Zyprexa 2.5 mg, 5mg, 7.5 mg,10 mg, 15 mg, 20 mg coated Tablets * Pharmacy Only: Prescription
Company:
Eli Lilly and Company (Ireland) LimitedStatus:
No Recent UpdateLegal 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
Updated on 20 January 2023
File name
63cae664ef871.pdf
Reasons for updating
- Document format updated
Legal category:Product subject to medical prescription which may not be renewed (A)
Updated on 11 January 2022
File name
Zyprexa_Tabs_ZY073_Dec21_IE-MT-NI_1641897275.pdf
Reasons for updating
- Change to section 4 - how to report a side effect
- Change to section 6 - marketing authorisation holder
- Change to section 6 - date of revision
- Improved presentation of PIL
Updated on 10 December 2020
File name
ZYPREXA SmPC_19Nov20_UK-IE_ZY71M_1607617764.pdf
Reasons for updating
- Change to section 2 - Qualitative and quantitative composition
- Change to section 3 - Pharmaceutical form
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 9 - Date of first authorisation/renewal of the authorisation
- Change to section 10 - Date of revision of the text
- Improved presentation of SPC
Legal category:Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Changes
Added (underline) deleted (strikethrough)
Formatting changes throughout the document.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Excipient with known effect: Each orodispersible tablet contains
0.60 mg aspartame (E951)
0.1125 mg sodium methyl parahydroxybenzoate (E219)
0.0375 mg sodium propyl parahydroxybenzoate (E217)
ZYPREXA VELOTAB 10 mg orodispersible tablets
Each orodispersible tablet contains 10 mg olanzapine.
Excipient with known effect:Each orodispersible tablet contains
0.80 mg aspartame (E951)
0.15 mg sodium methyl parahydroxybenzoate (E219)
0.05 mg sodium propyl parahydroxybenzoate (E217)
ZYPREXA VELOTAB 15 mg orodispersible tablets
Each orodispersible tablet contains 15 mg olanzapine.
Excipient with known effect: Each orodispersible tablet contains
1.20 mg aspartame (E951)
0.225 mg sodium methyl parahydroxybenzoate (E219)
0.075 mg sodium propyl parahydroxybenzoate (E217)
ZYPREXA VELOTAB 20 mg orodispersible tablets
Each orodispersible tablet contains 20 mg olanzapine.
Excipient with known effect: Each orodispersible tablet contains
1.60 mg aspartame (E951)
0.30 mg sodium methyl parahydroxybenzoate (E219)
0.10 mg sodium propyl parahydroxybenzoate (E217)
3. PHARMACEUTICAL FORM
Coated Tablets
ZYPREXA 2.5 mg coated tablets
ZYPREXA 2.5 mg tablets:Round, white, coated tablets imprinted with ‘LILLY’ and a numeric identicode ‘4112’.
ZYPREXA 5 mg coated tablets
ZYPREXA 5 mg tablets:Round, white, coated tablets imprinted with ‘LILLY’ and a numeric identicode ‘4115’.
ZYPREXA 7.5 mg coated tablets
ZYPREXA 7.5 mg tablets:Round, white, coated tablets imprinted with ‘LILLY’ and a numeric identicode ‘4116’.
ZYPREXA 10 mg coated tablets
ZYPREXA 10 mg tablets:Round, white, coated tablets imprinted with ‘LILLY’ and a numeric identicode ‘4117’.
ZYPREXA 15 mg coated tablets
ZYPREXA 15 mg tablets:Elliptical, blue, coated tablets debossed with ‘LILLY’ and a numeric identicode ‘4415’.
ZYPREXA 20 mg coated tablets
ZYPREXA 20 mg tablets:Elliptical, pink, coated tablets debossed with ‘LILLY’ and a numeric identicode ‘4420’.
4.4 Special warnings and precautions for use
Lactose
ZYPREXA tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose galactose malabsorption should not take this medicine.
Aspartame
ZYPREXA VELOTAB orodispersible tablet contains up to 1.6 mg aspartame in each tablet.
Aspartame is a source of phenylalanine. It may be harmful for people who have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.
Mannitol
ZYPREXA VELOTAB orodispersible tablet contains mannitol.
Sodium methyl parahydroxybenzoate and sodium propyl parahydroxybenzoate
Olanzapine orodispersible tablet contains sodium methyl parahydroxybenzoate and sodium propyl parahydroxybenzoate. , which may cause allergic reactions (possibly delayed).
These preservatives are known to cause urticaria. Generally, delayed type reactions such as contact dermatitis may occur, but rarely, immediate reactions with bronchospasm may occur.
Sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium‑free’.
MARKETING AUTHORISATION NUMBERS
ZYPREXA tablets:
EU/1/96/022/002: ZYPREXA 2.5 mg coated tablets - 28 tablets per box
EU/1/96/022/019: ZYPREXA 2.5 mg coated tablets - 56 tablets per box
EU/1/96/022/023: ZYPREXA 2.5 mg coated tablets - 35 tablets per box
EU/1/96/022/029: ZYPREXA 2.5 mg coated tablets - 70 tablets per box
EU/1/96/022/035: ZYPREXA 2.5 mg coated tablets - 98 tablets per box
EU/1/96/022/004: ZYPREXA 5 mg coated tablets - 28 tablets per box
EU/1/96/022/020: ZYPREXA 5 mg coated tablets - 56 tablets per box
EU/1/96/022/024: ZYPREXA 5 mg coated tablets - 35 tablets per box
EU/1/96/022/030: ZYPREXA 5 mg coated tablets - 70 tablets per box
EU/1/96/022/036: ZYPREXA 5 mg coated tablets - 98 tablets per box
EU/1/96/022/011: ZYPREXA 7.5 mg coated tablets - 28 tablets per box
EU/1/96/022/006: ZYPREXA 7.5 mg coated tablets - 56 tablets per box
EU/1/96/022/025: ZYPREXA 7.5 mg coated tablets - 35 tablets per box
EU/1/96/022/031: ZYPREXA 7.5 mg coated tablets - 70 tablets per box
EU/1/96/022/037: ZYPREXA 7.5 mg coated tablets - 98 tablets per box
EU/1/96/022/009: ZYPREXA 10 mg coated tablets - 28 tablets per box
EU/1/96/022/010: ZYPREXA 10 mg coated tablets - 56 tablets per box
EU/1/96/022/026: ZYPREXA 10 mg coated tablets - 35 tablets per box
EU/1/96/022/032: ZYPREXA 10 mg coated tablets - 70 tablets per box
EU/1/96/022/038: ZYPREXA 10 mg coated tablets - 98 tablets per box
EU/1/96/022/012: ZYPREXA 15 mg coated tablets - 28 tablets per box
EU/1/96/022/021: ZYPREXA 15 mg coated tablets - 56 tablets per box
EU/1/96/022/027: ZYPREXA 15 mg coated tablets - 35 tablets per box
EU/1/96/022/033: ZYPREXA 15 mg coated tablets - 70 tablets per box
EU/1/96/022/039: ZYPREXA 15 mg coated tablets - 98 tablets per box
EU/1/96/022/014: ZYPREXA 20 mg coated tablets - 28 tablets per box
EU/1/96/022/022: ZYPREXA 20 mg coated tablets - 56 tablets per box
EU/1/96/022/028: ZYPREXA 20 mg coated tablets - 35 tablets per box
EU/1/96/022/034: ZYPREXA 20 mg coated tablets - 70 tablets per box
EU/1/96/022/040: ZYPREXA 20 mg coated tablets - 98 tablets per box
ZYPREXA VELOTABS:
EU/1/99/125/001: 5 mg x 28 Velotabs
EU/1/99/125/005: 5 mg x 56 Velotabs
EU/1/99/125/009: 5 mg x 35 Velotabs
EU/1/99/125/013: 5 mg x 70 Velotabs
EU/1/99/125/017: 5 mg x 98 Velotabs
EU/1/99/125/002: 10 mg x 28 Velotabs
EU/1/99/125/006: 10 mg x 56 Velotabs
EU/1/99/125/010: 10 mg x 35 Velotabs
EU/1/99/125/014: 10 mg x 70 Velotabs
EU/1/99/125/018: 10 mg x 98 Velotabs
EU/1/99/125/003: 15 mg x 28 Velotabs
EU/1/99/125/007: 15 mg x 56 Velotabs
EU/1/99/125/011: 15 mg x 35 Velotabs
EU/1/99/125/015: 15 mg x 70 Velotabs
EU/1/99/125/019: 15 mg x 98 Velotabs
EU/1/99/125/004: 20 mg x 28 Velotabs
EU/1/99/125/008: 20 mg x 56 Velotabs
EU/1/99/125/012: 20 mg x 35 Velotabs
EU/1/99/125/016: 20 mg x 70 Velotabs
EU/1/99/125/020: 20 mg x 98 Velotabs
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
ZYPREXA tablets 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg: ZYPREXA tablets
Date of first authorisation: 27 September 1996
Date of latest renewal: 12 September 2006
ZYPREXA VELOTABS 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg:
Date of first authorisation: 3 February 2000
Date of latest renewal: 12 September 2006
10. DATE OF REVISION OF THE TEXT
21 19 November 2020February
Updated on 04 March 2020
File name
ZYPREXA SPC_Feb20_UK-IE_ZY70M_1583336612.pdf
Reasons for updating
- Change to section 4.8 - Undesirable effects
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- 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
4.8 Undesirable effects
Nervous system disorders |
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Somnolence |
Dizziness Akathisia6 Parkinsonism6 Dyskinesia6 |
Seizures where in most cases a history of seizures or risk factors for seizures were reported 11 Dystonia (including oculogyration) 11 Tardive dyskinesia11 Amnesia 9 Dysarthria Stuttering11 Restless Legs Syndrome11
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Neuroleptic malignant syndrome (see section 4.4) 12 Discontinuation symptoms7, 12 |
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Gastrointestinal disorders |
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Mild, transient anticholinergic effects including constipation and dry mouth |
Abdominal distension9 Salivary hypersecretion11 |
Pancreatitis11 |
|
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Ireland: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517; website: www.hpra.ie; e-mail: medsafety@hpra.ie, or United Kingdom: Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
10. DATE OF REVISION OF THE TEXT
21 February 2020 22 November 2018
ZY69MZY70M
Updated on 04 March 2020
File name
Zyprexa_Tabs_UK-IE-MT_PIL_Feb20_1583336536.pdf
Reasons for updating
- Change to section 4 - possible side effects
- Change to section 4 - how to report a side effect
- Change to section 6 - date of revision
Updated on 14 January 2019
File name
Zyprexa tablets UK-IE-MT combined PIL_Nov18_1547458258.pdf
Reasons for updating
- Change to section 4 - possible side effects
- Change to section 4 - how to report a side effect
- Change to section 6 - date of revision
Updated on 11 January 2019
File name
ZYPREXA SPC_NOV18_UK-IE_ZY69M_1547223791.pdf
Reasons for updating
- Change to section 4.8 - Undesirable effects
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 9 - Date of first authorisation/renewal of the authorisation
- Change to section 10 - Date of revision of the text
- Improved presentation of SPC
Legal category:Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
ZYPREXA®
olanzapine
1. NAME OF THE MEDICINAL PRODUCT
ZYPREXA * 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg coated tablets.
ZYPREXA VELOTAB * 5 mg, 10 mg, 15 mg, and 20 mg orodispersible tablets.
4.8 Undesirable effects
Tabulated list of adverse reactions, Nervous system disorder
Stuttering11added as an uncommon side effect
Reporting of suspected adverse reactions
UK reporting details updated
5.2 Pharmacokinetic properties
Hepatic impairment
A small study of the effect of impaired liver function in 6 subjects with clinically significant (Childs Pugh Classification A (n = 5) and B (n = 1)) cirrhosis revealed little effect on the pharmacokinetics of orally administered olanzapine (2.5 – 7.5 mg single dose): Subjects with mild to moderate hepatic dysfunction had slightly increased systemic clearance and faster elimination half-time compared to subjects with no hepatic dysfunction (n = 3). There were more smokers among subjects with cirrhosis (4/6; 67 %) than among subjects with no hepatic dysfunction (0/3; 0 %).
Smokers
In smoking subjects with mild hepatic dysfunction, mean elimination half-life (39.3 hours) was prolonged and clearance (18.0 l/hr) was reduced analogous to non-smoking healthy subjects (48.8 hours and 14.1 l/hr, respectively).
Smoking
In non-smoking […]
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of latest renewal: 27 12 September 2006
ZYPREXA VELOTABS:
Date of latest renewal: 27 12 September 2006
10. DATE OF REVISION OF THE TEXT
22 November 2018 23 February 2017
Updated on 08 March 2017
Reasons for updating
- New SPC for new product
Legal category:Product subject to medical prescription which may not be renewed (A)
Updated on 08 March 2017
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)
Free text change information supplied by the pharmaceutical company
Changes
Added (bold), Deleted (strikethrough)
4.8 Undesirable effects
Tabulated list of adverse reactions
Very common |
Common |
Uncommon |
Rare |
Not known |
… |
||||
Nervous system disorders |
||||
Somnolence |
Dizziness Akathisia6 Parkinsonism6 Dyskinesia6 |
Seizures where in most cases a history of seizures or risk factors for seizures were reported11 Dystonia (including oculogyration)11 Tardive dyskinesia11 Amnesia 9 Dysarthria Restless Legs Syndrome |
Neuroleptic malignant syndrome (see section 4.4)12 Discontinuation symptoms7, 12 |
|
10. DATE OF REVISION OF THE TEXT
15 September 201623 February 2017
Updated on 06 March 2017
File name
PIL_8803_400.pdf
Reasons for updating
- New PIL for new product
Updated on 06 March 2017
Reasons for updating
- Change to section 4 - possible side effects
- Change to section 6 - date of revision
Updated on 18 October 2016
Reasons for updating
- Change to section 2 - Qualitative and quantitative composition
- Change to section 3 - Pharmaceutical form
- Change to section 4.2 - Posology and method of administration
- Change to section 4.8 - Undesirable effects
- Change to section 6.1 - List of excipients
- Change to section 6.3 - Shelf life
- 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
In Section 2 (Qualitative and Quantitative Composition), formatting change only.
In Section 3 (Pharmaceutical Form), formatting change only.
In Section 4.2 (Posology and method of administration), formatting change only.
In Section 4.8 (Undesirable effects), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been added to Skin and subcutaneous tissue disorders with an unknown frequency.
In Section 6.1 (List of excipients), formatting change only.
In Section 6.3 (Shelf life), formatting change only.
In Section 10 (Date of revision of text), amended to 15 September 2016.
Updated on 17 October 2016
Reasons for updating
- Change to side-effects
- Change to date of revision
Updated on 19 May 2016
Reasons for updating
- Change to warnings or special precautions for use
- Change to date of revision
- Addition of information on reporting a side effect.
Updated on 15 January 2016
Reasons for updating
- Change to section 10 - Date of revision of the text
- Change to MA holder contact details
Legal category:Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Changes
Added (bold), Deleted (strikethrough):
7. MARKETING AUTHORISATION HOLDER
Eli Lilly Nederland B.V.
Grootslag 1‑5
NL‑3991 RA, Houten
Papendorpseweg 83
3528 BJ Utrecht
The Netherlands
10. DATE OF REVISION OF THE TEXT
Updated on 12 January 2016
Reasons for updating
- Change to date of revision
- Change to MA holder contact details
Updated on 04 June 2014
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.8 - Undesirable effects
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- Change to section 5.1 - Pharmacodynamic properties
- 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. CLINICAL PARTICULARS
4.2 Posology and method of administration
Section re-ordered:
Paragraph moved to end of section:
Paediatric population
Olanzapine is not recommended for use in children and adolescents below 18 years of age due to a lack of data on safety and efficacy. A greater magnitude of weight gain, lipid and prolactin alterations has been reported in short term studies of adolescent patients than in studies of adult patients (see sections 4.4, 4.8, 5.1 and 5.2).
Added subheading:
Special populations
Deleted (strikethrough):
Gender
The starting dose and dose range need not be routinely altered for female patients relative to male patients.
Added (bold):
Smokers
The starting dose and dose range need not be routinely altered for non-smokers relative to smokers. The metabolism of olanzapine may be induced by smoking. Clinical monitoring is recommended and an increase of olanzapine dose may be considered if necessary (see section 4.5).
4.4 Special warnings and precautions for use
Added (bold), Deleted (strikethrough):
Dementia-related psychosis and/or behavioural disturbances
Olanzapine is not approved for the treatment of dementia-related psychosis and/or behavioural disturbances and is not recommended for use in this particular group of patients with dementia-related psychosis and/or behavioural disturbances because of an increase in mortality and the risk of cerebrovascular accident.
Hyperglycaemia and diabetes
Patients treated with any antipsychotic agentsmedicines, including ZYPREXA, should be observed for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia, and weakness) and patients with diabetes mellitus or with risk factors for diabetes mellitus should be monitored regularly for worsening of glucose control.
Lipid alterations
Patients treated with any antipsychotic agentsmedicines, including ZYPREXA, should be monitored regularly for lipids in accordance with utilised antipsychotic guidelines, e.g. at baseline, 12 weeks after starting olanzapine treatment and every 5 years thereafter.
QT interval
However, as with other antipsychotics, caution should be exercised when olanzapine is prescribed with medicines known to increase QTc interval, especially in the elderly, in patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalaemia or hypomagnesaemia.
Postural hypotension
Postural hypotension was infrequently observed in the elderly in olanzapine clinical trials. As with other antipsychotics, iIt is recommended that blood pressure is measured periodically in patients over 65 years.
Paediatric population
Olanzapine is not indicated for use in the treatment of children and adolescents. Studies in patients aged 13-17 years showed various adverse reactions, including weight gain, changes in metabolic parameters and increases in prolactin levels. Long-term outcomes associated with these events have not been studied and remain unknown (see sections 4.8 and 5.1).
4.5 Interaction with other medicinal products and other forms of interaction
Deleted (strikethrough):
Paediatric population
Interaction studies have only been performed in adults.
4.6 Fertility, pregnancy and lactation
Added (bold), Deleted (strikethrough):
NeonatesNew born infants exposed to antipsychotics (including olanzapine) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery.
Added:
Fertility
Effects on fertility are unknown (see section 5.3 for preclinical information).
4.8 Undesirable effects
Added:
Summary of the safety profile
Note:Table re-formatted/re-ordered & ‘Not Known’ column added
Added:
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via UK: www.mhra.gov.uk/yellowcard or Ireland: IMB Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, www.imb.ie, imbpharmacovigilance@imb.ie.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Added (bold) Deleted (strikethrough):
Pharmacotherapeutic group: psycholeptics, diazepines, oxazepines, thiazepines and oxepines, ATC code N05A H03. diazepines, oxazepines and thiazepines, ATC code: N05A H03.
Paediatric population
The experienceControlled efficacy data in adolescents (ages 13 to 17 years) isare limited to short term efficacy datastudies in schizophrenia (6 weeks) and mania associated with bipolar I disorder (3 weeks), involving less than 200 adolescents. Olanzapine was used as a flexible dose starting with 2.5 and ranging up to 20 mg/day. During treatment with olanzapine, adolescents gained significantly more weight compared with adults. The magnitude of changes in fasting total cholesterol, LDL cholesterol, triglycerides, and prolactin (see sections 4.4 and 4.8) were greater in adolescents than in adults. There are no controlled data on maintenance of effect or and limited data onlong term safety (see sections 4.4 and 4.8). Information on long term safety is primarily limited to open-label, uncontrolled data.
10. DATE OF REVISION OF THE TEXT
Added (bold) Deleted (strikethrough):
27th May 2013 25 April 2014
Updated on 29 May 2014
Reasons for updating
- Change to warnings or special precautions for use
- Change to further information section
- Change to date of revision
- Addition of information on reporting a side effect.
Updated on 13 June 2013
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
In Section 4.4, Special warnings and precautions for use –
In Hyperglycaemia and diabetes, ‘Hyperglycaemia and/or development or exacerbation of diabetes occasionally associated with ketoacidosis or coma has been reported rarely, including some fatal cases (see section 4.8).’ is replaced with ‘Hyperglycaemia and/or development or exacerbation of diabetes occasionally associated with ketoacidosis or coma has been reported uncommonly, including some fatal cases (see section 4.8).’
In Discontinuation of treatment, ‘Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting have been reported very rarely (<0.01%) when oral olanzapine is stopped abruptly.’ Is replaced with ‘Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting have been reported rarely (≥0.01% and <0.1%) when oral olanzapine is stopped abruptly.’
In Seizures, ‘Seizures have been reported to occur rarely in patients when treated with olanzapine.’ Is replaced with ‘Seizures have been reported to occur uncommonly in patients when treated with olanzapine.’
In Section 4.8, Undesirable effects –
Frequency of occurrence of many side effects has been updated, and a few side effects have been added. Foot notes have also been added to cite the source of supporting data for these updates.
In Section 10, Date of revision of the text, the date of revision is updated.
Updated on 03 June 2013
Reasons for updating
- Change to side-effects
Updated on 11 July 2012
Reasons for updating
- Change to section 2 - Qualitative and quantitative composition
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.8 - Undesirable effects
- Change to section 4.9 - Overdose
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.2 - Pharmacokinetic properties
- 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
In Section 4.8, Undesirable effects - 'Urinary retention' is added as an uncommon event in the category 'Renal and Urinary disorders'.
The following adverse events are moved from footnote to table and frequency defined
Reproductive system and breast disorders – Common - Erectile dysfunction in males, decreased libido in males and females
Reproductive system and breast disorders – Uncommon
Amenorrhea, Breast enlargement, Galactorrhea in females, Gynaecomastia/ breast enlargement in males
In Sections 2, 4.2, 4.3, 4.8, 4.9, 5.1, 5.2 - Changes are made to align with the qrd template.
In Section 10, the date of revision of text is updated.Updated on 06 July 2012
Reasons for updating
- Change to side-effects
- Change to date of revision
- Change to improve clarity and readability
Updated on 10 May 2012
Reasons for updating
- Change to section 6.5 - Nature and contents of container
Legal category:Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Updated on 08 December 2011
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
In Section 4.4, Special warnings and precautions for use-
In subsection ‘Hyperglycemia and diabetes’ –
The statement ‘Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines’ is amended to ‘Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines, e.g. measuring of blood glucose at baseline, 12 weeks after starting olanzapine treatment and annually thereafter’
The statement ‘Weight should be monitored regularly’ is amended to ‘Weight should be monitored regularly, e.g. at baseline, 4, 8 and 12 weeks after starting olanzapine treatment and quarterly thereafter.’
In subsection ‘Lipid alterations’ –
The statement ‘Patients treated with any antipsychotic agents, including ZYPREXA/ZYPREXA VELOTAB, should be monitored regularly for lipids in accordance with utilised antipsychotic guidelines’ is amended to ‘Patients treated with any antipsychotic agents, including ZYPREXA/ZYPREXA VELOTAB, should be monitored regularly for lipids in accordance with utilised antipsychotic guidelines, e.g. at baseline, 12 weeks after starting olanzapine treatment and every 5 years thereafter.’
In subsection ‘Thromboembolism’ –
The statement ‘Temporal association of olanzapine treatment and venous thromboembolism has very rarely (<0.01%) been reported’ Is amended to ‘Temporal association of olanzapine treatment and venous thromboembolism has been reported uncommonly (≥ 0.1% and < 1%).’
In Section 4.8, Undesirable effects – in ‘’vascular disorders’, the frequency of ‘Thromboembolism (including pulmonary embolism and deep vein thrombosis) (see section 4.4)’ is changed from ‘not known’ to ‘uncommon’
In Section 10, Date of revision of the text, the date of revision is updated
Updated on 02 December 2011
Reasons for updating
- Change to side-effects
- Change to information about pregnancy or lactation
- Change to date of revision
Updated on 07 November 2011
Reasons for updating
- Change to section 4.6 - Pregnancy and lactation
- 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
In Section 4.6, Pregnancy and lactation, the following text has been added - 'Neonates exposed to antipsychotics (including olanzapine) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonis, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully.' and the following text has been deleted - 'Spontaneous reports have been very rarely received on tremor, hypertonia, lethargy and sleepiness, in infants born to mothers who had used olanzapine during the 3rd trimester.'
In Section 4.8, Undesirable effects - 'Drug withdrawal syndrome neonatal (see section 4.6)' is added under the 'Pregnancy, puerperium and perinatal conditions'
In Section 10, Date of revision of the text, the revision date is updated.
Updated on 03 November 2011
Reasons for updating
- Change to side-effects
- Change to information about pregnancy or lactation
- Change to date of revision
Updated on 03 February 2011
Reasons for updating
- Change to further information section
- Change to date of revision
- Introduction of new pack/pack size
Updated on 16 December 2010
Reasons for updating
- Change to section 6.5 - Nature and contents of container
- Change to section 8 - MA number
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may not be renewed (A)
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6. PHARMACEUTICAL PARTICULARS
6.5 Nature and contents of container
Re-formatted in its entirety due to addition of 98’s pack size.
8. MARKETING AUTHORISATION NUMBERS
Re-formatted in its entirety due to addition of 98’s pack size.
10. DATE OF REVISION OF THE TEXT
New date:
18 November 2010
Updated on 29 October 2010
Reasons for updating
- Change to further information section
- Change to date of revision
Updated on 24 September 2010
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
Legal category:Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
*This SPC has been re-formatted in its entirety due to QRD changes.
4. CLINICAL PARTICULARS
4.4 Special warnings and precautions for use
Added (bold) Deleted (strikethrough):
Hepatic function
Transient, asymptomatic elevations of hepatic transaminasesaminotransferases, ALT, AST have been seen commonly, especially in early treatment. Caution should be exercised and follow-up organised in patients with elevated ALT and/or AST, in patients with signs and symptoms of hepatic impairment, in patients with pre-existing conditions associated with limited hepatic functional reserve, and in patients who are being treated with potentially hepatotoxic medicines. In the event of elevated ALT and/or AST during treatment, follow-up should be organised and dose reduction should be considered. In cases where hepatitis (including hepatocellular, cholestatic or mixed liver injury) has been diagnosed, olanzapine treatment should be discontinued.
4.8 Undesirable effects
Adults
Added (bold) Deleted (strikethrough):
The most frequently (seen in ≥ 1% of patients) reported adverse reactions associated with the use of olanzapine in clinical trials were somnolence, weight gain, eosinophilia, elevated prolactin, cholesterol, glucose and triglyceride levels (see section 4.4), glucosuria, increased appetite, dizziness, akathisia, parkinsonism (see section 4.4), dyskinesia, orthostatic hypotension, anticholinergic effects, transient asymptomatic elevations of hepatic transaminasesaminotransferases (see section 4.4), rash, asthenia, fatigue and oedema.
Added (bold) Deleted (strikethrough):
Hepato-biliary disorders |
|||
|
Transient, asymptomatic elevations of hepatic |
|
Hepatitis (including hepatocellular, cholestatic or mixed liver injury) |
8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of normal range in approximately 30% of olanzapine treated patients with normal baseline prolactin value. In the majority of these patients the elevations were generally mild, and remained below two times the upper limit of normal range. In patients with schizophrenia, mean prolactin levels decreased with continued treatment, whereas mean increases were seen in patients with other diagnoses. The mean changes were modest Generally in olanzapine-treated patients potentially associated breast- and menstrual related clinical manifestations (e.g. amenorrhoea, breast enlargement, galactorrhea in females, and gynaecomastia/breast enlargement in males) were uncommon. Potentially associated sexual function-related adverse reactions (e.g. erectile dysfunction in males and decreased libido in both genders) were commonly observed.
Added (bold) Deleted (strikethrough):
Hepato-biliary disorders Very common: Elevations of hepatic |
10. DATE OF REVISION OF THE TEXT
New date:
06 September 2010
Detailed information on this product is available on the website of the European Medicines Agency http://www.ema.europa.eu
Updated on 05 March 2010
Reasons for updating
- Change to side-effects
- Change to further information section
- Change to date of revision
Updated on 18 January 2010
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. CLINICAL PARTICULARS
4.4 Special warnings and precautions for use
Added:
Sudden cardiac death
In postmarketing reports with olanzapine, the event of sudden cardiac death has been reported in patients with olanzapine. In a retrospective observational cohort study, the risk of presumed sudden cardiac death in patients treated with olanzapine was approximately twice the risk in patients not using antipsychotics. In the study, the risk of olanzapine was comparable to the risk of atypical antipsychotics included in a pooled analysis.
4.8 Undesirable effects
Added (bold):
Very common |
Common |
Uncommon |
Not known |
||||
Renal and urinary disorders |
|||||||
|
|
Urinary incontinence |
Urinary hesitation |
|
|||
Added:
8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of normal range in approximately 30% of olanzapine-treated patients with normal baseline prolactin value. In the majority of these patients the elevations were generally mild, and remained below two times the upper limit of normal range. In patients with schizophrenia, mean prolactin level changes decreased with continued treatment, whereas mean increases were seen in patients with other diagnoses. The mean changes were modest. Generally, in olanzapine-treated patients potentially associated breast- and menstrual-related clinical manifestations (e.g., amenorrhoea, breast enlargement, galactorrhea in females, and gynaecomastia/breast enlargement in males) were uncommon. Potentially associated sexual function-related adverse reactions (e.g., erectile dysfunction in males and decreased libido in both genders) were commonly observed.
Deleted:
8 Associated clinical manifestations (e.g., gynaecomastia, galactorrhoea, and breast enlargement) were rare. In most patients, levels returned to normal ranges without cessation of treatment.
10. DATE OF REVISION OF THE TEXT
New date:
21 December 2009
Updated on 16 July 2009
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. CLINICAL PARTICULARS
4.4 Special warnings and precautions for use
Neuroleptic Malignant Syndrome (NMS)
Added(bold) deleted(strikethrough):
Additional signs may include elevated creatinecreatinine phosphokinase
4.8 Undesirable effects
1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories. Following short term treatment (median duration 47 days), wWeight gain ≥ 7 % of baseline body weight was very common and (22.2 %), ≥ 15% was common (4.2 %) and ≥ 25 % was uncommon (0.8 %)of baseline body weight was common. Patients gaining ≥ 7 %, ≥ 15 % and ≥ 25 % of their baseline body weight with long-term exposure (at least 48 weeks) were very common (64.4 %, 31.7 % and 12.3 % respectively).
Long-term exposure (at least 48 weeks)
Added(bold) deleted(strikethrough):
In adult patients who completed 9-12 months of therapy, the rate of increase in mean blood glucose slowed after approximately 4- 6 months.
10. DATE OF REVISION OF THE TEXT
New date:
ZYPREXA tablets: 03 July 2009
ZYPREXA VELOTABS: 07 July 2009
Updated on 08 April 2009
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.9 - Overdose
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may not be renewed (A)
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4. CLINICAL PARTICULARS
4.4 Special warnings and precautions for use
Hyperglycaemia and diabetes
Added (bold) Deleted (strikethrough):
Appropriate clinical monitoring is advisable particularly in diabetic patients and in patients with risk factors for the development of diabetes mellitus for which regular glucose control is recommended.in accordance with utilised antipsychotic guidelines. Patients treated with any antipsychotic agents, including ZYPREXA, should be observed for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia, and weakness) and patients with diabetes mellitus or with risk factors for diabetes mellitus should be monitored regularly for worsening of glucose control. Weight should be monitored regularly.
Lipid alterations
Added:
Patients treated with any antipsychotic agents, including ZYPREXA, should be monitored regularly for lipids in accordance with utilised antipsychotic guidelines.
4.9 Overdose
Signs and symptoms
Deleted (strikethrough):
Fatal outcomes have been reported for acute overdoses as low as 450 mg but survival has also been reported following acute overdose of 1,500 mg approximately 2 g of oral olanzapine.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Added (bold) Deleted (strikethrough):
Pharmacotherapeutic group: antipsychotic, diazepines, oxazepines and thiazepines ATC code: N05A H03.
10. DATE OF REVISION OF THE TEXT
New date:
25 March 2009
Updated on 05 August 2008
Reasons for updating
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- 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. CLINICAL PARTICULARS
4.5 Interaction with other medicinal products and other forms of interaction
Changed:
General CNS activitymedicinal products
Caution should be exercised in patients who consume alcohol or receive medicinal products that can cause central nervous system depression.
4.8 Undesirable effects
Adults
Added under table to footnote 1:
Patients gaining ¡Ý 25% of their baseline body weight with long-term exposure were very common.
Added:
Long-term exposure (at least 48 weeks)
The proportion of patients who had adverse, clinically significant changes in weight gain, glucose, total/LDL/HDL cholesterol or triglycerides increased over time. In adult patients who completed 9-12 months of therapy, the rate of increase in mean blood glucose slowed after approximately 4-6 months.
Children and adolescents
Changed:
The following table summarises the adverse reactions reported with a greater frequency in adolescent patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-term clinical trials in adolescent patients. Clinically significant weight gain (¡Ý 7%) appears to occur more frequently in the adolescent population compared to adults with comparable exposures. The magnitude of weight gain and the proportion of adolescent patients who had clinically significant weight gain were greater with long-term exposure (at least 24 weeks) than with short-term exposure.
Added under table to footnote 9:
With long-term exposure (at least 24 weeks), approximately half of adolescent patients gained ¡Ý 15% and almost a third gained ¡Ý 25% of their baseline body weight. Among adolescent patients, mean weight gain was greatest in patients who were overweight or obese at baseline.
10. DATE OF REVISION OF THE TEXT
New date:
28 July 2008
Updated on 09 May 2008
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.8 - Undesirable effects
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 6.4 - Special precautions for storage
- 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
Please Note: This SPC has been Re-formatted in its entirety
4. CLINICAL PARTICULARS
4.2 Posology and method of administration
Added:
Children and adolescents
Olanzapine is not recommended for use in children and adolescents below 18 years of age due to a lack
of data on long term safety and efficacy. A greater magnitude of weight gain, lipid and prolactin
alterations has been reported in short term studies of adolescent patients than in studies of adult patients
(see sections 4.4, 4.8, 5.1 and 5.2).
4.4 Special warnings and precautions for use
Added:
During antipsychotic treatment, improvement in the patient's clinical condition may take several days to
some weeks. Patients should be closely monitored during this period.
Dementia-related psychosis and/or behavioural disturbances
Olanzapine is not approved for the treatment of dementia-related psychosis and/or behavioural
disturbances and is not recommended for use in this particular group of patients because of an increase
in mortality and the risk of cerebrovascular accident. In placebo-controlled clinical trials (6-12 weeks
duration) of elderly patients (mean age 78 years) with dementia-related psychosis and/or disturbed
behaviours, there was a 2-fold increase in the incidence of death in olanzapine-treated patients
compared to patients treated with placebo (3.5% vs. 1.5%, respectively). The higher incidence of death
was not associated with olanzapine dose (mean daily dose 4.4 mg) or duration of treatment. Risk
factors that may predispose this patient population to increased mortality include age > 65 years,
dysphagia, sedation, malnutrition and dehydration, pulmonary conditions (e.g., pneumonia, with or
without aspiration), or concomitant use of benzodiazepines. However, the incidence of death was
higher in olanzapine-treated than in placebo-treated patients independent of these risk factors.
In the same clinical trials, cerebrovascular adverse events (CVAE e.g., stroke, transient ischemic
attack), including fatalities, were reported. There was a 3-fold increase in CVAE in patients treated
with olanzapine compared to patients treated with placebo (1.3% vs. 0.4%, respectively). All
olanzapine- and placebo-treated patients who experienced a cerebrovascular event had pre-existing risk
factors. Age > 75 years and vascular/mixed type dementia were identified as risk factors for CVAE in
association with olanzapine treatment. The efficacy of olanzapine was not established in these trials.
Parkinson's disease
The use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with
Parkinson's disease is not recommended. In clinical trials, worsening of Parkinsonian symptomatology
and hallucinations were reported very commonly and more frequently than with placebo (see section
4.8), and olanzapine was not more effective than placebo in the treatment of psychotic symptoms. In
these trials, patients were initially required to be stable on the lowest effective dose of anti-
Parkinsonian medicinal products (dopamine agonist) and to remain on the same anti-Parkinsonian
medicinal products and dosages throughout the study. Olanzapine was started at 2.5 mg/day and titrated
to a maximum of 15 mg/day based on investigator judgement.
Neuroleptic Malignant Syndrome (NMS)
NMS is a potentially life-threatening condition associated with antipsychotic medicinal product. Rare
cases reported as NMS have also been received in association with olanzapine. Clinical manifestations
of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability
(irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs
may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal
failure. If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high
fever without additional clinical manifestations of NMS, all antipsychotic medicines, including
olanzapine must be discontinued.
Lipid alterations
Deleted:
Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting have been reported
very rarely (<0.01%) when olanzapine is stopped abruptly. Gradual dose reduction should be
considered when discontinuing olanzapine.
Anticholinergic activity
Deleted:
The use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with
Parkinson's disease is not recommended. In clinical trials, worsening of Parkinsonian symptomatology
and hallucinations were reported very commonly and more frequently than with placebo (see also 4.8
Undesirable effects), and olanzapine was not more effective than placebo in the treatment of psychotic
symptoms. In these trials, patients were initially required to be stable on the lowest effective dose of
anti-Parkinsonian medications (dopamine agonist) and to remain on the same anti-Parkinsonian
medications and dosages throughout the study. Olanzapine was started at 2.5 mg/day and titrated to a
maximum of 15 mg/day based on investigator judgement.
Olanzapine is not approved for the treatment of dementia-related psychosis and/or behavioural
disturbances and is not recommended for use in this particular group of patients because of an increase
in mortality and the risk of cerebrovascular accident. In placebo-controlled clinical trials (6-12 weeks
duration) of elderly patients (mean age 78 years) with dementia-related psychosis and/or disturbed
behaviours, there was a 2-fold increase in the incidence of death in olanzapine-treated patients
compared to patients treated with placebo (3.5% vs. 1.5% , respectively). The higher incidence of death
was not associated with olanzapine dose (mean daily dose 4.4 mg) or duration of treatment. Risk
factors that may predispose this patient population to increased mortality include age >65 years,
dysphagia, sedation, malnutrition and dehydration, pulmonary conditions (e.g., pneumonia, with or
without aspiration), or concomitant use of benzodiazepines. However, the incidence of death was
higher in olanzapine-treated than in placebo-treated patients independent of these risk factors.
In the same clinical trials, cerebrovascular adverse events (CVAE e.g., stroke, transient ischemic
attack), including fatalities, were reported. There was a 3-fold increase in CVAE in patients treated
with olanzapine compared to patients treated with placebo (1.3% vs. 0.4%, respectively). All
olanzapine- and placebo-treated patients who experienced a cerebrovascular event had pre-existing risk
factors. Age >75 years and vascular/mixed type dementia were identified as risk factors for CVAE in
association with olanzapine treatment. The efficacy of olanzapine was not established in these trials.
During antipsychotic treatment, improvement in the patient's clinical condition may take several days to
some weeks. Patients should be closely monitored during this period.
Added:
Discontinuation of treatment
Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting have been reported
very rarely (<0.01%) when olanzapine is stopped abruptly.
QT interval
In clinical trials, clinically meaningful QTc prolongations (Fridericia QT correction [QTcF] ¡Ý 500
milliseconds [msec] at any time post baseline in patients with baseline QTcF<500 msec) were
uncommon (0.1% to 1%) in patients treated with olanzapine, with no significant differences in
associated cardiac events compared to placebo. However, as with other antipsychotics, caution should
be exercised when olanzapine is prescribed with medicines known to increase QTc interval, especially
in the elderly, in patients with congenital long QT syndrome, congestive heart failure, heart
hypertrophy, hypokalaemia or hypomagnesaemia.
Thromboembolism
Temporal association of olanzapine treatment and venous thromboembolism has very rarely (< 0.01%)
been reported. . A causal relationship between the occurrence of venous thromboembolism and
treatment with olanzapine has not been established. However, since patients with schizophrenia often
present with acquired risk factors for venous thromboembolism all possible risk factors of VTE e.g.
immobilisation of patients, should be identified and preventive measures undertaken.
General CNS activity
Given the primary CNS effects of olanzapine, caution should be used when it is taken in combination
with other centrally acting medicines and alcohol. As it exhibits in vitro dopamine antagonism,
olanzapine may antagonize the effects of direct and indirect dopamine agonists.
Deleted:
There are limited data on co-medication with lithium and valproate (see section 5.1). There are no
clinical data available on olanzapine and carbamazepine co-therapy, however a pharmacokinetic study
has been conducted (see section 4.5).
Neuroleptic Malignant Syndrome (NMS): NMS is a potentially life-threatening condition associated
with antipsychotic medication. Rare cases reported as NMS have also been received in association with
olanzapine. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status,
and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and
cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria
(rhabdomyolysis), and acute renal failure. If a patient develops signs and symptoms indicative of NMS,
or presents with unexplained high fever without additional clinical manifestations of NMS, all
antipsychotic medicines, including olanzapine must be discontinued.
Tardive Dyskinesia
Deleted:
Given the primary CNS effects of olanzapine, caution should be used when it is taken in combination
with other centrally acting medicines and alcohol. As it exhibits in vitro dopamine antagonism,
olanzapine may antagonize the effects of direct and indirect dopamine agonists.
Postural hypotension
Deleted:
In clinical trials, clinically meaningful QTc prolongations (Fridericia QT correction [QTcF] ¡Ý500
milliseconds [msec] at any time post baseline in patients with baseline QTcF<500 msec) were
uncommon (0.1% to 1%) in patients treated with olanzapine, with no significant differences in
associated cardiac events compared to placebo. However, as with other antipsychotics, caution should
be exercised when olanzapine is prescribed with medicines known to increase QTc interval, especially
in the elderly, in patients with congenital long QT syndrome, congestive heart failure, heart
hypertrophy, hypokalaemia or hypomagnesaemia.
Temporal association of olanzapine treatment and venous thromboembolism has very rarely (<0.01%)
been reported. . A causal relationship between the occurrence of venous thromboembolism and
treatment with olanzapine has not been established. However, since patients with schizophrenia often
present with acquired risk factors for venous thromboembolism all possible risk factors of VTE e.g.
immobilisation of patients, should be identified and preventive measures undertaken.
Added:
Use in children and adolescents under 18 years of age
Olanzapine is not indicated for use in the treatment of children and adolescents. Studies in patients aged
13-17 years showed various adverse reactions, including weight gain, changes in metabolic parameters
and increases in prolactin levels. Long-term outcomes associated with these events have not been
studied and remain unknown (see sections 4.8 and 5.1).
4.5 Interaction with other medicinal products and other forms of interaction
Added:
Interaction studies have only been performed in adults.
CNS medicinal products
Caution should be exercised in patients who receive medicinal products that can cause central nervous
system depression.
The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with
Parkinson's disease and dementia is not recommended (see section 4.4).
QTc interval
Caution should be used if olanzapine is being administered concomitantly with medicinal products
known to increase QTc interval (see section 4.4).
4.8 Undesirable effects
Changed in its entirety:
Adults
The most frequently (seen in ¡Ý 1% of patients ) reported adverse reactions associated with the use of
olanzapine in clinical trials were somnolence, weight gain, eosinophilia, elevated prolactin, cholesterol,
glucose and triglyceride levels (see section 4.4), glucosuria, increased appetite, dizziness, akathisia,
parkinsonism (see section 4.4), dyskinesia, orthostatic hypotension, anticholinergic effects, transient
asymptomatic elevations of hepatic transaminases (see section 4.4), rash, asthenia, fatigue and oedema.
The following table lists the adverse reactions and laboratory investigations observed from
spontaneous reporting and in clinical trials. Within each frequency grouping, adverse reactions are
presented in order of decreasing seriousness. The frequency terms listed are defined as follows: Very
common (¡Ý10%), common (¡Ý 1% and < 10%), uncommon (¡Ý 0.1% and < 1%), rare (¡Ý 0.01% and
< 0.1%), very rare (< 0.01%), not known (cannot be estimated from the data available).
TABLE
1Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories.
Weight gain ¡Ý 7% of baseline body weight was very common and ¡Ý 15% of baseline body weight was
common.
2Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were
greater in patients without evidence of lipid dysregulation at baseline.
3Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high (¡Ý 6.2 mmol/l).
Changes in total fasting cholesterol levels from borderline at baseline (¡Ý 5.17 - < 6.2 mmol) to high
(¡Ý 6.2 mmol) were common.
4
Observed for fasting normal levels at baseline (< 5.56 mmol/l) which increased to high (¡Ý 7 mmol/l).
Changes in fasting glucose from borderline at baseline (¡Ý 5.56 - < 7 mmol/l) to high (¡Ý 7 mmol/l) were
very common.
5
Observed for fasting normal levels at baseline (< 1.69 mmol/l) which increased to high
(¡Ý 2.26 mmol/l). Changes in fasting triglycerides from borderline at baseline (¡Ý 1.69 mmol/l -
< 2.26 mmol/l) to high (¡Ý 2.26 mmol/l) were very common.
6In clinical trials, the incidence of parkinsonism and dystonia in olanzapine-treated patients was
numerically higher, but not statistically significantly different from placebo. Olanzapine-treated
patients had a lower incidence of parkinsonism, akathisia and dystonia compared with titrated doses of
haloperidol. In the absence of detailed information on the pre-existing history of individual acute and
tardive extrapyramidal movement disorders, it can not be concluded at present that olanzapine produces
less tardive dyskinesia and/or other tardive extrapyramidal syndromes.
7Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been reported
when olanzapine is stopped abruptly.
8Associated clinical manifestations (e.g., gynaecomastia, galactorrhoea, and breast enlargement) were
rare. In most patients, levels returned to normal ranges without cessation of treatment.
Additional information on special populations
In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher
incidence of death and cerebrovascular adverse reactions compared to placebo (see also section 4.4).
Very common adverse reactions associated with the use of olanzapine in this patient group were
abnormal gait and falls. Pneumonia, increased body temperature, lethargy, erythema, visual
hallucinations and urinary incontinence were observed commonly.
In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with
Parkinson¡¯s disease, worsening of Parkinsonian symptomatology and hallucinations were reported very
commonly and more frequently than with placebo.
In one clinical trial in patients with bipolar mania, valproate combination therapy with olanzapine
resulted in an incidence of neutropenia of 4.1%; a potential contributing factor could be high plasma
valproate levels. Olanzapine administered with lithium or valproate resulted in increased levels (¡Ý10%)
of tremor, dry mouth, increased appetite, and weight gain. Speech disorder was also reported
commonly. During treatment with olanzapine in combination with lithium or divalproex, an increase of
>7% from baseline body weight occurred in 17.4% of patients during acute treatment (up to 6 weeks).
Long-term olanzapine treatment (up to 12 months) for recurrence prevention in patients with bipolar
disorder was associated with an increase of ¡Ý7% from baseline body weight in 39.9% of patients.
Children and adolescents
Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years.
Although no clinical studies designed to compare adolescents to adults have been conducted, data from
the adolescent trials were compared to those of the adult trials.
The following table summarises the adverse reactions reported with a greater frequency in adolescent
patients (aged 13-17 years) than in adult patients or adverse reactions only identified during clinical
trials in adolescent patients. Clinically significant weight gain (¡Ý 7%) appears to occur more frequently
in the adolescent population.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
The frequency terms listed are defined as follows: Very common (¡Ý 10%), common (¡Ý 1% and < 10%).
TABLE
9Weight gain > 7% of baseline body weight (kg) was very common and ¡Ý 15% of baseline body weight
was common.
10Observed for fasting normal levels at baseline (< 1.016 mmol/l) which increased to high
(¡Ý 1.467 mmol/l) and changes in fasting triglycerides from borderline at baseline (¡Ý 1.016 mmol/l -
< 1.467 mmol/l) to high (¡Ý 1.467 mmol/l).
11Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/l) to high
(¡Ý 5.17 mmol/l) were observed commonly. Changes in total fasting cholesterol levels from borderline
at baseline (¡Ý 4.39 - < 5.17 mmol/l) to high (¡Ý 5.17 mmol/l) were very common.
12Elevated plasma prolactin levels were reported in 47.4% of adolescent patients.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Added:
Paediatric population
The experience in adolescents (ages 13 to 17 years) is limited to short term efficacy data in
schizophrenia (6 weeks) and mania associated with bipolar I disorder (3 weeks), involving less than
200 adolescents. Olanzapine was used as a flexible dose starting with 2.5 and ranging up to 20 mg/day.
During treatment with olanzapine, adolescents gained significantly more weight compared with adults.
The magnitude of changes in fasting total cholesterol, LDL cholesterol, triglycerides, and prolactin (see
sections 4.4 and 4.8) were greater in adolescents than in adults. There are no data on maintenance of
effect and limited data on long term safety (see sections 4.4 and 4.8).
5.2 Pharmacokinetic properties
Paediatric population
Adolescents (ages 13 to 17 years): The pharmacokinetics of olanzapine are similar between adolescents
and adults. In clinical studies, the average olanzapine exposure was approximately 27% higher in
adolescents. Demographic differences between the adolescents and adults include a lower average body
weight and fewer adolescents were smokers. Such factors possibly contribute to the higher average
exposure observed in adolescents.
6. PHARMACEUTICAL PARTICULARS
6.4 Special precautions for storage
Changed:
ZYPREXA tablets: Store in the original package in order to protect from light and moisture.
10. DATE OF REVISION OF THE TEXT
New date:
22 April 2008
Updated on 07 May 2008
Reasons for updating
- Change to warnings or special precautions for use
- Change to side-effects
- Change to storage instructions
Updated on 05 February 2008
Reasons for updating
- Change to warnings or special precautions for use
- Change to side-effects
- Change to date of revision
Updated on 28 January 2008
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. CLINICAL PARTICULARS
4.4 Special warnings and precautions for use
Delete:
Text in bold
Hyperglycaemia and/or development or exacerbation of diabetes, occasionally associated with ketoacidosis or coma, has been reported very rarely, including some fatal cases (see section 4.8).
Added:
Text in bold
particularly in diabetic patients and in patients with risk factors for the development of diabetes mellitus for which regular glucose control is recommended.
Added:
Text in bold
Lipid alterations should be managed as clinically appropriate, particularly in dyslipidemic patients and in patients with risk factors for the development of lipids disorders.
4.8 Undesirable effects
Added:
Notes to Table (see Bold)
Metabolism and nutrition disorders Very common (>10%): Weight gain1. Common (1-10%): Increased appetite. Elevated glucose levels (see note 2 below). Elevated triglyceride levels3,4. Elevated cholesterol levels3,5 Glycosuria. |
Nervous system disorders Very common (>10%): Somnolence. Common (1-10%): Dizziness, akathisia, parkinsonism, dyskinesia. (See also note 6 below). |
Added:
Corresponding notes under table
1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories. Weight gain ¡Ý 7% of baseline body weight was very common and ¡Ý 15% of baseline body weight was common.
2Observed for fasting normal levels at baseline (< 5.56mmol/l) which increased to high (¡Ý 7mmol/l). Changes in fasting glucose from borderline at baseline (¡Ý 5.56 - < 7mmol/l) to high (¡Ý 7mmol/l) were very common.
3 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline.
4Observed for fasting normal levels at baseline (< 1.69mmol/l) which increased to high (¡Ý 2.26mmol/l). Changes in fasting triglycerides from borderline at baseline (¡Ý 1.69mmol/l - < 2.26mmol/l) to high (¡Ý 2.26mmol/l) were very common.
5Observed for fasting normal levels at baseline (< 5.17mmol/l) which increased to high (¡Ý 6.2mmol/l). Changes in total fasting cholesterol levels from borderline at baseline (¡Ý 5.17-< 6.2mmol/l) to high (¡Ý 6.2mmol/l) were very common.
6In clinical trials, the incidence of parkinsonism and dystonia in olanzapine-treated patients was numerically higher, but not statistically significantly different from placebo. Olanzapine-treated patients had a lower incidence of parkinsonism, akathisia and dystonia compared with titrated doses of haloperidol. In the absence of detailed information on the pre-existing history of individual acute and tardive extrapyramidal movement disorders, it can not be concluded at present that olanzapine produces less tardive dyskinesia and/or other tardive extrapyramidal syndromes.
Changed:
In next table - All text under heading
Metabolism and nutrition disorders Rare (0.01-0.1%): Hyperglycaemia and/or development or exacerbation of diabetes occasionally associated with ketoacidosis or coma has been spontaneously reported rarely, including some fatal cases (see section 4.4). Very rare (<0.01%): Hypertriglyceridaemia, hypercholesterolaemia and hypothermia. |
10. DATE OF REVISION OF THE TEXT
New date:
Updated on 30 November 2007
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)
Free text change information supplied by the pharmaceutical company
4. CLINICAL PARTICULARS
4.8 Undesirable effects
Insert - fatigue:
General disorders and administration site conditions
Common (1-10%): Asthenia, fatigue, oedema.
10. DATE OF REVISION OF THE TEXT
New date:
21 November 2007
Updated on 12 October 2007
Reasons for updating
- Change to warnings or special precautions for use
- Change to side-effects
- Change to date of revision
Updated on 17 September 2007
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. CLINICAL PARTICULARS
4.4 Special warnings and precautions for use
Added:
Undesirable alterations in lipids have been observed in olanzapine-treated patients in placebo-controlled clinical trials (see section 4.8). Lipid alterations should be managed as clinically appropriate.
4.8 Undesirable effects
Changes to table of undesirable effects based on adverse event reporting and laboratory investigations from clinical trials:
Added to ‘Metabolism and nutrition disorders’:
Common (1-10%): Elevated cholesterol levels.
Changes to table of undesirable effects based on post-marketing spontaneous reports:
Added (in bold text) to ‘Nervous system disorders:
Very rare (<0.01%): dystonia, (including oculogyration)
Added to ‘Skin and subcutaneous tissue disorders’:
Very rare (<0.01%): Alopecia.
10. DATE OF REVISION OF THE TEXT
New date:
30 August 2007
Updated on 23 February 2007
Reasons for updating
- Change of manufacturer
Updated on 26 October 2006
Reasons for updating
- Introduction of new strength
- Change to section 1 - Name of medicinal product
- Change to section 2 - Qualitative and quantitative composition
- Change to section 3 - Pharmaceutical form
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.7 - Effects on ability to drive and use machines
- Change to section 4.8 - Undesirable effects
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 6.1 - List of excipients
- Change to section 6.3 - Shelf life
- Change to section 6.5 - Nature and contents of container
- Change to section 8 - MA number
- Change to section 9 - Date of renewal of authorisation
- 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
Addition of 20mg oral tablets, which are expected to be launched in December 2006.
1. NAME OF THE MEDICINAL PRODUCT
Addition of 20mg tablets.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Addition of 20mg tablets.
Addition of amount of lactose/coated tablet.
Addition of amount of aspartame, sodium methyl parahydroxybenzoate or sodium propyl parahydroxybenzoate/orodispersible tablet.
3. PHARMACEUTICAL FORM
Addition of 20mg tablets.
4. CLINICAL PARTICULARS
4.2 Posology and method of administration
Deleted:
Children and adolescents: Olanzapine has not been studied in subjects under 18 years of age.
Replaced by:
There is no experience in children.
4.3 Contra-indications
Olanzapine replaced by active ingredient.
4.4 Special warnings and precautions for use
Added (new text in bold):
In cases where hepatitis (including hepatocellular, cholestatic, or mixed liver injury) has been diagnosed, olanzapine treatment should be discontinued.
Statements on lactose, aspartame, sodium methyl parahydroxybenzoate and sodium propyl parahydroxybenzoate moved to end of section.
4.7 Effects on ability to drive and use machines
Added:
No studies on the effects on the ability to drive and use machines have been performed.
4.8 Undesirable effects
Changes to table of undesirable effects based on adverse event reporting and laboratory investigations from clinical trials:
Moved from ‘Investigations’ to ‘Cardiac disorders’:
QT prolongation (see also section 4.4).
Changes to table of undesirable effects based on post-marketing spontaneous reports:
Removed from ‘Hepatobiliary disorders’:
Very rare (<0.01%): Hepatitis.
Added to ‘Hepatobiliary disorders’:
Rare (0.01-0.1%): Hepatitis (including hepatocellular, cholestatic, or mixed liver injury).
Added:
Investigations
Increased transaminases.
Very rare (<0.01%): Increased alkaline phosphatase. Increased total bilirubin.
Moved from ‘Vascular disorders’ to new ‘Cardiac disorders’ section:
QTc prolongation, ventricular tachycardia/fibrillation, and sudden death (see also section 4.4).
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Moved from section 4.1.1:
In a multinational, double-blind, comparative study of schizophrenia, schizoaffective, and related disorders which included 1,481 patients with varying degrees of associated depressive symptoms (baseline mean of 16.6 on the Montgomery-Asberg Depression Rating Scale), a prospective secondary analysis of baseline to endpoint mood score change demonstrated a statistically significant improvement (p=0.001) favouring olanzapine (-6.0) versus haloperidol (-3.1).
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablet core
Hydroxypropylcellulose replaced by Hyprolose.
Tablet coat
2.5mg, 5mg, 7.5mg, and 10mg tablet: Propylene glycol added.
Addition of 20mg tablet excipients.
6.3 Shelf-life
Shelf-life added for 20mg tablets.
6.5 Nature and contents of container
Addition of 20mg tablets.
8. MARKETING AUTHORISATION NUMBERS
Addition of 20mg tablets.
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
New date of renewal:
12 September 2006
10. DATE OF REVISION OF THE TEXT
New date:
13 September 2006
Updated on 02 October 2006
Reasons for updating
- Change to side-effects
- Change to date of revision
Updated on 05 December 2005
Reasons for updating
- Change to side-effects
- Change to date of revision
Updated on 25 November 2005
Reasons for updating
- Change to section 1 - Name of medicinal product
- Change to section 2 - Qualitative and quantitative composition
- Change to section 3 - Pharmaceutical form
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 6.3 - Shelf life
- Change to section 6.5 - Nature and contents of container
- Change to section 8 - MA number
- 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 14 April 2005
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 18 February 2005
Reasons for updating
- Change to section 2 - Qualitative and quantitative composition
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 6.1 - List of excipients
- Change to section 6.4 - Special precautions for storage
- 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 18 February 2005
Reasons for updating
- Change to side-effects
Updated on 21 September 2004
Reasons for updating
- New PIL for medicines.ie
Updated on 22 March 2004
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)
Updated on 16 December 2003
Reasons for updating
- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.8 - Undesirable effects
- Change to section 5.1 - Pharmacodynamic properties
- 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 02 June 2003
Reasons for updating
- New SPC for medicines.ie
Legal category:Product subject to medical prescription which may not be renewed (A)