Dolutegravir + Tipranavir = Precautionary

Effect on Concentration

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

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 13-Jul-2018

Summary

Sources

Effects of enzyme inducers, tipranavir and efavirenz, on the pharmacokinetics of the integrase inhibitor, dolutegravir (S/GSK1349572). ^

Study Design

GSK investigators planned two new trials in healthy volunteers to assess interactions between dolutegravir and efavirenz or tipranavir/ritonavir. In the first study 12 volunteers took a single 100-mg dose of dolutegravir. After more than 6 days taking no drug, they took 50 mg of dolutegravir once daily for 5 days, then dolutegravir plus 600 mg of efavirenz once daily for 14 days. In the second study 18 volunteers took 50 mg of dolutegravir once daily for 5 days, then 500/200 mg of tipranavir/ritonavir twice daily (without dolutegravir) for 7 days, then dolutegravir plus tipranavir/ritonavir for 5 days.

Study Results

Dolutegravir concentrations in plasma were lower when taken with efavirenz than when taken alone--57% lower for AUC, 39% lower for maximum concentration (Cmax), and 75% lower for minimum concentration (Cmin). Although dolutegravir trough concentrations dropped about 75% with efavirenz, the levels attained were equivalent to those found to be efficacious in an earlier dose-ranging study in people with HIV. Coadministration of tipranavir/ritonavir lowered dolutegravir plasma concentrations--59% for AUC, 46% for Cmax, and 76% for Cmin. Although dolutegravir trough concentrations dropped about 75% with tipranavir/ritonavir, the levels attained were equivalent to those found to be efficacious in an earlier dose-ranging study in people with HIV.

Study Conclusions

The manufacturer states that the dose of DTG should be increased to 50mg BID when co-administered with EFV. Until further data are available, careful monitoring of HIV surrogate markers, including CD4 count and HIV PCR is warranted. The manufacturer states that the dose of DTG should be increased to 50mg BID when co-administered with tipranavir/r. Until further data are available, careful monitoring of HIV surrogate markers, including CD4 count and HIV PCR is warranted.

References

Song I, Borland J, Lou Y, Chen S, Patel P, Guta P, Piscitelli S. Effects of enzyme inducers, tipranavir and efavirenz, on the pharmacokinetics of the integrase inhibitor, dolutegravir (s/gsk1349572). International Workshop On Clinical Pharmacology Of Hiv Therapy . Miami, Florida. 12; May 2011.