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Drug Interactions between Opsumit and Zokinvy

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

macitentan lonafarnib

Applies to: Opsumit (macitentan) and Zokinvy (lonafarnib)

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of macitentan, which is primarily metabolized by the isoenzyme. In ten healthy subjects, administration of a single 10 mg oral dose of macitentan on day 5 of treatment with the potent CYP450 3A4 inhibitor ketoconazole (400 mg daily for 24 days) resulted in an approximately 2-fold increase in macitentan systemic exposure (AUC) compared to administration alone. Additionally, there was a 26% reduction in the AUC of the active metabolite, which has been reported to be approximately 5-fold less potent than macitentan in vitro, but whose systemic exposure in human is 2.5-fold higher than that of macitentan. The clinical significance of these changes has not been established. Macitentan was well tolerated with or without ketoconazole in the study, and there were no relevant differences in safety parameters between the treatments.

MANAGEMENT: According to the product labeling, concomitant use of macitentan with potent CYP450 3A4 inhibitors such as itraconazole, ketoconazole, posaconazole, voriconazole, conivaptan, nefazodone, cobicistat, delavirdine, protease inhibitors, and ketolide and certain macrolide antibiotics should generally be avoided. Alternative treatment options for pulmonary arterial hypertension are recommended when potent CYP450 3A4 inhibitors are needed as part of HIV treatment.

References

  1. "Product Information. Opsumit (macitentan)." Actelion Pharmaceuticals US Inc (2013):

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Drug and food interactions

Major

lonafarnib food

Applies to: Zokinvy (lonafarnib)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of lonafarnib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. When a single 50 mg oral dose of lonafarnib was administered following pretreatment with the potent CYP450 3A4 inhibitor ketoconazole (200 mg once daily for 5 days) in healthy study subjects, lonafarnib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 270% and 425%, respectively, compared to lonafarnib administered alone. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to lonafarnib may increase the risk and/or severity of adverse effects such as nausea, vomiting, diarrhea, anorexia, electrolyte disturbances, liver enzyme elevations, myelosuppression, infection, and hypertension.

ADJUST DOSING INTERVAL: Food does not have clinically relevant effects on the oral bioavailability of lonafarnib. When a single 75 mg oral dose of lonafarnib was administered with a high-fat meal (952 calories; approximately 43% from fat) in healthy subjects, lonafarnib Cmax and AUC decreased by 55% and 29%, respectively, compared to administration under fasted conditions. When administered with a low-fat meal (421 calories; approximately 12% from fat), lonafarnib Cmax decreased by 25% and AUC decreased by 21% relative to fasting. However, administration with food may help improve gastrointestinal tolerance to lonafarnib, which may commonly cause nausea, vomiting, diarrhea, and abdominal pain.

MANAGEMENT: Lonafarnib should be administered with the morning and evening meals and an adequate amount of water. Patients should avoid consumption of grapefruit or grapefruit juice and Seville oranges (also known as bitter or sour oranges).during treatment with lonafarnib.

References

  1. "Product Information. Zokinvy (lonafarnib)." Eiger BioPharmaceuticals (2020):

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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