Tobacco smoke, not nicotine, induces the liver enzyme CYP1A2, which metabolises clozapine and olanzapine. When a smoker stops — including on admission to a smoke-free ward — the induction fades over days and plasma levels can rise substantially.
For clozapine this can cause sedation, hypotension and seizures. Nicotine replacement does not prevent the change, because it does not contain the inducing compounds.
- Record smoking status for every patient on clozapine or olanzapine.
- When a patient stops smoking, consider a dose reduction and check a clozapine level within about a week.
- Expect the reverse when a patient restarts smoking after discharge: levels fall and relapse risk rises.
- Do not assume nicotine replacement protects against the interaction.
Why it matters
A hospital admission is often an unplanned smoking cessation, and the interaction is easily missed.
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