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Clozapine and Oestrogen Interaction — MRCPsych Paper B MCQ

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HardSchizophrenia & PsychosisClozapine and Oestrogen InteractionMRCPsych Paper B

A 43-year-old non-smoking woman with treatment-resistant schizophrenia is stable on clozapine 500 mg daily. Her steady-state trough clozapine concentration is 0.60 mg/L. There is no acute infection and her caffeine intake is unchanged. She starts a combined oral contraceptive containing ethinylestradiol and levonorgestrel. Which pharmacokinetic effect is most likely?

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Reveal the answer and explanation

Correct answer: A — An increased level, because the hormonal contraceptive inhibits CYP1A2, CYP3A4 and CYP2C19

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

B is correct. The clozapine SmPC identifies hormonal contraceptives, including combined oestrogen-progestogen preparations, as inhibitors of CYP1A2, CYP3A4 and CYP2C19. CYP1A2 is particularly important in clozapine clearance, so starting the contraceptive may raise the clozapine concentration and increase dose-related adverse effects such as sedation, constipation, tachycardia or seizures. Clinical review and repeat trough-level monitoring are appropriate, with dose adjustment according to the measured concentration and tolerability. Option C reverses the interaction: this is inhibition, not induction. Options A and E incorrectly deny an interaction with oral preparations. Option D is also incorrect because the SmPC includes both combined and progestogen-only hormonal contraceptives rather than restricting the effect to progestogen-only products.

Reference: Viatris. Clozaril 200 mg Tablets, Summary of Product Characteristics, section 4.5: Interaction with other medicinal products and other forms of interaction. Revised February 2026. https://www.medicines.org.uk/emc/product/102057/smpc