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Clozapine–hormonal contraceptive interaction — DFSRH MCQ

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EasySchizophreniaClozapine–hormonal contraceptive interactionDFSRH

A 32-year-old woman with treatment-resistant schizophrenia is stable on clozapine 300 mg daily. She has no current adverse effects and takes no other medication. She requests highly effective contraception that is least likely to necessitate monitoring or adjustment of her clozapine dose. Pregnancy has been reasonably excluded, and she is medically eligible for all contraceptive methods. Her periods are regular and light. After counselling, she would accept either intrauterine contraception, an implant, an injectable or combined hormonal contraception. Which is the most appropriate contraceptive plan?

Educational content. Not a substitute for clinical judgement or local policy.

Reveal the answer and explanation

Correct answer: A — Insert a copper intrauterine device to avoid hormonal inhibition of clozapine metabolism

Explanation lettering: E = shown as A · C = shown as B · A = shown as C · B = shown as D · D = shown as E

The copper intrauterine device is the best answer because the patient specifically prioritises a method least likely to require clozapine monitoring or dose adjustment. It contains no contraceptive hormone and therefore avoids the pharmacokinetic interaction described in the clozapine Summary of Product Characteristics. Clozapine is principally metabolised by CYP1A2 and CYP3A4; hormonal contraceptives, including estrogen–progestogen and progestogen-only preparations, may inhibit CYP1A2, CYP3A4 and CYP2C19, potentially increasing clozapine exposure and adverse effects. A is a plausible near-miss because the levonorgestrel intrauterine device acts mainly within the uterus and has low systemic exposure, but it remains a hormonal method and an interaction cannot be categorically excluded. B is incorrect because the clozapine product information explicitly includes progestogen-only hormonal contraception among potential inhibitors. C is incorrect because bypassing gastrointestinal absorption and first-pass administration does not establish absence of an interaction at hepatic CYP enzymes. D is a clinically reasonable alternative if combined hormonal contraception were strongly preferred: initiation should be coordinated with the clozapine prescriber, with assessment for toxicity, plasma-level monitoring where appropriate and possible dose adjustment. However, it does not satisfy her stated aim of minimising the need for such intervention. FSRH guidance also emphasises that contraceptive hormones can alter exposure to concomitant medicines and cause toxicity when exposure increases.

Reference: Clozaril 100 mg Tablets — Summary of Product Characteristics (February 2026) — https://www.medicines.org.uk/emc/product/10290/smpc FSRH CEU Guidance: Drug Interactions with Hormonal Contraception (May 2022) — https://www.fsrh.org/Common/Uploaded%20files/documents/drug-interactions-with-hormonal-contraception-5may2022.pdf