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Clozapine Drug Interactions — MRCPsych Paper B MCQ

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HardSchizophrenia & PsychosisClozapine Drug InteractionsMRCPsych Paper B

A 37-year-old man with schizophrenia takes clozapine 500 mg daily. His adherence, tobacco smoking and caffeine intake have been stable, with a trough clozapine concentration of 0.45 mg/L. He develops a culture-confirmed lower respiratory tract infection for which ciprofloxacin is selected following microbiology advice. During treatment his infection is improving, but he becomes increasingly drowsy and develops myoclonic jerks. Which change in clozapine pharmacokinetics is most likely?

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Correct answer: C — Increased concentration because ciprofloxacin inhibits CYP1A2

Ciprofloxacin inhibits CYP1A2, an important pathway in clozapine metabolism, thereby reducing clozapine clearance and increasing its plasma concentration. Drowsiness and myoclonic jerks are compatible with concentration-related clozapine toxicity. The ciprofloxacin SmPC reports mean increases of 29% in clozapine and 31% in norclozapine concentrations during co-administration, although the magnitude varies between patients. Systemic inflammation can also inhibit CYP1A2 and may compound the increase during an infection. Ciprofloxacin does not induce CYP1A2 or CYP3A4, excluding A and C. CYP2D6 is only a subsidiary clozapine pathway and is not the principal mechanism here, excluding D. The interaction can increase both clozapine and norclozapine, excluding E. Clinical review, clozapine-level monitoring and an individually appropriate dose adjustment are required.

Reference: Electronic Medicines Compendium. Ciprofloxacin 250 mg film-coated tablets, Summary of Product Characteristics, sections 4.5 and 5.2 (current version). https://www.medicines.org.uk/emc/product/7256/smpc