Maraviroc + Atazanavir = Precautionary

Effect on Concentration

Maraviroc
Increase
Applies within class?
No
Atazanavir
No change
Applies within class?
No

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 20-Jul-2018

Summary

Sources

Maraviroc versus Atazanavir ^

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 darunavir/ritonavir has on the CCR5 antagonist maraviroc when the two are used in combination. (n=12) healthy men and women aged 21-55 were enrolled in a two-way cross over study to investigate the influence of darunavir/ritonavir on the plasma pharmacokinetics of maraviroc. Subjects received 150mg of maraviroc BID while subsequently receiving either a placebo or darunavir/ritonavir 600/100mg BID for days 1-9 and a single morning dose on day 10. There was a screening period of 28 days, two 10 day treatment periods with a minimum washout period of 14 days and a follow up visit 7-10 days after the last dose of the study drug. Maraviroc was administered under fasting conditions and darunavir/ritonavir was given with a standardized breakfast 1.5h after maraviroc dosing, on day 10. Serial blood samples were collected on days 1 to 9 predose and at 1, 2, 3, 4, 6, 8 and 12 hours post maraviroc dose on day 10. On days 8 and 10 darunavir/ritonavir concentrations were analyzed. Urine sampling was collected 0-12h post maraviroc dosing on day. 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 4.05% increase in AUC12 (2.94, 5.59) and a 2.29% increase in Cmax (1.46, 3.59) of maraviroc upon co-administration with the boosted protease inhibitor darunavir. This combination was generally well tolerated, with no serious adverse events. One volunteer discontinued treatment due to a rash.

Study Conclusions

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

References

Abel S, Russell D, Taylor-Worth RJ, Ridgway CE, Muirhead GJ. Effects of cyp3a4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. British Journal Of Clinical Pharmacology. 2008; S1: 27-37.