Suvorexant

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Suvorexant
Suvorexant.svg
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
MedlinePlus a614046
Pregnancy
category
  • US: C (Risk not ruled out)
Legal status
Routes of
administration
By mouth
Pharmacokinetic data
Bioavailability 82% (at 10 mg)
Protein binding >99%
Metabolism hepatic, CYP3A, CYP2C19
Biological half-life ~12 hours
Excretion Feces (66%), urine (23%)
Identifiers
CAS Registry Number 1030377-33-3 YesY
ATC code None
PubChem CID: 24965990
IUPHAR/BPS 2890
ChemSpider 4589156 YesY
UNII 081L192FO9 YesY
ChEMBL CHEMBL1083659 YesY
Synonyms MK-4305
Chemical data
Formula C23H23ClN6O2
Molecular mass 450.92 g/mol
 N (what is this?)

Suvorexant (INN, USAN) (trade name Belsomra) is a selective, dual orexin receptor antagonist marketed by Merck & Co. for the treatment of insomnia.[1] It is effective for insomnia, at least for four weeks and as compared to a placebo.[2]

Suvorexant was approved for sale by the U.S. Food and Drug Administration (FDA) on August 13, 2014.[3] The U.S. Drug Enforcement Agency (DEA) has placed it on the list of schedule IV controlled substances.[4] The drug became available in Japan in November 2014 and in the United States in February 2015.[5]

Medical uses[edit]

Suvorexant is used for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.[6]

It is unclear how this medication compares to others used for insomnia as no comparisons have been done.[2] It is also unclear if this medication is safe among people with a history of addiction, as they were excluded from the clinical trials of suvorexant.[2]

Special populations[edit]

This drug is not recommended in people with liver impairment.[7] 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.[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]

There have been reports of people performing complex tasks (such as cooking and eating, making phone calls, driving, having sex) with little recollection of the events after taking suvorexant.[10]

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.[7][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 be adjusted.[7][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 (OX1) and orexin receptor type 2 (OX2) is thought to suppress wake drive.[6] Animal studies report the binding affinities for OX1 (0.55 nM) and OX2 (0.35 nM).[12]

Pharmacokinetics[edit]

The bioavailability of suvorexant is at 82%. It is highly protein-bound. Food delays the time to max concentration. 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]

Abuse liability[edit]

According to the U.S. Drug Enforcement Agency (DEA), suvorexant produces similar reinforcing effects to those of zolpidem in humans and thus may have a similar abuse liability.[13] As such, suvorexant has been designated a schedule IV controlled substances in the U.S. under the Controlled Substances Act.[13]

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. ^ a b c "Suvorexant: A Dual Orexin Receptor Antagonist for the Treatment of Sleep Onset and Sleep Maintenance Insomnia.". Ann Pharmacother 49: 477–483. Feb 9, 2015. doi:10.1177/1060028015570467. PMID 25667197. 
  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://en.apdnews.com/news/7ff7b8a890574d1cbb50675732d6873a.html.  Missing or empty |title= (help)
  6. ^ a b "Highlights of prescribing information" (PDF). 
  7. ^ 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.
  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. doi:10.1586/17512433.2014.966813. PMID 25318834. 
  10. ^ "Belsomra". drugs.com. Retrieved 20 February 2015. 
  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.
  12. ^ "Suvorexant Advisory Committee Meeting Briefing Document" (PDF). May 22, 2013. Retrieved Feb 7, 2015. 
  13. ^ a b "Schedules of controlled substances: placement of suvorexant into Schedule IV. Final rule" (PDF). Fed Regist 79 (167): 51243–7. 2014. PMID 25167596. 

External links[edit]