Bone marrow suppressants (e.g., carbamazepine, chloramphenicol), sulfonamides (e.g., co-trimoxazole), pyrazolone analgesics (e.g., phenylbutazone), azapropazone, penicillamine, cytotoxic agents and long-acting depot injections of antipsychotics (e.g., flupentixol, fluphenazine, haloperidol, pipotiazine, risperidone, zuclopenthixol): Increased risk of agranulocytosis; concomitant use is not recommended.
Ritonavir: Plasma concentration of clozapine is increased by ritonavir (increased risk of toxicity). Concomitant use is not recommended.
Benzodiazepines: Concomitant use may increase risk of circulatory collapse, which may lead to cardiac and/or respiratory arrest.
Alcohol, antihistamines, monoamine oxidase inhibitors (MAOIs), CNS depressants, including narcotics: Enhanced central effects; additive CNS depression and cognitive and motor performance interference when used in combination with these drugs.
Anticholinergics (e.g., atropine-like drugs): Clozapine potentiates the action of these drugs through additive anticholinergic activity.
Antihypertensives: Clozapine can potentiate the hypotensive effects of these drugs due to its sympathomimetic antagonistic effects.
Type 1C antiarrhythmics (e.g., flecainide, propafenone, encainide, quinidine): Increased risk of arrhythmias.
Highly protein bound drugs (e.g., warfarin, digoxin): Clozapine may increase the plasma concentrations of these drugs due to displacement from plasma proteins.
Tricyclic antidepressants and antimuscarinics: Increased antimuscarinic side effects.
Caffeine, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, ciprofloxacin and amprenavir: Increased clozapine plasma concentration.
Omeprazole, rifampicin: Reduced clozapine plasma concentration.
Lithium: Increased risk of extrapyramidal side-effects and possibly neurotoxicity.
Phenytoin: Metabolism of clozapine is accelerated by phenytoin (reduced clozapine plasma concentration).
Cimetidine: Effects of clozapine possibly enhanced by cimetidine.
Citalopram: Plasma concentration of clozapine possibly increased by citalopram (increased risk of toxicity).
Erythromycin: Plasma concentration of clozapine possibly increased by erythromycin (possible increased risk of convulsions).
Other interaction: Smoking: May decrease clozapine plasma levels, resulting in decreased effectiveness of previously effective clozapine dose.