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Sodium valproate parenteral

Updated 2 Feb 2023 | Valproate (in epilepsy)


Parenteral formulations of sodium valproate.

Drugs List

  • EPILIM 400mg powder + solvent for solution for injection
  • EPISENTA 300mg/3ml injection
  • sodium valproate 300mg/3ml injection
  • sodium valproate 300mg/3ml solution for injection vial
  • sodium valproate 400mg powder + solvent for solution for injection
  • sodium valproate 400mg/4ml injection
  • sodium valproate 400mg/4ml solution for injection vial
  • Therapeutic Indications


    Epilepsy - short-term use as replacement therapy


    Daily dosage requirements vary according to age and body weight.

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


    Patients established on oral sodium valproate
    Continue on the same dose via continuous or intermittent intravenous infusion. Intravenous sodium valproate is only indicated where oral administration is temporarily not possible.

    Patients newly initiated on sodium valproate
    Initial dose of 10mg/kg (usually 400mg to 800mg) by slow IV injection followed by additional doses via either a continuous IV infusion or intermittent IV infusions up to a maximum of 2.5g daily.
    Some manufacturers advise a usual maintenance dose of 1g to 2g daily (as a continuous IV infusion or as three to four divided doses by intermittent IV infusion or slow IV injection).


    Daily requirement for children is usually in the range 20mg/kg to 30mg/kg daily, up to a maximum of 40mg/kg daily but only in patients in whom plasma valproic acid levels can be monitored.
    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: 10mg/kg by intravenous injection.
    Maintenance dose: Up to a maximum of 2.5g daily, by continuous intravenous infusion, or by intermittent intravenous infusion or intravenous injection, given in two to four divided doses. The usual range is 1g to 2g daily (20mg/kg to 30mg/kg daily).

    Children aged 1 month to 12 years
    Initial dose: 10mg/kg by intravenous injection.
    Maintenance dose: 20mg/kg to 40mg/kg by continuous intravenous infusion or divided into two to four doses as intermittent intravenous infusions or slow intravenous injections.


    The following alternative dosing schedule may be suitable:

    Initiation therapy
    10mg/kg twice daily by intravenous injection.

    Additional Dosage Information

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

    Combined therapy with other anticonvulsants:
    When starting sodium valproate in patients already on other anticonvulsants the manufacturer advises that these should be tapered slowly. Initiation of sodium valproate therapy should be then 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. When barbiturates are being administered concomitantly and particularly if sedation is observed (particularly in children) the dosage of barbiturate should be reduced.


    For slow intravenous injection, intermittent intravenous infusion or continuous intravenous infusion.

    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 valproate is quoted as between 40mg/L to 100mg/L (278 to 694 micromols per litre).

    The manufacturer advises close monitoring of plasma levels and if necessary dosage adjustments have to be performed during the change over to a parenteral therapy, during parenteral therapy and during the switch back to oral therapy, in particular in such patients receiving higher doses of valproate or in patients receiving drugs potentially influencing the metabolism of valproate. Clinical interpretation of plasma valproic acid levels may be altered in elderly patients and those with renal impairment.


    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
    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
    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
    Staff & patients: Must comply with Pregnancy Prevention Programme
    Treatment to be initiated and supervised by a specialist
    Do not give other medication through the same intravenous line
    Patient should be converted to oral therapy as soon as possible
    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
    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 patients with congenital metabolic or degenerative disorders associated with mental retardation, organic brain disease or severe seizure disorders. 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).

    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. Patients requiring continued treatment with oral formulations of valproate require 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.

    Valproate is contraindicated in patients known to have mitochondrial disorders caused by mutations in the nuclear gene encoding the mitochondrial enzyme POLG, e.g. Alpers-Huttenlocher Syndrome, and in children under two years of age who are suspected of having a POLG-related disorder. POLG-related disorders should be suspected in 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 at treatment initiation, prior to surgery and following cases of spontaneous bruising or bleeding.

    Advise patients with underlying carnitine palmitoyltransferase type II deficiency 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 states that valproate is contraindicated for the treatment of epilepsy unless suitable alternatives are either ineffective or not tolerated. Further details can be found in the manufacturers pregnancy prevention programme documentation.

    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 (Schaefer 2015). 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 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), 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.

    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 (LactMed, 2020).

    Side Effects

    Attention disturbances
    Behavioural disturbances
    Bone marrow failure
    Changes in hair colour
    Changes in hair texture
    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
    Gingival hyperplasia
    Hair disorder
    Hair growth abnormal
    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
    Increases in hepatic enzymes
    Interstitial nephritis
    Liver damage
    Macrocytic anaemia
    Male infertility
    Male pattern baldness
    Myelodysplastic syndrome
    Nail disorders
    Peripheral oedema
    Pleural effusion
    Polycystic ovaries
    Psychomotor hyperactivity
    Red cell aplasia
    Reduction of fibrinogen
    Renal failure
    Reversible confusional states
    Stevens-Johnson syndrome
    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: December 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 400mg Powder and Solvent for solution for injection/infusion. Sanofi. Revised December 2020.
    Summary of Product Characteristics: Episenta solution for injection (sodium valproate). Desitin Pharma Ltd. Revised December 2020.
    Summary of Product Characteristics: Sodium Valproate 100mg/ml Solution for Injection or Infusion. Seacross Pharmaceuticals. Revised April 2022.
    Summary of Product Characteristics: Sodium Valproate 100mg/ml Solution for Injection or Infusion. Wockhardt UK Ltd. Revised July 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: 11 January 2019

    MHRA Drug Safety Update November 2017
    Available at:
    Last accessed: 11 January 2019

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

    NICE Evidence Services Available at: Last accessed: 09 December 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: 09 December 2020

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