Epilim Chrono 500mg Prolonged Release Tablets

  • Name:

    Epilim Chrono 500mg Prolonged Release Tablets

  • Company:
    info
  • Active Ingredients:

    Sodium Valproate, Valproic Acid

  • Legal Category:

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

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 02/04/20

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Summary of Product Characteristics last updated on medicines.ie: 2/4/2020
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.

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When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 11 August 2020 Ed-HCP

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Updated on 11 August 2020 Ed-Ptnt

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Updated on 11 August 2020 Ed-HCP

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Updated on 2 April 2020 SmPC

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  • 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)

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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 2 April 2020 PIL

Reasons for updating

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

Updated on 17 March 2020 PIL

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  • Change to other sources of information section

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Addition of QR Code

Updated on 16 March 2020 Ed-HCP

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  • Replace document

Updated on 9 December 2019 SmPC

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 9 December 2019 PIL

Reasons for updating

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

Updated on 30 October 2019 Ed-HCP

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  • Add New Doc

Updated on 17 October 2019 Ed-Ptnt

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Updated on 17 October 2019 Ed-HCP

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Updated on 17 October 2019 Ed-Ptnt

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Updated on 17 October 2019 Ed-HCP

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Updated on 17 October 2019 Ed-HCP

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Updated on 17 October 2019 Ed-HCP

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Updated on 17 October 2019 Ed-HCP

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Updated on 17 October 2019 Ed-HCP

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Updated on 18 April 2019 PIL

Reasons for updating

  • Change to section 4 - possible side effects

Updated on 18 April 2019 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects

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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 PIL

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 SmPC

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

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

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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 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 Chrono 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.

 

Epilim Chrono formulations are prolonged release formulations which demonstrate in pharmacokinetic studies less fluctuation in plasma concentration compared with other established conventional and prolonged release Epilim formulations.

Updated on 16 August 2018 PIL

Reasons for updating

  • Change to section 6 - what the product contains
  • Change to section 6 - what the product looks like and pack contents

Updated on 16 August 2018 SmPC

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 2 August 2018 PIL

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 2 August 2018 SmPC

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 4.6 - Pregnancy and lactation

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

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directly impacts on SmPC sections 4.2, 4.3, 4.4 and 4.6, but there’s also minor QRD editorial updates to 4.5, 4.8, 4.9 and 5.2 that the HPRA to request  the harmonise

Updated on 29 November 2017 PIL

Reasons for updating

  • New PIL for new product

Updated on 29 November 2017 PIL

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 SmPC

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)

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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 15 August 2017 SmPC

Reasons for updating

  • New SmPC for new product

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

Updated on 21 July 2017 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • 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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Type IAIN – C.I.3.A Update the SmPCs (section 4.2) at the request of the HPRA to harmonise the location of the warning related to valproate use in female children, female adolescents, WOCBP and pregnant women to improve the clarity

Updated on 17 July 2017 SmPC

Reasons for updating

  • Improved presentation of SPC

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

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Upload of improved version

Updated on 5 June 2017 SmPC

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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Type IIC – CCDS v17, 18, 20

Updated on 4 November 2016 SmPC

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 3 November 2016 PIL

Reasons for updating

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

Updated on 12 May 2015 SmPC

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)

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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 1 May 2015 PIL

Reasons for updating

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

Updated on 22 December 2014 SmPC

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 6 November 2013 PIL

Reasons for updating

  • Change to side-effects

Updated on 1 November 2013 SmPC

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

Updated on 24 August 2012 SmPC

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 SmPC

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 PIL

Reasons for updating

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

Updated on 18 May 2011 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • 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

Addtion of information for use in manic episodes in bipolar disorder & update of undesirable effects following Article 31 approval.

Updated on 2 February 2011 PIL

Reasons for updating

  • Changes to therapeutic indications

Updated on 4 October 2010 SmPC

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 PIL

Reasons for updating

  • Change due to user-testing of patient information

Updated on 8 October 2009 SmPC

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 5 January 2009 PIL

Reasons for updating

  • Change to warnings or special precautions for use

Updated on 5 January 2009 SmPC

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

Update to section 4.4 of SPC.

Updated on 24 July 2008 PIL

Reasons for updating

  • Change to, or new use for medicine

Updated on 18 July 2008 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • 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 be renewed (B)

Free text change information supplied by the pharmaceutical company

Update section 7, 8 and 10

Updated on 18 July 2008 PIL

Reasons for updating

  • Change to marketing authorisation holder

Updated on 4 July 2008 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • 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

Update section 4.1 and 4.2, section 10.

Updated on 3 June 2008 SmPC

Reasons for updating

  • New SPC for medicines.ie

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

Updated on 8 August 2007 PIL

Reasons for updating

  • Improved electronic presentation

Updated on 18 December 2006 PIL

Reasons for updating

  • Improved electronic presentation

Updated on 4 January 2006 PIL

Reasons for updating

  • Improved electronic presentation

Updated on 13 October 2004 PIL

Reasons for updating

  • New PIL for medicines.ie