Moderate
Estradiol × Phenobarbital
Estrogens — natural and semisynthetic×Antiepileptics. Barbiturates
Mechanism
Phenobarbital is a strong CYP3A4 inducer; it lowers oestradiol levels by 40–60%. On menopausal hormone therapy, menopausal symptoms may return. On combined oral contraceptives, unplanned pregnancy risk arises.
Symptoms
Return of vasomotor symptoms: hot flushes, night sweats, sleep disturbance. On oral contraceptives: breakthrough bleeding, conception risk.
Management
On menopausal hormone therapy, raise the oestradiol dose or switch to transdermal forms. For contraception on phenobarbital, combined oral contraceptives are unsuitable — choose a levonorgestrel IUS, copper IUD, or depot medroxyprogesterone acetate. In young women with epilepsy, consider switching phenobarbital to levetiracetam or lamotrigine (no CYP3A4 induction).
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.