Clozapine Interactions

Polycyclic aromatic hydrocarbons in tobacco smoke (not nicotine) potently induce CYP1A2, the enzyme responsible for roughly 70% of clozapine metabolism, lowering clozapine plasma levels by up to 50% in smokers. Sudden smoking cessation can cause clozapine levels to rise 50-72% within 3-5 days, risking sedation, seizures, and toxicity.

Caffeine inhibits CYP1A2, the main enzyme that metabolizes clozapine. High caffeine intake (especially energy drinks) can dramatically raise clozapine levels, with case reports of life-threatening toxicity including multiorgan failure.