Medical Editor: John P. Cunha, DO, FACOEP
What Is Clozaril?
Clozaril (clozapine) is an antipsychotic medication that is used to treat severe schizophrenia symptoms in people who have not responded to other medications. Clozaril is also used to help reduce the risk of suicidal behavior in people with schizophrenia or similar disorders.
What Are Side Effects of Clozaril?
Side effects of Clozaril include:
- constipation,
- drooling (especially at night),
- sleep problems,
- increased sweating,
- weight gain,
- dry mouth,
- blurred vision,
- drowsiness,
- dizziness,
- spinning sensation,
- headache, or
- shaking (tremor).
Many of these side effects (especially drowsiness) lessen as your body gets used to Clozaril.
Dosage for Clozaril?
Clozaril is taken orally in tablet form, and an orally-disintegrating tablet that can be taken without water is available. While you are taking clozapine, your blood may need to be tested every week for the first 6 months of treatment. It has been associated with agranulocytosis in some patients, a potentially fatal decrease in a certain type of white blood cells.
What Drugs, Substances, or Supplements Interact with Clozaril?
Clozaril may interact with alcohol, other antipsychotic medications, armodafinil, modafinil, arsenic trioxide, bosentan, cimetidine, conivaptan, dexamethasone, nefazodone, imatinib, isoniazid, phenobarbital and other barbiturates, St. John's wort, tacrolimus, antibiotics, antifungals, antidepressants, anti-malaria medications, atropine, belladonna, clidinium, dicyclomine, scopolamine, heart or blood pressure medications, HIV/AIDS medications, medicines to prevent or treat nausea and vomiting, migraine headache medicines, narcotics, or seizure medications. Tell your doctor all medications and supplements you use.
Clozaril During Pregnancy and Breastfeeding
Clozaril is not expected to be harmful to an unborn baby. Do not use clozapine without telling your doctor if you are pregnant or plan to become pregnant during treatment. Clozapine can pass into breast milk and may harm a nursing baby. Breastfeeding while using Clozaril is not recommended.
Additional Information
Our Clozaril Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
QUESTION
Schizophrenia is the most disabling mental illness. See AnswerGet emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).
You may get infections more easily, even serious or fatal infections. Call your doctor right away if you have signs of infection such as:
- fever, flu-like symptoms, extreme weakness;
- mouth sores, skin sores;
- new or worsening cough, trouble breathing;
- pain or burning when you urinate; or
- vaginal itching or discharge.
Further doses may be delayed until your infection clears up.
High doses or long-term use of clozapine can cause a serious movement disorder that may not be reversible. The longer you use clozapine, the more likely you are to develop this disorder, especially if you are a woman or an older adult.
Clozapine can increase your risk of seizure, especially at high doses. Avoid any activity that could be dangerous if you have a seizure or lose consciousness.
Call your doctor at once if you have:
- uncontrolled muscle movements in your face (chewing, lip smacking, frowning, tongue movement, blinking or eye movement);
- a seizure (blackout-out or convulsions);
- severe constipation;
- dry or hard bowel movements, or painful gas;
- nausea, vomiting, stomach pain or bloating;
- heart problems--chest pain, fast or pounding heartbeats, fluttering in your chest, slow heartbeats, shortness of breath, and sudden dizziness (like you might pass out);
- liver problems--loss of appetite, stomach pain (upper right side), tiredness, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
- severe nervous system reaction--very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out; or
- signs of a blood clot in the lung--chest pain, sudden cough, wheezing, rapid breathing, coughing up blood.
Untreated constipation may lead to serious bowel complications, hospitalization, or death. Tell your doctor right away if you are not having bowel movements at least 3 times per week.
Common side effects may include:
- weight gain;
- dizziness, tremor;
- fast heart rate;
- headache, drowsiness;
- nausea, constipation;
- dry mouth, or increased salivation;
- vision problems; or
- fever, increased sweating.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
SLIDESHOW
Schizophrenia: Symptoms, Types, Causes, Treatment See SlideshowSIDE EFFECTS
The following adverse reactions are discussed in more detail in other sections of the labeling:
- Severe Neutropenia [see WARNINGS AND PRECAUTIONS]
- Orthostatic Hypotension, Bradycardia, and Syncope [see WARNINGS AND PRECAUTIONS]
- Falls [see WARNINGS AND PRECAUTIONS]
- Seizures [see WARNINGS AND PRECAUTIONS]
- Myocarditis, Cardiomyopathy, and Mitral Valve Incompetence [see WARNINGS AND PRECAUTIONS]
- Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see WARNINGS AND PRECAUTIONS]
- Gastrointestinal Hypomotility with Severe Complications [See WARNINGS AND PRECAUTIONS]
- Eosinophilia [see WARNINGS AND PRECAUTIONS]
- QT Interval Prolongation [see WARNINGS AND PRECAUTIONS]
- Metabolic Changes (Hyperglycemia and Diabetes Mellitus, Dyslipidemia, and Weight Gain) [see WARNINGS AND PRECAUTIONS]
- Neuroleptic Malignant Syndrome [see WARNINGS AND PRECAUTIONS]
- Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
- Fever [see WARNINGS AND PRECAUTIONS]
- Pulmonary Embolism [see WARNINGS AND PRECAUTIONS]
- Anticholinergic Toxicity [see WARNINGS AND PRECAUTIONS]
- Interference with Cognitive and Motor Performance [see WARNINGS AND PRECAUTIONS]
- Tardive Dyskinesia [see WARNINGS AND PRECAUTIONS]
- Cerebrovascular Adverse Reactions [see WARNINGS AND PRECAUTIONS]
- Recurrence of Psychosis and Cholinergic Rebound after Abrupt Discontinuation [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The most commonly reported adverse reactions (≥5%) across CLOZARIL clinical trials were: CNS reactions, including sedation, dizziness/vertigo, headache, and tremor; cardiovascular reactions, including tachycardia, hypotension, and syncope; autonomic nervous system reactions, including hypersalivation, sweating, dry mouth, and visual disturbances; gastrointestinal reactions, including constipation and nausea; and fever. Table 9 summarizes the most commonly reported adverse reactions (≥5%) in CLOZARIL-treated patients (compared to chlorpromazine-treated patients) in the pivotal, 6-week, controlled trial in treatment-resistant schizophrenia.
Table 9: Common Adverse Reactions (≥5%) in the 6-Week, Randomized, Chlorpromazine-controlled Trial in Treatment-Resistant Schizophrenia
| Adverse Reaction | CLOZARIL (N=126) (%) | Chlorpromazine (N=142) (%) |
| Sedation | 21 | 13 |
| Tachycardia | 17 | 11 |
| Constipation | 16 | 12 |
| Dizziness | 14 | 16 |
| Hypotension | 13 | 38 |
| Fever (hyperthermia) | 13 | 4 |
| Hypersalivation | 13 | 1 |
| Hypertension | 12 | 5 |
| Headache | 10 | 10 |
| Nausea/vomiting | 10 | 12 |
| Dry mouth | 5 | 20 |
Table 10 summarizes the adverse reactions reported in CLOZARIL-treated patients at a frequency of 2% or greater across all CLOZARIL studies (excluding the 2-year InterSePT™ Study). These rates are not adjusted for duration of exposure.
Table 10: Adverse Reactions (≥2%) Reported in CLOZARIL-treated Patients (N=842) Across all CLOZARIL Studies (excluding the 2-year InterSePT™ Study)
| Body System Adverse Reaction* | CLOZARIL N=842 Percentage of Patients |
| Central Nervous System | |
| Drowsiness/Sedation | 39 |
| Dizziness/Vertigo | 19 |
| Headache | 7 |
| Tremor | 6 |
| Syncope | 6 |
| Disturbed Sleep/Nightmares | 4 |
| Restlessness | 4 |
| Hypokinesia/Akinesia | 4 |
| Agitation | 4 |
| Seizures (convulsions) | 3† |
| Rigidity | 3 |
| Akathisia | 3 |
| Confusion | 3 |
| Fatigue | 2 |
| Insomnia | 2 |
| Cardiovascular | |
| Tachycardia | 25† |
| Hypotension | 9 |
| Hypertension | 4 |
| Gastrointestinal | |
| Constipation | 14 |
| Nausea | 5 |
| Abdominal Discomfort/Heartburn | 4 |
| Nausea/Vomiting | 3 |
| Vomiting | 3 |
| Diarrhea | 2 |
| Urogenital | |
| Urinary Abnormalities | 2 |
| Autonomic Nervous System | |
| Salivation | 31 |
| Sweating | 6 |
| Dry Mouth | 6 |
| Visual Disturbances | 5 |
| Skin | |
| Rash | 2 |
| Hemic/Lymphatic | |
| Leukopenia/Decreased WBC/Neutropenia | 3 |
| Miscellaneous | |
| Fever | 5 |
| Weight Gain | 4 |
| †Rate based on population of approximately 1700 exposed during premarket clinical evaluation of CLOZARIL. | |
Table 11 summarizes the most commonly reported adverse reactions (>10% of the CLOZARIL or olanzapine group) in the InterSePT™ Study. This was an adequate and well-controlled, two-year study evaluating the efficacy of CLOZARIL relative to olanzapine in reducing the risk of suicidal behavior in patients with schizophrenia or schizoaffective disorder. The rates are not adjusted for duration of exposure.
Table 11: Incidence of Adverse Reactions in Patients Treated with CLOZARIL or Olanzapine in the InterSePT™ Study (≥10% in the CLOZARIL or olanzapine group)
| Adverse Reactions | CLOZARIL N=479 % Reporting | Olanzapine N=477 % Reporting |
| Salivary hypersecretion | 48 | 6 |
| Somnolence | 46 | 25 |
| Weight increased | 31 | 56 |
| Dizziness (excluding vertigo) | 27 | 12 |
| Constipation | 25 | 10 |
| Insomnia | 20 | 33 |
| Nausea | 17 | 10 |
| Vomiting | 17 | 9 |
| Dyspepsia | 14 | 8 |
Dystonia
Class Effect
Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of clozapine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Central Nervous System
Delirium, EEG abnormal, myoclonus, paresthesia, possible cataplexy, status epilepticus, obsessive compulsive symptoms, restless leg syndrome, and post-discontinuation cholinergic rebound adverse reactions.
Cardiovascular System
Atrial or ventricular fibrillation, ventricular tachycardia, palpitations, QT interval prolongation, Torsades de Pointes, mitral valve incompetence associated with clozapine-related cardiomyopathy, myocardial infarction, cardiac arrest, myocarditis, and periorbital edema.
Endocrine System
Pseudopheochromocytoma
Gastrointestinal System
Acute pancreatitis, dysphagia, salivary gland swelling, colitis, megacolon, intestinal ischemia or infarction.
Hepatobiliary System
Cholestasis, hepatitis, jaundice, hepatotoxicity, hepatic steatosis, hepatic necrosis, hepatic fibrosis, hepatic cirrhosis, liver injury (hepatic, cholestatic, and mixed), and liver failure.
Immune System Disorders
Angioedema, leukocytoclastic vasculitis.
Urogenital System
Acute interstitial nephritis, nocturnal enuresis, priapism, renal failure, and retrograde ejaculation.
Skin And Subcutaneous Tissue Disorders
Hypersensitivity reactions: photosensitivity, vasculitis, erythema multiforme, skin pigmentation disorder, and Stevens-Johnson Syndrome.
Musculoskeletal System And Connective Tissue Disorders
Myasthenic syndrome, rhabdomyolysis, and systemic lupus erythematosus.
Respiratory System
Aspiration, pleural effusion, pneumonia, lower respiratory tract infection, sleep apnea.
Hemic And Lymphatic System
Mild, moderate, or severe leukopenia, agranulocytosis, granulocytopenia, WBC decreased, deep-vein thrombosis, elevated hemoglobin/hematocrit, erythrocyte sedimentation rate (ESR) increased, sepsis, thrombocytosis, and thrombocytopenia.
Vision Disorders
Narrow-angle glaucoma.
Miscellaneous
Creatine phosphokinase elevation, hyperuricemia, hyponatremia, polyserositis, and weight loss.
Read the entire FDA prescribing information for Clozaril (Clozapine)
© Clozaril Patient Information is supplied by Cerner Multum, Inc. and Clozaril Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.
Health Solutions From Our Sponsors