Drug-Drug:
- Bosentan is metabolized by and induces the CYP3A4 and 2C9 enzyme systems.
- May ↓ effectiveness of hormonal contraceptives (additional method of contraception recommended).
- Significantly ↓ cyclosporine levels; cyclosporine significantly ↑ bosentan levels (concurrent use contraindicated).
- ↑risk of hepatotoxicity with glyburide (concurrent use contraindicated).
- Lopinavir/ritonavir or other ritonavir — containing regimens significantly ↑ levels (initiate bosentan at 62.5 mg once daily or every other day if receiving ritonavir-containing regimen for
10 days) (if initiating ritonavir in patient already receiving bosentan, discontinue bosentan for 36 hr before initiating ritonavir; can resume bosentan after 10 days at 62.5 mg once daily or every other day). - Ketoconazole↑ levels.
- May ↓ levels of atorvastatin, lovastatin, sildenafil, simvastatin, sirolimus, tacrolimus, tadalafil, and warfarin..
