Drug Interaction Report

ADJUST DOSE: Coadministration of a protease inhibitor (PI) in combination with bosentan may increase the plasma concentration of bosentan and decrease that of the PI, unless ritonavir is included as a pharmacokinetic booster. Both PIs and bosentan are primarily metabolized by CYP450 3A4. Because PIs are also inhibitors of CYP450 3A4, they can inhibit the metabolic clearance of bosentan. Conversely, bosentan may induce the metabolism of PIs, although the effects are probably not significant in the presence of ritonavir, which is a potent CYP450 3A4 inhibitor.

MANAGEMENT: Protease inhibitors should generally not be used in combination with bosentan unless ritonavir is also added as a pharmacokinetic booster. Dose adjustment of bosentan has been recommended. In patients who are starting bosentan and have been receiving PI therapy for at least 10 days, it has been recommended to start bosentan at 62.5 mg once daily or every other day based upon individual tolerability. When starting PI therapy in patients already on bosentan, it has been recommended to discontinue bosentan for at least 36 hours prior to initiation of PI therapy. After at least 10 days following the initiation of PI therapy, bosentan may be resumed at 62.5 mg once daily or every other day based upon individual tolerability. According to some authorities, use of the fixed combination atazanavir-cobicistat with bosentan is not recommended.

ADJUST DOSING INTERVAL: Food may reduce the systemic bioavailability of amprenavir from fosamprenavir oral suspension. The mechanism of interaction has not been described. According to the product labeling, administration of fosamprenavir oral suspension (1400 mg single dose) with a high-fat meal (967 kcal, 67 g fat, 33 g protein, 58 g carbohydrate) reduced amprenavir peak plasma concentration (Cmax) by 46% and systemic exposure (AUC) by 28% compared to administration in a fasted state. The time to reach peak plasma level (Tmax) was delayed by 0.72 hours. In contrast, the same high-fat meal did not affect the pharmacokinetics of amprenavir from fosamprenavir tablets.

MANAGEMENT: Fosamprenavir suspension should be administered on an empty stomach in adults, but with food in pediatric patients to aid palatability and compliance. If emesis occurs within 30 minutes after dosing the suspension, the dose should be repeated. Fosamprenavir tablets may be taken with or without food.