Drug Interactions between Dutrebis and fosamprenavir

MONITOR: Coadministration of fosamprenavir (with or without ritonavir) and raltegravir may decrease the plasma concentrations of both amprenavir and raltegravir. The mechanism of interaction has not been described. In 14 study subjects, administration of fosamprenavir 1400 mg twice a day (under fasting conditions) in combination with raltegravir 400 mg twice a day for 14 days decreased the amprenavir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 27%, 36% and 43%, respectively. When the same dosages were given without regards to food, amprenavir Cmax, AUC and Cmin decreased by 15%, 17% and 32%, respectively. In 14 study subjects, administration of fosamprenavir 700 mg plus ritonavir 100 mg twice a day (under fasting conditions) in combination with raltegravir 400 mg twice a day for 14 days decreased the amprenavir Cmax, AUC and Cmin by 14%, 17% and 20%, respectively. When the same dosages were given without regards to food, amprenavir Cmax, AUC and Cmin decreased by 15%, 17% and 32%, respectively. In 13 study subjects, administration of fosamprenavir 1400 plus ritonavir 100 mg once a day (under fasting conditions) in combination with raltegravir 400 mg twice a day for 14 days decreased the amprenavir Cmax, AUC and Cmin by 18%, 24% and 50%, respectively. When the same dosages were given without regards to food, amprenavir Cmax and AUC increased by 27% and 13%, respectively, but the Cmin decreased by 17%.

MANAGEMENT: Caution is advised if fosamprenavir is prescribed in combination with raltegravir. Appropriate dosages of the combination with respect to safety and efficacy have not been established.