Clozaril 25mg Tablets *

  • Company:

    Mylan IRE Healthcare Limited
  • Status:

    No Recent Update
  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)
  • Active Ingredient(s):

    *Additional information is available within the SPC or upon request to the company

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 19 April 2021

File name

IE-SmPC-Clozaril 25mg-14Ap2021-CRN00C61G-TIB-clean_1618835874.pdf

Reasons for updating

  • Other

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Addition to section 1 of the Irish SmPCs only. The wording "Ireland – Clozaril Official Recommendations" which includes details of the Clozaril Patient Monitoring Service (CPMS)

Updated on 24 February 2021

File name

IE-PIL-Clozaril 25mg 100mg-CRN00C52Z-Art613-clean_1614199426.pdf

Reasons for updating

  • Change to section 6 - manufacturer
  • Change to section 6 - date of revision

Updated on 17 October 2019

File name

IE-SmPC-Clozaril 25mg-11Oct2019-CRN008WLL-WS582-(incl off rec)_1571322315.pdf

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

File name

IE-PIL-Clozaril 25mg 100mg-11Oct2019-CRN008WLL-WS582-clean_1571322289.pdf

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 20 May 2019

File name

IE-PIL-Clozaril 25mg 100mg-15May2019-V094-clean_1558347483.pdf

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

File name

IE-SmPC-Clozaril 25mg-15May2019-V094-(incl off rec)_1558347506.pdf

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

File name

IE-PIL-Clozaril 25mg 100mg-13Mar2019-CRN008JT7-clean_1552647192.pdf

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 15 March 2019

File name

IE-SmPC-Clozaril 25mg-13Mar2019-CRN008JT7-(incl off rec)_1552647218.pdf

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

File name

IE-PIL-Clozaril 25mg 100mg-12Dec2018-CRN008Q7Q-clean_1545057849.pdf

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

File name

IE-SmPC-Clozaril 25mg-12Dec2018-CRN008Q7Q-emc (inc off rec)_1545057896.pdf

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

File name

Upload IE-SmPC-Clozaril 25mg-01Jun2018-CRN2203852-emc (inc off rec).docx

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

File name

IE-PIL-Clozaril 25mg 100mg-01Jun2018-CRN2203852-emc.pdf

Reasons for updating

  • Change to section 6 - marketing authorisation holder
  • Change to section 6 - marketing authorisation number

Updated on 29 May 2018

File name

IE-SmPC-Clozaril 25mg-08Mar2018-CRN2198661-emc (inc off rec).docx

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

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

File name

IE-PIL-Clozaril 25mg 100mg-08Mar2018-CRN2198661-emc.pdf

Reasons for updating

  • New individual PIL (was previously included in a combined PIL)

Updated on 26 April 2018

File name

PIL_16986_750.pdf

Reasons for updating

  • New PIL for medicines.ie

Updated on 21 March 2018

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

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

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

File name

PIL_16986_750.pdf

Reasons for updating

  • New PIL for new product

Updated on 13 March 2018

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

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

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

4.4 Special warnings and precautions for use

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

November 2016August 2017

Updated on 23 August 2017

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

4.4 Special warnings and precautions for use

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

November 2016August 2017

Updated on 09 November 2016

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

Correction to section 1 to include the Irish Official Recommendations for Clozaril

Updated on 09 November 2016

Reasons for updating

  • Change to section 1 - Name of medicinal product

Free text change information supplied by the pharmaceutical company

Correction to section 1 to include the Irish Official Recommendations for Clozaril

Updated on 07 November 2016

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

None provided

Updated on 07 November 2016

Reasons for updating

  • New SPC for new product

Free text change information supplied by the pharmaceutical company

None provided