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Clozapine Fact Sheet

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Medication Name (brand): 

Novartis; also available in generic formulations.

  • 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.


Antagonist of several dopamine receptors.

  • 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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