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sodium valproate (Epilim)


  • sodium valproate is an anticonvulsant which is also used to Rx bipolar disorder, and is sometimes used to reduce incidence of migraine attacks
  • it's actions are attributed to:
    • the blockade of voltage dependent Na+ channels
    • increased brain levels of gamma-aminobutyric acid (GABA)
  • it does not have any significant hypnotic effect and has less sedative effects than some older anticonvulsants
  • has been shown to be effective in the treatment of absence seizures (petit mal), tonic-clonic seizures (grand mal) and myoclonic seizures.
  • it has similar efficacy to lithium carbonate in the Rx of mania
  • serum levels are of limited utility but may be useful in assessing compliance


  • rapidly absorbed after oral dose in fasting patients with peak blood levels at 1-4hrs
  • absorption is delayed if taken with food with peak blood levels at 3-7hrs but abdorption is still almost complete
  • gastric irritation is less likely to occur with the enteric coated tablets
  • correlation between the daily dose per bodyweight and plasma levels of drug has been poor
  • correlation between plasma levels of drug and CNS actions has been poor
  • correlation between saliva levels and plasma levels of drug is poor
  • CSF levels are 5-15% of plasma levels
  • protein binding sites become saturated at plasma levels > 120 microgram/mL, or in patients with hypoalbuminaemia, causing free drug levels to rise dramatically with further dosage increase
  • 40-60% metabolised by glucuronidation, most of remainder metabolised by oxidation
  • 1-3% excreted unchanged in urine
  • plasma half-life is variable but appears to be 8-12 hours


  • pregnancy (category D) - if taken in 1st TM, 1-2% risk of neural tube defects, and may be associated with other fetal changes
  • PH HS to valproate
  • urea cycle disorders
  • hepatic porphyria


  • prenatal use in women who may become pregnant is not advised unless necessary or contraception is used
  • lactation
  • children - increased risk of pancreatitis, hepatitis; avoid concurrent salicylates or barbiturates
  • liver or renal dysfunction
  • ornithine transcarbamylase (OTC) deficiency
  • surgery - prolonged bleeding time and/or thrombocytopenia may occur
  • suicidality - may increase risk of suicidal thoughts or behaviour
  • avoid abrupt withdrawal as risk of seizure
  • weight gain may occur
  • diabetes mellitus or dental caries as Epilim syrup contains sucrose 3.6 g/5 mL
  • operating machinery or driving, particularly if high dose, rapid cessation, or other anticonvulsants or sedatives used

adverse effects

  • fetal malformations
  • dose-related cognitive deficits in children if taken during pregnancy
  • may increase risk of autism spectrum disorder when taken prenatally (adjusted hazard ratio 2.9)
  • fatigue
  • nausea
  • may cause some sedation, impaired memory, confusion, nystagmus
  • very uncommonly may cause other CNS effects such as ataxia
  • gastric irritation
  • sleeping disorders
  • flu-like illness
  • suicidality risk
  • alopecia
  • HS reactions
  • osteopenia / osteoporosis
  • prolonged bleeding time
  • deafness - reversible and irreversible
  • other more rare adverse effects

usual dose

  • dose is usually bd
  • adults:
    • start at 600mg/day and increase by 200mg/d every 3 days until control achieved or max. 2,500mg/day
    • most require 1,000 to 2,000 mg/day (i.e. 20 to 30 mg/kg/day)
    • it may be necessary to raise the dose by 5 to 10 mg/kg/day when used in combination with anticonvulsants which induce liver enzyme activity, e.g. phenytoin, phenobarbitone and carbamazepine.
  • iv dose for severe acute migraine:
    • requires further study but 900-1200mg iv valproate appeared to substantially reduce migraine headache pain within 60 minutes in ~75% of patients 1)
valproate.txt · Last modified: 2014/11/24 10:40 by

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