Sodium Valproate

Usage

  • A good ‘all rounder’. Used first line in genetic generalised epilepsies (e.g. CAE, JAE, JME) and in refractory epilepsies such as Dravet Syndrome.
  • Avoid use in suspected mitochondrial disorders.
  • In the very young (<2 years old), consider the risk of hepatotoxicity. The aetiology of the neurological problem is helpful in deciding whether to use or not.
  • There are significant concerns regarding teratogenicity and all women of child bearing age must be alerted to this.
  • See Interactions | Precautions tab on this page and the section: AED Prescribing - Pregnancy

Resources

Side effects

Possible side effects:

  • Appetite and weight gain (very common and can be intolerable).

Other notable side effects:

  • Thrombocytopenia (usually dose-related)
  • Sedation
  • Rash
  • Dystonia/tremor (at higher doses)
  • Pancreatitis
  • Hepatotoxicity is idiosyncratic and those at most risk are children under the age of 2, metabolic aetiology, and/or multiple drugs, avoid in mitochondrial disorders
  • There is some association with ovarian cysts.
  • Rarely a picture of pseudodementia is described.

For a complete list of adverse effects, appropriate formularies should be consulted.

Dosing

  • The below initiation and escalation doses are only a guide and need to be individualised based on patient (age, weight, co-morbidities), disease (seizure type, frequency, duration) and medication (metabolism, interactions, side-effect profile) characteristics.

 

  • Situations that require more careful consideration include children with higher weights, polytherapy, or multiple co-morbidities. Consultation with appropriate formularies or a paediatric neurologist may be required in specific circumstances.

Commonly used regime (without lamotrigine)

  • Start 5mg/kg/day increasing weekly by 5-10mg/kg/day in two divided doses (depending upon the weight of child).
  • Usual dose range is 10-30mg/kg/day.
  • Dosages per kilogram can only be used up to weights of 30-40kgs.
  • High doses of around 35mg/kg/day can be used with care and potential monitoring of platelets. At dosages above this, advice could be sought from a paediatric neurologist regarding efficacy and side-effect profile.
  • ***If the patient is on lamotrigine, see section: Lamotrigine and sodium valproate combination.

Preparations

  • Syrup formulation is 40mg/ml – rounding to multiples of 40mg doses is convenient.
  • Tablet 100mg - crushable
  • Tablet Enteric Coated 200mg and 500mg.

Monitoring

  • FBC and LFT - at baseline and 6-8 weeks after starting.
  • Valproate levels can be measured but are variable and may not correlate to clinical efficacy – levels are done for a reason and not routinely measured.

Interactions | Precautions

Valproate in Pregnancy

  • Sodium valproate has been associated with significant concerns of teratogenicity (i.e. malformations, cognitive impairment, and Autistic Spectrum Disorder). This is particularly true at higher dosages.
  • The risk of teratogenicity increases with increasing dosage.
  • It is important clinicians and women of child bearing age are aware of this risk.
  • Ideally, pregnancies in women with epilepsy should be planned and managed by a neurologist.
  • Medication choices should be selected and discussed keeping in mind the safety of mother and foetus.
  • The Epilepsy Society Australia (ESA) has developed guidelines and position statements on certain clinical issues. Click the link to access the ESA Valproate Position Statement - September 2020.
  • The NICE Guideline [NG217] on Epilepsies in children, young people and adults, was updated in April 2022 with advice regarding valproate use in women of childbearing age.  See section 5.1.4 here.
  • See also section: AED Prescribing - Pregnancy

 

Information last reviewed: 5/05/2023.