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Fluoroquinolone-Clozapine Interaction — MRCPsych Paper B MCQ

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HardSchizophrenia & PsychosisFluoroquinolone-Clozapine InteractionMRCPsych Paper B

A 42-year-old non-smoking man takes clozapine 450 mg daily and has a stable trough clozapine concentration. He develops a culture-confirmed urinary tract infection without fever or a systemic inflammatory response. His adherence, caffeine intake and smoking status remain unchanged. Which antibiotic, if prescribed, is most likely to cause a clinically important increase in his clozapine concentration through inhibition of its metabolism?

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Correct answer: B — Ciprofloxacin

Ciprofloxacin is the correct answer. It inhibits CYP1A2, an important pathway in clozapine metabolism, and can therefore increase clozapine exposure and precipitate concentration-related adverse effects such as sedation, confusion, tachycardia, myoclonus or seizures. The ciprofloxacin SmPC documents increases of approximately 29% in clozapine and 31% in N-desmethylclozapine concentrations after co-administration, although larger and clinically severe increases can occur in practice. Amoxicillin, cefalexin, nitrofurantoin and trimethoprim do not produce the same established CYP1A2-mediated interaction. Infection itself can also increase clozapine concentrations through inflammation-mediated suppression of metabolism, but the stem excludes systemic inflammation to isolate the pharmacokinetic interaction.

Reference: Electronic Medicines Compendium, Ciprofloxacin 250 mg film-coated tablets, SmPC sections 4.4 and 4.5, revised 2026: https://www.medicines.org.uk/emc/product/7256/smpc