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Clozaril (Clozapine) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

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

  • Agranulocytosis. [see Warnings and Precautions]
  • Orthostatic Hypotension, Bradycardia, and Syncope. [see Warnings and Precautions]
  • Seizures. [see Warnings and Precautions]
  • Myocarditis and Cardiomyopathy. [see Warnings and Precautions]
  • Increased Mortality in Elderly Patients with Dementia-Related Psychosis. [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]
  • 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 8 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 8. 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 9 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 9. Adverse Reactions (≥2%) Reported in CLOZARIL-treated Patients (N=842) Across all CLOZARIL Studies (excluding the 2-year InterSePT Study) TM
† Rate based on population of approximately 1700 exposed during premarket clinical evaluation of CLOZARIL.
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

Table 10 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, 2-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. TM

Table 10. Incidence of Adverse Reactions in Patients Treated with CLOZARIL or Olanzapine in the InterSePT Study (>10% in the CLOZARIL or olanzapine group) TM
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

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. Class effect:

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.

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.

Urogenital System

Acute interstitial nephritis, nocturnal enuresis, priapism, and renal failure.

Skin

Hypersensitivity reactions: photosensitivity, vasculitis, erythema multiforme, and Stevens-Johnson Syndrome.

Musculoskeletal System

Myasthenic syndrome and rhabdomyolysis.

Respiratory System

Aspiration, pleural effusion, pneumonia, lower respiratory tract infection.

Hemic and Lymphatic System

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.



REPORTS OF SUSPECTED CLOZARIL SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Clozaril. The information is not vetted and should not be considered as verified clinical evidence.

Possible Clozaril side effects / adverse reactions in 30 year old male

Reported by a physician from Denmark on 2011-10-03

Patient: 30 year old male

Reactions: White Blood Cell Count Decreased, Neutrophil Count Decreased, Constipation

Suspect drug(s):
Levetiracetam
    Dosage: 1000 mg;qd
    Indication: Epilepsy

Valproic Acid
    Dosage: 2000 mg;qd

Clozaril
    Dosage: 400 mg;qd
    Indication: Schizophrenia
    Start date: 2004-04-28

Other drugs received by patient: Lactulose; Lansoprazole



Possible Clozaril side effects / adverse reactions in 36 year old female

Reported by a individual with unspecified qualification from United Kingdom on 2011-10-03

Patient: 36 year old female

Reactions: Electrocardiogram QT Prolonged, Ventricular Extrasystoles, Dyspnoea, Tachycardia, Condition Aggravated, Mental Disorder, Treatment Noncompliance

Adverse event resulted in: hospitalization

Suspect drug(s):
Clozaril
    Dosage: 50 mg, 1 in 1 d, oral
    Administration route: Oral
    Indication: Schizophrenia
    End date: 2003-12-15

Risperidone
    Indication: Product Used FOR Unknown Indication

Amisulpride (Amisulpride)
    Indication: Product Used FOR Unknown Indication



Possible Clozaril side effects / adverse reactions in 59 year old female

Reported by a physician from Denmark on 2011-10-04

Patient: 59 year old female

Reactions: Neutrophil Count Increased, Agranulocytosis, Pyrexia, Oropharyngeal Pain, White Blood Cell Count Increased

Adverse event resulted in: hospitalization

Suspect drug(s):
Clozaril
    Dosage: 300 mg
    Start date: 2011-02-03
    End date: 2011-04-06

Mirtazapine

Mirtazapine



See index of all Clozaril side effect reports >>

Drug label data at the top of this Page last updated: 2013-11-13

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