Sodium Valproate

Main article: Valproic acid

Template:Drugbox Sodium valproate (INN) or valproate sodium (USAN) is the sodium salt of valproic acid and is an anticonvulsant used in the treatment of epilepsy, anorexia nervosa, panic attack, anxiety disorder, posttraumatic stress disorder, migraine and bipolar disorder, as well as other psychiatric conditions requiring the administration of a mood stabilizer. Sodium valproate can be used to control acute episodes of mania and acute stress reaction. Side effects can include tiredness, tremors, nausea, vomiting and sedation.[1] The intravenous formulations are used when oral administration is not possible.

In pregnancy, valproate has the highest risk of birth defects of any of the commonly used antiepilepsy drugs. However, some epilepsy can only be controlled by valproate, and seizures also pose grave risk to mother and child.

Some of the common adverse effects include tiredness, tremor, sedation and gastrointestinal disturbances. In addition, about 10% of the users experience reversible hair loss. [2]

Safety in pregnancy

The risk of birth defects with valproate is two to five times higher than other frequently used antiepileptic drugs (absolute rates of birth defects 6-11%). Children born to mothers using valproate have significantly lower IQ scores (9 points). However, some epilepsy can only be controlled by valproate, and seizures during pregnancy can have grave consequences for both mother and child. Doctors recommend women who intend to become pregnant should be switched to a different drug using combined therapy if possible, which takes several months. Women who are already pregnant and taking high doses of valproate should try to lower their doses.[3][4][5]

All antiepileptic medications have been shown to be associated with higher risks of fetal abnormalities (mostly for spina bifida) since at least 1983, with the risks being related to the strength of medication used and use of more than one drug.[6][7]

Valproate has also been recognised as sometimes causing a specific facial change ("facial phenotype") termed "fetal valproate syndrome".[8] Sodium valproate has been associated with the rare condition paroxysmal tonic upgaze of childhood, also known as Ouvrier-Billson syndrome, from childhood or fetal exposure (this condition resolved after discontinuing valproate therapy.[9][10]

While developmental delay is usually associated with altered physical characteristics (dysmorphic features), this is not always the case.[11]

A 2005 study found rates of autism among children exposed to sodium valproate before birth in the cohort studied were 8.9%.[12] The normal incidence for autism in the general population is estimated at less than one percent.[13] Valproate may best be avoided in women with localisation epilepsy, where more effective and less risky alternatives, such as carbamazepine, are available.[11] A 2008 study [14] also suggested a correlation between higher rates of autism in children whose mothers were treated for seizure disorders during pregnancy using sodium valproate (less than 1% for children who did not receive the drug in utero vs. 6.3% for children who did). However, only 632 children were followed in this study, prompting criticism that this study was too small to determine whether a definitive correlation existed between the use of sodium valproate in pregnant mothers and higher autism rates in their children, or whether other antiseizure medications used during pregnancy may cause this effect.

One multicentre trial in the UK and US compared cognitive function in 309 children born to mothers with epilepsy; it found sodium valproate use was associated with an IQ level eight points lower in children born to mothers taking sodium valproate than mothers taking other antiepileptic drugs.[15] The authors of the study attempted to correct for confounding factors, but this was an observational study, so could not prove a causal link. Proving a causal link requires a randomised-controlled trial, which is not ethical to perform.[16] Stronger evidence likely will not become available.

A class action lawsuit is currently underway in the United Kingdom regarding the claim that the drug used in pregnancy caused a range of problems in children, including autism, learning and social difficulties, ADHD, spinal stenosis,[specify] facial abnormalities, vision defects, dyslexia, developmental coordination disorder, and delayed speech and motor development.[17][18][19]

Mechanism of action

Sodium valproate is a weak blocker of sodium ion channels; it is also a weak inhibitor of enzymes that deactivate GABA such as GABA transaminase. It may also stimulate the synthesis of GABA, but the direct mechanism is not known. Because of its many mechanisms of action, sodium valproate has efficacy in all partial and generalised seizures including absence seizures.

Formulations

Trade names are in bold, followed by the manufacturer.

United States

Australia

  • Epilim Crushable Tablets Sanofi
  • Epilim Sugar Free Liquid Sanofi
  • Epilim Syrup Sanofi
  • Epilim Tablets Sanofi
  • Sodium Valproate Sandoz Tablets Sanofi
  • Valpro Tablets Alphapharm
  • Valproate Winthrop Tablets Sanofi
  • Valprease tablets Sigma

UK

  • Depakote Tablets (as in USA)
  • Tablets – Orlept by Wockhardt and Epilim by Sanofi
  • Oral solution – Orlept Sugar Free by Wockhardt and Epilim by Sanofi
  • Syrup – Epilim by Sanofi-Aventis
  • Intravenous injection – Epilim Intravenous by Sanofi
  • Extended release tablets – Epilim Chrono by Sanofi is a combination of sodium valproate and valproic acid in a 2.3:1 ratio.
  • Enteric-coated tablets – Epilim EC200 by Sanofi is a 200-mg sodium valproate enteric-coated tablet.

UK only

  • Capsules – Episenta prolonged release by Beacon
  • Sachets – Episenta prolonged release by Beacon
  • Intravenous solution for injection – Episenta solution for injection by Beacon

Germany, Switzerland, Norway, Finland, Sweden

  • Tablets – Orfiril by Desitin Pharmaceuticals
  • Intravenous injection – Orfiril IV by Desitin Pharmaceuticals

South Africa

  • Syrup – Convulex by Byk Madaus
  • Tablets – Epilim by Sanofi-synthelabo

Canada

  • Intravenous injection – Epival or Epiject by Abbott Laboratories.
  • Syrup – Depakene by ratio-Valproic.

Japan

  • Tablets – Depakene by Kyowa Hakko Kirin
  • Extended release tablets – Depakene-R by Kyowa Hakko Kogyo and Selenica-R by Kowa
  • Syrup – Depakene by Kyowa Hakko Kogyo

Europe

In much of Europe, Depakine and Depakine Chrono (tablets) are equivalent to Epilim and Epilim Chrono above.

Taiwan

  • Tablets (white round tablet) – Depakine (Chinese: 帝拔癲; pinyin: di-ba-dian) by Sanofi Winthrop Industrie (France)


See also

References

External links

  • Chemical Land21: Sodium Valproate
  • RXList.com: Depacon (Sodium Valproate)
  • British National Formulary Edition 58
  • Med Broadcast.com: Epival
  • Drugs.com: Depaken Syrup
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