Efavirenz + Voriconazole = Precautionary

Effect on Concentration

Efavirenz
Increase
Applies within class?
No
Voriconazole
Decrease
Applies within class?
No

Pharmacologic Effects

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

Interaction History

N/A

Last Updated 30-Jul-2018

Summary

Sources

Efavirenz versus Voriconazole ^

Study Design

In study one, A randomized, placebo–controlled (with respect to voriconazole), 2‐period, multiple‐dose intragroup fixed‐dose sequence study was conducted in 34 healthy male subjects to evaluate the interactions between voriconazole (triazole antifungal agent) and efavirenz (reverse transcriptase inhibitor). In period 1, subjects received 200 mg twice‐daily (bid) voriconazole (n = 17) or placebo (n = 17) for 3 days (400‐mg bid loading doses on day 1). In period 2, following a 7‐day washout, subjects received 400 mg once‐daily (qd) efavirenz alone for 10 days (days 11–20). Then efavirenz was coadministered with 200 mg bid voriconazole or placebo for the next 9 days (days 21–29). Serial plasma voriconazole and efavirenz concentrations were measured on days 3, 19, and 29, and the safety data were collected throughout the study.

Study Results

In study one, he 400‐mg qd efavirenz dose substantially reduced the steady‐state mean voriconazole area under the curve over the dosing interval (AUC0–12) by 80% (90% confidence interval [CI], 75%–84%) and peak concentration (Cmax) by 66% (90% CI, 57%–73%). The decrease in voriconazole exposure during coadministration is probably mainly due to the induction of CYP2C19 and CYP2C9 by efavirenz. The 200 mg bid voriconazole increased the steady‐state mean AUC0–24 and Cmax of efavirenz by 43% (90% CI, 36%–51%) and 37% (90% CI, 29%–46%), respectively. The increase in efavirenz exposure during coadministration is probably due to the inhibition of CYP3A4 by voriconazole.

Study Conclusions

Author’s concluded that coadministration should be avoided, but future data suggested that when co‐administered, voriconazole dose should be increased to 400 mg q12 h and efavirenz dose decreased to 300 mg q24 h in order to provide systemic exposures similar to standard‐dose monotherapy.

References

Damle B, LaBadie R, Crownover P, Glue P. Pharmacokinetic interactions of efavirenz and voriconazole in healthy volunteers. British Journal Of Clinical Pharmacology. 2008; 4: 523-530.