Stiripentol

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Stiripentol
Clinical data
Pronunciationstir"i pen' tol
Trade namesDiacomit
AHFS/Drugs.comMonograph
MedlinePlusa618069
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Identifiers
  • (RS)-(E)-4,4-dimethyl-1-[3,4(methylenedioxy)-phenyl]-1-penten-3-ol
JSmol)
  • O1c2ccc(cc2OC1)/C=C/C(O)C(C)(C)C
  • InChI=1S/C14H18O3/c1-14(2,3)13(15)7-5-10-4-6-11-12(8-10)17-9-16-11/h4-8,13,15H,9H2,1-3H3/b7-5+ checkY
  • Key:IBLNKMRFIPWSOY-FNORWQNLSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Stiripentol, sold under the brand name Diacomit, is an anticonvulsant medication used for the treatment of Dravet syndrome - a serious genetic brain disorder.[5][6]

The most common side effects include loss of appetite, weight loss, insomnia (difficulty sleeping), drowsiness, ataxia (inability to co‑ordinate muscle movements), hypotonia (low muscle strength) and dystonia (muscle disorders).[5]

Medical uses

In the European Union, stiripentol is indicated for use in conjunction with clobazam and valproate as adjunctive therapy of refractory generalized tonic-clonic seizures in people with severe myoclonic epilepsy in infancy (SMEI, Dravet's syndrome) whose seizures are not adequately controlled with clobazam and valproate.[5]

In the United States, stiripentol is indicated for the treatment of seizures associated with Dravet syndrome in people two years of age and older taking clobazam.[4] There are no clinical data to support the use of stiripentol as monotherapy in Dravet syndrome.[4]

It is used in some countries as an add-on therapy with

sodium valproate and clobazam for treating children with Dravet syndrome whose seizures are not adequately controlled.[7][8][9][10] As of 2017, it was not known whether stiripentol remains useful as children become adolescents or adults.[11]

Contraindications

Stiripentol must not be used in people who have had psychosis (a serious mental state with a distorted sense of reality) with attacks of delirium (a mental state with confusion, excitement, restlessness and hallucinations).[5]

Adverse effects

Very common (more than 10% of people) adverse effects include loss of appetite, weight loss, insomnia, drowsiness, ataxia, hypotonia, and dystonia.[9]

Common (between 1% and 10% of people) adverse effects include neutropenia (sometimes severe), aggressiveness, irritability, behavior disorders, opposing behavior, hyperexcitability, sleep disorders, hyperkinesias, nausea, vomiting, and elevated gamma-glutamyltransferase.[9]

Interactions

Stiripentol inhibits several cytochrome P450 isoenzymes and so interacts with many anticonvulsants and other medicines.[9]

Pharmacology

As with most anticonvulsants, the precise mechanism of action is unknown. Regardless, stiripentol has been shown to have anticonvulsant effects of its own.

Stiripentol increases

ATP-sensitive potassium channels.[14]

Stiripentol also improves the effectiveness of many other anticonvulsants, possibly due to its inhibition of certain enzymes, slowing the drugs' metabolism and increasing blood plasma levels.[9]

Chemistry

Stiripentol is an α-ethylene alcohol; its chemical formula is 4,4-dimethyl-1-[3,4-(methylendioxy)-phenyl]-1penten-3-ol. It is chiral and used medically as the racemate. The R enantiomer appears to be around 2.5 times more active than the S enantiomer.[15]

History

Stiripentol was discovered in 1978 by scientists at Biocodex and clinical trials started over the next few years.[15] It was originally developed for adults with focal seizures, but failed a Phase III trial.[11]

In December 2001, the

severe myoclonic epilepsy of infancy (SMEI, also known as Dravet's syndrome) in children and in January 2007, the EMA granted the drug a marketing authorisation for use of the drug as an add-on to other anti-seizure drugs.[5][9] It was approved in Canada for this use in May 2013.[16][17] As of 2017, it was also approved for this use in Japan.[8]

In August 2018, stiripentol was approved by the US Food and Drug Administration (FDA) as an adjunctive therapy for Dravet Syndrome.[18]

Society and culture

Economics

Prior to approval in the US, parents of children with Dravet Syndrome were paying around $1,000 for a month supply to obtain it from Europe.[19]

References

  1. ^ a b "Diacomit". Therapeutic Goods Administration (TGA). 13 December 2019. Retrieved 17 September 2021.
  2. ^ a b "AusPAR: Stiripentol". Therapeutic Goods Administration (TGA). 19 December 2019. Retrieved 17 September 2021.
  3. ^ "Diacomit 250mg hard capsules - Summary of Product Characteristics (SmPC)". (emc). 31 May 2019. Retrieved 8 November 2020.
  4. ^ a b c "Diacomit- stiripentol capsule Diacomit- stiripentol powder, for suspension". DailyMed. 15 May 2020. Retrieved 8 November 2020.
  5. ^ a b c d e f "Diacomit EPAR". European Medicines Agency. 17 September 2018. Retrieved 8 November 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  6. ^ "Stiripentol Monograph for Professionals". Drugs.com. 31 August 2020. Retrieved 8 November 2020.
  7. PMID 28521067
    .
  8. ^
    S2CID 25051912
    .
  9. ^ a b c d e f Diacomit (stiripentol) SPC (PDF) (Report).
  10. PMID 36066395
    .
  11. ^
    S2CID 205759047
    .
  12. S2CID 14199574.[dead link
    ]
  13. PMID 15886413
    .
  14. S2CID 22024222
    .
  15. ^ a b "Scientific evaluation" (PDF). EMA. 2007.
  16. ^ Stiripentol (Diacomit): For Severe Myoclonic Epilepsy in Infancy (Dravet Syndrome) (PDF) (Report). Canadian Agency for Drugs and Technologies in Health. April 2015.
  17. ^ "Diacomit Product information". Health Canada. Retrieved 8 November 2020.
  18. ^ "Drug Approval Package: Diacomit (stiripentol)". U.S. Food and Drug Administration (FDA). 7 September 2018. Retrieved 8 November 2020.
  19. PMID 24526870
    .

External links

  • "Stiripentol". Drug Information Portal. U.S. National Library of Medicine.
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