TaperCommunityclozapine
Boxed Warning
Severe neutropenia/agranulocytosis (REMS-required ANC monitoring), orthostatic hypotension/cardiovascular and respiratory effects, seizures, myocarditis and cardiomyopathy, increased mortality in elderly with dementia-related psychosis.
Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia and reduces suicide risk in schizophrenia. Reserved for treatment-resistant cases because of severe agranulocytosis risk requiring lifelong blood monitoring (REMS program).
12.5mg, 25mg, 50mg, 100mg, 200mg tablets; orally disintegrating
Tablets: 25mg, 100mg; ODT: 12.5mg, 25mg, 100mg, 150mg, 200mg; Oral suspension: 50mg/mL
Category B
D2 antagonist (modest), strong 5-HT2A, M1, alpha-1, H1 antagonism. Broad receptor profile — drives both efficacy and side-effect burden.
Very slow taper essential. Rebound psychosis on clozapine discontinuation can be more severe than original presentation. Coordinate with hematology and the REMS program.
Clozapine is unique — discontinuation should not be attempted without a clear plan and continuous mood/psychosis monitoring.
1-3 days after stopping
1-2 weeks
4-8 weeks
Risk of supersensitivity psychosis after stopping is real and well-described
Toxicity
Agranulocytosis (~1%), myocarditis, seizures (dose-dependent), severe constipation/ileus, hypersalivation, weight gain, metabolic syndrome, orthostasis, sedation, NMS.
Pharmacokinetics
Hepatic via CYP1A2 (major), CYP3A4, CYP2D6.
~97%
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