Liverpool HIV Interactions

Do Not Coadminister

Efavirenz (EFV)

Desogestrel (COC)

Quality of Evidence: Moderate

Summary:

Coadministration is expected to reduce the contraceptive efficacy of desogestrel and therefore a reliable method of barrier contraception must be used in addition to hormonal contraceptives. Desogestrel is a prodrug that requires activation to etonogestrel. Activation to etonogestrel is by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Coadministration of efavirenz and desogestrel was administered as a COC to HIV+ women (n=16). An increased risk of contraceptive failure (evaluated by measuring serum progesterone) was observed and efavirenz C12 concentrations decreased by 22% and were below the target of 1000 ng/ml in 3/16 subjects. When compared to values obtained from administration without efavirenz to HIV-negative women (n=14), etonogestrel trough concentrations decreased by 61% in HIV+ women administered desogestrel/ethinylestradiol and efavirenz (n=16). In addition, efavirenz has been shown to reduce the exposure of progestogens and unintended pregnancy have been observed when used with levonorgestrel or etonogestrel containing implants.

Description:

Barrier contraception should always be used in combination with other methods of contraception (for example, oral or other hormonal contraceptives). Because of the long half-life of efavirenz, use of adequate contraceptive measures for 12 weeks after discontinuation of efavirenz is recommended.

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

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. Barrier contraception should always be used in combination with other methods of contraception. Hormonal methods that contain progesterone may have decreased effectiveness.

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

Etonogestrel and ethinylestradiol concentrations were determined in 16 HIV+ women receiving desogestrel/ethinylestradiol (0.15/0.03 mg/day) and efavirenz (600 mg once daily) and 14 HIV-negative women receiving desogestrel/ethinylestradiol (0.15/0.03 mg/day) alone. Etonogestrel and ethinylestradiol trough concentrations were decreased by 61% and 9% in the presence of efavirenz.

Significant decrease of ethinylestradiol with nevirapine, and of etonogestrel with efavirenz in HIV-positive women. Landolt NK, Phanuphak N, Ubolyam S, et al. J Acquir Immune Defic Syndr, 2014, 66(2): e50-2.

Coadministration of desogestrel/ethinylestradiol (0.15/0.03 mg/day) and efavirenz (600 mg once daily) was studied in 16 HIV+ women. Serum progesterone in three subjects was greater than 3.0 ng/ml (which might indicate ovulation). Efavirenz C12 concentrations decreased significantly by 22% and were below the target of 1000 ng/ml in three subjects.

Efavirenz, in contrast to nevirapine, is associated with unfavorable progesterone and antiretroviral levels when coadministered with combined oral contraceptives. Landolt NK, Phanuphak N, Ubolyam S, et al. J Acquir Immune Defic Syndr, 2013, 62(5): 534-9.

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