Sodium valproate
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Sodium valproate
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| Systematic (IUPAC) name | |
| sodium 2-propylpentanoate | |
| Identifiers | |
| CAS number | |
| ATC code | N03 |
| PubChem | |
| Chemical data | |
| Formula | C8H15NaO2 |
| Mol. mass | 166.20 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Protein binding | 90–95% |
| Metabolism | 75% by CYP enzymes |
| Half life | 9–18 hours |
| Excretion | 20% excreted as glucuronide |
| Therapeutic considerations | |
| Pregnancy cat. | |
| Legal status | |
| Routes | Oral, i.v. |
Sodium valproate (INN) or valproate sodium (USAN) is the sodium salt of valproic acid and is an anticonvulsant used in the treatment of epilepsy and bipolar disorder, as well as other psychiatric conditions requiring the administration of a mood stabilizer. The intravenous formulations are used when oral administration is not possible.
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[edit] Formulations
Trade names are in bold, followed by the manufacturer.
[edit] U.S.
- Intravenous injection – Depacon by Abbott Laboratories.
- Syrup – Depakene by Abbott Laboratories. (Note Depakene capsules are valproic acid).
[edit] UK and Australia
- Tablets – Orlept by Wockhardt and Epilim by Sanofi-Aventis.
- Oral solution – Orlept Sugar Free by Wockhardt and Epilim by Sanofi-Aventis.
- Syrup – Epilim by Sanofi-Aventis.
- Intravenous injection – Epilim Intravenous by Sanofi-Aventis.
- Extended release tablets – Epilim Chrono by Sanofi-Aventis. A combination of sodium valproate and valproic acid in a 2.3:1 ratio.
- Enteric-coated tablets – Epilim EC200 by Sanofi-synthélabo. A 200 mg sodium valproate enteric-coated tablet.
[edit] Germany, Switzerland, Norway
- Tablets – Orfiril by Desitin Pharmaceuticals
- Intravenous injection – Orfiril IV by Desitin Pharmaceuticals
[edit] South Africa
- Syrup – Convulex by Byk Madaus
- Tablets – Epilim by sanofi~synthelabo
[edit] Canada
- Intravenous injection – Epival or Epiject by Abbott Laboratories.
- Syrup – Depakene by Abbott Laboratories. Generic formulations include Apo-Valproic and ratio-Valproic.
[edit] Japan
- Tablets – Depakene by Kyowa Hakko Kogyo.
- Extended release tablets – Depakene-R by Kyowa Hakko Kogyo and Selenica-R by Kowa.
- Syrup – Depakene by Kyowa Hakko Kogyo.
[edit] Others
In much of Europe, Depakine and Depakine Chrono are equivalent to Epilim and Epilim Chrono above.
[edit] Safety in pregnancy
All antiepilepic 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.[1][2] Valproate has also been recognised as sometimes causing a specific facial changes ("facial phenotype") termed "fetal valproate syndrome".[3] Sodium valproate has been associated with the rare condition Paroxysmal tonic upgaze of childhood from childhood exposure(Epileptic Disord. 2007 Sep;9(3):332-6) and also fetal exposure (This condition resolved after discontinuing valproate therapy. Ouvrier-Billson syndrome (J Child Neurol. 1988 Jul;3(3):177-80) is the name used for this condition, to honor the discoverer.
Whilst developmental delay is usually associated with altered physical characterists (dysmorphic features), this may occur on its own.[4]
A 2005 study found rates of autism among children exposed to sodium valproate before birth in the cohort studied were 8.9%.[5] The normal incidence for autism in the general population is estimated at less than one percent.[6] It has been suggested that Valproate may best be avoided in women with localisation epilepsy, where there are more effective and less risky alternatives such as carbamazepine.[4]
A class action 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, facial abnormalities, vision defects, dyslexia, dyspraxia, delayed speech and motor development.[7][unreliable source?]
[edit] See also
[edit] References
- ^ Koch S, Göpfert-Geyer I, Jäger-Roman E, et al (February 1983). "[Anti-epileptic agents during pregnancy. A prospective study on the course of pregnancy, malformations and child development]" (in German). Dtsch. Med. Wochenschr. 108 (7): 250–7. PMID 6402356.
- ^ Moore SJ, Turnpenny P, Quinn A, et al (July 2000). "A clinical study of 57 children with fetal anticonvulsant syndromes". J. Med. Genet. 37 (7): 489–97. PMID 10882750.
- ^ DiLiberti JH, Farndon PA, Dennis NR, Curry CJ (November 1984). "The fetal valproate syndrome". Am. J. Med. Genet. 19 (3): 473–81. doi:. PMID 6439041.
- ^ a b Adab N, Kini U, Vinten J, et al (November 2004). "The longer term outcome of children born to mothers with epilepsy". J. Neurol. Neurosurg. Psychiatr. 75 (11): 1575–83. doi:. PMID 15491979. “This argues that the fetal valproate syndrome constitutes a real clinical entity that includes developmental delay and cognitive impairments, but that some children might exhibit some developmental delay without marked dysmorphism.”
- ^ Rasalam AD, Hailey H, Williams JH, et al (August 2005). "Characteristics of fetal anticonvulsant syndrome associated autistic disorder". Dev Med Child Neurol 47 (8): 551–5. PMID 16108456.
- ^ http://www.autism-society.org/site/PageServer?pagename=about_home
- ^ http://www.irwinmitchell.com/PressOffice/PressReleases/epilepsy-drug-claims.htm
[edit] External links
- Chemical Land21: Sodium Valproate
- RXList.com: Depacon (Sodium Valproate)
- British National Formulary Edition 50
- Med Broadcast.com: Epival
- Drugs.com: Depaken Syrup
