Suvorexant

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Suvorexant
MK4305 structure.png
Systematic (IUPAC) name
[(7R)-4-(5-chloro-1,3-benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone
Clinical data
Trade names Belsomra
AHFS/Drugs.com entry
Pregnancy cat.
Legal status
Routes oral
Identifiers
CAS number 1030377-33-3 N
ATC code None
PubChem CID 24965990
ChemSpider 24662178 N
ChEBI CHEBI:82698 N
Chemical data
Formula C23H23ClN6O2 
Mol. mass 450.920 g/mol (free base)
 N (what is this?)  (verify)

Suvorexant (trade name Belsomra) is a selective dual orexin receptor antagonist marketed by Merck & Co. for the treatment of insomnia.[1] Evidence looks promising.[2]

It was approved for sale by the U.S. Food & Drug Administration on August 13, 2014.[3] In the United States, the DEA has placed suvorexant on the list of schedule IV controlled substances, with an effective date of September 29, 2014.[4] According to the official website, the drug will be available in the U.S. in early 2015.[5] Suvorexant is set to hit the market in Japan somewhere in November 2014.[6]

Medical uses[edit]

Suvorexant is used for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.[7]

Contraindications[edit]

Suvorexant is contraindicated in people diagnosed with narcolepsy.[8]

Side effects[edit]

Issues include sleepiness the next day and issues with driving.[9] Other concerns include unusual dreams and thoughts of suicide.[9]

Interactions[edit]

Suvorexant is not recommended if people are also taking medications that strongly inhibit the liver enzyme CYP3A like itraconazole, lopinavir/ritonavir, clarithromycin, ritonavir, ketoconazole, indinavir/ritonavir, or conivaptan.[10][11] If this medication is used with medication that moderately inhibit the liver enzyme CYP3A, like verapamil, erythromycin, diltiazem, or dronedarone, it is recommended that the dose of suvorexant is adjusted.[10][11]

Mechanism of action[edit]

Suvorexant exerts its therapeutic effect in insomnia through antagonism of orexin receptors. The orexin neuropeptide signaling system is a central promoter of wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors orexin receptor type 1 and orexin receptor type 2 is thought to suppress wake drive.[7]

Pharmacokinetics[edit]

The bioavailability of suvorexant is at 82%. It is highly protein bound. Suvorexant is extensively metabolized by the liver. Suvorexant is renally excreted (23% unchanged) and through feces (66% unchanged). The elimination half life is reported to be 12 hours.[8]

Special populations[edit]

This drug is not recommended in people with liver impairment.[10] Suvorexant pregnancy category is currently classified as Category C.[8] Based on animal testing, this medication may cause fetal harm during pregnancy and should only be given in pregnancy if the potential benefit justifies the potential harm to the fetus. Evidence is inconclusive about whether using this medication while breastfeeding puts the infant at risk of harm.[10]

See also[edit]

References[edit]

  1. ^ Baxter, C. A.; Cleator, E.; Brands, K. M. J.; Edwards, J. S.; Reamer, R. A.; Sheen, F. J.; Stewart, G. W.; Strotman, N. A.; Wallace, D. J. (2011). "The First Large-Scale Synthesis of MK-4305: A Dual Orexin Receptor Antagonist for the Treatment of Sleep Disorder". Organic Process Research & Development 15 (2): 367–375. doi:10.1021/op1002853.  edit
  2. ^ Mieda, M; Sakurai, T (Feb 2013). "Orexin (hypocretin) receptor agonists and antagonists for treatment of sleep disorders. Rationale for development and current status.". CNS drugs 27 (2): 83–90. PMID 23359095. 
  3. ^ http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm409950.htm
  4. ^ https://www.federalregister.gov/articles/2014/02/13/2014-03124/schedules-of-controlled-substances-placement-of-suvorexant-into-schedule-iv
  5. ^ http://www.belsomra.com/. 
  6. ^ http://en.apdnews.com/news/7ff7b8a890574d1cbb50675732d6873a.html.  Missing or empty |title= (help)
  7. ^ a b "Highlights of prescribing information". 
  8. ^ a b c Product Information: BELSOMRA(R) oral tablets, suvorexant oral tablets. Merck Sharp & Dohme Corp. (per manufacturer), Whitehouse Station, NJ, 2014.
  9. ^ a b Jacobson, LH; Callander, GE; Hoyer, D (Nov 2014). "Suvorexant for the treatment of insomnia.". Expert review of clinical pharmacology 7 (6): 711–30. PMID 25318834. 
  10. ^ a b c d Label: BELSOMRA- Suvorexant Tablet, Film Coated"Label: BELSOMRA- Suvorexant Tablet, Film Coated." DailyMed. Merck Sharp & Dohme Corp. & the U.S. National Library of Medicine, 01 Aug. 2014. Web. 29 Oct. 2014.
  11. ^ a b "U.S. Food and Drug Administration." Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. U.S. Food and Drug Administration, 27 Oct. 2014. Web. 30 Oct. 2014.