Clozapine (US brand names Clozaril®, Fazaclo® ODT, Versacloz®, and generic) is a second-generation (“atypical”) antipsychotic. Here is basic information about this medication.

FDA-approved indications

1. Treatment resistant schizophrenia

2. Reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder

Dosage

Starting: 12.5 mg once or twice daily, with or without food

Titration: Increase the total daily dosage in increments of 25 mg to 50 mg per day

Target: 300 – 450 mg per day, in divided doses, by the end of 2 weeks

Subsequent increases: Increments of 100 mg or less, once or twice weekly

Maximum: 900 mg daily

Important instructions

1. Clozapine can cause severe neutropenia. As a result clozapine is available only through a restricted program under a Risk Evaluation Mitigation Strategy (REMS) called the Clozapine REMS Program (see Related Pages below).

Prior to initiating treatment with clozapine, a baseline ANC must be obtained. The baseline ANC must be at least 1500/µL for the general population, and at least 1000/µL for patients with documented Benign Ethnic Neutropenia (BEN). To continue treatment, the ANC must be monitored regularly.

2. Dose adjustments may be necessary in patients with concomitant use of:

Strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin): Use 1/3rd dose of clozapine

Moderate or weak CYP1A2 inhibitors (e.g., oral contraceptives, or caffeine): Monitor for side effects and consider reducing the dose of clozapine if necessary.

CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline); Monitor for side effects and consider reducing the dose of clozapine if necessary.

Strong CYP3A4 inducers (carbamazepine, phenytoin, St. John’s wort, and rifampin): Concomitant use of clozapine is not recommended. If necessary, consider increasing clozapine dose. Also, consider reducing the clozapine dosage when discontinuing co-administered enzyme inducers.

Moderate or weak CYP1A2 (tobacco smoking) or CYP3A4 inducers: Monitor for decreased effectiveness. Consider increasing the clozapine dose if necessary.

3. Seizures have occurred with clozapine treatment. The risk is dose-related. Use caution when administering clozapine to patients with a history of seizures or other predisposing risk factors for seizure.

Dosage forms and strengths

Oral tablet (Clozaril® and generic): 25 mg (scored) and 100 mg (scored). Generic also available in 12.5 mg, 50 mg, and 200 mg strengths.

Orally disintegrating tablet (Fazaclo® ODT and generic): 12.5 mg, 25 mg, 100 mg, 150 mg, and 200 mg

Oral suspension (Versacloz®): 50 mg/mL

Please refer to Prescribing Information (see link below) for complete discussion of dosage, administration, warnings and precautions, contraindications, etc.