Category: pharmacological
Aliases: Clozaril, Versacloz, FazaClo
Atypical antipsychotic with broad receptor activity: 5-HT2A, D4, D2 (lower affinity than typicals), α1, H1, M1-5 antagonism. Indicated for treatment-resistant schizophrenia and reduction of suicidal behavior. Narrow therapeutic index: agranulocytosis risk (~1%) mandates lifelong WBC monitoring under REMS. Primarily metabolized by CYP1A2 (major) and CYP3A4 (minor). Smoking induces CYP1A2 and substantially lowers clozapine exposure; smoking cessation is a clinical interaction. Active metabolite norclozapine. PK (Clozaril label, 100 mg PO bid SS): Cmax 319 ng/mL (range 102-771), Cmin 122 ng/mL (41-343), Tmax 2.5 h (range 1-6), t½ 12 h single-dose / 14 h SS, F 27-50% (avg 40%), protein binding 97%. Smoking induces CYP1A2 → lowers exposure ~50%; smoking cessation can produce toxicity at unchanged dose. Major fluvoxamine + ciprofloxacin DDIs (CYP1A2 inhibition).
PO: 14h