FAZACLO ODT

Clinical safety rating: caution

Comprehensive clinical and safety monograph for FAZACLO ODT (FAZACLO ODT).

How it works

Clozapine is an atypical antipsychotic that antagonizes serotonin 5-HT2A and dopamine D2 receptors, with higher affinity for 5-HT2A. It also blocks muscarinic M1, histaminergic H1, and adrenergic α1 and α2 receptors.

What the body does with it

Metabolism	Primarily hepatic via CYP1A2, with minor contributions from CYP2D6, CYP3A4, and CYP2C19. Major metabolites: norclozapine (desmethylclozapine) and clozapine N-oxide.
Excretion	Renal: 50% as metabolites (30% conjugated, 20% desmethylclozapine), 30% as unchanged; Fecal: 30% (biliary/fecal elimination of metabolites).
Half-life	Terminal elimination half-life: 14 hours (range 6-26 hours) at steady state; increases with dose/duration. Context: Twice-daily dosing achieves steady state in 5-7 days.
Protein binding	97% bound (primarily alpha1-acid glycoprotein and albumin).
Volume of Distribution	3-4 L/kg (apparent Vd), indicating extensive tissue distribution (e.g., brain, liver).
Bioavailability	Oral (ODT): 60-70% due to first-pass metabolism (clozapine); bioavailability similar to conventional tablets.
Onset of Action	Oral (ODT): Sedation within 1-2 hours; antipsychotic effect: 2-4 weeks for initial response.
Duration of Action	Sedation: 6-12 hours after single dose; antipsychotic effect: sustained with continuous dosing (monitoring required).

Classification & Brands

Dosing & administration

Clozapine (FAZACLO ODT) is an atypical antipsychotic. For schizophrenia, the typical starting dose is 12.5 mg orally once daily or twice daily, titrated by 25-50 mg/day to a target dose of 300-450 mg/day divided, up to a maximum of 900 mg/day. For treatment-resistant schizophrenia, the target dose is 300-450 mg/day, with doses above 500 mg/day requiring slower titration. The oral disintegrating tablet is taken sublingually or swallowed whole.

Dosage form	TABLET, ORALLY DISINTEGRATING
Renal impairment	Severe renal impairment (CrCl < 30 mL/min): Use with caution; dose reduction may be necessary due to increased risk of accumulation. No specific GFR-based dose guidelines exist; initiate at 12.5 mg once daily, titrate slowly with close monitoring. In end-stage renal disease (ESRD), avoid use or use with extreme caution.
Liver impairment	Clozapine is extensively metabolized in the liver. In hepatic impairment: For Child-Pugh Class A (mild): No adjustment necessary. For Child-Pugh Class B (moderate): Consider a 50% dose reduction and slow titration. For Child-Pugh Class C (severe): Contraindicated or use with extreme caution; limited data exist. Monitor liver function tests regularly.
Pediatric use	Not FDA-approved for pediatric patients under 18 years. However, off-label use for treatment-resistant schizophrenia in adolescents (≥13 years) is sometimes considered: Starting dose 12.5 mg once or twice daily, titrate by 25-50 mg/day to target 300-450 mg/day, maximum 900 mg/day. Weight-based dosing is not established; dosing is based on adult protocol with slower titration.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for FAZACLO ODT (FAZACLO ODT).

Breastfeeding	Clozapine is excreted in breast milk. The M/P ratio is approximately 0.5-0.8. Reports of adverse effects in breastfed infants (e.g., sedation, agranulocytosis). Breastfeeding is not recommended; if used, monitor infant for drowsiness, blood dyscrasias, and poor feeding.
Teratogenic Risk	Pregnancy Category B. No evidence of teratogenicity in animal studies; however, adequate human studies are lacking. Use only if benefit outweighs risk. First trimester: limited human data; animal studies show no fetal harm. Second/third trimester: no known teratogenic effects; monitor for maternal hypotension and neonatal extrapyramidal symptoms.

Warnings & precautions

■ FDA Black Box Warning

Severe neutropenia; myocarditis, cardiomyopathy, and mitral valve incompetence; seizure; orthostatic hypotension, bradycardia, syncope; increased mortality in elderly patients with dementia-related psychosis.

Side Effect Profile

Serious Effects

Absolute Contraindications

History of clozapine-induced neutropenia or agranulocytosis, uncontrolled epilepsy, myeloproliferative disorders, severe central nervous system depression or comatose states, paralytic ileus, concurrent use with other agents that suppress bone marrow function, hypersensitivity to clozapine.

Clinical Precautions

Precautions

Severe neutropenia (absolute neutrophil count <500/μL requires discontinuation), myocarditis (especially during first 2 months), seizures (dose-related), orthostatic hypotension with syncope, QT prolongation, eosinophilia, thromboembolism, anticholinergic toxicity, hepatotoxicity, hyperglycemia, dyslipidemia, weight gain, tardive dyskinesia, withdrawal symptoms.

Clinical Tips & Counseling

Drug interactions

Loading safety data…

FAZACLO ODT

Clinical safety rating: caution

Comprehensive clinical and safety monograph for FAZACLO ODT (FAZACLO ODT).

How it works

What the body does with it

Metabolism	Primarily hepatic via CYP1A2, with minor contributions from CYP2D6, CYP3A4, and CYP2C19. Major metabolites: norclozapine (desmethylclozapine) and clozapine N-oxide.
Excretion	Renal: 50% as metabolites (30% conjugated, 20% desmethylclozapine), 30% as unchanged; Fecal: 30% (biliary/fecal elimination of metabolites).
Half-life	Terminal elimination half-life: 14 hours (range 6-26 hours) at steady state; increases with dose/duration. Context: Twice-daily dosing achieves steady state in 5-7 days.
Protein binding	97% bound (primarily alpha1-acid glycoprotein and albumin).
Volume of Distribution	3-4 L/kg (apparent Vd), indicating extensive tissue distribution (e.g., brain, liver).
Bioavailability	Oral (ODT): 60-70% due to first-pass metabolism (clozapine); bioavailability similar to conventional tablets.
Onset of Action	Oral (ODT): Sedation within 1-2 hours; antipsychotic effect: 2-4 weeks for initial response.
Duration of Action	Sedation: 6-12 hours after single dose; antipsychotic effect: sustained with continuous dosing (monitoring required).

Classification & Brands

Dosing & administration

Dosage form	TABLET, ORALLY DISINTEGRATING
Renal impairment	Severe renal impairment (CrCl < 30 mL/min): Use with caution; dose reduction may be necessary due to increased risk of accumulation. No specific GFR-based dose guidelines exist; initiate at 12.5 mg once daily, titrate slowly with close monitoring. In end-stage renal disease (ESRD), avoid use or use with extreme caution.
Liver impairment	Clozapine is extensively metabolized in the liver. In hepatic impairment: For Child-Pugh Class A (mild): No adjustment necessary. For Child-Pugh Class B (moderate): Consider a 50% dose reduction and slow titration. For Child-Pugh Class C (severe): Contraindicated or use with extreme caution; limited data exist. Monitor liver function tests regularly.
Pediatric use	Not FDA-approved for pediatric patients under 18 years. However, off-label use for treatment-resistant schizophrenia in adolescents (≥13 years) is sometimes considered: Starting dose 12.5 mg once or twice daily, titrate by 25-50 mg/day to target 300-450 mg/day, maximum 900 mg/day. Weight-based dosing is not established; dosing is based on adult protocol with slower titration.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for FAZACLO ODT (FAZACLO ODT).

Breastfeeding	Clozapine is excreted in breast milk. The M/P ratio is approximately 0.5-0.8. Reports of adverse effects in breastfed infants (e.g., sedation, agranulocytosis). Breastfeeding is not recommended; if used, monitor infant for drowsiness, blood dyscrasias, and poor feeding.
Teratogenic Risk	Pregnancy Category B. No evidence of teratogenicity in animal studies; however, adequate human studies are lacking. Use only if benefit outweighs risk. First trimester: limited human data; animal studies show no fetal harm. Second/third trimester: no known teratogenic effects; monitor for maternal hypotension and neonatal extrapyramidal symptoms.