rifampicin and ethinylestradiol/levonorgestrel

Rifampicin is a potent inducer of hepatic cytochrome P450 enzymes, particularly CYP3A4. Ethinylestradiol and levonorgestrel are metabolised by CYP3A4. Induction increases their metabolic clearance, leading to reduced plasma concentrations of both hormones.

Plasma levels of ethinylestradiol and levonorgestrel are significantly decreased, which can result in contraceptive failure and unintended pregnancy. Breakthrough bleeding may occur as a sign of reduced contraceptive efficacy.

Avoid co-prescription where possible. If rifampicin is essential, advise a non-hormonal contraceptive method or an alternative contraception (e.g., barrier method or copper intrauterine device) for the entire duration of rifampicin therapy and for at least 28 days after stopping. Monitor for breakthrough bleeding and arrange pregnancy testing if appropriate.

Well-established interaction, supported by pharmacokinetic studies and clinical reports of unintended pregnancies and breakthrough bleeding in women using combined oral contraceptives with rifampicin.