CLOZAPINE
Clozapine is an atypical antipsychotic indicated for severely ill patients with schizophrenia who have not responded adequately to standard antipsychotic treatments. It is also approved to reduce the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are judged to be at chronic risk. Due to the potential for severe neutropenia and seizures, the drug is reserved for patients who have failed other therapeutic options.
How CLOZAPINE Works
The precise mechanism of action for clozapine is unknown, though its efficacy is proposed to be mediated through the antagonism of dopamine type 2 (D2) and serotonin type 2A (5-HT2A) receptors. By acting as an antagonist, the drug blocks these specific biological targets to produce its therapeutic effects. Clozapine also functions as an antagonist at several other receptor sites, including adrenergic, cholinergic, histaminergic, and additional dopaminergic and serotonergic receptors.
Details
- Status
- Prescription
- First Approved
- 1996-08-30
- Routes
- ORAL
- Dosage Forms
- TABLET, ORALLY DISINTEGRATING, TABLET
Companies
CLOZAPINE Approval History
What CLOZAPINE Treats
2 indicationsCLOZAPINE is approved for 2 conditions since its original approval in 1996. These indications span multiple therapeutic areas including oncology, immunology, and more.
- Treatment-resistant schizophrenia
- Recurrent suicidal behavior in schizophrenia or schizoaffective disorder
CLOZAPINE Boxed Warning
SEVERE NEUTROPENIA; ORTHOSTATIC HYPOTENSION, BRADYCARDIA, AND SYNCOPE; SEIZURE; MYOCARDITIS, PERICARDITIS, AND CARDIOMYOPATHY; INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Severe Neutropenia Clozapine tablets have caused severe neutropenia which is associated with an increased risk of serious and potentially fatal infections. Prior to initiating clozapine tablets treatment, obtain baseline ANC(s). Clozapine tablets initiation is not recommended in patients with a basel...
WARNING: SEVERE NEUTROPENIA; ORTHOSTATIC HYPOTENSION, BRADYCARDIA, AND SYNCOPE; SEIZURE; MYOCARDITIS, PERICARDITIS, AND CARDIOMYOPATHY; INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Severe Neutropenia Clozapine tablets have caused severe neutropenia which is associated with an increased risk of serious and potentially fatal infections. Prior to initiating clozapine tablets treatment, obtain baseline ANC(s). Clozapine tablets initiation is not recommended in patients with a baseline ANC less than 1500/μL (less than 1000/μL for those with Benign Ethnic Neutropenia (also known as Duffy-null associated neutrophil count)). See recommendations for dosage modifications based on ANC levels during clozapine tablets treatment [see Dosage and Administration (2.3 , 2.4) ] . Consider a hematology consultation before initiating clozapine tablets or during clozapine tablets treatment [see Warnings and Precautions (5.1) ] . Orthostatic Hypotension, Bradycardia, Syncope Orthostatic hypotension, bradycardia, syncope, and cardiac arrest have occurred with clozapine tablets treatment. The risk is highest during the initial titration period, particularly with rapid dose escalation. These reactions can occur with the first dose, with doses as low as 12.5 mg per day, or when restarting patients who have had even a brief interruption in treatment with clozapine tablets. Initiate treatment at 12.5 mg once or twice daily; titrate slowly; and use divided dosages to minimize risk. Use clozapine tablets cautiously in patients with cardiovascular or cerebrovascular disease or conditions predisposing to hypotension (e.g., dehydration, use of antihypertensive medications) [see Dosage and Administration (2.2 , 2.6) , Warnings and Precautions (5.2) ] . Seizures Seizures have occurred with clozapine tablets treatment. The risk is dose - related. Initiate treatment at 12.5 mg, titrate gradually, and use divided dosing. Use caution when administering clozapine tablets to patie
CLOZAPINE Competitive Set
ProThree rings of competition based on shared molecular targets and treated indications.
Direct competitors
Same target(s) AND same indication — head-to-head.
MoA expansion candidates
Same target(s), different indications — where else is this mechanism being explored?
Indication competitors
Same indication, different mechanism — what else might this patient receive?
Filters applied: drops same-active-ingredient (505(b)(2) reformulations), route-mismatch (topical vs systemic), and cross-therapeutic-area matches in same-indication rings.
Clinical Trial Registry
17 trials| Trial | Sponsor ID | Phase | Status | Title |
|---|---|---|---|---|
| NCT04580134 | ( STU-2020-0989 ) | Ph 4 | recruiting | CLOZAPINE Response in Biotype-1 |
| NCT05208190 REVISIT-C | I20-02054 1R01MH120317-01A1 | Ph 4 | recruiting | Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial |
| NCT06969755 BEEST | BEEST 1R01MH134883-01A1 | Ph 4 | recruiting | Biomarkers to Enhance Early Schizophrenia Treatment |
| NCT05741502 | 2021H0388 | Ph 4 | terminated | An Exploratory Analysis of Immune and Inflammatory Response Associated With Clozapine |
| NCT05603104 INTENSIFY | 2022-502185-24-00 (EU CT #) | Ph 3 | recruiting | Intensified Pharmacological Treatment for Schizophrenia, Major Depressive Disorder and Bipolar Depression After a First-time Treatment Failure |
| NCT05316883 BiCS | BiCS2019 | Ph 4 | recruiting | Biomarkers in Clozapine-responding Schizophrenia |
| NCT07262736 | MY20090488 | Ph 1 | completed | Pharmacokinetics of Clozapine and Norclozapine and the Effect of Pantoprazole |
| NCT05958875 INTENSIFY SZ | 2023-506602-39-00 (EU CT#) | Ph 4 | recruiting | The Effect of a Six Week Intensified Pharmacological Treatment for Schizophrenia Compared to Treatment as Usual in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment. |
| NCT02639702 | 096/2015 | Ph 4 | recruiting | Switching From Twice-Daily to Once-Daily Clozapine Dosing in Schizophrenia |
| NCT03772951 | HKQ201813 | Ph 4 | completed | The Efficacy of Computerized Cognitive Remediation Therapy for Chronic Schizophrenia |
| NCT02286206 PK-CLZ | H14-01644 | Ph 4 | withdrawn | Study of the Effect of Dosing on Clozapine Levels |
| NCT03807882 | T/IM-F/18-19/08 | Ph 4 | completed | Comparison of Maintenance ECT Versus Clozapine in Treatment-resistant Schizophrenia |
| NCT01639872 CLOCS results posted | 1R01DA032533-01A1 D13012 1R01DA032533-01A1 | Ph 4 | completed | Clozapine for Cannabis Use in Schizophrenia |
| NCT00981526 results posted | 2008-P-000790 | Ph 4 | completed | Telmisartan as an Adjunctive Treatment for Metabolic Problems in Patients With Schizophrenia |
| NCT02374567 GAP | GAP-2014 | Ph 3 | terminated | Pharmacovigilance in Gerontopsychiatric Patients |
| NCT01663077 | KBK2012 03/11 | Ph 4 | completed | Clozapine Plasma Levels and the Relationship to the Genetic Polymorphism in Shizophrenic Patients |
| NCT02625103 | CLO-MEAS 2015-002520-82 | Ph 4 | completed | The Significance of Deviation in Time From the 12-hour Standard Serum-clozapine Monitoring. |
Active Pipeline
Ongoing clinical trials by development phase
Key Completed Trials
Completed studies with published results, ranked by significance
Trial Timeline
Full development history with FDA approval milestones
Understanding FDA Approval Types
| Count | Type | What it means |
|---|---|---|
| - | ORIG | Original approval - drug first enters market |
| - | SUPPL - Efficacy | New indication (new disease/condition approved) |
| - | SUPPL - Labeling | Label text changes (warnings, dosing updates) |
| - | SUPPL - Manufacturing | Production changes (new facility) |
| - | SUPPL - Chemistry | Formulation changes (new dosage strength) |
Green lines in the timeline show ORIG and Efficacy approvals - the clinically meaningful milestones.
CLOZAPINE FDA Label Details
Indications & Usage
CLOZAPINE is indicated for the treatment of Treatment-resistant schizophrenia; Recurrent suicidal behavior in schizophrenia or schizoaffective disorder.
WARNING: SEVERE NEUTROPENIA; ORTHOSTATIC HYPOTENSION, BRADYCARDIA, AND SYNCOPE; SEIZURE; MYOCARDITIS, PERICARDITIS, AND CARDIOMYOPATHY; INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Severe Neutropenia Clozapine tablets have caused severe neutropenia which is associated with...
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Full clinical data, patents, trials, and competitive landscape for clozapine.
Data Sources
Data sourced from official FDA and NIH databases. Click links to verify on original sources.