Concomitant use of Opsumit® (macitentan) Film-Coated Tablet 10mg with dual moderate CYP3A4/CYP2C9 inhibitors that could result in an increase in exposure to Opsumit®

A Dear Healthcare Professional Letter has been issued by Johnson & Johnson Pte Ltd to inform healthcare professionals of a potential drug-drug interaction (DDI) between Opsumit^® (macitentan) and dual moderate CYP3A4/CYP2C9 inhibitors that could result in an increase in systemic exposure to Opsumit^®. A review has found CYP2C9 to be responsible for 26% of metabolism of macitentan as opposed to the previous understanding that it would provide a minor contribution. Co-administration of fluconazole (400 mg qd), a dual moderate CYP2C9 and CYP3A4 inhibitor, could result in a 3.8-fold increase in macitentan exposure due to the dual inhibition of the two most important metabolic pathways. Nonetheless, no safety concerns have been identified with the concurrent administration of dual CYP3A4/CYP2C9 inhibitors (e.g. fluconazole/amiodarone) and macitentan 10 mg and there is no change in the current recommended dose of macitentan 10 mg once daily. The package insert for Opsumit^® will be updated accordingly to reflect the new DDI information. Healthcare professionals are advised to exercise caution when macitentan is administered concomitantly with moderate dual inhibitors of CYP3A4 and CYP2C9, or with both a moderate CYP3A4 inhibitor and a moderate CYP2C9 inhibitor. Please refer to the letter for details. Published: 9 Nov 2020

Dear Healthcare Professional Letters