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Strong CYP3A4 inducers (e.g., rifampicin) can significantly reduce the exposure to macitentan. Concomitant use of macitentan with strong CYP3A4 inducers should be avoided.
Concomitant administration of strong CYP3A4 inhibitors (e.g., ketoconazole) can approximately double the exposure to macitentan. Many HIV medications (e.g., ritonavir) are strong CYP3A4 inhibitors. Concomitant use of macitentan with strong CYP3A4 inhibitors should be avoided. When a strong CYP3A4 inhibitor is required as part of HIV treatment, alternative PAH treatment options should be used.
According to predictions from physiologically based pharmacokinetic models, concomitant use of moderate dual CYP3A4 and CYP2C9 inhibitors (e.g., fluconazole) is expected to increase macitentan exposure by approximately fourfold, with no relevant impact on the exposure to its active metabolite. Concomitant use of macitentan with moderate dual CYP3A4 and CYP2C9 inhibitors (e.g., fluconazole and amiodarone) should be avoided.
Concurrent treatment with macitentan and both a moderate CYP3A4 inhibitor and a moderate CYP2C9 inhibitor should also be avoided.
FDA，2025.04
