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Fazaclo (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].

  • •Patients with Phenylketonuria [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 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 8 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 8. 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

Tachycardia

Constipation

Dizziness

Hypotension

Fever (hyperthermia)

Hypersalivation

Hypertension

Headache

Nausea/vomiting

Dry mouth

21

17

16

14

13

13

13

12

10

10

5

13

11

12

16

38

4

1

5

10

12

20

Table 9 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 9. 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
     Dizziness/Vertigo
     Headache
     Tremor


39
19
7
6

     Syncope
     Disturbed Sleep/Nightmares
     Restlessness
     Hypokinesia/Akinesia

6
4
4
4

     Agitation
     Seizures (convulsions)
     Rigidity
     Akathisia
     Confusion
     Fatigue
     Insomnia

4
3†
3
3
3
2
2

Cardiovascular
     Tachycardia
     Hypotension
     Hypertension   


25†
9
4

Gastrointestinal
     Constipation
     Nausea
     Abdominal Discomfort/Heartburn
     Nausea/Vomiting
     Vomiting
     Diarrhea


14
5
4
3
3
2

Urogenital
     Urinary Abnormalities     


2

Autonomic Nervous System
     Salivation
     Sweating
     Dry Mouth
     Visual Disturbances


31
6
6
5

Skin
     Rash


2

Hemic/Lymphatic
     Leukopenia/Decreased WBC/Neutropenia   


3

Miscellaneous
     Fever
     Weight Gain


5
4

  •  † Rate based on population of approximately 1700 exposed during premarket clinical evaluation of clozapine.

Table 10 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 10. 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

Olanzapine

N = 479

N = 477

% Reporting

% 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.

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.

Drug label data at the top of this Page last updated: 2013-07-22

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