Jump To

VERSACLOZ SIDE EFFECTS

  • Generic Name: clozapine oral suspension
  • Brand Name: Versacloz
  • Drug Class: How Do Second Generation Antipsychotics Work?
Last updated on MDtodate: 10/8/2022

SIDE EFFECTS

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

  • Severe Neutropenia.
  • Orthostatic Hypotension, Bradycardia, and Syncope.
  • Falls.
  • Seizures.
  • Myocarditis and Cardiomyopathy.
  • Increased Mortality in Elderly Patients with Dementia-Related Psychosis.
  • Gastrointestinal Hypomotility and Severe Complications
  • Eosinophilia
  • QT Interval Prolongation
  • Metabolic Changes (Hyperglycemia and Diabetes Mellitus, Dyslipidemia, and Weight Gain)
  • Neuroleptic Malignant Syndrome
  • Hepatotoxicity
  • Fever
  • Pulmonary Embolism
  • Anticholinergic Toxicity
  • Interference with Cognitive and Motor Performance
  • Tardive Dyskinesia
  • Cerebrovascular Adverse Reactions
  • Recurrence of Psychosis and Cholinergic Rebound after Abrupt Discontinuation

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 clozapine 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 clozapine-treated patients (compared to chlorpromazine-treated patients) in the pivotal, 6-week, controlled trial in treatment-resistant schizophrenia.

Table 1: Common Adverse Reactions (≥5%) in the 6-Week, Randomized, Chlorpromazine- controlled Trial in Treatment-Resistant Schizophrenia

Adverse Reaction Clozapine
(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 2 summarizes the adverse reactions reported in clozapine-treated patients at a frequency of 2% or greater across all clozapine studies (excluding the 2-year InterSePT™ Study). These rates are not adjusted for duration of exposure.

Table 2: Adverse Reactions (≥2%) Reported in Clozapine-treated Patients (N=842) across all Clozapine Studies (excluding the 2-year InterSePT™ Study)

Body System
Adverse Reaction
Clozapine
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 clozapine.

 

Table 3 summarizes the most commonly reported adverse reactions (>10% of the clozapine or olanzapine group) in the InterSePT™ Study. This was an adequate and well-controlled, two-year study evaluating the efficacy of clozapine 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 3: Incidence of Adverse Reactions in Patients Treated with Clozapine or Olanzapine in the InterSePT™ Study (≥10% in the clozapine or olanzapine group)

Adverse Reactions Clozapine
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, 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, and renal failure.

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 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, and weight loss.

 

SRC: NLM .

Read Next Article

PHP Code Snippets Powered By : XYZScripts.com