Clozapine is metabolised mainly by CYP1A2, which is induced by the hydrocarbons in tobacco smoke. Stopping smoking — including on admission to a smoke-free ward — can raise levels sharply within days; restarting can drop them. Nicotine replacement does not induce the enzyme.
Check a trough level when starting or changing dose, when smoking status changes, when a CYP1A2 inhibitor such as fluvoxamine or ciprofloxacin is added, during infection or inflammation, when response is poor, or when toxicity is suspected. Take it about 12 hours after the last dose.
- Check a level when a patient stops or starts smoking.
- Check after adding fluvoxamine, ciprofloxacin or another CYP1A2 inhibitor.
- Check during significant infection or inflammation.
- Take trough samples about 12 hours after the last dose.
Why it matters
Most clozapine toxicity follows a predictable change in clearance that nobody checked.
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