A 31-year-old woman taking a combined oral contraceptive begins self-medicating with St John's wort for mild low mood. Three weeks later she notices intermenstrual spotting and is worried about contraceptive failure. What is the underlying mechanism?

• A Inhibition of CYP2D6, raising ethinylestradiol concentrations
• B Induction of CYP3A4, accelerating metabolism of ethinylestradiol and progestin ✓
• C Irreversible inhibition of monoamine oxidase, altering steroid clearance
• D Displacement of progestin from plasma protein binding sites

Explanation

St John's wort is a potent inducer of CYP3A4 and P-glycoprotein, lowering plasma levels of combined oral contraceptives and causing breakthrough bleeding, unintended ovulation, and contraceptive failure. It also induces CYP enzymes to reduce levels of ciclosporin, warfarin, indinavir, and digoxin. Inhibition of CYP2D6 would raise, not lower, co-administered drug levels, and the herb's weak MAO-inhibiting and serotonin reuptake properties relate to its mood effects and interactions with serotonergic drugs, not contraception.

Reference: Stahl's Essential Psychopharmacology, 5th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.