clozapine

General information

• Class: Antipsychotic
• Common US brands: CLOZARIL
• Typical dose range: Initiate 12.5 mg once or twice on day 1; increase by 25–50 mg/day in divided doses as tolerated.
• Therapeutic drug monitoring recommended; reference range 350–600 ng/mL.
• Last reviewed: 2026-02-23

Dosing & forms

• Forms/strengths: 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.
• Frequency: Initiate 12.5 mg once or twice on day 1; increase by 25–50 mg/day in divided doses as tolerated.
• Typical range: Initiate 12.5 mg once or twice on day 1; increase by 25–50 mg/day in divided doses as tolerated.
• Therapeutic range: 350–600 ng/mL

Mechanism (brief)

Mechanism not fully known. Proposed efficacy via antagonism at dopamine D2 and serotonin 5‑HT2A receptors; also antagonizes adrenergic, cholinergic, and histaminergic receptors.

Metabolism & Half‑life

• Metabolism: CYP1A2, CYP3A4, CYP2D6
• Half‑life: Single-dose mean 8 h; Single-dose range 4–12 h; Steady-state mean 12 h; Steady-state range 4–66 h

Therapeutic Drug Monitoring (TDM)

Recommended: Yes

Reference range: 350–600 ng/mL

Sampling: Trough at steady state: ~12 h post‑dose (or immediately before morning dose if BID).

Monitoring highlights

• 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).

Sources

• CLOZARIL (clozapine) label — DailyMed (2025)
• AGNP Consensus Guidelines for TDM in Psychiatry (update) — Pharmacopsychiatry (2018)
• Therapeutic Drug Monitoring in Psychiatry (Review) — Frontiers/PMC (2024)
• Clozapine TDM Guidance — TEWV NHS (2023)
• TDM standardized to 12‑h post‑dose — Acta Psychiatr Scand (2017)
• Smoking cessation and clozapine levels — PMC (2023)
• Clozaril label: inflammation may increase levels — DailyMed (2025)
• Clozaril label: fluvoxamine ~3x increase — DailyMed (2025)
• Fluvoxamine markedly increases clozapine levels — PubMed (1996)
• 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)