Clozapine

The mechanism of action of clozapine is unknown. However, it has been proposed that the therapeutic efficacy of Clozapine ODT in schizophrenia is mediated through antagonism of the dopamine type 2 (D 2 ) and the serotonin type 2A (5-HT 2A ) receptors.

• Clozapine orally disintegrating tablets (Clozapine ODT) is an atypical antipsychotic indicated for: Treatment of severely ill patients with schizophrenia who fail to respond adequately to standard antipsychotic treatment. Because of the risks of severe neutropenia and of seizure associated with its use, Clozapine ODT should be used only in patients who have failed to respond adequately to standard antipsychotic treatment ( 1.1 ) Reducing the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are judged to be at chronic risk for re-experiencing suicidal behavior ( 1.2 ) 1.1 Treatment-resistant Schizophrenia Clozapine Orally Disintegrating Tablets (Clozapine ODT) are indicated for the treatment of severely ill patients with schizophrenia who fail to respond adequately to standard antipsychotic treatment.ICD-10: F20.9, G40.909

• Clozapine ODT is contraindicated in patients with a history of hypersensitivity to clozapine (e.g., photosensitivity, vasculitis, erythema multiforme, or Stevens-Johnson Syndrome) or any other component of Clozapine ODT [see Adverse Reactions (6.2) ] .contraindicated

Recommended starting oral dosage is 12.5 mg once daily or twice daily. ( 2.2 ) If well-tolerated, increase the total daily dosage in increments of 25 mg to 50 mg per day at target dosage of 150 mg to 225 mg twice per day by the end of two weeks. ( 2.2 ) Subsequently may increase the doage in increments up to 100 mg, once or twice weekly. ( 2.2 ) Maximum daily dosage is 450 mg twice daily. ( 2.2 ) Administer with or without food. Clozapine ODT may be allowed to disintegrate or chewed, and may be taken with or without water. See additional administration instructions in the full prescribing information. ( 2.2 ) See dosage modification based on ANC results. ( 2.3 , 2.4 ) See recommendations for discontinuing Clozapine ODT treatment ( 2.5 ), restarting Clozapine ODT after interrupting dosing (2.6), dosage modifications for drug interactions ( 2.7 ), dosage recommendations in patients with renal or hepatic impairment and CYP2D6 poor metabolizers ( 2.8 ) in the full prescribing information. Tablets rapidly disintegrate after placement in the mouth and may be chewed if desired. No water is needed. ( 2.2 ) 2.1 Absolute Neutrophil Count Testing Prior to Clozapine ODT Initiation Prior to initiating Clozapine ODT treatment, obtain a baseline absolute neutrophil count (ANC). Clozapine ODT initiation is not recommended in patients with an ANC less than 1500/µL [see Warnings and Precautions (5.1) ] . For patients with documented Benign Ethnic Neutropenia (BEN) (also known as Duffy-null associated neutrophil count)), obtain at least two baseline ANC levels.

Severe neutropenia: See ( 5.1 ) Gastrointestinal Hypomotility with Severe Complications: Severe gastrointestinal adverse reactions have occurred with the use of clozapine. If constipation is identified, close monitoring and prompt treatment is advised. ( 5.7 ) Eosinophilia: Assess for organ involvement (e.g., myocarditis, pancreatitis, hepatitis, colitis, nephritis). Discontinue if these occur. ( 5.8 ) QT Interval Prolongation: Can be fatal. Consider additional risk factors for prolonged QT interval (disorders and drugs). ( 5.9 ) Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include ( 5.10 ): Hyperglycemia and Diabetes Mellitus: Monitor for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Monitor glucose regularly in patients with diabetes or at risk for diabetes. Dyslipidemia: Undesirable alterations in lipids have occurred in patients treated with atypical antipsychotics. Weight Gain: Significant weight gain has occurred. Monitor weight gain. Neuroleptic Malignant Syndrome (NMS): Immediately discontinue and monitor closely. Assess for co-morbid conditions. ( 5.11 ) Hepatotoxicity: Can be fatal. Monitor for hepatotoxicity. Discontinue treatment if hepatitis or transaminase elevations combined with other symptoms occur. ( 5.12 ) Fever: Evaluate for infection and for neutropenia, NMS. ( 5.13 ) Pulmonary Embolism (PE): Consider PE if respiratory distress, chest pain, or deep vein thrombosis occurs.

The following adverse reactions are discussed in more detail in other sections of the labeling: Severe Neutropenia [see Warnings and Precautions (5.1) ] Orthostatic Hypotension, Bradycardia, and Syncope [see Warnings and Precautions (5.2) ] Falls [see Warnings and Precautions (5.3) ] Seizures [see Warnings and Precautions (5.4) ] Myocarditis, Pericarditis, Cardiomyopathy, and Mitral Valve Incompetence [see Warnings and Precautions (5.5) ] Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions (5.6) ] Gastrointestinal Hypomotility with Severe Complications [see Warnings and Precautions (5.7) ] Eosinophilia [see Warnings and Precautions (5.8) ] QT Interval Prolongation [see Warnings and Precautions (5.9) ] Metabolic Changes (Hyperglycemia and Diabetes Mellitus, Dyslipidemia, and Weight Gain) [see Warnings and Precautions (5.10) ] Neuroleptic Malignant Syndrome [see Warnings and Precautions (5.11) ] Hepatotoxicity [see Warnings and Precautions (5.12) ] Fever [see Warnings and Precautions (5.13) ] Pulmonary Embolism [see Warnings and Precautions (5.14) ] Anticholinergic Toxicity [see Warnings and Precautions (5.15) ] Interference with Cognitive and Motor Performance [see Warnings and Precautions (5.16) ] Tardive Dyskinesia [see Warnings and Precautions (5.17) ] Patients with Phenylketonuria [see Warnings and Precautions (5.18) ] Cerebrovascular Adverse Reactions [see Warnings and Precautions (5.19) ] Recurrence of Psychosis and Cholinergic Rebound after Abrupt Discontinuation [see Warnings and Precautions (5.20) ] Most common adver…

Lactaton: Infants exposed to Clozapine ODT through breast milk should be monitored for excess sedation and neutropenia. ( 8.2 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including Clozapine ODT, during pregnancy. Healthcare providers are encouraged to advise patients to register by calling the National Pregnancy Registry for Atypical Antipsychotics at1-866-961-2388 or visiting http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs, including Clozapine ODT, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery ( see Clinical Considerations ). Available data from published epidemiologic studies over decades of use with clozapine during pregnancy have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes ( see Data ). There are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics, including Clozapine ODT, during pregnancy ( see Clinical Considerations ).

Metabolism

Absorption In humans, Clozapine ODT (25 mg and 100 mg) is equally bioavailable relative to a clozapine oral solution. Clozapine ODT is bioequivalent to Clozaril ® (clozapine) tablets.

10.1 Overdosage Experience The most commonly reported signs and symptoms associated with Clozapine ODT overdose are: sedation, delirium, coma, tachycardia, hypotension, respiratory depression or failure; and hypersalivation. There are reports of aspiration pneumonia, cardiac arrhythmias, and seizure. Fatal overdoses have been reported with clozapine, generally at doses above 2500 mg. There have also been reports of patients recovering from overdoses well in excess of 4 g. 10.2 Management of Overdosage There are no specific antidotes for Clozapine ODT overdose. Establish and maintain an airway; ensure adequate oxygenation and ventilation. Monitor cardiac status and vital signs. Use general symptomatic and supportive measures. Consider the possibility of multiple-drug involvement. Contact a Certified Poison Control Center for the most up to date information on the management of overdosage (1-800-222-1222).

• Sep 26, 1989NDANDA019758Heritage Life
• May 27, 1999ANDAANDA075417Mylan
• Feb 6, 2013NDANDA203479Douglas Pharms
• Sep 15, 2015ANDAANDA201824Mylan
• Nov 25, 2015ANDAANDA202873Accord Hlthcare
• Nov 25, 2015ANDAANDA090308Barr Labs Inc
• Nov 29, 2016ANDAANDA206433Aurobindo Pharma
• Dec 12, 2024ANDAANDA212923Aurobindo Pharma

1. 1Neutropenia18,81515%
2. 2Hospitalisation12,26210.0%
3. 3Death11,7449.5%
4. 4Schizophrenia4,6093.7%
5. 5White Blood Cell Count Increased4,4773.6%
6. 6White Blood Cell Count Decreased4,4323.6%
7. 7Neutrophil Count Increased4,1473.4%
8. 8Drug Ineffective3,9133.2%
9. 9Malaise3,7723.1%
10. 10Off Label Use3,6863.0%
11. 11Pneumonia3,2272.6%
12. 12Treatment Noncompliance3,1802.6%
13. 13Neutrophil Count Decreased3,1392.5%
14. 14Drug Interaction3,0952.5%
15. 15Haemoglobin Decreased3,0842.5%

Recent PubMed references pinned to Clozapine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Beyond Clozapine: Myocarditis and Cardiomyopathy Associated with Antipsychotic Medications-An Updated Narrative Review for Psychiatric Practice.
  Psychopharmacology bulletin · 2026 · Sarangal M, Sarangal C
  PMID 42267232DOI 10.64719/pb.18531
• The Key to Clozapine Mystery May Lie in its Shape.
  Schizophrenia bulletin · 2026 · de Filippis R, De Fazio P
  PMID 42241485DOI 10.1093/schbul/sbag061
• Clozapine-Induced "Pseudo-Agranulocytosis": Bone Marrow Suppression or Increased Neutrophil Margination?
  Schizophrenia bulletin · 2026 · Miller BJ, Ghani N, Kota V, et al.
  PMID 42241476DOI 10.1093/schbul/sbag024
• Clozapine-Associated Neutropenia among People on Clozapine in Japan: A Nationally Representative Retrospective Cohort Study.
  Schizophrenia bulletin · 2026 · Trott M, Northwood K, Hata T, et al.
  PMID 42212910DOI 10.1093/schbul/sbag087
• Underprescription of Clozapine: A Narrative Review Regarding 'Clozaphobia'.
  Human psychopharmacology · 2026 · Brito Castro R, Ferreira JJ, Gama-Marques J, et al.
  PMID 42136059DOI 10.1002/hup.70050
• [Association of single-nucleotide variants of ABCG2 and ABCB1 genes with clinical and laboratory parameters during clozapine therapy].
  Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova · 2026 · Kidyaeva AV, Tulendinov ER, Agaev AM, et al.
  PMID 42133418DOI 10.17116/jnevro202612604177
• Risk factors associated with blood dyscrasia during clozapine treatment: a systematic review and meta-analysis.
  Psychological medicine · 2026 · Casetta C, Loane E, Taylor D, et al.
  PMID 42112559DOI 10.1017/S0033291726104371
• Identifying Clinical Characteristics of Young People with Treatment-Resistant Schizophrenia Undergoing Community Initiation of Clozapine.
  Schizophrenia bulletin · 2026 · Conaty O, Thompson A, McGorry P, et al.
  PMID 42104793DOI 10.1093/schbul/sbag071

The 10 most recently updated of 182 ClinicalTrials.gov registrations naming Clozapine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Biomarkers to Enhance Early Schizophrenia Treatment
  Recruiting · Phase 4 · Interventional · 180 enrolled · Northwell Health
  NCT06969755updated 2026-06-12
• No Guts No Glory Probiotics
  Recruiting · Phase 2 · Phase 3 · Interventional · 112 enrolled · University Medical Center Groningen
  NCT07606014updated 2026-05-26
• Metabolic Effects of Adjunctive Lumateperone Treatment in Clozapine-Treated Patients With Schizophrenia
  Recruiting · Phase 4 · Interventional · 50 enrolled · University of Massachusetts, Worcester
  NCT06174116updated 2026-05-22
• Rivastigmine as an Antidote for Clozapine and Other Anticholinergic-Induced CNS Depression and Delirium: A Study of 100 Cases
  Completed · Phase 4 · Interventional · 100 enrolled · Alexandria University
  NCT07545382updated 2026-05-19
• CLOZAPINE Response in Biotype-1
  Recruiting · Phase 4 · Interventional · 524 enrolled · University of Texas Southwestern Medical Center
  NCT04580134updated 2026-05-11
• The Combination of Pharmacotherapy and Cognitive Behavioral Psychotherapy Under the Recovery Perspective.
  Active not recruiting · Phase 1 · Interventional · 107 enrolled · Rakitzi, Stavroula
  NCT06993662updated 2026-05-07
• Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial
  Recruiting · Phase 4 · Interventional · 280 enrolled · New York State Psychiatric Institute
  NCT05208190updated 2026-05-04
• Τhe Combination of Pharmacotherapy With RECOVERYTRSGR and RECOVERYTRSBDGR.
  Active not recruiting · Phase 4 · Interventional · 84 enrolled · Dr. Stavroula Rakitzi
  NCT07047651updated 2026-05-01
• Elpipodect (MK-8189) Multiple Dose Study in Healthy Volunteers and Schizophrenia Participants (MK-8189-003)
  Completed · Phase 1 · Interventional · 55 enrolled · Merck Sharp & Dohme LLC
  NCT02181803updated 2026-04-29
• Evaluating the Effect of the STEP@STAH Semaglutide Protocol on the Physical Health Measures of Atypical Antipsychotic-Treated Patients
  Active not recruiting · Phase 4 · Interventional · 20 enrolled · St Andrew's Healthcare
  NCT06754163updated 2026-04-28

CPIC-curated drug–gene pairs for Clozapine. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• ANKK1CPIC D (provisional)
• CYP2D6CPIC B/C (provisional)FDA label: Actionable PGx
• HTR2CCPIC C (provisional)ClinPGx 3
• MC4RCPIC C (provisional)ClinPGx 3

Ranked by 2D fingerprint (Tanimoto) similarity over PubChem structures. Structural proximity only — not a claim of therapeutic equivalence.

• QuetiapineAtypical Antipsychotic77%

Frequently asked questions

How does Clozapine work?

The mechanism of action of clozapine is unknown. However, it has been proposed that the therapeutic efficacy of Clozapine ODT in schizophrenia is mediated through antagonism of the dopamine type 2 (D 2 ) and the serotonin type 2A (5-HT 2A ) receptors.

What is Clozapine used for?

According to FDA labeling, Clozapine carries indications including: Clozapine orally disintegrating tablets (Clozapine ODT) is an atypical antipsychotic indicated for: Treatment of severely ill patients with schizophrenia who fail to respond adequately to standard antipsychotic treatment. Because of the risks of severe neutropenia and of seizure associated with its use, Clozapine ODT should be used only in patients who have failed to respond adequately to standard antipsychotic treatment ( 1.1 ) Reducing the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are judged to be at chronic risk for re-experiencing suicidal behavior ( 1.2 ) 1.1 Treatment-resistant Schizophrenia Clozapine Orally Disintegrating Tablets (Clozapine ODT) are indicated for the treatment of severely ill patients with schizophrenia who fail to respond adequately to standard antipsychotic treatment.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Clozapine?

Clozapine is classified as Diazepines, oxazepines, thiazepines and oxepines, Atypical Antipsychotic, Adrenergic alpha-Antagonists, Cholinergic Muscarinic Antagonists, Dopamine Antagonists, Histamine H1 Receptor Antagonists, Serotonin Antagonists, Decreased Acetylcholine Activity, Decreased Dopamine Activity, Decreased Histamine Activity, Decreased Norepinephrine Activity, Decreased Serotonin Activity, Increased Granulocytic Cell Destruction.

What are the brand names for Clozapine?

Clozapine is marketed under brand names including Clozaril, Versacloz.

What are the contraindications for Clozapine?

Clozapine labeling lists contraindications including: Clozapine ODT is contraindicated in patients with a history of hypersensitivity to clozapine (e.g., photosensitivity, vasculitis, erythema multiforme, or Stevens-Johnson Syndrome) or any other component of Clozapine ODT [see Adverse Reactions (6.2) ] .. Always consult the full prescribing information and a clinician.