Maraviroc + Etravirine = Precautionary

Effect on Concentration

Maraviroc
Decrease
Applies within class?
No
Etravirine
No change
Applies within class?
No

Pharmacologic Effects

Maraviroc
Effect
N/A
Applies within class?
No
Etravirine
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 20-Jul-2018

Summary

Sources

Maraviroc versus Etravirine ^

Study Design

The design of this study was a phase I, open-label, placebo-controlled, randomized two period crossover study in healthy subjects to assess the effect etravirine has on the CCR5 antagonist maraviroc when the two are used in combination. (n=14) healthy men and women aged 18-55 were enrolled in a two-way cross over study to investigate the influence of etravirine on the plasma pharmacokinetics of maraviroc. Maraviroc was administered under fasting conditions. Etravirine was given 15 min after a standardized breakfast and n more than 5 minutes apart. Serial blood samples were collected on days before dosing on days 11-19 and predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12h following maraviroc dosing on day 20 in the 20 day treatment period, or before dosing on days 1-9 and then predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12h following maraviroc dosing on day 10 in the 10 day treatment. Etrivirine blood samples were analyzed prior to dosing on days 6 to 9 and 16 to 19 and predose and 1, 2, 3, 4, 6, 8, and 12h following maraviroc dosing on days 10 and 20. Urine was also collected from 0 to 12h post maraviroc dosing on days 10 or 20. Geometric least squares ratios and 90% confidence intervals were estimated.

Study Results

Based on GMRs and 90% confidence intervals, when compared with maraviroc + placebo there was a 0.47 decrease in AUC12 (0.38, 0.58) and a 0.40 decrease in Cmax (0.28, 0.57) of maraviroc upon co-administration with the non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine. Two volunteers discontinued treatment due to a maculopapular rash. The most common side effects were changes in bowel habits, flatulence, fatigue, dry skin, and rash.

Study Conclusions

Per the authors, clinically significant alterations in maraviroc exposure can be attributed to the co-administration with HIV NNRTIs (or other modulators of CYP3A4 activity). However dosage adjustments can compensate for the PK alterations.1

References

Kakuda TN. Pharmacokinetic interactions of maraviroc with darunavir-ritonavir, etravirine, and etravirine-darunavir-ritonavir in healthy volunteers: results of two drug interaction trials. Antimicrobial Agents And Chemotherapy . 2016; 5: 2290-2296.