Clozaril 25mg Tablets
- Name:
Clozaril 25mg Tablets
- Company:
Mylan IRE Healthcare Limited
- Active Ingredients:
- Legal Category:
Product subject to medical prescription which may not be renewed (A)
Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 17/10/19

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Mylan IRE Healthcare Limited

Company Products
When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.
Updated on 17 October 2019 SPC
Reasons for updating
- Change to section 4.8 - Undesirable effects
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Updated on 17 October 2019 PIL
Reasons for updating
- Change to section 4 - possible side effects
- Change to section 6 - date of revision
Updated on 20 May 2019 PIL
Reasons for updating
- Change to section 6 - what the product looks like and pack contents
- Change to section 6 - date of revision
Updated on 20 May 2019 SPC
Reasons for updating
- Change to section 6.5 - Nature and contents of container
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Updated on 15 March 2019 PIL
Reasons for updating
- Change to section 4 - possible side effects
- Change to section 6 - date of revision
Updated on 15 March 2019 SPC
Reasons for updating
- Change to section 4.8 - Undesirable effects
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Updated on 17 December 2018 PIL
Reasons for updating
- Change to section 6 - what the product looks like and pack contents
- Change to section 6 - date of revision
Updated on 17 December 2018 SPC
Reasons for updating
- Change to section 6.5 - Nature and contents of container
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Updated on 11 June 2018 SPC
Reasons for updating
- Change to section 7 - Marketing authorisation holder
- Change to section 8 - Marketing authorisation number(s)
Legal category: Product subject to medical prescription which may not be renewed (A)
Updated on 11 June 2018 PIL
Reasons for updating
- Change to section 6 - marketing authorisation holder
- Change to section 6 - marketing authorisation number
Updated on 29 May 2018 SPC
Reasons for updating
- New individual SPC (was previously included in combined SPC)
Legal category: Product subject to medical prescription which may not be renewed (A)
Updated on 16 May 2018 SPC
Reasons for updating
- New individual SPC (was previously included in combined SPC)
Legal category: Product subject to medical prescription which may not be renewed (A)
Updated on 13 May 2018 PIL
Reasons for updating
- New individual PIL (was previously included in a combined PIL)
Updated on 26 April 2018 PIL
Reasons for updating
- New PIL for medicines.ie
Updated on 21 March 2018 PIL
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
Free text change information supplied by the pharmaceutical company
4.4 Special warnings and precautions for use
Falls
Clozaril may cause seizures, somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.
Updated on 21 March 2018 SPC
Reasons for updating
- New SPC for new product
Legal category: Product subject to medical prescription which may not be renewed (A)
Updated on 21 March 2018 SPC
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
4.4 Special warnings and precautions for use
Falls
Clozaril may cause seizures, somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.
Updated on 20 March 2018 PIL
Reasons for updating
- New PIL for new product
Updated on 13 March 2018 SPC
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
4.4 Special warnings and precautions for use
Myocardial infarction
here have been post marketing reports of myocardial infarction including fatal cases. Causality assessment was difficult in the majority of these cases because of serious pre-existing cardiac disease and plausible alternative causes.
QT interval prolongation
As with other antipsychotics, caution is advised in patients with known cardiovascular disease or family history of QT prolongation.
Anticholinergic effects
Clozaril exerts anticholinergic activity, which may produce undesirable effects throughout the body. Careful supervision is indicated in the presence of prostatic enlargement and narrow-angle glaucoma. Probably on account of its anticholinergic properties, Clozaril has been associated with varying degrees of impairment of intestinal peristalsis, ranging from constipation to intestinal obstruction, faecal impaction, paralytic ileus, megacolon and intestinal infarction/ischaemia (see section 4.8). On rare occasions these cases have been fatal. Particular care is nece
Falls
Clozaril may cause seizures, somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.
Updated on 13 March 2018 PIL
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
Free text change information supplied by the pharmaceutical company
4.4 Special warnings and precautions for use
Myocardial infarction
here have been post marketing reports of myocardial infarction including fatal cases. Causality assessment was difficult in the majority of these cases because of serious pre-existing cardiac disease and plausible alternative causes.
QT interval prolongation
As with other antipsychotics, caution is advised in patients with known cardiovascular disease or family history of QT prolongation.
Anticholinergic effects
Clozaril exerts anticholinergic activity, which may produce undesirable effects throughout the body. Careful supervision is indicated in the presence of prostatic enlargement and narrow-angle glaucoma. Probably on account of its anticholinergic properties, Clozaril has been associated with varying degrees of impairment of intestinal peristalsis, ranging from constipation to intestinal obstruction, faecal impaction, paralytic ileus, megacolon and intestinal infarction/ischaemia (see section 4.8). On rare occasions these cases have been fatal. Particular care is nece
Falls
Clozaril may cause seizures, somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.
Updated on 23 August 2017 PIL
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 10 - Date of revision of the text
Free text change information supplied by the pharmaceutical company
Cardiovascular disorders
In patients who are diagnosed with cardiomyopathy while on Clozaril treatment, there is potential to develop mitral valve incompetence. Mitral valve incompetence has been reported in cases of cardiomyopathy related to Clozaril treatment. These cases of mitral valve incompetence reported either mild or moderate mitral regurgitation on two-dimensional echocardiography (2DEcho) (see section 4.8).
4.8 Undesirable effects
Table 4: Treatment-emergent adverse experience frequency estimate from spontaneous and clinical trial reports
Adverse reactions are ranked under headings of frequency, using the following convention: Very common (³1/10), common (³1/100 to <1/10), uncommon (³1/1,000 to <1/100), rare (³1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).
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 |
10. DATE OF REVISION OF THE TEXT
Updated on 23 August 2017 SPC
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Cardiovascular disorders
In patients who are diagnosed with cardiomyopathy while on Clozaril treatment, there is potential to develop mitral valve incompetence. Mitral valve incompetence has been reported in cases of cardiomyopathy related to Clozaril treatment. These cases of mitral valve incompetence reported either mild or moderate mitral regurgitation on two-dimensional echocardiography (2DEcho) (see section 4.8).
4.8 Undesirable effects
Table 4: Treatment-emergent adverse experience frequency estimate from spontaneous and clinical trial reports
Adverse reactions are ranked under headings of frequency, using the following convention: Very common (³1/10), common (³1/100 to <1/10), uncommon (³1/1,000 to <1/100), rare (³1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).
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 |
10. DATE OF REVISION OF THE TEXT
Updated on 9 November 2016 SPC
Reasons for updating
- Change to section 1 - Name of medicinal product
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Updated on 9 November 2016 PIL
Reasons for updating
- Change to section 1 - Name of medicinal product
Free text change information supplied by the pharmaceutical company
Updated on 7 November 2016 SPC
Reasons for updating
- New SPC for new product
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Updated on 7 November 2016 PIL
Reasons for updating
- New SPC for new product