clozapine

Antipsychotic

Brands: CLOZARIL

Last reviewed 2025-12-28

Reviewed by PsychMed Editorial Team.

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Quick answers

What is clozapine?
Clozapine (brand Clozaril, owned by Novartis/Sandoz) is a second-generation antipsychotic (SGA). Clozaril refers to the oral tablet; two additional branded formulations—FazaClo (an orally disintegrating tablet, or ODT) and Versacloz (an oral suspension)—support patients who cannot swallow standard tablets.
What is CLOZARIL?
CLOZARIL is a brand name for clozapine.
What is CLOZARIL (clozapine) used for?
Label indications include: Treatment-resistant schizophrenia; Reduction of recurrent suicidal behavior in schizophrenia or schizoaffective disorder.
What drug class is CLOZARIL (clozapine)?
Antipsychotic.
What is the mechanism of action of CLOZARIL (clozapine)?
Mechanism not fully known. Proposed efficacy via antagonism at dopamine D2 and serotonin 5‑HT2A receptors; also antagonizes adrenergic, cholinergic, and histaminergic receptors.
What strengths does CLOZARIL (clozapine) come in?
Oral tablets: 12.5 mg, 25 mg, 50 mg, 100 mg, 200 mg.
Is CLOZARIL (clozapine) a controlled substance?
No — it is not scheduled as a controlled substance under U.S. federal law.

Snapshot

Class: Antipsychotic
Common US brands: CLOZARIL
Therapeutic drug monitoring recommended; reference range 350–600 ng/mL.
Last reviewed: 2025-12-28

Clinical Highlights

Clozapine (brand Clozaril, owned by Novartis/Sandoz) is a second-generation antipsychotic (SGA). Clozaril refers to the oral tablet; two additional branded formulations—FazaClo (an orally disintegrating tablet, or ODT) and Versacloz (an oral suspension)—support patients who cannot swallow standard tablets. ODTs dissolve on the tongue without water, which aids adherence when swallowing is difficult. Oral suspensions are liquid formulations measured with an oral syringe so clinicians can titrate doses with finer precision.

In 1989 the FDA approved clozapine for treatment-resistant schizophrenia (TRS) or for intolerable motor side effects with other antipsychotics. TRS typically means two adequate antipsychotic trials have not delivered meaningful symptom reduction, and clozapine remains the only antipsychotic specifically approved for this population.
Early agranulocytosis reports—most notably eight Finnish deaths in 1975—delayed U.S. adoption and led to mandatory blood monitoring when clozapine launched. Effective June 2025 the FDA discontinued the U.S. clozapine REMS program, so ANC monitoring is now clinician-guided rather than tied to a dispensing registry, though vigilance for neutropenia is still prudent.
Clozapine gained a 2002 indication to reduce recurrent suicidal behavior in schizophrenia or schizoaffective disorder and is recommended in APA guidelines when persistent aggression or suicidality endures despite other antipsychotics.
A 2025 Finland/Sweden register study found clozapine use was associated with lower psychiatric hospitalization versus other oral antipsychotics across schizophrenia-spectrum disorders and several affective disorders (including bipolar disorder and psychotic depression), without evidence of increased mortality; borderline personality disorder did not show benefit.
Multiple manufacturers (Teva, Hikma, Sun, Aurobindo, Accord, Apotex, Mylan/Viatris, among others) supply generic tablets and ODTs; Versacloz 50 mg/mL oral suspension remains brand-only in the United States.
The compare view, clozapine evidence feed, and clozapine print page can support counseling and shared decision-making; the schizophrenia hub and bipolar disorder hub include related care pathways for aggression or suicidality.

Dosing & Formulations

Oral tablets: 12.5 mg, 25 mg, 50 mg, 100 mg, 200 mg. FazaClo orally disintegrating tablets (ODT): 12.5 mg, 25 mg, 100 mg, 150 mg, 200 mg; dissolve on the tongue without water.

Versacloz oral suspension: 50 mg/mL in 120 mL bottles measured with an oral syringe.
No long-acting injectable formulation is available; patients needing depot therapy must consider other LAI antipsychotics.
Label initiation is 12.5 mg once or twice on day 1; increase by 25–50 mg/day in divided doses as tolerated.
Typical maintenance is 300–450 mg/day in divided doses; some patients require up to 600 mg/day. The labeled maximum is 900 mg/day.

Monitoring & Risks

ANC monitoring: Weekly for first 6 months, every 2 weeks for months 6–12, then monthly thereafter per label. Metabolic: Track weight/BMI and fasting lipids/glucose at baseline, 3 months, then periodically.

Clinical: Monitor for infection; inflammation or smoking changes can alter serum levels.
Early myocarditis vigilance: Follow local guidance (some protocols include troponin/CRP during initial weeks).
Boxed warning: Increased mortality in elderly patients with dementia-related psychosis (class warning).
Boxed warning: Historically boxed for severe neutropenia; the FDA removed the U.S. Clozapine REMS program effective June 2025 and clinicians now individualize ANC monitoring.

Drug Interactions

CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin) markedly raise levels—dose reduction and monitoring (clinical response or serum concentrations) are typically needed. CYP1A2 inducers (smoking, carbamazepine, omeprazole, rifampin) lower exposure—co-use is generally avoided when possible; if unavoidable, dose adjustments with monitoring are common.

CYP3A4/CYP2D6 modulators (ketoconazole, paroxetine) alter clozapine and norclozapine concentrations; adjust doses as needed.
Concomitant CNS depressants (benzodiazepines, opioids, alcohol) increase sedation and respiratory risk—slower initiation and closer monitoring are typical.
QTc-prolonging agents warrant ECG monitoring, especially in patients with additional cardiac risk factors.
Strong anticholinergics or opioids heighten gastrointestinal hypomotility risk; bowel function monitoring is emphasized.

Practice Notes

Lifestyle changes such as smoking cessation, sudden illness (particularly respiratory infections), or major caffeine shifts can markedly alter serum levels—patients are often counseled to report changes promptly. Bowel and sialorrhea strategies are often started proactively to improve adherence and prevent serious gastrointestinal complications.

Weight, waist circumference, fasting lipids, glucose, and HbA1c are monitored regularly; baseline cardiac assessment is often obtained during the initial months of therapy.
Counseling often covers seizure warning signs, infection symptoms, and when to seek urgent evaluation.

References

CLOZARIL (clozapine) label — DailyMed (2025)
FDA removes Clozapine REMS — FDA (2025)
Transdiagnostic Effectiveness AND Safety OF Clozapine IN Individuals With Psychotic, Affective, AND Personality Disorders: Nationwide AND Meta Analytic Comparisons With Other Antipsychotics — Lancet Psychiatry (2025)
Nssc Clozapine First 2021
Everypalmer2017 Cigh
Cohen2017 Clozapine GIH
Himmerich2021 Clozapine Guidance