Dolutegravir + Fosamprenavir = Precautionary

Effect on Concentration

Dolutegravir
Decrease
Applies within class?
No
Fosamprenavir
No change
Applies within class?
No

Pharmacologic Effects

Dolutegravir
Effect
N/A
Applies within class?
No
Fosamprenavir
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 13-Jul-2018

Summary

Sources

Effect of fosamprenavir-ritonavir on the pharmacokinetics of dolutegravir in healthy subjects. ^

Study Design

Song, et al, conducted a single-center, open-label, single-sequence study in twelve healthy adult subjects. Subjects received DTG 50 mg q24h for 5 days followed by DTG 50 mg q24h in combination with FPV/RTV 700/100 mg q12h for 10 days. (FPV is the prodrug of APV.) All doses were administered in the fasting state. Serial PK samples for DTG and amprenavir (APV) and safety assessments were obtained throughout the study. Non-compartmental PK analysis was performed and geometric least squares (GLS) mean ratios and 90% confidence intervals (CI) were generated by the mixed effect model for within-subject treatment comparison.

Study Results

Amprenavir levels were similar to those reported earlier in other studies of fosamprenavir. Compared with dolutegravir concentrations when the integrase inhibitor was taken alone, concentrations with fosamprenavir/ritonavir were substantially lower. Co-administration of FPV/RTV decreased DTG plasma exposures: AUC,Cmax, and Cwere reduced by 35%, 24%, and 49%, respectively. APV PK parameters were similar to historical values. GLS mean ratios (and 90% confidence intervals) -- AUC 0.651 (0.542 to 0.782) -- Cmax 0.763 (0.632 to 0.921) -- Ctrough 0.510 (0.413 to 0.629)

Study Conclusions

Although the authors concluded that no dose adjustment is needed when dolutegravir is co-administered with fosamprenavir/ritonavir in integrase inhibitor-naive patients, the manufacturer states that the dose of DTG should be increased to 50mg BID when co-administered with FPV/r. Use with caution and monitor closely when co-administering these agents.

References

Song I, Borland J, Chen S, Peppercorn A, Wajima T, Piscitelli SC. Effect of fosamprenavir-ritonavir on the pharmacokinetics of dolutegravir in healthy subjects. Antimicrobial Agents And Chemotherapy . 2014; 11: 6696-6700.