Drug Interaction Report
2 potential interactions and/or warnings found for the following 2 drugs:
- cobicistat
- macitentan
Interactions between your drugs
cobicistat macitentan
Applies to: cobicistat, macitentan
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. Similarly, physiologically based pharmacokinetic (PBPK) modeling predicts that coadministration with ketoconazole (200 mg twice daily) may increase macitentan exposure by approximately 3-fold. 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. Clinical data with other potent inhibitors of CYP450 3A4 have not been evaluated.
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 (6)
- (2013) "Product Information. Opsumit (macitentan)." Actelion Pharmaceuticals US Inc
- (2024) "Product Information. Opsynvi (macitentan-tadalafil)." Actelion Pharmaceuticals US Inc
- (2024) "Product Information. Opsynvi 10/40 (macitentan-tadalafil)." Janssen-Cilag Pty Ltd
- (2025) "Product Information. Opsynvi (macitentan-tadalafil)." Janssen Inc
- (2024) "Product Information. Opsumit (macitentan)." Janssen-Cilag Ltd
- (2023) "Product Information. Opsumit (macitentan)." Janssen-Cilag Ltd
Drug and food/lifestyle interactions
macitentan food/lifestyle
Applies to: macitentan
GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of macitentan, which is primarily metabolized by CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. The interaction has not been studied with grapefruit juice but has been reported for ketoconazole, a potent CYP450 3A4 inhibitor. In ten healthy subjects, coadministration of a single 10 mg oral dose of macitentan on day 5 of treatment with ketoconazole (400 mg daily for 24 days) resulted in an approximately 2-fold increase in macitentan systemic exposure compared to administration alone. However, the clinical significance of the interaction is unclear. 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
MANAGEMENT: Until further information is available, patients receiving macitentan therapy should avoid the consumption of grapefruit or grapefruit juice.
References (6)
- (2013) "Product Information. Opsumit (macitentan)." Actelion Pharmaceuticals US Inc
- (2024) "Product Information. Opsynvi (macitentan-tadalafil)." Actelion Pharmaceuticals US Inc
- (2024) "Product Information. Opsynvi 10/40 (macitentan-tadalafil)." Janssen-Cilag Pty Ltd
- (2025) "Product Information. Opsynvi (macitentan-tadalafil)." Janssen Inc
- (2024) "Product Information. Opsumit (macitentan)." Janssen-Cilag Ltd
- (2023) "Product Information. Opsumit (macitentan)." Janssen-Cilag Ltd
Therapeutic duplication warnings
No duplication 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.
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
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