Liverpool HIV Interactions

Potential Interaction

Efavirenz (EFV)

Ethinylestradiol

Quality of Evidence: Low

Summary:

The effect of efavirenz on ethinylestradiol exposure varies according to the hormonal contraceptive method. Coadministration of a combined oral contraceptive (COC) containing ethinylestradiol/norgestimate (0.035/0.25 mg once daily) and efavirenz (600 mg once daily) for 14 days had no effect on the Cmax, AUC or Cmin of ethinylestradiol or efavirenz. However, coadministration of a vaginal ring releasing etonogestrel/ethinylestradiol (120/15 µg/day) in HIV positive women treated with efavirenz containing regimen (600 mg once daily) decreased in ethinylestradiol exposure by 53-57%. With both methods, progestogen levels were markedly decreased and therefore use with efavirenz is not recommended as it may impair the contraceptive efficacy. Note, use of ethinylestradiol as part of gender affirming treatment is not recommended due to thrombotic risks.

Description:

Coadministration of an oral contraceptive (ethinylestradiol/norgestimate 0.035/0.25 mg once daily) and efavirenz (600 mg once daily) had no effect on the AUC or Cmax of ethinylestradiol, but decreased Cmin by 8%. The AUC, Cmax and Cmin of the active metabolites of norgestimate (norelgestromin and levonorgestrel) decreased by 64%, 46% and 82% (norelgestromin) and by 83%, 80% and 86% (levonorgestrel). No clinically significant interaction on efavirenz was observed. The clinical significance of these effects is not known. A reliable method of barrier contraception must be used in addition to hormonal contraceptives.

Sustiva Summary of Product Characteristics, Bristol-Myers Squibb Pharmaceuticals Ltd, May 2023.

Coadministration of an oral contraceptive (ethinylestradiol/norgestimate 0.035/0.25 mg once daily) and efavirenz (600 mg once daily) was studied in 21 subjects for 14 days. There was no change in the Cmax, AUC or Cmin of ethinylestradiol. The Cmax, AUC and Cmin of the active metabolites of norgestimate (norelgestromin and levonorgestrel) decreased by 46%, 64% and 82% (norelgestromin) and by 80%, 83% and 86% (levonorgestrel, n=6)). A reliable method of barrier contraception should be used in addition to hormonal contraceptives. Females of reproductive potential should use effective contraception during treatment with efavirenz and for 12 weeks after discontinuing efavirenz due to the long half-life of efavirenz.

Efavirenz US Prescribing Information, Aurobindo Pharma Limited, October 2021.

The use of a vaginal ring releasing etonogestrel/ethinylestradiol (120/15 µg/day) in HIV positive women treated with an efavirenz containing regimen (600 mg once daily)showed a decrease in etonogestrel exposure of 76-79% and in ethinylestradiol exposure of 53-57% compared to exposure of hormones in HIV positive women not yet on ART. Given the substantial decrease in hormone exposure, a reliable method barrier contraception must be used in addition to hormonal contraceptives.

Vaginal contraceptive hormone exposure profoundly altered by EFV- and ATV/r-based ART. Scarsi KK, Cramer YS, Gingrich D, et al. Conference on Retroviruses and Opportunistic Infections (CROI0, Washington, March 2018, abstract 141.

The effect of efavirenz (600 mg once daily) on the pharmacokinetics of a tricyclic oral contraceptive containing ethinyestradiol and norgestimate was studied in 21 female HIV- subjects. Efavirenz had no effect on ethinylestradiol Cmax (6% increase) or AUC (10% decrease). Exposure to the active metabolites of norgestimate - norgestromin and levonorgestrel - were significantly decreased. The Cmax and AUC of norgestromin decreased by 46% and 74%, respectively, while the AUC of levonorgestrel decreased by 83% (n=6). Efavirenz pharmacokinetics were similar to historical data. Although there was no significant effect on the estrogen component, the significant decrease in the progestogen component reinforces the need for additional barrier contraception when taking oral contraceptives with efavirenz.

Effect of efavirenz on the pharmacokinetics of ethinylestradiol and norgestimate in healthy female subjects. Sevinsky H, Eley T, He B, et al. 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, October 2008, abstract A-958.

Coadministration of a single dose ethinylestradiol (50 µg) with efavirenz (400 mg once daily) to 13 healthy volunteers resulted in a 37% increase in the AUC and a non-significant (8%) increase in Cmax of ethinylestradiol. A single dose of ethinylestradiol had no effect on the AUC or Cmax of efavirenz.

Lack of a pharmacokinetic interaction between efavirenz (DMP 266) and ethinyloestradiol in healthy female volunteers. Joshi AS, Fiske WD, Benedek IH, et al. 5th Conference on Retroviruses and Opportunistic Infections, 1998, abstract 348.

View all available interactions with Efavirenz (EFV) by clicking here.