Clozapine odt

Clozapine Side Effects

In Summary

Commonly reported side effects of clozapine include: hypotension, fever, tachycardia, constipation, dizziness, headache, nausea, sedated state, vomiting, and weight gain. Other side effects include: syncope, and diaphoresis. See below for a comprehensive list of adverse effects.

For the Consumer

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

Along with its needed effects, clozapine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking clozapine:

More common

• Blurred vision
• confusion
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fainting
• fast, pounding, or irregular heartbeat or pulse
• fever
• shakiness in the legs, arms, hands, or feet
• sleepiness or unusual drowsiness
• sweating
• trembling or shaking of the hands or feet
• unusual tiredness or weakness

Less common

• Anxiety
• black, tarry stools
• chest pain
• chills
• convulsions
• cough or hoarseness
• decrease in the frequency of urination
• decrease in urine volume
• difficult or labored breathing
• difficulty in passing urine (dribbling)
• discouragement
• dry mouth
• feeling sad or empty
• fever with or without chills
• frequent strong or increased urge to urinate
• general feeling of tiredness or weakness
• headache
• hyperventilation
• irritability
• lack of appetite
• loss of bladder control
• loss of interest or pleasure
• lower back or side pain
• muscle spasm or jerking of the arms or legs
• painful or difficult urination
• pounding in the ears
• restlessness or need to keep moving
• severe or continuing headache
• shakiness and unsteady walk
• slurred speech
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• sudden jerky movements of the body
• sudden loss of consciousness
• swollen glands
• throat discomfort
• tightness in the chest
• trouble concentrating
• trouble sleeping
• unsteadiness, trembling, or other problems with muscle control or coordination

Rare

• Absence of or decrease in movement
• change in appetite
• dark urine
• decreased sexual ability
• difficult or fast breathing or sudden shortness of breath
• increased sweating
• increased thirst
• increased urination
• lip smacking or puckering
• muscle stiffness (severe)
• nausea
• puffing of the cheeks
• rapid or worm-like movements of the tongue
• swelling or pain in the leg
• uncontrolled chewing movements
• uncontrolled movements of the arms and legs
• unusual bleeding or bruising
• unusually pale skin
• vomiting
• weakness
• yellow eyes or skin

Incidence not known

• Abdominal or stomach pain
• bloating
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• clay-colored stools
• confusion as to time, place, or person
• constipation
• diarrhea
• epileptic seizure that will not stop
• feeling that others are watching you or controlling your behavior
• feeling that others can hear your thoughts
• feeling, seeing, or hearing things that are not there
• holding false beliefs that cannot be changed by fact
• inability to move the eyes
• increased blinking or spasms of the eyelid
• indigestion
• itching or skin rash
• joint pain
• light-colored stools
• muscle twitching
• pains in the stomach, side, or abdomen, possibly radiating to the back
• rhythmic movement of the muscles
• severe mood or mental changes
• sticking out of the tongue
• swelling around the eyes
• swelling of the body or feet and ankles
• trouble with speaking
• unpleasant breath odor
• unusual behavior
• unusual excitement, nervousness, or restlessness
• unusual facial expressions
• unusual weight gain
• upper right abdominal or stomach pain
• vomiting of blood

Some side effects of clozapine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Acid or sour stomach
• belching
• feeling of constant movement of self or surroundings
• heartburn
• relaxed and calm sensation of spinning
• sleepiness

Less common

• Blurred or loss of vision
• change or problem with discharge of semen
• disturbed color perception
• double vision
• halos around lights
• inability to sit still
• increase in body movements
• muscle ache or pain
• muscle weakness
• night blindness
• nightmares
• overbright appearance of lights
• pain in the back, neck, or legs
• pain in the chest below the breastbone
• severe muscle stiffness
• sore tongue
• stuffy nose
• tunnel vision
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

Incidence not known

• Blistering, peeling, or loosening of the skin
• hives
• increased sensitivity of the skin to sunlight
• painful or prolonged erection of the penis
• red skin lesions, often with a purple center
• red, irritated eyes
• reddening of the skin, especially around the ears
• severe stomach pain
• severe sunburn
• sores, welting, or blisters
• swelling of the eyes, face, or inside of the nose
• swelling of the salivary glands

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.

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

Nervous system

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

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; 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.

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 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.

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

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

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.

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

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

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

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.

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

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

Ocular

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

Postmarketing reports: Narrow angle glaucoma, periorbital edema

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

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

Respiratory

Aspiration of ingested food usually occurred in patients with dysphagia or in acute overdose.

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

Renal

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

Postmarketing reports: Renal failure

Hypersensitivity

Frequency not reported: Angioedema

Postmarketing reports: hypersensitivity reactions

Endocrine

Postmarketing reports: Pseudopheochromocytoma