 24 hours of treatment

Calcium antagonists, mepivacaine

The co-administration may have an additive inhibitory effect on AV conduction, intraventricular impulse spreading and contraction force

Class III antiarrhythmic agents, mepivacaine

The co-administration of mepivacaine with class III antiarrhythmic agents (e. g. amiodarone) should be done with close observation and ECG monitoring due to cardiac effects can be additives

Local anaesthetics, mepivacaine

The combination of local anaesthetics has additive effects on CNS and cardiovascular system

Mepivacaine, non-depolarizing muscle relaxants

Mepivacaine prolongs the effect of the non-depolarizing muscle relaxant

Mepivacaine, pregnancy

Mepivacaine should be given in early pregnancy only if there is not available other local anaesthetic drugs

Mepivacaine, psychotropic drugs

Long-term or permanent therapy with neuroleptics may decrease the sensitivity to local anaesthetics

Mepivacaine, vasoconstrictors

The co-administration may prolong the effect of mepivacaine

Mepolizumab (Nucala)

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

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

CYP450 enzymes, mepolizumab [2] ---> SmPC of [2] of EMA

Cytochrome P450 enzymes, efflux pumps and protein-binding mechanisms are not involved in the clearance of mepolizumab.

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

There are no fertility data in humans. Animal studies showed no adverse effects of anti-IL5 treatment on fertility (see section 5.3).

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

As a precautionary measure, it is preferable to avoid the use of Nucala during pregnancy. Administration of Nucala to pregnant women should only be considered if the expected benefit to the mother is greater than any possible risk to the fetus.

Mepolizumab [1], systemic pro-inflammatory markers ---> SmPC of [1] of EMA

Elevation of systemic pro-inflammatory markers in severe asthma is minimal and there is no evidence of IL-5 receptor alpha expression on hepatocytes. The potential for drug-drug interactions with mepolizumab is therefore considered low.

             CONTRAINDICATIONS of Mepolizumab (Nucala)

             - 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/nucala-epar-product-information_en.pdf  16/07/2024      

Mequitazine

Ability to drive, mequitazine

Somnolence may occur

Alcohol, antihistamines ---> SmPC of [mequitazine] of eMC 

Antihistamines potentiate the sedative effects of alcohol

Alcohol, mequitazine

The co-administration may enhance the sedative effect. The alcohol intake should be avoided

Aluminium, mequitazine

Aluminium salts may form insoluble complexes with mequitazine, what may decrease the absorption and effect of mequitazine. It is recommended to separate the times of administration by at least 2 hours

Amiodarone, mequitazine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Anticholinergics, mequitazine

The co-administration of mequitazine and other anticholinergic drugs may enhance the anticholinergic effects of mequitazine

Antidiarrheals, mequitazine

Antidiarrhoeals may reduce the absorption of mequitazine

Antiparkinsonian agents, mequitazine

The co-administration of mequitazine and other anticholinergic drugs may enhance the anticholinergic effects of mequitazine

Arsenic, mequitazine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Atropine, mequitazine

The co-administration of mequitazine and other anticholinergic drugs may enhance the anticholinergic effects of mequitazine

Barbiturates, mequitazine

Central nervous system depressants may enhance the sedative effects of mequitazine

Benzodiazepines, mequitazine

Central nervous system depressants may enhance the sedative effects of mequitazine

Bepridil, mequitazine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Breast-feeding, mequitazine

Mequitazine is excreted into breast milk. Women who are taking mequitazine should avoid breast feed

Bupropion, mequitazine

Mequitazine should not be used with CYP2D6 inhibitor drugs. The increased plasma levels of mequitazine may increase the risk of QT interval prolongation

CNS depressants, mequitazine

Central nervous system depressants may enhance the sedative effects of mequitazine

CYP2D6 inhibitors, mequitazine

Mequitazine should not be used with CYP2D6 inhibitor drugs. The increased plasma levels of mequitazine may increase the risk of QT interval prolongation

Cinacalcet, mequitazine

Mequitazine should not be used with CYP2D6 inhibitor drugs. The increased plasma levels of mequitazine may increase the risk of QT interval prolongation

Cisapride, mequitazine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Clonidine, mequitazine

Central nervous system depressants may enhance the sedative effects of mequitazine

Diphemanil, mequitazine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Disopyramide, mequitazine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Dofetilide, mequitazine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Dolasetron, mequitazine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Dronedarone, mequitazine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Duloxetine, mequitazine

Mequitazine should not be used with CYP2D6 inhibitor drugs. The increased plasma levels of mequitazine may increase the risk of QT interval prolongation

Erythromycin, mequitazine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Fluoxetine, mequitazine

Mequitazine should not be used with CYP2D6 inhibitor drugs. The increased plasma levels of mequitazine may increase the risk of QT interval prolongation

Hydroquinidine, mequitazine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Ibutilide, mequitazine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Mequitazine, mizolastine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Mequitazine, moderate CYP2D6 inhibitors

Mequitazine should not be used with CYP2D6 inhibitor drugs. The increased plasma levels of mequitazine may increase the risk of QT interval prolongation

Mequitazine, monoamine oxidase inhibitors

The co-administration of mequitazine mit MAOI and within 2 weeks after MAOI discontinuation is contraindicated

Mequitazine, moxifloxacin

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Mequitazine, neuroleptics

Central nervous system depressants may enhance the sedative effects of mequitazine

Mequitazine, paroxetine

Mequitazine should not be used with CYP2D6 inhibitor drugs. The increased plasma levels of mequitazine may increase the risk of QT interval prolongation

Mequitazine, pregnancy

Mequitazine crosses the placental barrier. The use during pregnancy is not recommended

Mequitazine, quinidine

Mequitazine should not be used with CYP2D6 inhibitor drugs. The increased plasma levels of mequitazine may increase the risk of QT interval prolongation

Mequitazine, sedative antidepressants

Central nervous system depressants may enhance the sedative effects of mequitazine

Mequitazine, sotalol

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Mequitazine, spiramycin

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Mequitazine, strong CYP2D6 inhibitors

Mequitazine should not be used with CYP2D6 inhibitor drugs. The increased plasma levels of mequitazine may increase the risk of QT interval prolongation

Mequitazine, sun

Patients should be advised to minimise exposure to sunlight

Mequitazine, terbinafine

Mequitazine should not be used with CYP2D6 inhibitor drugs. The increased plasma levels of mequitazine may increase the risk of QT interval prolongation

Mequitazine, toremifene

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Mequitazine, vincamine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

QT interval prolonging drugs, mequitazine

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Mercaptamine (Cysteamine) (Procysbi)

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

Cysteamine may cause drowsiness. When starting therapy, patients should not engage in potentially hazardous activities until the effects of the medicinal product on each individual are known.

Bicarbonate, cysteamine [2] ---> SmPC of [2] of EMA

Bicarbonate should be administered at least one hour before or one hour after PROCYSBI to avoid potential earlier release of cysteamine.

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

Cysteamine excretion in human milk is unknown. However, due to the results of animal studies in breast-feeding females and neonates (see section 5.3), breast-feeding is contra-indicated in women taking PROCYSBI

Cysteamine [1], Fanconi's syndrome ---> SmPC of [1] of EMA

Cysteamine can be administered with electrolyte (except bicarbonate) and mineral replacements necessary for management of Fanconi syndrome as well as vitamin D and thyroid hormone.

Cysteamine [1], fertility ---> SmPC of [1] of EMA

Effects on fertility have been seen in animal studies (see section 5.3). Azoospermia has been reported in male cystinosis patients.

Cysteamine [1], foods ---> SmPC of [1] of EMA

Cysteamine bitartrate should not be administered with food rich in fat or proteins, or with frozen food like ice-cream. Patients should try to consistently avoid meals and dairy products for at least 1 hour before and 1 hour after PROCYSBI dosing.

Cysteamine [1], indometacin ---> SmPC of [1] of EMA

Indomethacin and cysteamine have been used simultaneously in some patients. In cases of patients with kidney transplants, anti-rejection treatments have been used with cysteamine.

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

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

If a pregnancy is diagnosed or planned, the treatment should be carefully reconsidered.

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

Therefore, cysteamine bitartrate should not be used during pregnancy, particularly during the first trimester, unless clearly necessary (see section 4.4).

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

Women of childbearing potential should be informed about the risk of teratogenicity and advised to use an adequate method of contraception during the course of treatment. A negative pregnancy test should be confirmed before starting treatment.

             CONTRAINDICATIONS of Mercaptamine (Cysteamine) (Procysbi)

             - Hypersensitivity to the active substance, any form of cysteamine (mercaptamine), or to any of the excipients listed in section 6.1.

             - Hypersensitivity to penicillamine

             - Breast-feeding

             https://www.ema.europa.eu/en/documents/product-information/procysbi-epar-product-information_en.pdf 26/05/2023

Other trade names: Cystagon,

Mercaptopurine (Xaluprine)

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

No studies on the effect on the ability to drive and use machines have been performed. A detrimental effect on these activities cannot be predicted from the pharmacology of the active substance.

Acenocoumarol, mercaptopurine

The co-administration may decrease the anticoagulant effect

Allopurinol, mercaptopurine [2] ---> SmPC of [2] of EMA

When allopurinol and Xaluprine are administered concomitantly it is essential that only a quarter of the usual dose of Xaluprine is given since allopurinol decreases the rate of metabolism of 6-mercaptopurine via xanthine oxidase.

Allopurinol/lesinurad [1], mercaptopurine ---> SmPC of [1] of EMA

Serum concentrations of 6-mercaptopurine and azathioprine can reach toxic levels unless dose reduction is undertaken.

Aminosalicylates, mercaptopurine [2] ---> SmPC of [2] of EMA

As there is in vitro evidence that aminosalicylate derivatives inhibit the TPMT enzyme, which metabolises 6 -mercaptopurine, they should be administered with caution to patients receiving concurrent mercaptopurine therapy

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

Serum antiepileptic levels should be closely monitored

Atracurium, mercaptopurine

Decreased effect of the muscle relaxant

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

6-mercaptopurine has been identified in the colostrum and breast-milk of women receiving azathioprine treatment and thus women receiving Xaluprine should not breast-feed.

Caelyx pegylated liposomal [1], mercaptopurine ---> SmPC of [1] of EMA

In patients with AIDS, exacerbation of cyclophosphamide-induced haemorrhagic cystitis and enhancement of the hepatotoxicity of 6-mercaptopurine have been reported with standard doxorubicin hydrochloride.

Cheese, mercaptopurine [2] ---> SmPC of [2] of EMA

The dose should not be taken with milk or dairy products since they contain xanthine oxidase, and might therefore lead to reduced plasma concentrations of mercaptopurine

Cotrimoxazole, mercaptopurine

Decreased absorption of mercaptopurine

Cytotoxic agents, phenytoin ---> SmPC of [mercaptopurine] of EMA

Cytotoxic agents may decrease the intestinal absorption of phenytoin. Careful monitoring of the phenytoin serum levels is recommended.

Dairy products, mercaptopurine [2] ---> SmPC of [2] of EMA

The dose should not be taken with milk or dairy products since they contain xanthine oxidase, and might therefore lead to reduced plasma concentrations of mercaptopurine

Doxacurium, mercaptopurine

Decreased effect of the muscle relaxant

Doxorubicine [1], mercaptopurine ---> SmPC of [1] of eMC

The concomitant administration of known hepatotoxic chemotherapeutic agents (e.g. mercaptopurine, methotrexate, streptozocin) could potentially increase the toxicity of doxorubicin as a result of reduced hepatic clearance of the drug.

Febuxostat [1], mercaptopurine ---> SmPC of [1] of EMA

Febuxostat, xanthine oxidase inhibitor, increases the plasma concentrations of mercaptopurine leading to toxicity. The concomitant use is not recommended.

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

There are reports of successful fatherhood/motherhood after receiving treatment during childhood or adolescence. Transient profound oligospermia has been reported following exposure to 6-mercaptopurine in combination with corticosteroids.

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

Xaluprine may be taken with food or on an empty stomach, but patients should standardise the method of administration. The dose should not be taken with milk or dairy products since they contain xanthine oxidase

Mercaptopurine [1], milk ---> SmPC of [1] of EMA

The dose should not be taken with milk or dairy products since they contain xanthine oxidase, and might therefore lead to reduced plasma concentrations of mercaptopurine

Mercaptopurine [1], olsalazine ---> SmPC of [1] of EMA

As there is in vitro evidence that aminosalicylate derivatives inhibit the TPMT enzyme, which metabolises 6 -mercaptopurine, they should be administered with caution to patients receiving concurrent mercaptopurine therapy

Mercaptopurine [1], oral anticoagulants ---> SmPC of [1] of EMA

Inhibition of the anticoagulant effect of warfarin, when given with 6 -mercaptopurine, has been reported. Monitoring of the INR (International Normalised Ratio) value is recommended during concomitant administration with oral anticoagulants.

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

Cytotoxic agents may decrease the intestinal absorption of phenytoin. Careful monitoring of the phenytoin serum levels is recommended.

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

Xaluprine should not be given to patients who are pregnant or likely to become pregnant without careful assessment of risk versus benefit

Mercaptopurine [1], sulfasalazine ---> SmPC of [1] of EMA

As there is in vitro evidence that aminosalicylate derivatives inhibit the TPMT enzyme, which metabolises 6 -mercaptopurine, they should be administered with caution to patients receiving concurrent mercaptopurine therapy

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

Vaccinations with other live organism vaccines are not recommended in immunocompromised individuals (see section 4.4).

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

Inhibition of the anticoagulant effect of warfarin, when given with 6 -mercaptopurine, has been reported. Monitoring of the INR (International Normalised Ratio) value is recommended during concomitant administration with oral anticoagulants.

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

Both sexually active men and women should use effective methods of contraception during treatment and for at least three months after receiving the last dose.

Mercaptopurine [1], xanthine oxidase inhibitors ---> SmPC of [1] of EMA

Other xanthine oxidase inhibitors, such as febuxostat, may decrease the metabolism of mercaptopurine and concomitant administration is not recommended as data are insufficient to determine an adequate dose reduction.

Mercaptopurine [1], yellow fever vaccine ---> SmPC of [1] of EMA

Concomitant administration of yellow fever vaccine is contraindicated, due to the risk of fatal disease in immunocompromised patients

Mercaptopurine, mesalazine [2] ---> SmPC of [2] of eMC

Mesalazine inhibits thiopurine methyltransferase. In patients receiving azathioprine or 6-mercaptopurine, caution is recommended for concurrent use of mesalazine as this can increase the potential for blood dyscrasias

Mercaptopurine, methotrexate [2] ---> SmPC of [2] of EMA

Methotrexate leads to increased plasma levels of mercaptopurines. The combination may require an adjustment of the dose

Mercaptopurine, metocurine

Decreased effect of the muscle relaxant

Mercaptopurine, mirikizumab [2] ---> SmPC of [2] of EMA

Population pharmacokinetic data analyses indicated that the clearance of mirikizumab was not impacted by concomitant administration in patients with ulcerative colitis.

Mercaptopurine, mivacurium

Decreased effect of the muscle relaxant

Mercaptopurine, pancuronium

Decreased effect of the muscle relaxant

Mercaptopurine, phenprocoumon

Weakening of phenprocoumon effect with the use concomitant or prior of 6-mercaptopurine

Mercaptopurine, tisopurine

The inhibition of xanthine oxidase increases plasma levels of mercaptopurine

Mercaptopurine, trastuzumab

Trastuzumab may increase the risk of neutropenia and anemia

Mercaptopurine, trimethoprim [2] ---> SmPC of [2] of eMC

Cytotoxic agents increase the risk of haematologic toxicity when given with trimethoprim.

Mercaptopurine, trimethoprim/sulfamethoxazol

Decreased absorption of mercaptopurine

Mercaptopurine, tubocuranine

Decreased effect of the muscle relaxant

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

The pharmacokinetics of ustekinumab was not impacted by concomitant use of MTX, NSAIDs, 6-mercaptopurine, azathioprine and oral corticosteroids in patients with psoriatic arthritis, Crohn's disease or ulcerative colitis

Mercaptopurine, vecuronium

Decreased effect of the muscle relaxant

             CONTRAINDICATIONS of Mercaptopurine (Xaluprine)  

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

             - Concomitant use with yellow fever vaccine

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

Other trade names: Mercaptopurina Aspen, Xaluprine (previously Mercaptopurine Nova Laboratories),

Meropenem

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

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

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

There have been many reports of increases in the anti-coagulant effects of orally administered anti-coagulant agents, including warfarin in patients who are concomitantly receiving antibacterial agents.

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

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

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

Probenecid competes with meropenem for active tubular secretion and thus inhibits the renal excretion of meropenem with the effect of increasing the elimination half-life and plasma concentration of meropenem.

Meropenem [1], valproic acid ---> SmPC of [1] of eMC

Decreases in blood levels of valproic acid have been reported when it is co-administered with carbapenem agents resulting in a 60-100 % decrease in valproic acid levels in about two days.

Meropenem [1], warfarin ---> SmPC of [1] of eMC

Simultaneous administration of antibiotics with warfarin may augment its anti-coagulant effects.

           CONTRAINDICATIONS of Meropenem

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

           - Hypersensitivity to any other carbapenem antibacterial agent.

           - Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other type of beta-lactam antibacterial agent (e.g. penicillins or cephalosporins).

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

Meropenem/vaborbactam (Vaborem)

Ability to drive, meropenem/vaborbactam [2] ---> SmPC of [2] of EMA

Vaborem has moderate influence on the ability to drive and use machines. Seizures have been reported during treatment with meropenem alone, especially in patients treated with anticonvulsants

Alprazolam, meropenem/vaborbactam [2] ---> SmPC of [2] of EMA

When coadministering Vaborem with medicinal products that are predominantly metabolised by CYP3A4, there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Antibiotics, oral anticoagulants ---> SmPC of [meropenem/vaborbactam] of EMA

There have been many reports of increases in the anticoagulant effects of orally administered anticoagulants, including warfarin in patients, who are concomitantly receiving antibacterial agents.

Breast-feeding, meropenem/vaborbactam [2] ---> SmPC of [2] of EMA

Because a risk to the newborns/infants cannot be excluded, breastfeeding must be discontinued prior to initiating therapy.

Carbapeneme, valproic acid ---> SmPC of [meropenem/vaborbactam] of EMA

Data from in vitro and animal studies suggest that carbapenems may inhibit the hydrolysis of valproic acid's glucuronide metabolite (VPA g) back to valproic acid, thus decreasing the serum concentrations of valproic acid.

Contraceptives, meropenem/vaborbactam [2] ---> SmPC of [2] of EMA

Vaborem may decrease the efficacy of hormonal contraceptive medicinal products containing oestrogen and/or progesterone.

Convulsions, meropenem/vaborbactam [2] ---> SmPC of [2] of EMA

Seizures have been reported during treatment with meropenem (see section 4.8).

Cyclosporine, meropenem/vaborbactam [2] ---> SmPC of [2] of EMA

When coadministering Vaborem with medicinal products that are predominantly metabolised by CYP3A4, there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Dabigatran, meropenem/vaborbactam [2] ---> SmPC of [2] of EMA

When coadministering Vaborem with medicinal products that are transported by P-gp (e.g. dabigatran, digoxin) there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Digoxin, meropenem/vaborbactam [2] ---> SmPC of [2] of EMA

When coadministering Vaborem with medicinal products that are transported by P-gp (e.g. dabigatran, digoxin) there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Drugs primarily metabolised by CYP1A2, meropenem/vaborbactam [2] ---> SmPC of [2] of EMA

When coadministering Vaborem with medicinal products that are predominantly metabolised by CYP1A2 (e.g theophylline), there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Drugs primarily metabolised by CYP2C, meropenem/vaborbactam [2] ---> SmPC of [2] of EMA

When coadministering Vaborem with medicinal products that are predominantly metabolised by CYP2C, there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Drugs primarily metabolised by CYP3A4, meropenem/vaborbactam [2] ---> SmPC of [2] of EMA

When coadministering Vaborem with medicinal products that are predominantly metabolised by CYP3A4, there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Fertility, meropenem/vaborbactam [2] ---> SmPC of [2] of EMA

The effects of meropenem/vaborbactam on fertility in humans have not been studied. Animal studies conducted with meropenem and vaborbactam do not indicate harmful effects with respect to fertility (see section 5.3).

Meropenem/vaborbactam [1], midazolam ---> SmPC of [1] of EMA

When coadministering Vaborem with medicinal products that are predominantly metabolised by CYP3A4, there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Meropenem/vaborbactam [1], nifedipine ---> SmPC of [1] of EMA

When coadministering Vaborem with medicinal products that are predominantly metabolised by CYP3A4, there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Meropenem/vaborbactam [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

When coadministering Vaborem with medicinal products that are transported by P-gp (e.g. dabigatran, digoxin) there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Meropenem/vaborbactam [1], phenytoin ---> SmPC of [1] of EMA

When coadministering Vaborem with medicinal products that are predominantly metabolised by CYP2C, there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Meropenem/vaborbactam [1], pregnancy ---> SmPC of [1] of EMA

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

Meropenem/vaborbactam [1], probenecide ---> SmPC of [1] of EMA

Co-administration of probenecid with Vaborem is not recommended, as it may result in increased plasma concentrations of meropenem and vaborbactam.

Meropenem/vaborbactam [1], quinidine ---> SmPC of [1] of EMA

When coadministering Vaborem with medicinal products that are predominantly metabolised by CYP3A4, there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Meropenem/vaborbactam [1], simvastatine ---> SmPC of [1] of EMA

When coadministering Vaborem with medicinal products that are predominantly metabolised by CYP3A4, there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Meropenem/vaborbactam [1], sirolimus ---> SmPC of [1] of EMA

When coadministering Vaborem with medicinal products that are predominantly metabolised by CYP3A4, there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Meropenem/vaborbactam [1], sodium valproate ---> SmPC of [1] of EMA

Concomitant administration of meropenem and valproic acid has been associated with reductions in valproic acid concentrations with subsequent loss in seizure control.

Meropenem/vaborbactam [1], tacrolimus ---> SmPC of [1] of EMA

When coadministering Vaborem with medicinal products that are predominantly metabolised by CYP3A4, there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Meropenem/vaborbactam [1], theophylline ---> SmPC of [1] of EMA

When coadministering Vaborem with medicinal products that are predominantly metabolised by CYP1A2 (e.g theophylline), there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Meropenem/vaborbactam [1], valproic acid ---> SmPC of [1] of EMA

Concomitant administration of meropenem and valproic acid has been associated with reductions in valproic acid concentrations with subsequent loss in seizure control.

Meropenem/vaborbactam [1], valpromide ---> SmPC of [1] of EMA

Concomitant administration of meropenem and valproic acid has been associated with reductions in valproic acid concentrations with subsequent loss in seizure control.

Meropenem/vaborbactam [1], venlafaxine ---> SmPC of [1] of EMA

In vitro data suggest that vaborbactam may inhibit CYP2D6. Patients taking CYP2D6 substrates with narrow therapeutic index should be monitored for signs of toxicity.

Meropenem/vaborbactam [1], warfarin ---> SmPC of [1] of EMA

When coadministering Vaborem with medicinal products that are predominantly metabolised by CYP2C, there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Meropenem/vaborbactam [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should be advised to use alternative effective contraceptive methods during treatment with Vaborem and for a period of 28 days after discontinuation of treatment.

            CONTRAINDICATIONS of Meropenem/vaborbactam (Vaborem)

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

            - Hypersensitivity to any carbapenem antibacterial agent.

            - Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other type of beta-lactam antibacterial agent (e.g. penicillins, cephalosporins or monobactams).

            https://www.ema.europa.eu/en/documents/product-information/vaborem-epar-product-information_en.pdf 16/10/2025 

Other trade names: Vabomere,

Mesalazine

Azathioprine, mesalazine [2] –––> SmPC of [2] of eMC

Mesalazine inhibits thiopurine methyltransferase. In patients receiving azathioprine or 6–mercaptopurine, caution is recommended for concurrent use of mesalazine as this can increase the potential for blood dyscrasias

Breast–feeding, mesalazine [2] –––> SmPC of [2] of eMC

Caution should be exercised if using Mesalazine while breast–feeding and only if the benefit outweighs the risks.

Coumarin anticoagulants, mesalazine [2] –––> SmPC of [2] of eMC

Administration of mesalazine with coumarin–type anticoagulants could result in decreased anticoagulant activity. Prothrombin time should be closely monitored if this combination is essential.

Foods, mesalazine [2] –––> SmPC of [2] of eMC

Mesalazine is recommended to be administered with food

Furosemide, mesalazine

Possible attenuation of the diuretic effect

Glucocorticoids, mesalazine

Increased risk of gastrointestinal haemorrhage and ulceration.

Lactitol, mesalazine

Decreased mesalazine effect

Lactulose, mesalazine

Possible decrease in mesalazine release due to pH reduction

Medicinal products metabolized by TPMT, mesalazine

Mesalazine, thiopurine methyl transferase (TPMT) inhibitor, may increase the plasma levels of medicinal products metabolized by TPMT. Caution is recommended

Mercaptopurine, mesalazine [2] –––> SmPC of [2] of eMC

Mesalazine inhibits thiopurine methyltransferase. In patients receiving azathioprine or 6–mercaptopurine, caution is recommended for concurrent use of mesalazine as this can increase the potential for blood dyscrasias

Mesalazine [1], nephrotoxic substances –––> SmPC of [1] of eMC

Caution is recommended for the concomitant use of mesalazine with known nephrotoxic agents, as these may increase the risk of renal adverse reactions.

Mesalazine [1], NSAID –––> SmPC of [1] of eMC

Caution is recommended for the concomitant use of mesalazine with known nephrotoxic agents, as these may increase the risk of renal adverse reactions.

Mesalazine [1], pregnancy –––> SmPC of [1] of eMC

Mesalazine should be used during pregnancy only when clearly indicated.

Mesalazine [1], warfarin –––> SmPC of [1] of eMC

Administration of mesalazine with coumarin–type anticoagulants could result in decreased anticoagulant activity. Prothrombin time should be closely monitored if this combination is essential.

Mesalazine, probenecide

Possible attenuation of the uricosuric effect

Mesalazine, rifampicin

Possible attenuation of the tuberculostatic effect

Mesalazine, spironolactone

Possible attenuation of the diuretic effect

Mesalazine, sulfinpyrazone

Possible attenuation of the uricosuric effect

Mesalazine, sulfonylureas

Possible increase in the blood glucose–lowering effects

Mesalazine, thioguanine [2] –––> SmPC of [2] of eMC

As there is in vitro evidence that aminosalicylate derivatives inhibit the TPMT enzyme, they should be administered with caution to patients receiving concurrent tioguanine therapy

           CONTRAINDICATIONS of Mesalazine

           – History of hypersensitivity to salicylates (including mesalazine) or any of the excipients

           – Severe renal impairment (GFR < 30 ml/min/1.73 m²) and/or severe hepatic impairment.

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

Mesna

Ability to drive, mesna

Nauseas and vomiting may occur

Aminoglycoside antibiotics, mesna

Mesna inactivates the aminoglycoside antibiotic

Breast-feeding, mesna

It use should be avoided during the breast-feeding or lactation should be discontinued during therapy

Mesna, pregnancy

It should not be used during pregnancy unless clearly necessary

Metacholine

Betablockers, metacholine

The response to methacholine may be exaggerated or prolonged. The co-administration is contraindicated

Breast-feeding, metacholine

Should not be used during breast-feeding

Metacholine, pregnancy

Should not be used in pregnant women unless clearly necessary

Metamizole

Ability to drive, metamizole

Possible decreased ability to react

Acetylsalicylic acid, metamizole ---> SmPC of [clopidogrel/acetylsalicylic acid] of EMA

Metamizole may reduce the effect of ASA on platelet aggregation when taken concomitantly. Therefore, this combination should be used with caution in patients taking low dose ASA for cardioprotection

Alcohol, metamizole

Alcohol may change the metamizole effect

Breast-feeding, metamizole

Contraindicated

Chlorpromazine, metamizole

The co-administration may cause a severe hypothermia

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

Metamizole may reduce the effect of ASA on platelet aggregation when taken concomitantly. Therefore, this combination should be used with caution in patients taking low dose ASA for cardioprotection

Cyclosporine, metamizole

Decreased cyclosporine plasma levels.

Indocyanine green, metamizole

Extinction attenuation

Metamizole, methotrexate [2] ---> SmPC of [2] of EMA

Administration of additional haematotoxic medicinal products (e.g. metamizole) increases the probability of severe haematoxic effects of methotrexate.

Metamizole, pregnancy

Strict indication in the first and second trimester. Contraindicated in the third trimester

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

Metamizole has the potential to decrease tacrolimus concentrations.

Metamizole, warfarin

The co-administration may enhance or decrease the anticoagulant effect

Metformin

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

Patients should be alerted to the risk of hypoglycaemia when metformin is used in combination with other antidiabetic agents (sulphonylureas, insulin, repaglinide).

Acarbose, metformin

A further lowering of blood glucose may increase the potential for hypoglycemia and it may be necessary to decrease the metformin dose.

ACE inhibitors, metformin ---> SmPC of [vildagliptin/metformin] of EMA

ACE-inhibitors may decrease the blood glucose levels.

Alcohol, metformin ---> SmPC of [canagliflozin/metformin] of EMA

There is increased risk of lactic acidosis in acute alcohol intoxication due to the metformin active substance of this medicinal product. Consumption of alcohol and medicinal products containing alcohol should be avoided.

Aliskiren, metformin ---> SmPC of [aliskiren/amlodipine] of EMA

Coadministration of aliskiren had no significant impact on metformin pharmacokinetics. As a result no dose adjustment is necessary.

Aliskiren/amlodipine [1], metformin ---> SmPC of [1] of EMA

Coadministration of aliskiren had no significant impact on metformin pharmacokinetics. As a result no dose adjustment is necessary.

Aliskiren/amlodipine/hydrochlorothiazide [1], metformin ---> SmPC of [1] of EMA

Risk of lactic acidosis induced by a possible functional renal failure linked to hydrochlorothiazide.

Aliskiren/hydrochlorothiazide [1], metformin ---> SmPC of [1] of EMA

Co-administration of aliskiren had no significant impact on atorvastatin, metformin or amlodipine pharmacokinetics. As a result no dose adjustment for aliskiren or these co-administered medicinal products is necessary.

Amlodipine/valsartan/hydrochlorothiazide [1], metformin ---> SmPC of [1] of EMA

Metformin should be used with caution because of the risk of lactic acidosis induced by possible functional renal failure linked to hydrochlorothiazide.

Anticoagulants, metformin

Metformin potentiates the effect of anticoagulants.

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

Cobicistat reversibly inhibits MATE1, and concentrations of metformin may be increased when co-administered with EVOTAZ. Careful patient monitoring and dose adjustment of metformin is recommended in patients who are taking EVOTAZ.

Azilsartan medoxomil [1], metformin ---> SmPC of [1] of EMA

No clinically significant interactions have been reported in studies of azilsartan medoxomil or azilsartan given with amlodipine, antacids, chlortalidone, digoxin, fluconazole, glyburide, ketoconazole, metformin, and warfarin.

Beta2-adrenergic agonists, metformin ---> SmPC of [canagliflozin/metformin] of EMA

Beta-2 agonists have intrinsic hyperglycaemic activity. Should be more frequent blood glucose monitoring performed

Betablockers, metformin ---> SmPC of [brinzolamide/timolol] of EMA

The beta-blocker may increase the hypoglycaemic effect of insulin. Blockade of beta-adrenoreceptors may mask the symptoms of hypoglycaemia

Bictegravir/emtricitabine/tenofovir alafenamide [1], metformin ---> SmPC of [1] of EMA

In patients with moderate renal impairment, close monitoring should be considered when starting coadministration of bictegravir with metformin, due to the increased risk for lactic acidosis in these patients.

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

A decision should be made whether to discontinue nursing or to discontinue metformin

Calcium antagonists, metformin

Decreased hypoglycemic effect

Cationic substances eliminated by renal tubular secretion, metformin ---> SmPC of [linagliptin/metformin] of EMA

Cationic active substances that are eliminated by renal tubular secretion may interact with metformin by competing for common renal tubular transport systems and hence delay the elimination of metformin

Cephalexin, metformin

The co-administration may increase the serum levels of either one and/or both principle actives due to competition for the active tubular secretion.

Chlorpromazine, metformin

Decreased hypoglycemic effect

Cimetidine, metformin ---> SmPC of [vildagliptin/metformin] of EMA

Cationic active substances that are eliminated by renal tubular secretion may interact with metformin by competing for common renal tubular transport systems and hence delay the elimination of metformin

Clonidine, metformin

Increased or decreased hypoglycemic effect of metformin

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

Cobicistat, MATE1 inhibitor, may increase the plasma levels of metformin

Colesevelam [1], metformin ---> SmPC of [1] of EMA

Co-administration of colesevelam and metformin extended-release (ER) tablets increases the exposure of metformin.

Crizotinib [1], metformin ---> SmPC of [1] of EMA

Crizotinib is an inhibitor of OCT1 and OCT2 in vitro. Therefore, crizotinib may have the potential to increase plasma concentrations of coadministered drugs that are substrates of OCT1 or OCT2

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

Based on theoretical considerations REZOLSTA is expected to increase metformin plasma concentrations. (MATE1 inhibition). Careful patient monitoring and dose adjustment of metformin is recommended in patients who are taking REZOLSTA.

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

Based on theoretical considerations DRV/COBI is expected to increase metformin plasma concentrations. MATE1 inhibition. Careful patient monitoring and dose adjustment of metformin is recommended in patients who are taking Symtuza.

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

No dose adjustment needed for metformin when co-administered with Exviera + ombitasvir/paritaprevir/ritonavir.

Diuretics, metformin

Diuretics may increase the risk of lactic acidosis due to their potential to decrease renal function. Diuretics have also hyperglycemic effect.

Dofetilide [1], metformin ---> SmPC of [1] of EMA

Caution should be taken when drugs that are actively secreted via this route are co-administered with dofetilide

Dolutegravir [1], metformin ---> SmPC of [1] of EMA

Dolutegravir, OCT2 inhibitor, may increase plasma levels of metformin. A dose adjustment of metformin may be necessary.

Dolutegravir/abacavir/lamivudine [1], metformin ---> SmPC of [1] of EMA

Dolutegravir, OCT2 inhibitor, may increase plasma levels of metformin. A dose adjustment of metformin may be necessary.

Dolutegravir/rilpivirine [1], metformin ---> SmPC of [1] of EMA

Dolutegravir increased metformin concentrations. A dose adjustment of metformin should be considered when starting and stopping co-administration of Juluca with metformin, to maintain glycaemic control

Dronedarone [1], metformin ---> SmPC of [1] of EMA

No interaction was observed between dronedarone and metformin, an OCT1 and OCT2 substrate.

Dulaglutide [1], metformin ---> SmPC of [1] of EMA

No dose adjustment for metformin IR is recommended when given with dulaglutide.

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

Cobicistat reversibly inhibits MATE1, and concentrations of metformin may be increased when co-administered with Genvoya. Careful patient monitoring and dose adjustment of metformin is recommended in patients who are taking Genvoya.

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

Cobicistat, MATE1 inhibitor, may increase the plasma levels of metformin

Empagliflozin/linagliptin [1], metformin ---> SmPC of [1] of EMA

Interaction studies conducted in healthy volunteers suggest that the pharmacokinetics of linagliptin were not influenced by co-administration with metformin and glibenclamide.

Emtricitabine/rilpivirine/tenofovir alafenamide [1], metformin ---> SmPC of [1] of EMA

No dose adjustment is required.

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

No dose adjustment is required.

Estrogens, metformin

Decreased hypoglycemic effect

Fampridine [1], metformin ---> SmPC of [1] of EMA

OCT2 is the transporter responsible for the active secretion of fampridine. Thus, concomitant use of fampridine with medicinal products that are substrates of OCT2 is cautioned

Felodipine/ramipril [1], metformin ---> SmPC of [1] of eMC

Concomitant treatment with ACE inhibitors and antidiabetic agents may cause a pronounced hypoglycaemic effect with the risk of hypoglycaemia.

Foods, metformin [2] ---> SmPC of [2] of eMC

Food decreases the extent and slightly delays the absorption of metformin.

Furosemide, metformin

Furosemide may increase the plasma levels of metformin and metformin may decrease the plasma levels of furosemide

Glibenclamide, metformin

The co-administration may enhance the hypoglycemic effect

Gliclazide [1], metformin ---> SmPC of [1] of eMC

Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when other antidiabetic agents are taken

Glimepiride [1], metformin ---> SmPC of [1] of eMC

Potentiation of the blood-sugar-lowering effect and possible hypoglycaemia

Glucocorticoids, metformin [2] ---> SmPC of [2] of eMC

Glucocorticoids (systemic and local routes), beta-2-agonists, and diuretics have intrinsic hyperglycaemic activity. Inform the patient and perform more frequent blood glucose monitoring, especially at the beginning of treatment.

Glucosamine, metformin

Possible hyperglycemia

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

Guanfacine may be an inhibitor of OCT1 at maximal portal vein concentrations. Concomitant administration of guanfacine with OCT1 substrates with a similar Tmax (e.g., metformin) may result in increases in Cmax of these medicinal products.

H2 antagonists, metformin

Increased or decreased hypoglycemic effect of metformin

Hydrochlorothiazide, metformin ---> SmPC of [amlodipine/valsartan/hydrochlorothiazide] of EMA

Metformin should be used with caution because of the risk of lactic acidosis induced by possible functional renal failure linked to hydrochlorothiazide.

Hyperglycemic agents, metformin ---> SmPC of [ertugliflozin/metformin] of EMA

Glucocorticoids (given by systemic and local routes), beta 2 agonists, and diuretics have intrinsic hyperglycaemic activity. The patient should be informed and more frequent blood glucose monitoring performed

Hypoglycemic drugs, metformin

Possible increase of hypoglycaemic effect

IMAOs, metformin

The co-administration may improve the glucose tolerance and enhance the hypoglycemic effect

Indapamide [1], metformin ---> SmPC of [1] of eMC

Increased risk of metformin induced lactic acidosis due to the possibility of functional renal failure associated with diuretics and more particularly with loop diuretics.

Iodinated contrast media, metformin [2] ---> SmPC of [2] of eMC

Intravascular administration of iodinated contrast agents may lead to renal failure, resulting in metformin accumulation and a risk of lactic acidosis.

Iodixanol, metformin

Use of iodinated contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking metformin

Iohexol, metformin

Use of iodinated contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking metformin

Iomeprol, metformin

Use of iodinated contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking metformin

Iopamidol, metformin

Use of iodinated contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking metformin

Ioxaglic acid, metformin

Use of iodinated contrast media may result in a transient impairment of renal function and this may precipitate lactic acidosis in diabetics who are taking metformin

Isavuconazole, metformin ---> SmPC of [ertugliflozin/metformin] of EMA

Inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration.

Isoniazid, metformin

Decreased hypoglycemic effect

Lacosamide [1], metformin ---> SmPC of [1] of EMA

There was no clinically relevant interaction between lacosamide and metformin.

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

Co-administration of lamotrigine (OCT2 inhibitor) with renally excreted medicinal products which are substrates of OCT2 may result in increased plasma levels of these drugs.

Linagliptin [1], metformin ---> SmPC of [1] of EMA

In clinical studies linagliptin had no clinically relevant effect on the pharmacokinetics of metformin

Linagliptin/metformin [1], metformin ---> SmPC of [1] of EMA

Co-administration of multiple daily doses of 10 mg linagliptin with 850 mg metformin hydrochloride, an OCT substrate, had no relevant effect on the pharmacokinetics of metformin in healthy subjects.

Loop diuretics, metformin

Diuretics may increase the risk of lactic acidosis due to their potential to decrease renal function. Diuretics have also hyperglycemic effect.

Losartan/hydrochlorothiazide [1], metformin ---> SmPC of [1] of eMC

Metformin should be used with caution because of the risk of lactic acidosis induced by possible functional renal failure linked to hydrochlorothiazide.

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

When the patient plans to become pregnant and during pregnancy, diabetes should not be treated with metformin but insulin should be used to maintain blood glucose levels

Metformin [1], sympathomimetics ---> SmPC of [1] of eMC

Glucocorticoids (systemic and local routes), beta-2-agonists, and diuretics have intrinsic hyperglycaemic activity. Inform the patient and perform more frequent blood glucose monitoring, especially at the beginning of treatment.

Metformin, miglitol

Decreased bioavailability of metformin

Metformin, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Use of naltrexone / bupropion with other OCT2 substrates (e.g., metformin) in clinical trials did not indicate the need for dose adjustment or other precautions.

Metformin, nicotinic acid

Decreased hypoglycemic effect

Metformin, nifedipine

Increased absorption, plasma levels and hypoglycemic effect of metformin

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

Niraparib is an inhibitor of MATE1 and MATE2. Increased plasma concentrations of co-administered medicinal products that are substrates of these transporters (e.g. metformin) cannot be excluded.

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

No dose adjustment needed for metformin when co-administered with Viekirax with and without dasabuvir.

Metformin, oral contraceptives

Decreased hypoglycemic effect

Metformin, 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

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

Based on in vitro data, palbociclib may inhibit the uptake transporter organic cationic transporter OCT1 and then may increase the exposure of medical product substrates of this transporter (e.g., metformin).

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

Dose adjustments (decrease or increase) of insulin and antidiabetic medicinal products may be required when administered concomitantly with pasireotide

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

Concomitant administration of Veltassa showed reduced bioavailability of ciprofloxacin, levothyroxine and metformin. However, there was no interaction when Veltassa and these medicinal products were taken 3 hours apart.

Metformin, phenothiazines

Decreased hypoglycemic effect

Metformin, phenprocoumon

Weakening of phenprocoumon effect with the use concomitant or prior of metformin

Metformin, phenytoin

Decreased hypoglycemic effect

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

Interaction studies have shown that pioglitazone has no relevant effect on either the pharmacokinetics or pharmacodynamics of metformin

Metformin, pioglitazone/glimepiride [2] ---> SmPC of [2] of EMA

Potentiation of the blood-glucose-lowering effect and, thus, in some instances hypoglycaemia may occur

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

Caution is advised when pitolisant is administered with a substrate of OCT1 (e.g. metformin (biguanides))

Metformin, procainamide

Increased metformin systemic exposure. Close monitoring of glycaemic control

Metformin, quinolones

The co-administration may cause hyperglycemia or hypoglycemia

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

Plasma exposure of metformin increased when co-administered with ranolazine. The exposure of other OCT2 substrates may be affected to a similar

Metformin, reserpine

Increased or decreased hypoglycemic effect of metformin

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

Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of this transporter which exhibit a narrow therapeutic index

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

No dose adjustment is required.

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

Caution is advised when metformin is co-administered with rucaparib.

Metformin, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Co-administration of Entresto with metformin reduced both Cmax and AUC of metformin by 23%. The clinical relevance of these findings is unknown.

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

Safinamide inhibits OCT1 in vitro at clinically relevant portal vein concentrations. Therefore, caution is necessary when safinamide is taken concomitantly with medicinal products that are OCT1 substrates and have a tmax similar to safinamide (2 hours)

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

Semaglutide did not change the overall exposure or Cmax of metformin following dosing of 500 mg twice daily over 3.5 days.

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

Co-administration of multiple twice-daily doses of 1,000 mg metformin with 50 mg sitagliptin did not meaningfully alter the pharmacokinetics of sitagliptin in patients with type 2 diabetes.

Metformin, somatropin

Somatropin may antagonize the hypoglycemic effect of metformin.

Metformin, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

In vitro studies did not show any relevant interaction

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

Based on in vitro studies, telaprevir may potentially increase plasma concentrations of medicinal products in which excretion is dependent upon multidrug and toxin extrusion (MATE)-1 and MATE2-K

Metformin, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Metformin should be used with precaution: risk of lactic acidosis induced by a possible functional renal failure linked to hydrochlorothiazide.

Metformin, tetracosactide

Decreased hypoglycemic effect

Metformin, thyroid hormones

Decreased hypoglycemic effect

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

Coadministration of XELJANZ did not have an effect on the PK of metformin, indicating that XELJANZ does not interfere with the organic cationic transporter (OCT2) in healthy volunteers.

Metformin, topiramate [2] ---> SmPC of [2] of eMC

When topiramate is added or withdrawn in patients on metformin therapy, careful attention should be given to the routine monitoring for adequate control of their diabetic disease state.

Metformin, trimethoprim ---> SmPC of [ertugliflozin/metformin] of EMA

Inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration.

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

Vandetanib, inhibitor of organic cation transporter 2, may increase the exposition of metformin. Careful monitoring

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

Population pharmacokinetic analysis showed no effect on vardenafil pharmacokinetics of both medicinal products concomitant administered

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

Varenicline did not affect the pharmacokinetics of metformin. Metformin had no effect on varenicline pharmacokinetics.

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

Results from studies conducted with this oral antidiabetic have shown no clinically relevant pharmacokinetic interactions.

Metformin, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Results from clinical trials conducted with the oral antidiabetics pioglitazone, metformin and glyburide in combination with vildagliptin have shown no clinically relevant pharmacokinetic interactions in the target population.

Metformin, xipamide

Increased risk of metformin-induced lactate acidosis due to the possibility of functional renal failure associated with a diuretic treatment

           CONTRAINDICATIONS of Metformin

           - Hypersensitivity to metformin hydrochloride or to any of the other excipients.

           - Diabetic ketoacidosis, diabetic pre-coma.

           - Renal failure or renal dysfunction (e.g., serum creatinine levels > 135 µmol/L in males and > 110 µmol/L in females)

           - Acute conditions with the potential to alter renal function such as:

           - dehydration

           - severe infection

           - shock

           - intravascular administration of iodinated contrast agents

           - Acute or chronic disease which may cause tissue hypoxia such as:

           - cardiac or respiratory failure

           - recent myocardial infarction

           - shock

           - Hepatic insufficiency, acute alcohol intoxication, alcoholism

           - Lactation

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

Metformin/saxagliptin/dapagliflozin (Qtrilmet)

Ability to drive, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

When driving or using machines, it should be taken into account that dizziness has been reported in studies with saxagliptin.

ACE inhibitors, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Some medicinal products can adversely affect renal function which may increase the risk of lactic acidosis. When starting or using such product in combination with metformin, close monitoring of renal function is necessary.

AIIRA, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Some medicinal products can adversely affect renal function which may increase the risk of lactic acidosis. When starting or using such product in combination with metformin, close monitoring of renal function is necessary.

Alcohol, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in the case of fasting, malnutrition or hepatic impairment. Consumption of alcohol and medicinal products containing alcohol should be avoided

Antacids, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

In studies conducted in healthy subjects, neither the pharmacokinetics of saxagliptin nor its major metabolite were meaningfully altered

Beta2-adrenergic agonists, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Glucocorticoids (given by systemic and local routes), beta-2 agonists, and diuretics have intrinsic hyperglycaemic activity. The patient should be informed and more frequent blood glucose monitoring performed

Breast-feeding, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

This medicinal product should not be used while breast-feeding.

Carbamazepine, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Glycaemic control should be carefully assessed when saxagliptin is used concomitantly with a potent CYP3A4/5 inducer.

Cimetidine, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Co-administration of metformin with inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration;

Coxibs, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Some medicinal products can adversely affect renal function which may increase the risk of lactic acidosis. When starting or using such product in combination with metformin, close monitoring of renal function is necessary.

Crizotinib, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] 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

Dapagliflozin, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

In studies conducted in healthy subjects, neither the pharmacokinetics of saxagliptin nor its major metabolite were meaningfully altered

Dexamethasone, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Glycaemic control should be carefully assessed when saxagliptin is used concomitantly with a potent CYP3A4/5 inducer.

Digoxin, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

In studies conducted in healthy subjects, neither the pharmacokinetics of saxagliptin nor its major metabolite were meaningfully altered

Diltiazem, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Co-administration of saxagliptin with the moderate CYP3A4/5-inhibitor diltiazem, increased the Cmax and AUC of saxagliptin by 63% and 2.1-fold, respectively. These pharmacokinetic effects are not clinically meaningful and do not require dose adjustment.

Diuretics, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Glucocorticoids (given by systemic and local routes), beta-2 agonists, and diuretics have intrinsic hyperglycaemic activity. The patient should be informed and more frequent blood glucose monitoring performed

Dolutegravir, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Co-administration of metformin with inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration;

Ethinylestradiol/norgestimate, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Saxagliptin did not meaningfully alter the pharmacokinetics of the active components of a combined oral contraceptive (ethinylestradiol and norgestimate)

Famotidine, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

In studies conducted in healthy subjects, neither the pharmacokinetics of saxagliptin nor its major metabolite were meaningfully altered

Foods, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Qtrilmet dose is taken orally once daily at the same time of the day with food to reduce the gastrointestinal adverse reactions associated with metformin. Each tablet is to be swallowed whole.

Glibenclamide, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

In studies conducted in healthy subjects, neither the pharmacokinetics of saxagliptin nor its major metabolite were meaningfully altered

Glucocorticoids, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Glucocorticoids (given by systemic and local routes), beta-2 agonists, and diuretics have intrinsic hyperglycaemic activity. The patient should be informed and more frequent blood glucose monitoring performed

Hydrochlorothiazide, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

In interaction studies conducted in healthy subjects, using mainly a single-dose design, dapagliflozin did not alter the pharmacokinetics of hydrochlorothiazide

Inhibitors of both OCT1 and OCT2, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] 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

Insulin secretagogues, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

A lower dose of insulin or insulin secretagogue may be required to reduce the risk of hypoglycaemia when these agents are used in combination with Qtrilmet

Insulin, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

A lower dose of insulin or insulin secretagogue may be required to reduce the risk of hypoglycaemia when these agents are used in combination with Qtrilmet

Iodinated contrast media, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Qtrilmet must be discontinued prior to, or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable

Isavuconazole, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Co-administration of metformin with inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration;

Ketoconazole, metformin/saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Co-administration of saxagliptin with the potent inhibitor of CYP3A4/5 ketoconazole, increased the Cmax and AUC of saxagliptin by 62% and 2.5-fold. These pharmacokinetic effects are not clinically meaningful and do not require dose adjustment.