Clozapine Fact Sheet

Medication Name (brand):

Clozapine

Manufacturer:

Novartis; also available in generic formulations.

Indications:

Management of severely ill schizophrenic patients who fail to respond to standard drug treatment.
Reduction in the risk of suicide in schizophrenia and schizoaffective disorder.
Off-label use for a variety of disorders, including bipolar and schizoaffective disorder.

Mechanism:

Antagonist of several dopamine receptors.

Dosing:

Supplied in 25 mg and 100 mg breakable tablets.
Start at 12.5 mg QD or BID, and increase gradually by 25-50 mg/day to target dose of 300-450 mg after 2 weeks. Maximum recommended dose is 900 mg/day divided TID.
It may take 3 to 6 months for a therapeutic response.

Side Effects:

Most common are sedation, dizziness, hypersalivation (no good treatment; place towel on pillow), weight gain (substantial, 15-30 pound average wt. gain after one year), constipation, tachycardia (can treat with inderal).
EPS: Uncommon.
Glucose/Lipids: Associated with new onset diabetes and hyperlipidemia; worse in this regard than all atypicals.
EKG: No clear changes.
Prolactin level: Little or no increase.
Pregnancy category B.
BLACK BOX WARNINGS: Agranulocytosis: Most cases occur during the first 3 months of treatment. Incidence is 0.4%, and death rate is 0.012% (1 out of 10,000 patients); Seizures: About 5% incidence. Can be managed by reducing dose or adding Depakote; Myocarditis: Rare but often fatal; Cardiovascular collapse: 1/3000 patients; Mortality in elderly patients: 1.7 times the risk of placebo (class warning for all aypicals).

Drug-drug Interactions:

Does not affect hepatic enzyme systems, thus does not affect metabolism of other drugs.
Luvox, Tagamet, and erythromycin inhibit the metabolism of clozapine and therefore can increase blood levels.
Tegretol and nicotine induce clozapine metabolism and can decrease blood levels.
Half-life 12 hours.

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