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Clozaril

Last reviewed on RxList: 10/17/2016
Clozaril Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 10/12/2016

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. 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.

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. 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 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.

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.

Clozaril Consumer Information

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Serious and sometimes fatal infections may occur during treatment with clozapine. Call your doctor right away if you have signs of infection such as:

  • fever, chills, body aches, flu symptoms;
  • mouth and throat ulcers;
  • cough, sore throat;
  • rapid heart rate; or
  • rapid and shallow breathing.

Stop using clozapine and call your doctor at once if you have any of these serious side effects:

  • headache with chest pain and severe dizziness, fainting, fast or pounding heartbeats;
  • seizure (black-out or convulsions);
  • skin rash, bruising, severe tingling, numbness, pain, muscle weakness;
  • unusual tiredness, trouble breathing;
  • feeling short of breath (even at night or with mild exertion), swelling in your hands or feet;
  • feeling like you might pass out;
  • slow heart rate, weak pulse, slow breathing (breathing may stop);
  • high blood sugar (increased thirst, extreme hunger, fruity breath odor, increased urination, drowsiness);
  • very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors;
  • twitching or uncontrollable movements of your eyes, lips, tongue, face, arms, or legs; or
  • nausea, vomiting, loss of appetite, and jaundice (yellowing of your skin or eyes).

Less serious side effects may include:

  • constipation;
  • dry mouth, blurred vision;
  • drooling, especially at night;
  • increased sweating;
  • drowsiness, dizziness, spinning sensation; or
  • sleep problems.

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.

Read the entire detailed patient monograph for Clozaril (Clozapine)

Clozaril Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in more detail in other sections of the labeling:

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, and post-discontinuation cholinergic rebound adverse reactions.

Cardiovascular System

Atrial or ventricular fibrillation, ventricular tachycardia, QT interval prolongation, Torsades de Pointes, myocardial infarction, cardiac arrest, and periorbital edema.

Endocrine System

Pseudopheochromocytoma.

Gastrointestinal System

Acute pancreatitis, dysphagia, salivary gland swelling.

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.

Hemic and Lymphatic System

Mild, moderate, or severeleukopenia, 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, and weight loss.

Read the entire FDA prescribing information for Clozaril (Clozapine)

Related Resources for Clozaril

Read the Clozaril User Reviews »

© 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.

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