Medically Reviewed on 6/1/2022

Generic Name: clozapine

Brand Names: Clozaril, Versacloz

Drug Class: Antipsychotics, 2nd Generation

What is clozapine, and what is it used for?

Clozapine is a second generation atypical antipsychotic medication used for treatment-resistant schizophrenia and to reduce the risk of suicidal behavior in patients with schizophrenia.

Antipsychotic medications are essential for treating delusion and hallucination, the positive symptoms of schizophrenia. Clozapine is not commonly used as a first-line therapy because of its adverse effects, however, the advantages of clozapine include the following:

  • Reduces suicidal behavior even as first-line therapy in patients with non-treatment-resistant schizophrenia and schizoaffective disorder.
  • Improves cognition and thereby, quality of life in patients with schizophrenia.
  • Decreases the incidence of schizophrenia relapse.
  • Has lower risk compared to other antipsychotic drugs for drug-related movement disorders known as extrapyramidal symptoms and tardive dyskinesia, which results from long-term use of antipsychotic drugs.

Clozapine reduces the symptoms of schizophrenia by modifying the activity of dopamine and serotonin, two key chemicals (neurotransmitters) in the brain that appear to be involved in schizophrenia. Dopamine has many functions including regulation of movement, memory, motivation and pleasure, while serotonin’s functions include regulation of mood, emotions, sleep cycle, and digestion.

Imbalance in the neurotransmitter levels and/or abnormal neurotransmission play a major role in psychiatric disorders. Overactivity of dopamine in certain pathways of the brain leads to positive symptoms of schizophrenia such as hallucinations, delusions, and abnormal activity of serotonin is responsible for negative symptoms such as apathy, lack of pleasure, and emotions. 

Clozapine reduces both positive and negative symptoms of schizophrenia by blocking dopamine D2 and D4 receptors and serotonin 5-HT2A receptors in nerve cells (neurons). Unlike most other antipsychotics, clozapine binds only transiently to D2 and has a stronger affinity for D4, which is the reason for lower risk for extrapyramidal symptoms. Clozapine also has antagonistic effects on many other neurotransmitters which cause its adverse effects.


  • Do not use clozapine to treat patients with a history of serious hypersensitivity to clozapine or any of its components.
  • Clozapine can severely reduce absolute neutrophil count (ANC), resulting in neutropenia and increased risk for serious infections. Monitor patient’s ANC levels regularly.
  • Clozapine is available only through Risk Evaluation and Mitigation Strategy (REMS) program of the FDA because of the risk for severe neutropenia.
  • Use clozapine with caution in patients with a history of seizure or other factors for predisposition to seizure. Clozapine has a dose-related risk for seizures.
  • Clozapine is associated with heart muscle disease (cardiomyopathy) and inflammation (myocarditis). Evaluate patient’s heart condition before treatment, monitor closely during treatment and discontinue therapy if there are signs of cardiomyopathy.
  • Use with caution in patients with history of cardiovascular, cerebrovascular disease or factors predisposing for low blood pressure (hypotension). Clozapine can cause postural (orthostatic) hypotension, fainting (syncope), slow heart rate (bradycardia) and cardiac arrest, and the risk is highest during initial dose titration.
  • Do not use clozapine to treat elderly patients with dementia-related psychosis. There is an increased risk for mortality.
  • Clozapine can cause drowsiness and motor and sensory instability that may lead to falls and consequently fractures and other injuries. Perform fall risk assessment, especially in patients with other predisposing factors such as medications or diseases.
  • Clozapine is associated with development of eosinophilia, a condition with high count of eosinophils, a type of inflammatory white blood cells, and drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) that can involve inflammation of multiple organs including the pancreas, heart muscle (myocardium), kidney, liver and colon.
  • Disturbances in heart rhythm such as QT prolongation, torsades de pointes and potentially life-threatening ventricular arrhythmia resulting in cardiac arrest and sudden death have been reported with clozapine use.
  • Clozapine is associated with metabolic changes such as increase in blood glucose (hyperglycemia) and blood fats (dyslipidemia), and lead to weight gain. Monitor the patient’s glucose and blood fat levels for effective management.
  • Antipsychotic drugs including clozapine can cause neuroleptic malignant syndrome, a life-threatening reaction with high fever, irregular pulse and heart rate, muscle rigidity, changes in blood pressure and altered state of mind.
  • Clozapine is toxic to the liver. Use with caution in patients with hepatic impairment, monitor the patient, and discontinue if signs of hepatotoxicity occur.
  • Clozapine can worsen certain pre-existing conditions, use with caution in patients who have:
  • Clozapine is associated with development of blood clots including deep vein thrombosis and pulmonary embolism. Monitor the patient for symptoms.
  • Use with caution in certain eye conditions such as narrow angle glaucoma, clozapine can exacerbate the condition.
  • Clozapine can cause sedation and impair mental and physical abilities. Advise patients appropriately.
  • Antipsychotic drugs including clozapine can cause potentially irreversible tardive dyskinesia, particularly with prolonged treatment with high doses.
  • If clozapine has to be abruptly discontinued because of severe neutropenia or other conditions, monitor the patient carefully for recurrence of psychosis and other withdrawal effects.


What's Schizophrenia? Symptoms, Types, Causes, Treatment See Slideshow

What are the side effects of clozapine?

Common side effects of clozapine include:

Less common side effects of clozapine include:

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.

Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

What are the dosages of clozapine?


  • 25 mg
  • 50 mg
  • 100 mg
  • 200 mg

Oral Suspension (Versacloz)

  • 50 mg/mL



Indicated for reducing risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder in patients who are judged to be at chronic risk to re-experience suicidal behavior

Also indicated for treatment-resistant schizophrenia in patients who fail to respond adequately to standard antipsychotic treatment

  • 12.5 mg orally once daily or every 12 hours initially; increase in increments of 25-50 mg/day, if well tolerated, to achieve target dosage of 300-450 mg/day (administered in divided doses) by end of 2 weeks
  • Subsequently, may increase dose once or twice weekly in increments of up to 100 mg; not to exceed 900 mg/day
  • Maintenance: Generally, patients who respond should continue maintenance treatment on their effective dose beyond the acute episode

Re-initiation of therapy

  • If therapy interrupted for 48 hours or longer, must reinitiate dose at 12.5 mg once a day or twice a day to minimize risk of hypotension, bradycardia, and syncope; if dose well tolerated, may increase more rapidly than with initial titration, unless cardiopulmonary arrest occurred during initial titration, then titrate with extreme caution

Discontinuation of therapy

  • Method of treatment discontinuation depends on patient’s last absolute neutrophil count (ANC)
  • Reduce dose gradually over a period of 1-2 weeks if termination not related to neutropenia; taper gradually to avoid withdrawal symptoms and minimize risk of relapse; for schizophrenia, guidelines recommend gradual taper over 6-24 months (American Psychiatric Association guidelines recommend reducing dose 10% each month)
  • For abrupt clozapine discontinuation for a reason unrelated to neutropenia, continue existing ANC monitoring until ANC is 1500/mm3 or greater
  • If benign patient has benign ethnic neutropenia (BEN); monitor until ANC is 1000/mm3 or greater, or above baseline
  • Additional ANC monitoring required for onset of fever during the 2 weeks after discontinuation
  • Monitor all patients carefully for the recurrence of psychotic symptoms and symptoms related to cholinergic rebound (e.g., profuse sweating, headache, nausea, vomiting, diarrhea)

Dosage Modifications

Coadministration with CYP inhibitors

  • Strong CYP1A2 inhibitors: Use one-third clozapine dose
  • Moderate or weak CYP1A2 inhibitors: Monitor for adverse reactions; consider reducing clozapine dose if needed
  • CYP2D6 or CYP3A4 inhibitors: Monitor for adverse reactions; consider reducing clozapine dose if needed
  • CYP2D6 poor metabolizers: Clozapine dose reduction may be needed

Coadministration with CYP inducers

  • Strong CYP3A4 inducers: Coadministration not recommended; if the inducer is necessary, clozapine dose may need to be increased
  • Moderate or weak CYP1A2 or CYP3A4 inducers: Monitor for decreased effectiveness; consider increasing clozapine dose if necessary

Renal or hepatic impairment

  • Dose reduction may be necessary with significant renal or hepatic impairment

Dosing Considerations

  • Required laboratory monitoring
  • Before initiating, obtain complete blood count (CBC) with differential for baseline ANC; to continue treatment, ANC must be monitored regularly
  • In order to initiate treatment, ANC must be 1500/mm3 or greater for the general population and 1000/mm3 or greater for patients with documented benign ethnic neutropenia


Lower initial dosage of 12.5-25 mg/day indicated; may be titrated more slowly than in younger adults

Elderly patients, particularly those with compromised cardiovascular functioning, may be more susceptible to orthostatic hypotension and tachycardia; anticholinergic effects are also common (constipation, confusion, urinary retention)


  • Safety and efficacy not established.


  • The most common symptoms of clozapine overdose include sedation, delirium, coma, rapid heart rate, low blood pressure, respiratory depression or failure, and excessive salivation. There have been reports of aspiration pneumonia, irregular heart rhythms, seizure, and death with severe overdose.
  • There are no specific antidotes for clozapine. Overdose is treated with symptomatic and supportive care including respiratory support and monitoring of heart function and other vital signs.
  • In case of overdose, immediately seek medical help or contact Poison Control.

What drugs interact with clozapine?

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

  • Severe Interactions of clozapine include:
    • amisulpride
    • dronedarone
    • eliglustat
    • flibanserin
    • irinotecan
    • irinotecan liposomal
    • lomitapide
    • lonafarnib
    • nirmatrelvir
    • nirmatrelvir/ritonavir
    • saquinavir
    • thioridazine
  • Clozapine has serious interactions with at least 146 different drugs.
  • Clozapine has moderate interactions with at least 439 different drugs.
  • Mild Interactions of clozapine include:

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

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Pregnancy and breastfeeding

  • Animal reproductive studies do not show impairment of fertility or fetal harm with the use of clozapine during pregnancy. There are, however, no adequate or well-controlled studies of clozapine in pregnant women. Clozapine should be used during pregnancy only if clearly needed.
  • There are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics during pregnancy.
  • Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms) and/or withdrawal symptoms in newborns following delivery.
  • Clozapine is present in breast milk. A decision to discontinue the drug or nursing should be made after considering potential adverse effects on the baby and the nursing mother’s need for therapy.
  • There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including clozapine, during pregnancy. Health care providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmental

What else should I know about clozapine?

  • Take clozapine exactly as prescribed. Do not miss your doses. In case you miss doses for more than 2 days, consult your physician before restarting your medication.
  • Report immediately to your physician if you develop flu-like illness, fever, lethargy, weakness or infections.
  • Clozapine is associated with risks of drowsiness and seizure. Avoid potentially hazardous activities such as driving or operating heavy machinery while on therapy.
  • Consult your physician immediately if you feel faint or have any heart-related symptoms.


Clozapine is a second generation atypical antipsychotic medication used for treatment-resistant schizophrenia and to reduce the risk of suicidal behavior in patients with schizophrenia. Clozapine is associated with heart muscle disease (cardiomyopathy) and inflammation (myocarditis). Common side effects of clozapine include sedation, drowsiness (somnolence), dizziness, vertigo, tremor, headache, visual disturbances, insomnia, EEG pattern changes, rapid heart rate (tachycardia), low blood pressure (hypotension), fainting (syncope), excessive salivation (hypersalivation), and others. Consult your doctor if pregnant or breastfeeding.

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Medically Reviewed on 6/1/2022