Efavirenz + Atovaquone = Precautionary

Effect on Concentration

Efavirenz
No change
Applies within class?
No
Atovaquone
Decrease
Applies within class?
No

Pharmacologic Effects

Efavirenz
Effect
N/A
Applies within class?
No
Atovaquone
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 16-Jul-2018

Summary

Sources

Efavirenz versus Atovaquone ^

Study Design

In this study, the pharmacokinetic (PK) interaction between efavirenz (EFV) and atovaquone was evaluated in HIV-positive adults (n=10). Subjects were randomly assigned to atovaquone 750mg BID with food for 14 days (Phase 1), followed by a washout period and then atovaquone 1500mg BID for 14 days (Phase 2), or vice versa. Blood samples were collected on day 14 of each phase for PK analysis. A previous open-label, multi center, phase 1 study compared single-dose atovaquone/proguanil 250/100 mg PK between healthy volunteers and HIV-infected volunteers who were stable on ART regimens containing EFV (n=20).

Study Results

Using geometric mean ratios and 90% confidence intervals, the AUC and Cavg were both 0.53 (0.43-0.64) when co-administered with EFV, compared to atovaquone alone when dosed at 750mg BID. When dosed at 1500mg BID the AUC and Cavg were both 0.56 (0.43-0.73) compared to atovaquone alone. Additionally, 4 out of 10 subjects in the atovaquone 750mg BID group had an atovaquone Cavg < 14mcg/ml - the concentration associated with sucessful PCP treatment. In the previous study, the geometric mean ratio (95% confidence interval) of the AUC and Cmax for atovaquone relative to healthy volunteers was 0.25 (0.16-0.38) and 0.56 (0.39-0.80), respectively, for subjects on EFV. PK parameters for EFV were not reported.

Study Conclusions

Co-administration of atovaquone and EFV is not recommended

References

Van Luin M, Van der Ende ME, Richter C, Visser M, Faraj D, Van der Ven A, Kuks PF. Lower atovaquone/proguanil concentrations in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir. Aids. 2010; 8: 1223-1226.