Epilim Enteric 500mg Gastro-resistant Coated Tablets

*
Pharmacy Only: Prescription
  • Company:

    SANOFI
  • Status:

    No Recent Update
  • Legal Category:

    Product subject to medical prescription which may be renewed (B)
  • Active Ingredient(s):

    This medicinal product is subject to additional monitoring.

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

Updated on 17 January 2024

File name

1.3.1 Epilim EC 500mg SmPC IE (1).pdf

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation

Legal category:Product subject to medical prescription which may be renewed (B)

Updated on 10 November 2023

File name

1.3.1 Epilim EC 500mg SmPC IE.pdf

Reasons for updating

  • Change to section 5.3 - Preclinical safety data

Legal category:Product subject to medical prescription which may be renewed (B)

Updated on 10 November 2023

File name

1.3.1 Epilim EC 500mg SmPC IE.pdf

Reasons for updating

  • Change to section 5.3 - Preclinical safety data

Legal category:Product subject to medical prescription which may be renewed (B)

EDM Updated on 24 March 2023

File name

Epilim Ire - Valproate Patient Guide IE.pdf

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EDM Updated on 23 March 2023

File name

Epilim Valproate Patient Booklet_4.0.pdf

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Updated on 03 March 2023

File name

1.3.1 Package Leaflet Epilim EC 200mg & 500mg tablets (3).pdf

Reasons for updating

  • Change to section 2 - interactions with other medicines, food or drink

Updated on 03 March 2023

File name

1.3.1 SPC Epilim EC 500mg (1).pdf

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

Legal category:Product subject to medical prescription which may be renewed (B)

Updated on 01 March 2023

File name

1.3.1 Package Leaflet Epilim EC 200mg & 500mg tablets (1).pdf

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 4 - possible side effects
  • Change to section 4 - how to report a side effect

Updated on 01 March 2023

File name

1.3.1 SPC Epilim EC 500mg.pdf

Reasons for updating

  • Change to section 4.3 - Contraindications
  • 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 4.8 – Undesirable effects - how to report a side effect
  • Change to section 4.9 - Overdose

Legal category:Product subject to medical prescription which may be renewed (B)

Updated on 10 August 2022

File name

1.3.1 Package Leaflet Epilim EC 200mg & 500mg tablets (6).pdf

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 2 - pregnancy, breast feeding and fertility

Updated on 10 August 2022

File name

1.3.1 SPC Epilim EC 500mg (2).pdf

Reasons for updating

  • 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

Legal category:Product subject to medical prescription which may be renewed (B)

EDM Updated on 16 February 2022

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Epilim Shelf Barker_02.pdf

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EDM Updated on 16 February 2022

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Epilim A4 Pharmacy Poster_3.0.pdf

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EDM Updated on 16 February 2022

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Epilim Ireland ARAF Interactive Form_2.0.pdf

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EDM Updated on 16 February 2022

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Epilim Valproate Patient Booklet_4.0.pdf

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EDM Updated on 16 February 2022

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Epilim Valproate HCP Booklet_3.0.pdf

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Updated on 11 February 2022

File name

1.3.1 SPC Epilim EC 500mg.pdf

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 5.3 - Preclinical safety data

Legal category:Product subject to medical prescription which may be renewed (B)

Updated on 11 February 2022

File name

1.3.1 Package Leaflet Epilim EC 200mg & 500mg tablets.pdf

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 2 - driving and using machines
  • Change to section 2 - excipient warnings

Updated on 07 February 2022

File name

1.3.1 Package Leaflet Epilim EC 200mg & 500mg tablets (5).pdf

Reasons for updating

  • Change to Section 1 - what the product is
  • Change to section 1 - what the product is used for
  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 2 - driving and using machines
  • Change to section 2 - excipient warnings
  • Change to section 3 - dose and frequency
  • Change to section 3 - use in children/adolescents
  • Change to section 3 - how to take/use
  • Change to section 3 - duration of treatment
  • Change to section 3 - overdose, missed or forgotten doses
  • Change to section 4 - possible side effects
  • Change to section 4 - how to report a side effect

Updated on 15 October 2021

File name

1.3.1 SPC Epilim EC 500mg IE1267 S21.018.pdf

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 4.8 - Undesirable effects
  • Change to Section 4.8 – Undesirable effects - how to report a side effect

Legal category:Product subject to medical prescription which may be renewed (B)

Updated on 15 October 2021

File name

1.3.1 Package Leaflet Epilim EC IE1267 S21.018.pdf

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 2 - driving and using machines
  • Change to section 2 - excipient warnings

Updated on 22 September 2021

File name

1.3.1 Package Leaflet Epilim EC IE1273 EOP.pdf

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 2 - driving and using machines
  • Change to section 2 - excipient warnings

Updated on 22 September 2021

File name

1.3.1 SPC Epilim EC 500mg IE1273 EOP.pdf

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation

Legal category:Product subject to medical prescription which may be renewed (B)

Updated on 01 March 2021

File name

1.3.1 SPC Epilim EC 500mg (1).pdf

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.2 - Pharmacokinetic properties

Legal category:Product subject to medical prescription which may be renewed (B)

Updated on 23 February 2021

File name

1.3.1 SPC Epilim EC 500mg.pdf

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.2 - Pharmacokinetic properties

Legal category:Product subject to medical prescription which may be renewed (B)

Updated on 23 February 2021

File name

1.3.1 Package Leaflet Epilim EC 200mg & 500mg tablets.pdf

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 4 - how to report a side effect

Updated on 23 February 2021

File name

1.3.1 SPC Epilim EC 500mg annotated.pdf

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.2 - Pharmacokinetic properties

Legal category:Product subject to medical prescription which may be renewed (B)

EDM Updated on 18 February 2021

File name

Epilim RMP Pharmacy Poster.pdf

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EDM Updated on 09 February 2021

File name

MAT-IE-2001844(v1.0) Epilim Ireland ARAF Interactive.pdf

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EDM Updated on 08 October 2020

File name

Epilim Patient Booklet_Final_LR MAT-IE-2000324(v3.0).pdf

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EDM Updated on 21 September 2020

File name

Epilim Patient Guide MAT-IE-2000324(v3.0).pdf

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EDM Updated on 11 August 2020

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Epilim Patient Guide MAT-IE-2000324(v2.0).pdf

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EDM Updated on 11 August 2020

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Epilim HCP Guide MAT-IE-2000323(v2.0).pdf

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Updated on 06 July 2020

File name

1.3.1 Package Leaflet Epilim EC 200mg & 500mg tablets IE993 .pdf

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 2 - driving and using machines
  • Change to section 2 - excipient warnings

Free text change information supplied by the pharmaceutical company


 

Updated on 02 April 2020

File name

1.3.1 SPC Epilim EC 500mg IE993-IE994 .pdf

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 5.3 - Preclinical safety data

Legal category:Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Section 4.6

Pregnancy Exposure Risk related to valproate

Both valproate monotherapy and valproate polytherapy including other antiepileptics, are frequently associated with abnormal pregnancy outcomes. Available data suggest that antiepileptic polytherapy including valproate is associated with a greater risk of congenital malformations than valproate monotherapy. Valproate was shown to cross the placental barrier both in animal species and in humans (see section 5.2).

In animals: teratogenic effects have been demonstrated in mice, rats and rabbits (see section 5.3).

 

Congenital malformations

 

There are limited data on the long term outcomes.

Available data from a population based study show that children exposed to valproate in utero are at increased risk of autistic spectrum disorder (approximately 3-fold) and childhood autism (approximately 5-fold) compared to the unexposed population in the study.

Available data from another population based study show that children exposed to valproate in utero are at increased risk of developing attention deficit/hyperactivity disorder (ADHD) (approximately 1.5 fold) compared to the unexposed population in the study.

If a Woman plans a Pregnancy

 

5.3       Preclinical Safety Data

 

 

Animal studies show that in utero exposure to valproate results in morphological and functional alterations of the auditory system in rats and mice.

 

Carcinogenesis, mutagenesis

Valproate was not mutagenic in bacteria (Ames test), or mouse lymphoma L5178Y cells at thymidine kinase locus (mouse lymphoma assay) and did not induce DNA repair activity in primary culture of rat hepatocytes. In in vivo studies, when tested at teratogenic doses, results were contradictory depending on the route of administration. After oral administration, the main route of administration in humans, valproate did not induce either chromosome aberrations in rat bone marrow, or dominant lethal effects in mice. 

 

After intraperitoneal exposure to valproate, increased incidences of DNA and chromosome damage (DNA strand-breaks, chromosomal aberrations or micronuclei) have been reported in rodents. However, the relevance of the results obtained with the intraperitoneal route of administration is unknown.

Statistically significant higher incidences of sister-chromatid exchange (SCE) have been observed in epileptic patients exposed to valproate as compared to healthy subjects not exposed to valproate. However, there are confounding factors and contradictory results in 2 published studies. The biological significance of an increase in SCE frequency is not known.

 

Non-clinical data reveal no carcinogenicity hazard for humans based on conventional carcinogenicity studies.

 

Reproductive toxicology

Teratogenic effects (malformations of multiple organ systems) have been demonstrated in mice, rats, and rabbits.

In published literature, behavioural abnormalities have been reported in first generation offspring of mice and rats after in utero exposure. In mice, behavioural changes have also been observed in the 2nd and 3rd generations, albeit less pronounced in the 3rd generation, following an acute in utero exposure of the first generation to teratogenic doses. The underlying mechanisms of action and the relevance of these findings for humans are unknown.

Updated on 02 April 2020

File name

1.3.1 Package Leaflet Epilim EC 200mg & 500mg tablets IE993 .pdf

Reasons for updating

  • Change to section 2 - pregnancy, breast feeding and fertility

Updated on 17 March 2020

File name

1.3.1 epilim enteric pl IE729 766091.pdf

Reasons for updating

  • Change to other sources of information section

Free text change information supplied by the pharmaceutical company

Addition of QR code

EDM Updated on 16 March 2020

File name

Valproate_Epilim_Annual Risk acknowledgement form_final-2205036-15052018124629-636619851950937500.pdf

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Updated on 09 December 2019

File name

Epilim EC 500mg SmPC.pdf

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 5.2 - Pharmacokinetic properties

Legal category:Product subject to medical prescription which may be renewed (B)

Updated on 09 December 2019

File name

Epilim EC 200mg & 500mg tablets PIL.pdf

Reasons for updating

  • Change to section 2 - pregnancy, breast feeding and fertility

EDM Updated on 18 October 2019

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DHPC for Pharmacists_April_2018_approved-2205036-17042018172152-636595825230312500.pdf

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EDM Updated on 18 October 2019

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DHPC for Prescribers_April 2018_approved-2205036-17042018172612-636595827803125000.pdf

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EDM Updated on 18 October 2019

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Pharmacy warning sticker-2205036-17042018170547-636595815700937500.pdf

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EDM Updated on 18 October 2019

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Pharmacy warning sticker-2205036-17042018170547-636595815700937500.pdf

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EDM Updated on 18 October 2019

File name

Valproate HCP Booklet_2018-05-2205036-20062018101407-636650864482115000.pdf

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EDM Updated on 18 October 2019

File name

Valproate_Epilim_Annual Risk acknowledgement form_final-2205036-15052018124629-636619851950937500.pdf

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EDM Updated on 18 October 2019

File name

Valproate Patient Booklet_final_reformatted_19.06.2018-2205036-20062018090312-636650821952427500.pdf

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EDM Updated on 18 October 2019

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Valproate_Epilim_Patient Card_final-2205036-15052018124823-636619853060468750.pdf

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EDM Updated on 18 October 2019

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Valproate_Epilim_ A4 Pharmacy Poster_final-2205036-15052018124904-636619853514531250.pdf

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Updated on 07 August 2019

File name

1.3.1 SPC Epilim EC 500mg IE978.pdf

Reasons for updating

  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation

Legal category:Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

4.3          Contraindications

Epilim is contraindicated in the following situations:

Treatment of epilepsy

  • in pregnancy unless there is no suitable alternative treatment (see section 4.4 and 4.6).
  • in women of childbearing potential, unless the conditions of the pregnancy prevention programme are fulfilled (see section 4.4 and 4.6).

All indications

  • Hypersensitivity to sodium valproate
  • Active liver disease
  • Personal or family history of severe hepatic dysfunction, especially drug related
  • Porphyria
  • Valproate is contraindicated in patients known to have mitochondrial disorders caused by mutations in the nuclear gene encoding the mitochondrial enzyme polymerase γ (POLG), e.g. Alpers-Huttenlocher Syndrome, and in children under two years of age who are suspected of having a POLG-related disorder (see section 4.4).
  • Patients with known urea cycle disorders (see section 4.4)

…….

4.4          Special Warnings and Precautions for Use

Pregnancy Prevention Programme

Valproate has a high teratogenic potential and children exposed in utero to valproate have a high risk for congenital malformations and neurodevelopmental disorders (see section 4.6).

Epilim is contraindicated in the following situations:

 

Treatment of epilepsy

  •  
    • in pregnancy unless there is no suitable alternative treatment (see section 4.3 and 4.6).
    • in women of childbearing potential, unless the conditions of the pregnancy prevention programme are fulfilled (see section 4.3 and 4.6).

…….

Pregnancy planning.

For the indication epilepsy, iIf a woman is planning to become pregnant, a specialist experienced in the management of epilepsy, must reassess valproate therapy and consider alternative treatment options. Every effort should be made to switch to appropriate alternative treatment prior to conception, and before contraception is discontinued (see section 4.6). If switching is not possible, the woman should receive further counselling regarding the valproate risks for the unborn child to support her informed decision making regarding family planning.

…….

  1.  
    1. Fertility, pregnancy and lactation

…….

If a Woman plans a Pregnancy

F

or the indication epilepsy, iIf a woman is planning to become pregnant, a specialist experienced in the management of epilepsy, must reassess valproate therapy and consider alternative treatment options. Every effort should be made to switch to appropriate alternative treatment prior to conception, and before contraception is discontinued (see section 4.4). If switching is not possible, the woman should receive further counselling regarding the valproate risks for the unborn child to support her informed decision making regarding family planning

Updated on 18 April 2019

File name

PIL Epilim EC 200mg & 500mg tablets IE656 IE682.pdf

Reasons for updating

  • Change to section 4 - possible side effects

Updated on 18 April 2019

File name

SPC Epilim EC 500mg IE656 IE682.pdf

Reasons for updating

  • Change to section 4.8 - Undesirable effects

Legal category:Product subject to medical prescription which may be renewed (B)

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4.8       Undesirable Effects

Nervous system disorders:

Rare: reversible dementia associated with reversible cerebral atrophy, cognitive disorder, diplopia.

 

Renal and urinary disorders:

Common: urinary incontinence

Updated on 23 October 2018

File name

PIL epilim enteric 200mg and 500mg gastro resistant coated tablets.pdf

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 2 - driving and using machines
  • Change to section 2 - excipient warnings

Updated on 18 October 2018

File name

SPC epilim enteric 500mg gastro resistant coated tablets .pdf

Reasons for updating

  • 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 5.2 - Pharmacokinetic properties

Legal category:Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Even if she has amenorrhea she must follow all the advice on effective contraception.

 

Estrogen-containing products

Concomitant use with estrogen-containing products, including estrogen-containing

hormonal contraceptives, may potentially result in decreased valproate efficacy (see section 4.5). Prescribers should monitor clinical response (seizure control or mood control) when initiating or discontinuing estrogen-containing products.

 

On the opposite, valproate does not reduce efficacy of hormonal contraceptives.

 

Annual treatment reviews by a specialist

 

 

Co-administration of valproate and quetiapine may increase the risk of neutropenia/leucopenia.

 

Estrogen-containing products, including estrogen-containing hormonal contraceptives

Estrogens are inducers of the UDP-glucuronosyl transferase (UGT) isoforms involved in valproate glucuronidation and may increase the clearance of valproate, which would result in decreased serum concentration of valproate and potentially decreased valproate efficacy (see section 4.4). Consider monitoring of valproate serum levels.

 

On the opposite, valproate has no enzyme inducing effect; as a consequence, valproate

does not reduce efficacy of oestroprogestative agents in women receiving hormonal contraception.

Epilim usually has no enzyme-inducing effect; as a consequence, Epilim does not reduce the efficacy of oestroprogestative agents in women receiving hormonal contraception, including the oral contraceptive pill.

4.6       Fertility, pregnancy and lactation

 

However the available evidence does not suggest it prevents the birth defects or malformations due to valproate exposure.

 

 

Women of childbearing potential

Estrogen-containing products

Estrogen-containing products, including estrogen-containing hormonal contraceptives, may increase the clearance of valproate, which would result in decreased serum concentration of valproate and potentially decreased valproate efficacy (sections 4.4 and 4.5).

 

Risk in the neonate

 

The pharmacological (or therapeutic) effects of Epilim may not be clearly correlated with the total or free (unbound) plasma valproic acid levels.

 

Metabolism

The major pathway of valproate biotransformation is glucuronidation (~40%), mainly via UGT1A6, UGT1A9, and UGT2B7.

 

5.3       Preclinical Safety Data

 

Updated on 16 August 2018

File name

1.3.1 Leaflet PA54015002-3 EC 200,500mg.pdf

Reasons for updating

  • Change to section 6 - what the product contains
  • Change to section 6 - marketing authorisation holder

Updated on 16 August 2018

File name

1.3.1 SPC PA54015003 EC 500mg.pdf

Reasons for updating

  • Change to section 6.5 - Nature and contents of container

Legal category:Product subject to medical prescription which may be renewed (B)

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Section 6.5

 

Pack sizes of 30 or 100 tablets with 10 tablets per strip and 112 tablets. 

 

Updated on 07 August 2018

File name

1.3.1 Leaflet EC 200,500mg.pdf

Reasons for updating

  • Change to Section 1 - what the product is
  • Change to section 1 - what the product is used for
  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 2 - driving and using machines
  • Change to section 2 - excipient warnings
  • Change to section 3 - dose and frequency
  • Change to section 3 - use in children/adolescents
  • Change to section 3 - how to take/use
  • Change to section 3 - duration of treatment
  • Change to section 3 - overdose, missed or forgotten doses

Updated on 07 August 2018

File name

1.3.1 SPC EC 500mg 5401503.pdf

Reasons for updating

  • 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 4.5 - 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 4.9 - Overdose

Legal category:Product subject to medical prescription which may be renewed (B)

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4.2

Female children, female adolescents,and  women of childbearing potential and pregnant women

Epilim should must be initiated and supervised by a specialist experienced in the management of epilepsy or bipolar disorder. Valproate should not be used in female children and women of childbearing potential unless Treatment should only be initiated if other treatments are ineffective or not tolerated (see section 4.4 and 4.6) and the benefit and risk should be carefully reconsidered at regular treatment reviews.

Valproate is prescribed and dispensed according to the Valproate Pregnancy Prevention Programme (see section 4.3 and 4.4).

Preferably Epilim should preferably be prescribed as monotherapy and at the lowest effective dose, if possible as a prolonged release formulation to avoid high peak plasma concentrations. The daily dose should be divided into at least two single doses (see section 4.6).

.3         Contraindications

 

Epilim is contraindicated in the following situations:

 

Treatment of epilepsy

  • in pregnancy unless there is no suitable alternative treatment (see section 4.4 and 4.6).
  • in women of childbearing potential, unless the conditions of the pregnancy prevention programme are fulfilled (see section 4.4 and 4.6).
     
    Treatment of bipolar disorder
  • in pregnancy (see section 4.4 and 4.6).
  • in women of childbearing potential, unless the conditions of the pregnancy prevention programme are fulfilled  (see section 4.4 and 4.6).
     
    All indications
  • Hypersensitivity to sodium valproate
  • Active liver disease
  • Personal or family history of severe hepatic dysfunction, especially drug related
  • Hypersensitivity to sodium valproate or to any of the excipients
  • Porphyria.

 

4.4-Special Warnings and Special Precautions for Use- full changes

 

Updated on 29 November 2017

File name

PIL_9115_380.pdf

Reasons for updating

  • New PIL for new product

Updated on 29 November 2017

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 2 - driving and using machines
  • Change to section 2 - excipient warnings
  • Change to section 4 - possible side effects
  • Change to section 4 - how to report a side effect

Updated on 15 August 2017

Reasons for updating

  • New SPC for new product

Legal category:Product subject to medical prescription which may be renewed (B)

Updated on 15 August 2017

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Section 4.5 interactions – this has been added

- Nimodipine

In patients concomitantly treated with sodium valproate and nimodipine the exposure to nimodipine can be increased by 50%. The nimodipine dose should therefore be decreased in case of hypotension

Updated on 02 June 2017

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use

Legal category:Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Type IIC – CCDS v17, 18, 20

Updated on 04 November 2016

Reasons for updating

  • Change to section 4.3 - Contraindications
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may be renewed (B)

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Worksharing procedure for urea cycle disorders

Updated on 03 November 2016

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 6 - date of revision

Updated on 13 May 2015

Reasons for updating

  • Addition of black triangle
  • 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 4.6 - 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 be renewed (B)

Free text change information supplied by the pharmaceutical company

Black Triangle included.
Section 4.2: new paragraph 'Female children, female adolescents, women of childbearing potential and pregnant women'.
Section 4.3: new paragraph added regarding mitrochondrial disorders.
Section 4.4: new boxed wording titled 'Female children, female adolescents, women of childbearing potential and pregnant women'.
Paragraph title 'Women of childbearing potential' has been removed.
New information on 'Patients with known or suspected mitrochondrial disease' included.
Section 4.6: Majority of section has been updated with new paragraphs title 'Breastfeeding' and 'Fertility' added.
Section 4.8: 'Congenital malformations and development disorders' added.

Updated on 01 May 2015

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to information about pregnancy or lactation
  • Addition of black triangle

Updated on 22 December 2014

Reasons for updating

  • 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 4.9 - Overdose
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Section 4.4: updated to include:

Patients with an underlying carnitine palmitoyltransferase (CPT) type II deficiency should be warned of the greater risk of rhabdomyolysis when taking valproate.


Section 4.5: 4.5.3 updated to include:

Co-administration of valproate and quetiapine may increase the risk of neutropenia/leucopenia.


Section 4.6: 4.6.1 paragraph 'Risks associated with Epilim' updated:

In humans: Available data suggest an increased incidence of minor or major malformations including neural tube defects, craniofacial defects, malformation of the limbs, cardiovascular malformations and multiple anomalies involving various body systems in offspring born to mothers with epilepsy treated with valproate when compared to the incidence for certain other antiepileptic drugs.  Data from a meta-analysis (including registries and cohort studies) has shown an incidence of congenital malformations in children born to epileptic women exposed to valproate monotherapy during pregnancy at 10.73% (95% CI: 8.16 13.29).  Available data indicate dose dependency of this effect. 


'Risks in the neonate' updated:

Very rare cases of haemorrhagic syndrome have been reported in neonates whose mothers have taken valproate during pregnancy. This haemorrhagic syndrome is related to thrombocytopenia, hypofibrinogenemia and/or to decreases in other coagulation factors; afibrinogenemia has also been reported and may be fatal.  These are possibly associated with a decrease of coagulation factors. However, this syndrome has to be distinguished from the decrease of the vitamin-K factors induced by phenobarbital and other anti-epileptic enzyme inducing drugs.

Therefore, platelet count, fibrinogen plasma level, coagulation tests and coagulation factors should be investigated in neonates.

 

Cases of hypoglycaemia have been reported in neonates whose mothers have taken valproate during the third trimester of pregnancy.

 

Cases of hypothyroidism have been reported in neonates whose mothers have taken valproate during pregnancy.

 

Withdrawal syndrome (such as, in particular, agitation, irritability, hyper-excitability, jitteriness, hyperkinesia, tonicity disorders, tremor, convulsions and feeding disorders) may occur in neonates whose mothers have taken valproate during the last trimester of pregnancy.


Section 4.8: updated as follows:

The following CIOMS frequency rating is used, when applicable:

 

Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to ≤1/100); rare (≥1/10,000 to ≤1/1,000); very rare (≤1/10,000); not known (cannot be estimated from the available data).

 

Congenital, familial and genetic disorders: (see section 4.6. Fertility, Ppregnancy and Llactation)

 

Hepatobiliary disorders:

Common:  rare cases of liver injury (see section 4.4. Special warnings and precautions for use)

 

Gastrointestinal disorders:

Very common: (nausea,

Common:  vomiting, gingival disorder (mainly gingival hyperplasia), stomatitis. abdominal pain upper, diarrhoea)

 

The above three adverse events frequently occur at the start of treatment, but they usually disappear after a few days without discontinuing treatment. These problems can usually be overcome by taking Epilim with or after food or by using Enteric Coated Epilim.

 

Uncommon:  Very rare cases of pancreatitis, sometimes lethal, have been reported (see section 4.4 Special Warnings and Special Precautions for Use).

 

Nervous system disorders:

 

Very common: tremor

Common: extrapyramidal disorder, stupor*, somnolence, convulsion*, memory impairment, headache, nystagmus,

Uncommon: coma*, encephalopathy, lethargy* (see below), reversible parkinsonism, ataxia, paresthesia.

Rare: reversible dementia associated with reversible cerebral atrophy, cognitive disorder.

 

Sedation has been reported occasionally, usually when in combination with other anticonvulsants. In monotherapy it occurred early in treatment on rare occasions and is usually transient. 

 

*Rare cases of lethargy and confusion, occasionally progressing to stupor, sometimes with associated hallucinations or convulsions have been reported. Encephalopathy and coma have very rarely been observed. These cases have often been associated with too high a starting dose or too rapid a dose escalation or concomitant use of other anticonvulsants, notably phenobarbital or topiramate. They have usually been reversible on withdrawal of treatment or reduction of dosage.  Extrapyramidal disorders.

 

Very rare cases of reversible dementia associated with reversible cerebral atrophy have been reported.

Ataxia and transient and/or dose related fine postural tremor have occasionally been reported.

 

Extrapyramidal disorder which may not be reversible, including reversible Parkinsonism.

 

Cognitive disorders.

 

An increase in alertness may occur; this is generally beneficial but occasionally aggression, hyperactivity and behavioural disorders have been reported.

 

Cases of isolated and moderate hyperammonaemia without change in liver function may occur frequently and should not cause treatment discontinuation.  However, they may present clinically as vomiting, ataxia, and increasing clouding of consciousness.  Should these symptoms occur Epilim should be discontinued.

Hyperammonaemia associated with neurological symptoms has also been reported (see section 4.4.2 Precautions). In such cases further investigations should be considered.

 

Metabolic and nutrition disorders:

Common:  hyponatraemia.

Rare:  hyperammonaemia* (see section 4.4.2 Precautions)

 

*Cases of isolated and moderate hyperammonaemia without change in liver function may occur frequently and should not cause treatment discontinuation.  However, they may present clinically as vomiting, ataxia, and increasing clouding of consciousness.  Should these symptoms occur Epilim should be discontinued.

 

Hyperammonaemia associated with neurological symptoms has also been reported (see section 4.4.2 Precautions). In such cases further investigations should be considered.

 

Very rare cases of hyponatremia have been reported.

Syndrome of Inappropriate Secretion of ADH (SIADH)

 

Endocrine Disorders:

Uncommon:  Syndrome of Inappropriate Secretion of ADH (SIADH), hyperandrogenism (hirsutism, virilism, acne, male pattern alopecia, and/or androgen increased)

Rare:  hypothyroidism (see section 4.6 Fertility, pregnancy and lactation)

 

 

Blood and lymphatic system disorders: 

Frequent occurrence of Common:  anaemia, thrombocytopenia, rare cases of anaemia, leucopoenia or (see section 4.4.2 Precautions).

Uncommon:  pancytopenia., leucopenia.

 

The blood picture returned to normal when the drug was discontinued.

 

Rare:  Bbone marrow failure, including pure red cell aplasia.,  Aagranulocytosis, anaemia macrocytic, macrocytosis.

 

Isolated finding of a reduction in blood fibrinogen and/or increase in prothrombin time have been reported, usually without associated clinical signs and particularly with high doses (Epilim has an inhibitory effect on the second phase of platelet aggregation). Spontaneous bruising or bleeding is an indication for withdrawal of medication pending investigations (see also section 4.6 Fertility, Ppregnancy and Llactation).

 

           

Deficiency in Factor VIII / Von Willebrand.

 

Skin and subcutaneous tissue disorders:

Very rare: toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme, rash.

 

Common:  hypersensitivity, Ttransient and/or dose related alopecia., has often been reported. Regrowth normally begins within six months, although the hair may become more curly than previously.

Uncommon:  angioedema, rash, hair disorder (such as hair texture abnormal, hair colour changes, hair growth abnormal)

 

Rare:  toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome.

 

Musculoskeletal and connective tissue disorders:

Uncommon:  There have been reports of decreased bone mineral density decreased, osteopenia, osteoporosis and fractures in patients on long-term therapy with Epilim. The mechanism by which Epilim affects bone metabolism has not been identified.

Rare:  systemic lupus erythematosus (see section 4.4.2 Precautions), rhabdomyolysis (see section 4.4.2 Precautions)

 

 

Reproductive system and breast disorders:

Common:  dysmenorrhea

Uncommon:  amenorrhea

Rare:  male infertility, polycystic ovaries

            Amenorrhoea and dysmenorrhea have been reported.  

 

Very rarely gynaecomastia has occurred.

Male infertility.

 

Vascular disorders:

Common: haemorrhage (see section 4.4.2 Precautions and 4.6 Fertility, pregnancy and lactation).

Uncommon:  The occurrence of vasculitis has occasionally been reported.

 

Ear and labyrinth disorders:

Common:  Deafness, either reversible or irreversible has been reported rarely.

 

Renal and urinary disorders:

Uncommon: renal failure

There have been isolated reports of a reversible Fanconi’s syndrome (a defect in proximal renal tubular function giving rise to glycosuria, amino aciduria, phosphaturia, and uricosuria) but the mode of action is as yet unclear.

Very rRare: cases of enuresis, tubulointerstitial nephritishave been reported.

reversible Fanconi syndrome (a defect in proximal renal tubular function giving rise to glycosuria, amino aciduria, phosphaturia, and uricosuria) associated with Epilim therapy, but the mode of action is as yet unclear.

 

Immune system disorders:

Angioedema, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome.

Allergic reactions (ranging from rash to hypersensitivity reactions) have been reported.

 

Psychiatric disorders:

Common:  Cconfusional state, hallucinations, aggression*, agitation*, disturbance in attention*

Rare:  abnormal behaviour*, psychomotor hyperactivity*, learning disorder*

 

*These ADRs are principally observed in the paediatric population.

 

 

General disorders and administration site conditions:

Very rare cases of Uncommon: hypothermia, non-severe peripheral oedema peripheral have been reported.

 

Increase in weight may also occur. Since it is a risk factor for polycystic ovary syndrome, it should be carefully monitored (see section 4.4 Special Warnings and Special Precautions for Use).

 

Respiratory, thoracic and mediastinal disorders:

Uncommon: pleural effusion

 

Investigations:

Common:  Weight increased*

Rare:  Coagulation factors decreased (at least one), abnormal coagulation tests (such as prothrombin time prolonged, activated partial thromboplastin time prolonged, thrombin time prolonged, INR prolonged), biotin deficiency/biotinidase deficiency.

 

*Weight increase should be carefully monitored since it is a factor for polycystic ovary syndrome (see section 4.4.2 Precautions)

 

Neoplasms benign, malignant and unspecified (including cysts and polyps):

Rare:  myelodysplastic syndrome

 

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 IMB HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517; Website: www.hpraimb.ie; e-mail: imbpharmacovigilance@imb.iemedsafety@hpra.ie.


Section 4.9: updated as follows:

Signs of massive overdose, i.e. plasma concentration 10 to 20 times maximum therapeutic levels, usually include CNS depression or coma with muscular hypotonia, hyporeflexia, miosis, impaired respiratory function, metabolic acidosis, hypotension and circulatory collapse/shock. 

Deaths have occurred following massive overdose; nevertheless, a favourable outcome is usual.

 

Symptoms may however be variable and seizures have been reported in the presence of very high plasma levels (see also section 5.2 Pharmacokinetic Properties). Cases of intracranial hypertension related to cerebral oedema have been reported.

 

The presence of sodium content in the valproate formulations may lead to hypernatraemia when taken in overdose.



Updated on 02 April 2014

Reasons for updating

  • Change to dosage and administration

Updated on 06 November 2013

Reasons for updating

  • Change to side-effects

Updated on 01 November 2013

Reasons for updating

  • Change to section 4.8 - Undesirable effects

Legal category:Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Type IB variation relating to the Bone density disorder for sodium valproate.  

Updated on 24 August 2012

Reasons for updating

  • Change to section 7 - Marketing authorisation holder

Legal category:Product subject to medical prescription which may be renewed (B)

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Section 7 updated with the addition of T/A SANOFI

Updated on 13 April 2012

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

Legal category:Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Sections 4.2, 4.4, 4.5, 4.6 & 4.8 updated in line with version 13 of the Company Core Data Sheet with regard to:-
  • Extrapyramidal disorders
  • Interactions with Lamotrigine
  • Interactions with Felbamate
  • Male infertility
  • Peadiatric data in Bipolar Disorder
  • Alcohol intake
  • Use of contraception in women

Updated on 21 March 2012

Reasons for updating

  • Change to drug interactions
  • Change to information about drinking alcohol
  • Change to information about pregnancy or lactation

Updated on 18 May 2011

Reasons for updating

  • Change to section 4.8 - Undesirable effects

Legal category:Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Update Section 4.8 following Article 31 Approval.

Updated on 02 February 2011

Reasons for updating

  • Changes to therapeutic indications

Updated on 04 October 2010

Reasons for updating

  • 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

Legal category:Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Update to section 4.4 & 4.5 with regard to interaction with carbapenem agents.

Updated on 16 October 2009

Reasons for updating

  • Change due to user-testing of patient information

Updated on 07 October 2009

Reasons for updating

  • 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 4.9 - Overdose

Legal category:Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Warning regarding autism spectrum disorders to section 4.6
Additional adverse events to section 4.8
Addition of rifampicin and topiramate to section 4.5
Modification of section 4.9

Updated on 05 January 2009

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use

Legal category:Product subject to medical prescription which may be renewed (B)

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Update to section 4.4 of SPC.

Updated on 05 January 2009

Reasons for updating

  • Change to warnings or special precautions for use

Updated on 30 April 2008

Reasons for updating

  • New SPC for medicines.ie

Legal category:Product subject to medical prescription which may be renewed (B)

Updated on 30 April 2008

Reasons for updating

  • Change to marketing authorisation holder

Updated on 08 August 2007

Reasons for updating

  • Improved electronic presentation

Updated on 18 December 2006

Reasons for updating

  • Improved electronic presentation

Updated on 04 January 2006

Reasons for updating

  • Improved electronic presentation

Updated on 13 October 2004

Reasons for updating

  • New PIL for medicines.ie