Clozaril 25mg Tablets *

Infections and infestations       

Not known:

Sepsis*

Blood and lymphatic system disorders

Common:

Leukopenia/decreased WBC/neutropenia, eosinophilia, leukocytosis

Uncommon:

Agranulocytosis

Rare:

Anaemia

Very rare:

Thrombocytopenia, thrombocythaemia

Immune system disorders

Not known:

Angioedema*, leukocytoclastic vasculitis*

Endocrine disorders

Not known:

Pseudophaeochromocytoma*

Metabolism and nutrition disorders

Common:

Weight gain

Rare:

Diabetes mellitus, impaired glucose tolerance

Very rare:

Hyperosmolar coma, ketoacidosis, severe hyperglycaemia, hypercholesterolemia, hypertriglyceridemia

Psychiatric disorders

Common:

Dysarthria

Uncommon:

Dysphemia

Rare:

Agitation, restlessness

Nervous system disorders

Very common:

Drowsiness/sedation, dizziness

Common:

Seizures/convulsions/myoclonic jerks, extrapyramidal symptoms, akathisia, tremor, rigidity, headache

Uncommon:

Neuroleptic malignant syndrome

Rare:

Confusion, delirium

Very rare:

Tardive dyskinesia, obsessive compulsive symptoms

Not known:

Cholinergic syndrome (after abrupt withdrawal)*, EEG changes*, pleurothotonus*

Eye disorders

Common:

Blurred vision

Cardiac disorders

Very common:

Tachycardia

Common:

ECG changes

Rare:

Circulatory collapse, arrhythmias, myocarditis, pericarditis/pericardial effusion

Very rare:

Cardiomyopathy, cardiac arrest

Not known:

Myocardial infarction which may be fatal*, chest pain/angina pectoris*, atrial fibrillation*, palpitations*, mitral valve incompetence associated with clozapine related cardiomyopathy*

Vascular disorders

Common:

Syncope, postural hypotension, hypertension

Rare:

Thromboembolism

Not known:

Hypotension*, Venous thromboembolism

Respiratory, thoracic and mediastinal disorders

Rare:

Aspiration of ingested food, pneumonia and lower respiratory tract infection which may be fatal

Very rare:

Respiratory depression/arrest

Not known:

Nasal congestion*

Gastrointestinal disorders

Very common

Constipation, hypersalivation

Common:

Nausea, vomiting, anorexia, dry mouth

Rare:

Dysphagia

Very rare:

Intestinal obstruction/paralytic ileus/faecal impaction, parotid gland enlargement,

Not known:

Diarrhoea*, abdominal discomfort/heartburn/dyspepsia*, colitis*

Hepatobiliary disorders

Common:

Elevated liver enzymes

Rare:

Pancreatitis, hepatitis, cholestatic jaundice

Very rare:

Fulminant hepatic necrosis

Not known:

Hepatic steatosis*, hepatic necrosis*, hepatotoxicity*, hepatic fibrosis*, hepatic cirrhosis*, liver disorders including those hepatic events leading to life-threatening consequences such as liver injury (hepatic, cholestatic and mixed), liver failure which may be fatal and liver transplant*.

Skin and subcutaneous tissue disorders

Very rare:

Skin reactions

Not known

Pigmentation disorder*

Musculoskeletal and connective tissue disorders

Not known:

Muscle weakness*, muscle spasms*, muscle pain*, systemic lupus erythematosus*

Renal and urinary disorders

Common:

Urinary retention, urinary incontinence

Very rare:

Interstitial nephritis

Not known:

Renal failure*, Nocturnal enuresis*

Pregnancy, puerperium and perinatal conditions

Not known

Drug withdrawal syndrome neonatal (see 4.6)

Reproductive system and breast disorders

Very rare:

Priapism

Not known

Retrograde ejaculation*

General disorders and administration site conditions

Common:

Benign hyperthermia, disturbances in sweating/temperature regulation, fever, fatigue

Very rare:

Sudden unexplained death

Investigations

Infections and infestations       

Not known:

Sepsis*

Blood and lymphatic system disorders

Common:

Leukopenia/decreased WBC/neutropenia, eosinophilia, leukocytosis

Uncommon:

Agranulocytosis

Rare:

Anaemia

Very rare:

Thrombocytopenia, thrombocythaemia

Immune system disorders

Not known:

Angioedema*, leukocytoclastic vasculitis*

Endocrine disorders

Not known:

Pseudophaeochromocytoma*

Metabolism and nutrition disorders

Common:

Weight gain

Rare:

Diabetes mellitus, impaired glucose tolerance

Very rare:

Hyperosmolar coma, ketoacidosis, severe hyperglycaemia, hypercholesterolemia, hypertriglyceridemia

Psychiatric disorders

Common:

Dysarthria

Uncommon:

Dysphemia

Rare:

Agitation, restlessness

Nervous system disorders

Very common:

Drowsiness/sedation, dizziness

Common:

Seizures/convulsions/myoclonic jerks, extrapyramidal symptoms, akathisia, tremor, rigidity, headache

Uncommon:

Neuroleptic malignant syndrome

Rare:

Confusion, delirium

Very rare:

Tardive dyskinesia, obsessive compulsive symptoms

Not known:

Cholinergic syndrome (after abrupt withdrawal)*, EEG changes*, pleurothotonus*

Eye disorders

Common:

Blurred vision

Cardiac disorders

Very common:

Tachycardia

Common:

ECG changes

Rare:

Circulatory collapse, arrhythmias, myocarditis, pericarditis/pericardial effusion

Very rare:

Cardiomyopathy, cardiac arrest

Not known:

Myocardial infarction which may be fatal*, chest pain/angina pectoris*, atrial fibrillation*, palpitations*, mitral valve incompetence associated with clozapine related cardiomyopathy*

Vascular disorders

Common:

Syncope, postural hypotension, hypertension

Rare:

Thromboembolism

Not known:

Hypotension*, Venous thromboembolism

Respiratory, thoracic and mediastinal disorders

Rare:

Aspiration of ingested food, pneumonia and lower respiratory tract infection which may be fatal

Very rare:

Respiratory depression/arrest

Not known:

Nasal congestion*

Gastrointestinal disorders

Very common

Constipation, hypersalivation

Common:

Nausea, vomiting, anorexia, dry mouth

Rare:

Dysphagia

Very rare:

Intestinal obstruction/paralytic ileus/faecal impaction, parotid gland enlargement,

Not known:

Diarrhoea*, abdominal discomfort/heartburn/dyspepsia*, colitis*

Hepatobiliary disorders

Common:

Elevated liver enzymes

Rare:

Pancreatitis, hepatitis, cholestatic jaundice

Very rare:

Fulminant hepatic necrosis

Not known:

Hepatic steatosis*, hepatic necrosis*, hepatotoxicity*, hepatic fibrosis*, hepatic cirrhosis*, liver disorders including those hepatic events leading to life-threatening consequences such as liver injury (hepatic, cholestatic and mixed), liver failure which may be fatal and liver transplant*.

Skin and subcutaneous tissue disorders

Very rare:

Skin reactions

Not known

Pigmentation disorder*

Musculoskeletal and connective tissue disorders

Not known:

Muscle weakness*, muscle spasms*, muscle pain*, systemic lupus erythematosus*

Renal and urinary disorders

Common:

Urinary retention, urinary incontinence

Very rare:

Interstitial nephritis

Not known:

Renal failure*, Nocturnal enuresis*

Pregnancy, puerperium and perinatal conditions

Not known

Drug withdrawal syndrome neonatal (see 4.6)

Reproductive system and breast disorders

Very rare:

Priapism

Not known

Retrograde ejaculation*

General disorders and administration site conditions

Common:

Benign hyperthermia, disturbances in sweating/temperature regulation, fever, fatigue

Very rare:

Sudden unexplained death

Investigations