{
 "query": "clozapine",
 "ingredient": "clozapine",
 "slug": "clozapine",
 "rxcui": "2626",
 "brands": [
  "Clozaril",
  "Versacloz"
 ],
 "names": [
  "clozapine"
 ],
 "classes": [
  {
   "id": "N05AH",
   "name": "Diazepines, oxazepines, thiazepines and oxepines"
  }
 ],
 "alternatives": [
  "asenapine",
  "clothiapine",
  "loxapine",
  "olanzapine",
  "quetiapine"
 ],
 "label": {
  "route_mode": "ORAL",
  "route_counts": {
   "ORAL": 16
  },
  "boxed_warning": "WARNING: SEVERE NEUTROPENIA; ORTHOSTATIC HYPOTENSION, BRADYCARDIA, AND SYNCOPE; SEIZURE; MYOCARDITIS, PERICARDITIS AND CARDIOMYOPATHY; INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Severe Neutropenia CLOZARIL has caused severe neutropenia which is associated with an increased risk of serious and potentially fatal infections. Prior to initiating CLOZARIL treatment, obtain baseline ANC(s). CLOZARIL initiation is not recommended in patients with a baseline ANC less than 1500/\u03bcL (less than 1000/\u03bcL for those with Benign Ethnic Neutropenia (also known as Duffy-null associated neutrophil count)). See recommendations for dosage modifications based on ANC levels during CLOZARIL treatment [see Dosage and Administration ( 2.3 , 2.4 )] . Consider a hematology consultation before initiating CLOZARIL or during CLOZARIL treatment [see Warnings and Precautions ( 5.1 )] . Orthostatic Hypotension, Bradycardia, Syncope Orthostatic hypotension, bradycardia, syncope, and cardiac arrest have occurred with CLOZARIL 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...",
  "indications_and_usage": "is an atypical antipsychotic indicated for: \u2022 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, CLOZARIL should be used only in patients who have failed to respond adequately to standard antipsychotic treatment ( 1.1 ) \u2022 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 CLOZARIL is indicated for the 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, CLOZARIL should be used only in patients who have failed to respond adequately to standard antipsychotic treatment [see Warnings and Precautions ( 5.1 , 5.4 )]. The effectiveness of CLOZARIL in treatment-resistant schizophrenia was demonstrated in a 6-week, randomized, double-blind, active-controlled study comparing CLOZARIL and chlorpromazine in patients w...",
  "contraindications": "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 CLOZARIL [see Adverse Reactions ( 6.2 )]. Known hypersensitivity to clozapine or any other component of CLOZARIL. ( 4 )",
  "warnings_and_cautions": "\u2022 Severe neutropenia : See Boxed Warnings ( 5.1 ) \u2022 Gastrointestinal Hypomotility with Severe Complications : Severe gastrointestinal adverse reactions have occurred with the use of CLOZARIL. If constipation is identified, close monitoring and prompt treatment is advised. ( 5.7 ) \u2022 Eosinophilia : Assess for organ involvement (e.g., myocarditis, pancreatitis, hepatitis, colitis, nephritis). Discontinue if these occur. ( 5.8 ) \u2022 QT Interval Prolongation : Can be fatal. Consider additional risk factors for prolonged QT interval (disorders and drugs). ( 5.9 ) \u2022 Metabolic Changes : Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include: 1. 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. ( 5.10 ) 2. Dyslipidemia : Undesirable alterations in lipids have occurred in patients treated with atypical antipsychotics. ( 5.10 ) 3. Weight Gain : Significant weight gain has occurred. Monitor weight gain. ( 5.10 ) \u2022 Neuroleptic Malignan...",
  "warnings": "",
  "adverse_reactions": "The following adverse reactions are discussed in more detail in other sections of the labeling: \u2022 Severe Neutropenia [see Warnings and Precautions ( 5.1 )] \u2022 Orthostatic Hypotension, Bradycardia, and Syncope [see Warnings and Precautions ( 5.2 )] \u2022 Falls [see Warnings and Precautions ( 5.3 )] \u2022 Seizures [see Warnings and Precautions ( 5.4 )] \u2022 Myocarditis, Pericarditis, Cardiomyopathy, and Mitral Valve Incompetence [see Warnings and Precautions ( 5.5 )] \u2022 Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions ( 5.6 )] \u2022 Gastrointestinal Hypomotility with Severe Complications [See Warnings and Precautions ( 5.7) ] \u2022 Eosinophilia [see Warnings and Precautions ( 5.8 )] \u2022 QT Interval Prolongation [see Warnings and Precautions ( 5.9 )] \u2022 Metabolic Changes (Hyperglycemia and Diabetes Mellitus, Dyslipidemia, and Weight Gain) [see Warnings and Precautions ( 5.10 )] \u2022 Neuroleptic Malignant Syndrome [see Warnings and Precautions ( 5.11 )] \u2022 Hepatotoxicity [see Warnings and Precautions ( 5.12 )] \u2022 Fever [see Warnings and Precautions ( 5.13 )] \u2022 Pulmonary Embolism [see Warnings and Precautions ( 5.14 )] \u2022 Anticholinergic Toxicity [see Warnings and...",
  "drug_abuse_and_dependence": "",
  "controlled_substance": "",
  "recent_major_changes": "Boxed Warning Dosage and Administration ( 2 ) Warnings and Precautions ( 5.1 ) 6/2025 6/2025 6/2025 Warnings and Precautions ( 5.5 ) 1/2025",
  "information_for_patients": "Advise the patient to read the FDA-approved patient labeling (Medication Guide). Discuss the following issues with patients and caregivers: \u2022 Severe Neutropenia : Instruct patients (and caregivers) [see Warnings and Precautions ( 5.1 )]: \u25aa About the risk of developing severe neutropenia and infection with CLOZARIL treatment. \u25aa Instruct patients to immediately report to their health care provider any symptom or sign of during CLOZARIL treatment. \u25aa About the importance of having frequent ANC testing. \u2022 Orthostatic Hypotension, Bradycardia, and Syncope: Inform patients and caregivers about the risk of orthostatic hypotension and syncope, especially during the period of initial dose titration. Instruct them to strictly follow the clinician\u2019s instructions for dosage and administration [see Dosage and Administration ( 2.2 , 2.6 )]. Advise patients to consult their clinician immediately if they feel faint, lose consciousness or have signs or symptoms suggestive of bradycardia or arrhythmia [Warnings and Precautions ( 5.2 )] . \u2022 Seizures: Inform patients and caregivers about the significant risk of seizure during CLOZARIL treatment. Caution them about driving and any other potentially haza...",
  "spl_medguide": "MEDICATION GUIDE CLOZARIL (klow-zr-uhl) (clozapine) tablets, for oral use What is the most important information I should know about CLOZARIL? CLOZARIL can cause serious side effects including: \u2022 Severe neutropenia (low white blood cell (WBC) counts) that can lead to serious infections and death. Your healthcare provider will do WBC blood tests before starting treatment with CLOZARIL and weekly for the first 6 months. After your first 6 months of treatment, your healthcare provider will determine how frequent you will have blood tests. If you have symptoms of severe neutropenia or an infection, your healthcare provider will do more frequent WBC blood test(s) to check if CLOZARIL is causing your symptoms and may send you to see a blood specialist (hematologist). Tell your health care provider right away if you have any of the following symptoms or signs of neutropenia or infection: o feel like you have the flu \u2022 wounds that take a long time to heal o fever or chills \u2022 skin, throat, vaginal, urinary tract, or lung infection o feel extremely tired or weak \u2022 pain or burning while peeing o sores or ulcers inside your mouth, gums, or on your skin \u2022 unusual vaginal discharge or itching o ...",
  "clinical_studies": "14.1 Treatment-Resistant Schizophrenia The efficacy of CLOZARIL in treatment-resistant schizophrenia was established in a multicenter, randomized, double-blind, active-controlled (chlorpromazine) study in patients with a DSM-III diagnosis of schizophrenia who had inadequate responses to at least 3 different antipsychotics (from at least 2 different chemical classes) during the preceding 5 years. The antipsychotic trials must have been judged adequate; the antipsychotic dosages must have been equivalent to or greater than 1000 mg per day of chlorpromazine for a period of at least 6 weeks, each without significant reduction of symptoms. There must have been no period of good functioning within the preceding 5 years. Patients must have had a baseline score of at least 45 on the investigator-rated Brief Psychiatric Rating Scale (BPRS). On the 18-item BPRS, 1 indicates the absence of symptoms, and 7 indicates severe symptoms; the maximum potential total BPRS score is 126. At baseline, the mean BPRS score was 61. In addition, patients must have had a score of at least 4 on at least two of the following four individual BPRS items: conceptual disorganization, suspiciousness, hallucinatory ...",
  "brand_name": "Clozaril",
  "manufacturer": "HLS Therapeutics (USA), Inc.",
  "application_number": "NDA019758",
  "pharm_class_epc": [
   "Atypical Antipsychotic [EPC]"
  ],
  "route": [
   "ORAL"
  ],
  "effective_time": "20250606",
  "set_id": "90876802-0e3a-44c9-9ff7-1754dfbe736a",
  "has_boxed_warning": true,
  "controlled": false,
  "mentions_rems": false
 },
 "faers": {
  "total": 106473,
  "serious": 100806,
  "death": 17152,
  "hospitalization": 47318,
  "primary_suspect": 105720,
  "top_reactions": [
   [
    "Neutropenia",
    19466
   ],
   [
    "Hospitalisation",
    12735
   ],
   [
    "Death",
    10512
   ],
   [
    "Schizophrenia",
    4356
   ],
   [
    "Off Label Use",
    3976
   ],
   [
    "Drug Ineffective",
    3727
   ],
   [
    "White Blood Cell Count Decreased",
    3682
   ],
   [
    "Neutrophilia",
    3284
   ],
   [
    "Neutrophil Count Increased",
    3237
   ],
   [
    "White Blood Cell Count Increased",
    3109
   ],
   [
    "Treatment Noncompliance",
    2910
   ],
   [
    "Malaise",
    2893
   ],
   [
    "Neutrophil Count Decreased",
    2685
   ],
   [
    "Drug Interaction",
    2658
   ],
   [
    "Haemoglobin Decreased",
    2578
   ]
  ],
  "by_year": {
   "2019": 9057,
   "2020": 9558,
   "2021": 8659,
   "2022": 13919,
   "2023": 13134,
   "2024": 11703,
   "2025": 8284,
   "2026": 3393
  },
  "by_year_primary": {
   "2019": 9047,
   "2020": 9539,
   "2021": 8617,
   "2022": 13790,
   "2023": 12944,
   "2024": 11593,
   "2025": 8111,
   "2026": 3317
  }
 },
 "faers_base": {
  "total": 20692304,
  "serious_share": 0.5742697381596559,
  "death_share": 0.09102355155810585
 },
 "recalls": [
  {
   "class": "Class II",
   "date": "20200612",
   "reason": "Presence of foreign tablet: Consumer complaint of Clozapine Tablets 50mg being present in 500 count bottles of Clozapine Tablets USP 100mg.",
   "firm": "Aurobindo Pharma USA Inc.",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20180921",
   "reason": "Failed Disintegration Specifications: Out-of-specification disintegration test result obtained during routine stability testing.",
   "firm": "Teva Pharmaceuticals USA",
   "status": "Terminated"
  }
 ],
 "recall_total": 2,
 "drugsfda": {
  "applications": 16,
  "nda": 3,
  "anda": 13,
  "first_approval": "19890926",
  "rems": true,
  "rems_last": "20250613",
  "labeling_supplements": 77,
  "labeling_recent": 7,
  "sponsors": [
   "ACCORD HLTHCARE",
   "AUROBINDO PHARMA",
   "BARR LABS INC",
   "DOUGLAS PHARMS",
   "DR REDDYS LABS SA",
   "HERITAGE LIFE",
   "IVAX SUB TEVA PHARMS",
   "JAZZ"
  ],
  "unapproved": false,
  "first_approval_fmt": "09/26/1989"
 },
 "trials": {
  "total": 184,
  "completed": 109,
  "terminated": 20,
  "with_results": 27,
  "industry": 38,
  "phase3": 20,
  "results_share": 0.24770642201834864,
  "terminated_share": 0.10869565217391304
 },
 "pubmed": {
  "rct": 290,
  "meta": 214,
  "recent_rct": 21,
  "cochrane": [
   {
    "pmid": "28613395",
    "title": "Clozapine dose for schizophrenia",
    "year": "2017"
   },
   {
    "pmid": "28333365",
    "title": "Clozapine combined with different antipsychotic drugs for treatment-resistant schizophrenia",
    "year": "2017"
   },
   {
    "pmid": "27277334",
    "title": "Pharmacological interventions for clozapine-induced sinus tachycardia",
    "year": "2016"
   },
   {
    "pmid": "26397173",
    "title": "Clozapine for psychotic disorders in adults with intellectual disabilities",
    "year": "2015"
   },
   {
    "pmid": "24353163",
    "title": "Anticholinergic medication for non-clozapine neuroleptic-induced hypersalivation in people with schizophrenia",
    "year": "2013"
   },
   {
    "pmid": "21069690",
    "title": "Clozapine versus other atypical antipsychotics for schizophrenia",
    "year": "2010"
   },
   {
    "pmid": "19588385",
    "title": "Clozapine combined with different antipsychotic drugs for treatment resistant schizophrenia",
    "year": "2009"
   },
   {
    "pmid": "19160174",
    "title": "Clozapine versus typical neuroleptic medication for schizophrenia",
    "year": "2009"
   },
   {
    "pmid": "18646130",
    "title": "Pharmacological interventions for clozapine-induced hypersalivation",
    "year": "2008"
   },
   {
    "pmid": "10796559",
    "title": "Newer atypical antipsychotic medication versus clozapine for schizophrenia",
    "year": "2000"
   },
   {
    "pmid": "10796289",
    "title": "Clozapine versus typical neuroleptic medication for schizophrenia",
    "year": "2000"
   }
  ]
 },
 "payments": {
  "year": "2024",
  "usd": 146421.95,
  "records": 165,
  "by_name": [
   [
    "clozapine",
    145306.79
   ],
   [
    "Clozaril",
    1115.16
   ]
  ],
  "names_checked": [
   "clozapine",
   "Clozaril",
   "Versacloz"
  ],
  "source": "bulk-index"
 },
 "partd": {
  "year": "2024",
  "claims": 1180978,
  "beneficiaries": 68660,
  "spend": 108068170.68,
  "by_brand": [
   {
    "brand": "Clozapine",
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    "is_generic": true
   },
   {
    "brand": "Clozapine ODT",
    "claims": 36574,
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   },
   {
    "brand": "Clozaril",
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   },
   {
    "brand": "Versacloz",
    "claims": 928,
    "per_claim": 1453.5327694,
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   }
  ],
  "per_claim": 91.50735295661732
 },
 "mdl": [],
 "dsc": [
  {
   "date": "20250827",
   "title": "FDA removes risk evaluation and mitigation strategy (REMS) program for the antipsychotic drug Clozapine",
   "url": "https://www.fda.gov/drugs/drug-safety-communications/fda-removes-risk-evaluation-and-mitigation-strategy-rems-program-antipsychotic-drug-clozapine",
   "kind": "drug",
   "matched": "clozapine"
  },
  {
   "date": "20200128",
   "title": "FDA strengthens warning that untreated constipation caused by schizophrenia medicine clozapine (Clozaril) can lead to serious bowel problems",
   "url": "https://www.fda.gov/drugs/drug-safety-communications/fda-strengthens-warning-untreated-constipation-caused-schizophrenia-medicine-clozapine-clozaril-can",
   "kind": "drug",
   "matched": "clozaril"
  },
  {
   "date": "20150915",
   "title": "FDA modifies monitoring for neutropenia associated with schizophrenia medicine clozapine; approves new shared REMS program for all clozapine medicines",
   "url": "https://www.fda.gov/Drugs/DrugSafety/ucm461853.htm",
   "kind": "drug",
   "matched": "clozapine"
  }
 ],
 "settlements": [],
 "prescrire": null,
 "eml": {
  "listed": true,
  "status": "AddedToEml",
  "name": "clozapine",
  "matched": "clozapine",
  "stewardship": []
 },
 "exposure": {
  "years": [
   "2024",
   "2025",
   "2026"
  ],
  "reports_recent": 23021,
  "fills": 1180978,
  "per_million": 19493.165833741186,
  "ratio": 7.039913168181117,
  "median": 2768.949753790441
 },
 "scores": {
  "safety": {
   "score": 17,
   "letter": "F",
   "why": [
    "Carries an FDA boxed warning, the strongest warning the FDA issues (-30)",
    "FDA issued 3 Drug Safety Communication(s) naming this drug since 2010, most recently 2025 (-20)",
    "19,493 FDA reports naming it as the suspect drug per million Medicare fills, 7.0x the median drug on this site (-15)",
    "Subject to a REMS safety program: FDA requires special controls to use it (-10)",
    "Death appears in 1.8x the share of reports seen across all of FAERS (-3)",
    "Off-label use is among the five most-reported items: widely used beyond its approved evidence (-5)"
   ],
   "weight": 0.35
  },
  "evidence": {
   "score": 72,
   "letter": "C",
   "why": [
    "290 randomized trials and 214 systematic reviews/meta-analyses indexed in PubMed",
    "On the WHO Model List of Essential Medicines (shown for context; no score effect)",
    "11 independent Cochrane review(s) exist",
    "Only 25% of completed registered trials posted results (-15)"
   ],
   "weight": 0.25
  },
  "regulatory": {
   "score": 74,
   "letter": "C",
   "why": [
    "Recalls since 2016: 0 Class I, 2 Class II, 0 Class III across 13 generic makers (-3)",
    "REMS program in force (-10)",
    "7 label changes approved since 2021: the safety story is still moving (-8)",
    "Label lists recent major changes to warnings or indications (-5)"
   ],
   "weight": 0.15
  },
  "conflict": {
   "score": 85,
   "letter": "B",
   "why": [
    "Pharma paid doctors $146,422 tied to this drug last year (-15)",
    "Not named in any pending federal MDL"
   ],
   "weight": 0.15
  },
  "options": {
   "score": 100,
   "letter": "A",
   "why": [
    "Generic versions approved (13 applications)",
    "5 same-class alternatives exist"
   ],
   "weight": 0.1
  }
 },
 "total": 58,
 "grade": "D",
 "questions": [
  "In 2025 the FDA issued a safety communication about this drug (FDA removes risk evaluation and mitigation strategy (REMS) program for the antipsychotic drug Clozapine). Does that risk apply to me?",
  "This drug carries a boxed warning. Which specific risk does it cover, and does it apply to me?",
  "This drug has a REMS safety program. What monitoring does that require from us?",
  "The most-reported problems in FDA's adverse event data are neutropenia, hospitalisation, death, schizophrenia. How would we recognize and handle those?",
  "Off-label use is among the most-reported items for this drug. Is my use on-label, and if not, what evidence supports it?",
  "Why this one over asenapine, clothiapine, loxapine? What would make you pick one of those instead?",
  "What result are we expecting, by when, and what is the plan if it does not happen?",
  "If 100 people like me took this drug, how many would actually get better because of it, and how many would be harmed by it? (Doctors call these the number needed to treat and the number needed to harm.)"
 ]
}