Efavirenz + Bedaquiline = Unknown or no reaction

Effect on Concentration

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

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 10-Jul-2018

Summary

Sources

Safety, tolerability, and pharmacokinetic interactions of the antituberculous agent TMC207 (bedaquiline) with efavirenz in healthy volunteers: AIDS Clinical Trials Group study A5267 ^

Study Design

Healthy volunteers (n=33) were administered a single dose of bedaquiline 400 mg on study day 1 and underwent PK sampling for the drug and its less active metabolite (M2) on study days 1-14. Efavirenz 600 mg once nightly was administered on days 15-28. A second dose of bedaquiline 400 mg was administered on day 29, and PK sampling was conducted on days 29-43 for bedaquiline and M2. Efavirenz PK sampling occurred on day 28. All subjects were screened for CYP2B6 polymorphisms, which may decrease metabolism of efavirenz.

Study Results

Using non-compartmental analysis, the geometric mean ratio (GMR) for bedaquiline AUC was 0.82, indicating an 18% decrease in AUC with efavirenz (p<0.001). The bedaquiline Cmax slightly increased with efavirenz (NS). The AUC of the M2 metabolite did not significantly change with the addition of efavirenz, though the Cmax nearly doubled (p<0.001). Efavirenz Cmin, Cmax and AUC were not significantly different from historical controls, indicating that the presence of CYP2B6 polymorphisms did not affect the validity of the study population.

Study Conclusions

This non-linear mixed effects model was a re-analysis of the data previously published in JAIDS. Using non-compartmental modeling, the published article concluded the interaction was not clinically significant, which differs from these findings. A 40-50% decrease in overall drug exposure may be clinically significant, thus preventing these drug from being used together. Until more data is available, providers should use bedaquiline with efavirenz cautiously.

References

Dooley KE, Park JG, Swindells S, Allen R, Haas DW, Cramer Y. Safety, tolerability, and pharmacokinetic interactions of the antituberculous agent tmc207 (bedaquiline) with efavirenz in healthy volunteers: aids clinical trials group study a5267. Jaids: Journal Of Acquired Immunodeficiency Syndromes. 2012; 5: 455-462.