Note: This document contains side effect information about clozapine. Some dosage forms listed on this page may not apply to the brand name FazaClo.

Summary

Common side effects of FazaClo include: hypotension, fever, tachycardia, constipation, dizziness, headache, nausea, sedated state, vomiting, and weight gain. Other side effects include: syncope, and diaphoresis. Continue reading for a comprehensive list of adverse effects.

Applies to clozapine: oral conventional tablets, oral oral suspension, oral orally disintegrating tablets.

Side effects include:

Sedation, dizziness/vertigo, headache, tremor, tachycardia, hypotension, syncope, hypersalivation, sweating, dry mouth, visual disturbances, constipation, nausea, fever.

For Healthcare Professionals

Applies to clozapine: oral suspension, oral tablet, oral tablet disintegrating.

General

The most commonly reported side effects included salivary hypersecretion, somnolence, and weight gain.^[Ref]

Gastrointestinal

Very common (10% or more): Salivary hypersecretion/hypersalivation (up to 48%), salivation (up to 31%), constipation (up to 25%), nausea (up to 17%), vomiting (up to 17%), dyspepsia (up to 14%)

Common (1% to 10%): Abdominal discomfort/dyspepsia/heartburn, diarrhea, dry mouth

Rare (0.01% to 0.1%): Acute pancreatitis, Dysphagia, ileus impaction, pancreatitis

Very rare (less than 0.01%): Fecal impaction/intestinal obstruction/paralytic ileus, parotid gland enlargement

Frequency not reported: Colitis, swallowing difficulty, tongue protrusion

Postmarketing reports: Intestinal infarction/ischemia/fatal intestinal infarction/ischemia, megacolon/fatal megacolon, salivary gland swelling^[Ref]

Nervous system

The cumulative incidence of seizure at 1 year is approximately 5% based on pre-marketing testing. The risk is dose-related.

Extrapyramidal symptoms that occur appear to be milder and less frequent than other antipsychotic drugs. There have been no reports of tardive dyskinesia directly attributable to clozapine (the active ingredient contained in FazaClo) however, the syndrome has been reported in a few patients who were treated with other antipsychotics prior to receiving clozapine. A causal relationship can neither be established nor excluded.

Cholinergic syndrome occurred after abrupt withdrawal.^[Ref]

Very common (10% or more): Somnolence (up to 46%), drowsiness/sedation (up to 39%), dizziness (up to 27%), vertigo (up to 19%), headache (up to 10%)

Common (1% to 10%): Akathisia, akinesia, convulsions/myoclonic jerks/seizures, dysarthria, extrapyramidal symptoms, hypokinesia, syncope, tremor

Uncommon (0.1% to 1%): Neuroleptic malignant syndrome

Very rare (less than 0.01%): Tardive dyskinesia

Frequency not reported: Dystonia

Postmarketing reports: Abnormal EEG, cholinergic syndrome, clozapine-induced seizures, EEG changes, motor instability, myasthenic syndrome, myoclonus, paresthesia, pleurothotonus, possible cataplexy, post-discontinuation cholinergic rebound adverse reactions, sensory instability, status epilepticus^[Ref]

Metabolic

Diabetes mellitus occurred in patients without a history of hyperglycemia or diabetes mellitus.

Pooled data from 8 studies in patients with schizophrenia found the mean change in fasting blood glucose in clozapine (the active ingredient contained in FazaClo) treated patients was +11 mg/dL; pooled data from 10 studies revealed clozapine treatment was associated a mean increase of 13 mg/dl in total cholesterol; pooled data from 11 studies showed a weight gain of 7% or greater relative to baseline body weight occurred in 35% of patients with a mean weight gain of 3.7 kg.^[Ref]

Very common (10% or more): Increased weight/weight gain (up to 31%)

Common (1% to 10%): Anorexia

Rare (0.01% to 0.1%): Aggravated diabetes, diabetes mellitus, hyperosmolar coma, impaired glucose tolerance, ketoacidosis, severe hyperglycemia

Very rare (less than 0.01%): Hypercholesterolemia, hypertriglyceridemia

Frequency not reported: Pseudopheochromocytoma

Postmarketing reports: Hypernatremia, hyperuricemia, obesity, weight loss^[Ref]

Cardiovascular

Very common (10% or more): Tachycardia (up to 25%), hypotension (up to 13%), hypertension (up to 12%)

Common (1% to 10%): ECG changes, postural hypotension

Rare (0.01% to 0.1%): Arrhythmias, circulatory collapse, myocarditis, pericardial effusion, pericarditis, thromboembolism, ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia

Very rare (less than 0.01%): Cardiac arrest, cardiomyopathy/clozapine-related cardiomyopathy, QT prolongation, skin reactions, Torsade de pointes

Frequency not reported: Angina pectoris/chest pain, myocardial infarction/fatal myocardial infarction, pigmentation disorder, venous thromboembolism

Postmarketing reports: Atrial fibrillation, deep vein thrombosis, mitral valve incompetence, palpitations^[Ref]

Isolated cases of cardiac arrhythmias, pericarditis/pericardial effusion, and myocarditis have been reported. Postmarketing, very rare events of ventricular tachycardia, cardiac arrest, and QT prolongation which may be associated with Torsades de pointes have been observed, although there is no conclusive causal relationship to use of this drug.^[Ref]

Psychiatric

Very common (10% or more): Insomnia (up to 20%)

Common (1% to 10%): Agitation, confusion, disturbed sleep/nightmares, restlessness

Uncommon (0.1% to 1%): Dysphemia

Rare (0.01% to 0.1%): Delirium, dream activity intensification

Very rare (less than 0.01%): Obsessive compulsive disorder/symptoms

Frequency not reported: Neonatal drug withdrawal syndrome^[Ref]

Other

Very common (10% or more): Fever/hyperthermia (up to 13%)

Common (1% to 10%): Benign hyperthermia, fatigue, temperature regulation disturbance

Very rare (less than 0.01%): Sudden unexplained death

Postmarketing reports: Falls, polyserositis, sepsis^[Ref]

Hematologic

Common (1% to 10%): Decreased white blood cells, eosinophilia, leukocytosis, leukopenia, neutropenia

Uncommon (0.1% to 1%): Agranulocytosis

Rare (0.01% to 0.1%): Anemia

Very rare (less than 0.01%): Thrombocythemia, thrombocytopenia

Postmarketing reports: Elevated hematocrit, elevated hemoglobin, granulocytopenia, increased erythrocyte sedimentation rate, mild leukopenia, moderate leukopenia, severe leukopenia, thrombocytosis^[Ref]

During pre-marketing testing, the cumulative incidence of agranulocytosis at one year was reported to be 1.3%. Based on Clozaril National Registry (US patients) data collected up to April 1995, a hematologic risk analysis found the incidence of agranulocytosis rises steeply during the first 2 months, peaks at approximately the third month, and decreases at 6 months of therapy; after 6 months, the incidence decreases further, however, it never reaches zero. Individuals with an initial episode of moderate leukopenia (WBC of at least 2000/mm3 and less than 3000/mm3) are at an increased risk of having a subsequent episode of agranulocytosis.

In the UK, agranulocytosis occurred within the first 18 weeks in approximately 70% of patients who developed the condition.

In clinical trials, eosinophil counts of greater than 700/mm3 occurred in approximately 1% of patients. Eosinophilia has been co-reported with some cases of myocarditis (approximately 14%) and pericarditis/pericardial effusion, although it is unknown whether eosinophilia is a reliable predictor of carditis.^[Ref]

Genitourinary

Common (1% to 10%): Urinary abnormalities, urinary incontinence, urinary retention

Very rare (less than 0.01%): Dysmenorrhea, ejaculation change, impotence, priapism

Postmarketing reports: Nocturnal enuresis, retrograde ejaculation^[Ref]

Dermatologic

Common (1% to 10%): Rash, sweating/sweating disturbance

Frequency not reported: Leukocytoclastic vasculitis

Postmarketing reports: Erythema multiforme, photosensitivity, skin pigmentation disorder, Stevens-Johnson syndrome^[Ref]

Ocular

Common (1% to 10%): Blurred vision, visual disturbances

Postmarketing reports: Narrow angle glaucoma, periorbital edema^[Ref]

Hepatic

Common (1% to 10%): Elevated liver enzymes

Rare (0.01% to 0.1%): Cholestasis, cholestatic jaundice, hepatitis

Very rare (less than 0.01%): Fulminant hepatic necrosis

Postmarketing reports: Cholestatic injury, hepatic cirrhosis, hepatic fibrosis, hepatic injury, hepatic necrosis, hepatic steatosis, hepatotoxicity, jaundice, liver failure, liver transplant, mixed injury^[Ref]

Musculoskeletal

Common (1% to 10%): Rigidity

Rare (0.01% to 0.1%): Creatine phosphokinase elevation

Frequency not reported: Muscle pain, muscle spasms, muscle weakness, neck muscle spasm, systemic lupus erythematosus

Postmarketing reports: Rhabdomyolysis^[Ref]

Respiratory

Aspiration of ingested food usually occurred in patients with dysphagia or in acute overdose.^[Ref]

Rare (0.01% to 0.1%): Aspiration of ingested food, lower respiratory tract infection/fatal lower respiratory tract infection, pneumonia, pulmonary embolism, respiratory arrest, respiratory depression, respiratory depression/arrest with/without circulatory collapse

Very rare (less than 0.01%): Allergic asthma

Frequency not reported: Difficulty breathing, nasal congestion, throat tightness

Postmarketing reports: Pleural effusion, sleep apnea/sleep apnea syndrome^[Ref]

Renal

Very rare (less than 0.01%): Acute interstitial nephritis/interstitial nephritis

Postmarketing reports: Renal failure^[Ref]

Hypersensitivity

Frequency not reported: Angioedema

Postmarketing reports: hypersensitivity reactions^[Ref]

Endocrine

Postmarketing reports: Pseudopheochromocytoma^[Ref]