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Sodium valproate oral standard release

Updated 2 Feb 2023 | Valproate (in epilepsy)


Standard release oral formulations of sodium valproate.

Drugs List

  • EPILIM 100mg crushable tablets
  • EPILIM 200mg/5ml liquid
  • EPILIM 200mg/5ml syrup
  • EPILIM 200 gastro-resistant tablets
  • EPILIM 500 gastro-resistant tablets
  • sodium valproate 100mg tablets
  • sodium valproate 200mg gastro-resistant tablets
  • sodium valproate 200mg/5ml oral solution
  • sodium valproate 200mg/5ml oral solution sugar-free
  • sodium valproate 500mg gastro-resistant tablets
  • Therapeutic Indications


    Treatment of all forms of epilepsy

    Unlicensed Uses

    Migraine (prophylaxis)


    Daily dosage requirements vary according to age and weight.

    Optimum dosage is mainly determined by seizure control and routine measurement of plasma levels is unnecessary, although may be helpful where there is poor control or side effects are suspected.


    Initially 600mg daily, in divided doses, increasing by 200mg at three day intervals until control is achieved.
    The usual dose range is 1g to 2g per day, i.e. 20mg/kg to 30mg/kg body weight per day in divided doses.
    Where adequate control is not achieved within this range, the dose may be further increased to 2.5g per day.

    Migraine prophylaxis: (Unlicensed)
    Initial dose: 200mg twice daily.
    Dose may be increased to 1.2g to 1.5g daily in divided doses.


    In children requiring doses higher than 40mg/kg/day clinical chemistry and haematological parameters should be monitored.

    Children over 20kg:
    Initial dose: 400mg per day in divided doses (irrespective of weight). The dose is gradually increased until seizure control is achieved.
    Usual maintenance dose is in the range of 20mg/kg to 30mg/kg body weight per day in divided doses. Where adequate seizure control is not achieved, the dose can be increased to 35mg/kg body weight per day.

    Children under 20kg:
    20mg/kg of body weight per day, in divided doses; in severe cases this may be increased but only in patients in whom plasma valproic acid levels can be monitored.

    The following alternative dose schedule may be suitable:

    Children aged 12 to 18 years:
    Initial dose: 600mg daily in one to two divided doses, increased gradually in steps of 150mg to 300mg daily at 3 day intervals.
    Maintenance dose of 1g to 2g daily in two divided doses. Maximum dose 2.5g daily.

    Children aged 1 month to 12 years:
    Initial dose: 10mg/kg to 15mg/kg (maximum 600mg per dose) daily in 1 to 2 divided doses.
    Maintenance dose: 25mg/kg to 30mg/kg daily in 2 divided doses (up to 30mg/kg twice daily in infantile spasms). Monitor clinical chemistry and haematological parameters if dose exceeds 40mg/kg daily.


    The following alternative dose schedule may be suitable for treating epilepsy in neonates:

    Initially 20mg/kg once daily; maintenance dose 10mg/kg twice daily.

    Additional Dosage Information

    Combined therapy with other anticonvulsants:
    When starting sodium valproate in patients already on other anticonvulsants, these should be tapered slowly. Initiation of sodium valproate therapy should then be gradual, with target dose being reached after about 2 weeks. In certain cases it may be necessary to raise the dose by 5mg/kg to 10mg/kg per day when used in combination with anticonvulsants which induce liver enzyme activity, e.g. phenytoin, phenobarbital and carbamazepine. Once known liver enzyme inducers have been withdrawn it may be possible to maintain seizure control on a reduced dose of sodium valproate.

    Switching to different dosage forms:
    In patients where adequate control has been achieved, sodium valproate formulations are interchangeable with other sodium valproate conventional or prolonged release formulations of the same brand on an equivalent daily dosage basis.

    Nice has advised that generic switching of valproate preparations is not normally recommended due to the clinical implications of possible variations in plasma concentrations.

    Therapeutic Drug Monitoring

    Routine monitoring is no longer considered necessary unless the patient does not have satisfactory seizure control, adverse effects are a problem or a compliance check is required. The therapeutic range for plasma valproate levels is quoted as between 40mg/L to 100mg/L (278 to 694 micromols per litre). Clinical interpretation of plasma valproic levels may be altered in elderly patients due to age related changes in pharmacokinetics.


    Family history of severe hepatic impairment
    Patients not compliant with the Pregnancy Prevention Programme
    Urea cycle enzyme deficiency
    Hepatic disorder
    History of severe hepatic disorder
    Known or suspected mitochondrial disorder

    Precautions and Warnings

    Children under 3 years
    Females of childbearing potential
    Prepubertal females
    Carnitine deficiency
    Glucose-galactose malabsorption syndrome
    Hereditary fructose intolerance
    Renal impairment
    Systemic lupus erythematosus

    Children under 18 years: Increased risk of rare and severe adverse effects
    Confirm POLG mutation status if suspected in patient before initiating
    Mitochondrial disorder: May trigger or exacerbate condition/symptoms
    Advise patient drowsiness may affect ability to drive or operate machinery
    Consider prescribing by manufacturer to ensure seizure control maintenance
    Female: Specialist and patient to complete Annual Risk Acknowledgement Form
    Female:Ensure information including a Patient Guide is received& understood
    Staff & patients: Must comply with Pregnancy Prevention Programme
    Treatment to be initiated and supervised by a specialist
    Oral solution with maltitol unsuitable in hereditary fructose intolerance
    Presentations with sorbitol unsuitable in hereditary fructose intolerance
    Some formulations contain hydroxybenzoate
    Some formulations contain sucrose
    Exclude pregnancy prior to initiation of treatment
    Monitor haematological parameters before and during treatment
    Monitor hepatic function before treatment and during first 6 months
    Advise patients of risks/benefits & review need for treatment regularly
    May cause an increase in seizure frequency or onset of new seizure types
    Monitor for signs of suicide ideation or behaviour
    Monitor patient's weight
    Perform metabolic tests if urea cycle enzyme deficiency suspected
    Refer women considering pregnancy for specialist advice and monitoring
    Regular pregnancy tests required during therapy
    Advise patient of the risk of weight gain
    Advise patient to consult Doctor if spontaneous bruising occurs
    Advise patient to report any aggravated convulsions immediately
    Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
    Advise patients to report symptoms of acute pancreatitis immediately
    Discontinue treatment if abnormally low prothrombin time detected
    May give false positive in urine testing for ketones
    Changeover to or from other anti-epileptic drugs should be gradual
    Withdraw treatment gradually under supervision of a specialist
    Advise patient to seek advice at first indications of pregnancy
    Discontinue drug if bleeding abnormalities occur
    Discontinue if jaundice or other evidence of hepatic impairment occurs
    Discontinue if pancreatitis occurs
    Discontinue treatment if clinical symptoms of hyperammonaemia develop
    Consider dose reduction in renal impairment
    Not licensed for all indications in all age groups
    Advise patient to avoid alcohol during treatment
    Male & female: May cause infertility
    Female: Ensure adequate contraception during treatment
    Advise patient/carers to report signs of suicide ideation or behaviour

    Severe liver damage, including fatal hepatic impairment has been reported. Most cases occur during the first 6 months of treatment (the period of maximum risk being 2 to 12 weeks) and are usually associated with patients taking multiple anticonvulsants. Risks are increased in children under the age of 3 and in those with congenital metabolic or degenerative disorders, organic brain disease or severe seizure disorders associated with mental retardation. Consider monotherapy in children under the age of 3.

    Increased liver enzymes commonly occur and are usually transient. If detected, further biological investigations are required. Investigations which reflect protein synthesis (particularly prothrombin rate) are most relevant. Consider dose reduction and repeat investigations but in those with abnormally low prothrombin rate (particularly in association with a significant decrease in fibrinogen and coagulation factors or increases in bilirubin and transaminases) treatment should be withdrawn.

    Pancreatitis has been reported with an increased risk in young children, patients with severe seizures and patients with severe neurological impairment using combination anticonvulsant therapy. Patients experiencing nausea, vomiting or acute abdominal pain should have a prompt medical evaluation (including measurement of serum amylase).

    Sodium valproate is a known human teratogen. Use in female patients of child bearing potential is restricted to cases where alternatives are ineffective or not tolerated and requires compliance with the valproate pregnancy prevention programme. Specialists must inform patients of potential risks, reviewing treatment on an annual basis including completion of an Annual Risk Acknowledgement Form. All patients must use highly effective contraception, regardless of current sexual activity. Patients wanting to plan a pregnancy (or patients with an unplanned pregnancy) must be referred to their specialist for an urgent review. GPs are responsible for ensuring continued use of contraception, checking patients have an annual review and where the GP is responsible for prescribing sodium valproate, confirming a current Annual Risk Acknowledgement Form is in place. Further details can be found in the manufacturers pregnancy prevention programme documentation.

    As sodium valproate is generally used long term, use in prepubertal female children is also restricted to cases where alternatives are ineffective or not tolerated. Compliance with the valproate pregnancy prevention programme is not required however the patient and/or parent/caregiver/responsible person must be informed of risks should treatment continue once the child reaches puberty. Patients still prescribed sodium valproate following their first period require specialist review. If treatment is to continue, compliance with a pregnancy prevention programme is then required, regardless of whether the patient is sexually active.

    POLG-related disorders should be suspected in patients with a family history or suggestive symptoms of including unexplained encephalopathy, refractory epilepsy (focal, myoclonic), status epilepticus at presentation, developmental delays, psychomotor regression, axonal sensorimotor neuropathy, myopathy cerebellar ataxia, opthalmoplegia, or complicated migraine with occipital aura.

    Blood tests (full blood count, platelet count, bleeding time and coagulation tests) are recommended prior to treatment initiation, prior to surgery and following cases of spontaneous bruising or bleeding.

    Advise patients with underlying carnitine palmitoyltransferase type II deficiency that there is an increased risk of rhabdomyolysis when taking sodium valproate.

    Weight increase should be carefully monitored since it is a factor for polycystic ovary syndrome.

    Some adverse reactions are more severe or principally observed in the paediatric population. Young children are at particular risk of pancreatitis. Psychiatric disorders such as aggression, agitation, disturbance in attention, abnormal behaviour, psychomotor hyperactivity and learning disorder are predominantly observed in the paediatric population.

    Pregnancy and Lactation


    Sodium valproate is contraindicated during pregnancy.

    The manufacturer does not recommend sodium valproate as treatment for epilepsy during pregnancy unless there is no suitable alternative treatment.

    Valproate is a known human teratogen. Studies have shown congenital malformations in 10% of exposed neonates and neurodevelopment disorders in 30 to 40% of exposed children. Reported malformations include neural tube defects, facial dysmorphism, cleft lip and palate, craniostenosis, cardiac, renal and urogenital defects, limb defects (including bilateral aplasia of the radius) and multiple anomalies of various body systems. Following birth, cases of withdrawal syndrome, hypoglycaemia, hypothyroidism and haemorrhagic syndrome have also been reported. Use of high doses (above 1g daily) appear to carry an increased risk as does combination with other antiepileptic drugs. Evidence suggests that supplementation with folic acid has no effect on valproate-induced birth defects.

    Patients planning a pregnancy or those with an unplanned pregnancy require urgent referral to their specialist. In the interim, valproate must be continued (even if the patient is already pregnant) as abrupt cessation carries a risk of relapse and subsequent maternal and/or foetal harm. Specialists must switch all patients treated for migraine to a suitable alternative. Specialists should aim to switch all patients treated for epilepsy but where alternatives are ineffective or not tolerated, valproate may be continued with extreme caution. Further details can be found in the manufacturers pregnancy prevention programme documentation.


    Use sodium valproate with caution during breastfeeding.

    The manufacturer advises that the patient either discontinues sodium valproate or discontinues breastfeeding. Valproate is excreted in human milk with a concentration ranging from 1% to 10% of maternal serum levels. Haematological disorders have been reported in newborns and infants of treated women.

    LactMed (2020) indicates that valproic acid levels in breast milk are low and infant serum levels range from undetectable to low. Breastfeeding during valproic acid monotherapy does not appear to adversely affect infant growth or development. If valproic acid is needed to treat the mother, it is not necessarily a reason to discontinue breastfeeding. As such, sodium valproate may be used with caution when breastfeeding.

    In theory, breastfed infants are at risk for valproic acid-induced hepatotoxicity, so infants should be monitored for jaundice and other signs of liver damage during maternal therapy (LactMed, 2020).

    Side Effects

    Attention disturbances
    Behavioural disturbances
    Bone marrow failure
    Cognitive impairment
    Decrease in bone mineral density
    Dementia (reversible) associated with cerebral atrophy (reversible)
    Drug rash with eosinophilia and systemic symptoms (DRESS)
    Erythema multiforme
    Extrapyramidal effects
    Fanconi syndrome
    Gingival disorder
    Hair disorder
    Hair loss
    Hearing loss
    Hepatic failure
    Hepatic impairment
    Hypersensitivity reactions
    Impaired consciousness
    Impaired memory
    Inappropriate secretion of antidiuretic hormone
    Increased alertness
    Increased coagulation time
    Increased serum androgens
    Increased testosterone levels in females
    Increases in hepatic enzymes
    Interstitial nephritis
    Learning disorder
    Liver damage
    Macrocytic anaemia
    Male infertility
    Male pattern baldness
    Myelodysplastic syndrome
    Nail disorders
    Peripheral oedema
    Pleural effusion
    Polycystic ovaries
    Red cell aplasia
    Reduction of fibrinogen
    Renal failure
    Stevens-Johnson syndrome
    Suicidal tendencies
    Systemic lupus erythematosus
    Toxic epidermal necrolysis
    Urinary incontinence
    Virilism in females
    Weight gain


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: October 2020

    Reference Sources

    Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

    Summary of Product Characteristics: Epilim 100mg Crushable Tablets. Sanofi. Revised December 2020.
    Summary of Product Characteristics: Epilim 200 Gastro-resistant tablets. Sanofi. Revised December 2020.
    Summary of Product Characteristics: Epilim 500 Gastro-resistant tablets. Sanofi. Revised December 2020.
    Summary of Product Characteristics: Epilim Liquid. Sanofi. Revised December 2020.
    Summary of Product Characteristics: Epilim Syrup. Sanofi. Revised December 2020.

    Summary of Product Characteristics: Sodium Valproate 200mg Gastro-Resistant Tablets. Wockhardt UK Ltd. Revised September 2020.
    Summary of Product Characteristics: Sodium Valproate 500mg Gastro-Resistant Tablets. Wockhardt UK Ltd. Revised September 2020.
    Summary of Product Characteristics: Sodium Valproate 40mg/ml Oral Solution (sugar free) . Wockhardt UK Ltd. Revised September 2020.

    Educational Risk Minimisation Materials
    Available at:
    Valproate PREVENT programme. Last revised March 2019.
    Last accessed: 03 May 2019

    MHRA Drug Safety Update April 2018
    Available at:
    Last accessed: 25 April 2018

    MHRA Drug Safety Update November 2017
    Available at:
    Last accessed: 28 November 2018

    MHRA Drug Safety Update September 2018
    Available at:
    Last accessed: 25 September 2018

    NICE Evidence Services Available at: Last accessed: 07 October 2020

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at:
    Valproic Acid Last revised: 21 September 2020
    Last accessed: 07 October 2020

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