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Valproic acid oral

Updated 2 Feb 2023 | Valproate (in epilepsy)


Oral formulations of valproic acid.

Drugs List

  • CONVULEX 150mg capsules
  • CONVULEX 300mg capsules
  • CONVULEX 500mg capsules
  • valproic acid 150mg gastro-resistant capsules
  • valproic acid 300mg gastro-resistant capsules
  • valproic acid 500mg gastro-resistant capsules
  • Therapeutic Indications


    Treatment of all forms of epilepsy

    Treatment of generalised, partial or other epilepsy.


    Daily dosage requirements vary according to age and body weight.


    Initial dose: 600mg daily in two or four divided doses increasing by 300mg 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.
    Where adequate control is not achieved within this range, the dose may be further increased to 2.5g per day.


    Children over 20kg
    Initial dosage: Not more than 400mg daily (irrespective of weight) with spaced increases until control is achieved.
    The usual dose range is 20mg/kg to 30mg/kg per day.
    Where adequate control is not achieved within this range, the dose may be further increased to 35mg/kg per day.

    Children under 20kg
    20mg/kg daily.
    In severe cases this may be increased but only in patients in whom plasma valproic acid levels can be monitored. With doses above 40mg/kg daily, clinical chemistry and haematological parameters should be monitored.

    The following alternative dosing schedule may be suitable:

    Children aged 12 to 18 years
    Initial dose: 600mg daily, given in two to four divided doses. Increase in steps of 150mg to 300mg at three day intervals.
    Maintenance dose: 1g to 2g daily, given in two to four divided doses.
    Maximum dose: 2.5g daily, given in two to four divided doses.

    Children aged 1 month to 12 years
    Initial dose: 10mg/kg to 15mg/kg daily, given in two to four divided doses. Maximum dose: 600mg daily.
    Maintenance dose: 25mg/kg to 30mg/kg daily, given in two to four divided doses. Give up to 60mg/kg daily in two to four divided doses in infantile spasms.
    Monitor clinical chemistry and haematological parameters if dose exceeds 40mg/kg daily.

    Additional Dosage Information

    Switching from another anticonvulsant:
    When starting valproic acid in patients already on other anticonvulsants, these should be tapered slowly. Initiation of valproic acid 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 valproic acid. When barbiturates are being administered concomitantly and particularly if sedation is observed (particularly in children) the dosage of barbiturate should be reduced.


    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
    During surgery
    Females of childbearing potential
    Prepubertal females
    Haematological disorder
    Renal impairment
    Systemic lupus erythematosus

    Confirm POLG mutation status if suspected in patient before initiating
    May exacerbate or activate systemic lupus erythematosus
    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
    Increased risk of osteomalacia; consider vitamin D supplement
    Staff & patients: Must comply with Pregnancy Prevention Programme
    Treatment to be initiated and supervised by a specialist
    Exclude pregnancy prior to initiation of treatment
    Monitor haematological parameters before and during treatment
    Perform liver function tests before commencing therapy
    Advise patients of risks/benefits & review need for treatment regularly
    Monitor hepatic function regularly during first 6 months, then as indicated
    Monitor patient for signs and symptoms of depression
    Perform metabolic tests if urea cycle enzyme deficiency suspected
    Refer women considering pregnancy for specialist advice and monitoring
    Advise patient of the risk of weight gain
    Advise patient to report unexplained fever, sore throat, bruising, bleeding
    Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
    Advise patients to report symptoms of acute pancreatitis immediately
    Advise patients/carers to seek medical advice if suicidal intent develops
    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
    Male: May cause infertility
    Female: Ensure adequate contraception during treatment

    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 patients 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. At the first signs of hepatic injury, treatment should be discontinued.

    Monitor liver function prior to initiation and periodically during the first 6 months of treatment. 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.

    Valproic acid 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 valproic acid, confirming a current Annual Risk Acknowledgement Form is in place. Further details can be found in the manufacturers pregnancy prevention programme documentation.

    As valproic acid 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 valproic acid 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.

    Prior to initiation, undertake POLG mutation testing in patients where mitochondrial disorders are suspected. This includes patients with a family history or suggestive symptoms of a POLG-related disorder, 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.

    Pregnancy and Lactation


    Valproic acid is contraindicated during pregnancy.

    Valproic acid 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, valproic acid 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 should aim to switch all patients but where alternatives are ineffective or not tolerated, valproic acid may be continued with extreme caution. Further details can be found in the manufacturers pregnancy prevention programme documentation.


    Valproic acid should be used with caution during breastfeeding.

    Manufacturers advise either abstaining from breastfeeding or discontinuing valproic acid. LactMed, Schaefer (2015) and Briggs (2015) suggest breastfeeding does not need to be discontinued where treatment is required although prescribing restrictions are in place for all women of child bearing potential (see Precautions and Warnings).

    Valproate is excreted in human milk with a concentration ranging from 1% to 10% of maternal serum levels. Due to the low levels in infant serum, no definitive adverse reactions have been reported. Studies have shown no adverse effects on infant growth or development. Theoretically, breastfed infants are at risk of valproate-induced hepatotoxicity and so infants should be closely observed for jaundice or other signs of liver damage. A questionable case of thrombocytopenia has been reported and as such monitoring for spontaneous bruising or bleeding is also advised.


    Patients should be advised to consult their doctor immediately if they develop symptoms suggestive of pancreatitis (e.g. abdominal pain, nausea and vomiting).

    Patients should be warned of the risk of weight gain at the initiation of therapy, which may be marked and progressive, and the appropriate strategies should be adopted to minimise weight gain.

    Patients should be warned of the risk of transient drowsiness, which may affect the ability to drive or operate machinery, especially in cases of anticonvulsant polytherapy or association with benzodiazepines.

    Patients or their carers should be told how to recognise signs of blood or liver disorders and advised to seek immediate medical attention if symptoms develop.

    Patients and caregivers should be aware of the need to monitor for the emergence of suicidal thoughts and behaviour, and the need to seek medical advice immediately if they present.

    Advise female patients of child bearing potential of the terms of the valproate pregnancy prevention programme including potential risks should they become pregnant, the need for contraception and what action to take should they become pregnant or wish to plan a pregnancy.

    Advise prepubertal female patients (or their parent/carer/responsible person) of potential risks should valproate be continued once they reach puberty.

    Side Effects

    Allergic reaction
    Behavioural disturbances
    Decrease in bone mineral density
    Dementia (reversible) associated with cerebral atrophy (reversible)
    Erythema multiforme
    Exanthematous rash
    Extrapyramidal effects
    Fanconi's syndrome (reversible)
    Hair disorder
    Hair loss
    Hearing loss
    Hepatic failure
    Hepatic impairment
    Hypersensitivity reactions
    Impaired consciousness
    Increased alertness
    Increased coagulation time
    Increases in hepatic enzymes
    Irregular menstruation
    Liver damage
    Nail disorders
    Peripheral oedema
    Prolonged bleeding
    Reduction of fibrinogen
    Stevens-Johnson syndrome
    Suicidal tendencies
    Toxic epidermal necrolysis
    Weight gain

    Effects on Laboratory Tests

    Valproic acid is eliminated, via the kidneys, partly in the form of ketone bodies which may result in false positives in the urine testing of possible diabetics.


    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: May 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: Convulex capsules 150mg, 300mg & 500mg. G.L. Pharma UK Ltd. Revised January 2019.

    MHRA Drug Safety Update April 2018
    Available at:
    Last accessed: 11 January 2019

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at:
    Valproic acid Last revised: 16 March 2020
    Last accessed: 05 May 2020

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