Section 03 · Monograph
Clozapine
Reviewed Nov 2026FDA label
ClozarilAtypical antipsychotic
- Forms
- Tab: 25, 50, 100, 200mg | ODT: 12.5, 25, 100, 150, 200mg | Susp: 50mg/mL
- Dose
- PD psychosis (off-label): 6.25-50mg qHS; ANC monitoring required
- MOA
- 5-HT2A/D4 antagonism with low D2 affinity
Black Box Warning
- Severe neutropenia, which can lead to serious infection and death
- Orthostatic hypotension, bradycardia and syncope
- Seizures
- Myocarditis and cardiomyopathy
- Increased mortality in elderly patients with dementia-related psychosis
Indications
- Treatment-resistant schizophreniaFDA-labeled
- Reducing suicidal behavior in schizophrenia or schizoaffective disorderFDA-labeled
Off-Label Uses
- Parkinson's disease psychosis (low-dose, evidence-supported)Off-label
- Tardive dyskinesia/psychosis in movement disordersOff-label
Mechanism of Action
- Atypical antipsychotic with low D2 affinity and high 5-HT2A, D4 and muscarinic activity; does not worsen parkinsonian motor symptoms
Full Dosing
Adult / usual
- PD psychosis (off-label): start 6.25mg at bedtime, increase by 6.25-12.5mg weekly; typical 12.5-50mg/day
- Follow current label and program requirements for absolute neutrophil count (ANC) monitoring
- Re-titrate if therapy is interrupted
Contraindications
- History of serious hypersensitivity to clozapine
Drug Interactions
- CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) raise levels; smoking lowers levels
- Benzodiazepines and opioids: respiratory and cardiovascular collapse
- Carbamazepine and other marrow-suppressing drugs: avoid (agranulocytosis risk, lower levels)
Adverse Effects
- Sedation, sialorrhea, constipation (can be severe)
- Orthostatic hypotension, tachycardia
- Weight gain and metabolic syndrome
- Seizures, myocarditis
- Severe neutropenia
Monitoring Parameters
- ANC per current label; ECG, troponin and CRP early in treatment
- Weight, glucose, lipids
- Bowel function and orthostatic vital signs
Pregnancy & Lactation
- Limited data; weigh risks and benefits
- Present in milk; breastfeeding not recommended