Drug Interactions between ethinyl estradiol and Mavyret

GENERALLY AVOID: Coadministration of ethinyl estradiol-containing products with glecaprevir-pibrentasvir may increase the risk of alanine aminotransferase (ALT) elevations. In clinical trials, women using ethinyl estradiol-containing medications such as combined oral contraceptives were significantly more likely to have ALT elevations, in some cases greater than 20 times the upper limit of normal. ALT elevations are also associated with glecaprevir, particularly at high exposures, thus an additive risk may occur. Pharmacokinetically, glecaprevir-pibrentasvir may increase the plasma concentrations of ethinyl estradiol, presumably due to mild inhibition of CYP450 3A4-mediated metabolism. In 11 study subjects, once daily coadministration of ethinyl estradiol-norgestimate 35 mcg-250 mcg with glecaprevir-pibrentasvir 300 mg-120 mg increased ethinyl estradiol peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 31%, 28% and 38%, respectively. Likewise, once daily coadministration of ethinyl estradiol-levonorgestrel 20 mcg-100 mcg with glecaprevir-pibrentasvir 300 mg-120 mg to 12 study subjects increased ethinyl estradiol Cmax, AUC and Cmin by 30%, 40% and 56%, respectively. No effects were observed in the pharmacokinetics of glecaprevir and pibrentasvir.

MANAGEMENT: Concomitant use with glecaprevir-pibrentasvir should be generally avoided and is contraindicated by some authorities. It is recommended to switch to an alternative method of contraception (e.g., progestin-only contraception or non-hormonal methods) prior to starting and for two weeks following the completion of the hepatitis C treatment. Manufacturers of glecaprevir-pibrentasvir indicate that preparations containing 20 mcg or less of ethinyl estradiol may be coadministered. However, individual product labeling for the ethinyl estradiol-containing medication should be consulted for specific recommendations and patients should be closely monitored for ALT elevations throughout concomitant treatment.

GENERALLY AVOID: Coadministration of ethinyl estradiol-containing products with glecaprevir-pibrentasvir may increase the risk of alanine aminotransferase (ALT) elevations. In clinical trials, women using ethinyl estradiol-containing medications such as combined oral contraceptives were significantly more likely to have ALT elevations, in some cases greater than 20 times the upper limit of normal. ALT elevations are also associated with glecaprevir, particularly at high exposures, thus an additive risk may occur. Pharmacokinetically, glecaprevir-pibrentasvir may increase the plasma concentrations of ethinyl estradiol, presumably due to mild inhibition of CYP450 3A4-mediated metabolism. In 11 study subjects, once daily coadministration of ethinyl estradiol-norgestimate 35 mcg-250 mcg with glecaprevir-pibrentasvir 300 mg-120 mg increased ethinyl estradiol peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 31%, 28% and 38%, respectively. Likewise, once daily coadministration of ethinyl estradiol-levonorgestrel 20 mcg-100 mcg with glecaprevir-pibrentasvir 300 mg-120 mg to 12 study subjects increased ethinyl estradiol Cmax, AUC and Cmin by 30%, 40% and 56%, respectively. No effects were observed in the pharmacokinetics of glecaprevir and pibrentasvir.

MANAGEMENT: Concomitant use with glecaprevir-pibrentasvir should be generally avoided and is contraindicated by some authorities. It is recommended to switch to an alternative method of contraception (e.g., progestin-only contraception or non-hormonal methods) prior to starting and for two weeks following the completion of the hepatitis C treatment. Manufacturers of glecaprevir-pibrentasvir indicate that preparations containing 20 mcg or less of ethinyl estradiol may be coadministered. However, individual product labeling for the ethinyl estradiol-containing medication should be consulted for specific recommendations and patients should be closely monitored for ALT elevations throughout concomitant treatment.