Clozapine (US brand names Clozaril®, Fazaclo® ODT, Versacloz®, and generic) is a second-generation (“atypical”) antipsychotic. Here is basic information about this medication.
1. Treatment resistant schizophrenia
2. Reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder
Clozapine is metabolized by cytochrome P450 1A2, 2D6, and 3A4.
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
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.
Copyright 2016, Rajnish Mago, MD. All rights reserved. May not be reproduced in any form without express written permission.
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