Tobacco smoke induces the liver enzyme CYP1A2, which clears clozapine and olanzapine. When a patient stops smoking, perhaps on admission to a smoke-free ward or after a quit attempt, clozapine levels can rise substantially over one to two weeks. When they restart, levels fall and relapse risk rises.
Nicotine replacement does not induce CYP1A2; the effect comes from the smoke itself, so switching to patches or gum still removes the induction.
- Ask about smoking at every clozapine review, and record any change.
- Check a plasma level and watch for sedation, hypersalivation or seizures after a patient stops smoking.
- Expect levels to fall and relapse risk to rise if a patient resumes smoking after discharge.
- Remember that nicotine patches do not keep the enzyme induced.
Why it matters
Clozapine toxicity after admission is often a smoking change no one asked about.
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