Drug Interactions between fosamprenavir and Triumeq PD

ADJUST DOSE: Coadministration with potent inducers of UGT1A and CYP450 3A4 isoenzymes such as fosamprenavir/ritonavir may significantly decrease the plasma concentrations of dolutegravir, which is primarily metabolized by UGT1A1 with some contribution from CYP450 3A4. Dolutegravir is also a substrate of UGT1A3, UGT1A9, and P-glycoprotein in vitro. In 12 study subjects, administration of dolutegravir 50 mg once daily with fosamprenavir/ritonavir 700 mg/100 mg twice daily decreased dolutegravir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin; 24 hours postdose) by 24%, 35% and 49%, respectively, compared to administration without fosamprenavir/ritonavir. Using cross-study comparisons to historical pharmacokinetic data, dolutegravir did not appear to affect the pharmacokinetics of fosamprenavir or ritonavir.

MANAGEMENT: When prescribed in combination with fosamprenavir/ritonavir, the dosage of dolutegravir should be increased to 50 mg twice daily for both adults and pediatric patients 12 years of age and older who weigh at least 40 kg. The safety and efficacy of dosages above 50 mg twice daily have not been evaluated. For concomitant use of fosamprenavir/ritonavir with the fixed-dose combination product containing abacavir/dolutegravir/lamivudine, it is recommended to administer an additional dose of dolutegravir 50 mg/day, separated from the combination product by 12 hours. Alternative treatment combinations that do not include metabolic inducers should be considered whenever possible for integrase strand transfer inhibitor (INSTI)-experienced patients with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance.