Suvorexant

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Suvorexant
Suvorexant.svg
Suvorexant ball-and-stick model.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 belsomra
MedlinePlus a614046
Pregnancy
category
  • US: C (Risk not ruled out)
Dependence
liability
Moderate
Routes of
administration
By mouth
Legal status
Legal status
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 Number 1030377-33-3 N
ATC code None
PubChem CID 24965990
IUPHAR/BPS 2890
ChemSpider 4589156 N
UNII 081L192FO9 N
ChEMBL CHEMBL1083659 N
Synonyms MK-4305
Chemical data
Formula C23H23ClN6O2
Molar mass 450.92 g/mol
 NYesY (what is this?)  (verify)

Suvorexant, sold under the trade name Belsomra, is a medication for the treatment of insomnia.[1] It is effective for insomnia, at least for four weeks and as compared to a placebo.[2]

Suvorexant is a selective, dual orexin receptor antagonist made by Merck & Co. It was approved for sale by the U.S. Food and Drug Administration (FDA) on August 13, 2014.[3] The U.S. Drug Enforcement Administration (DEA) has placed it on the list of schedule IV controlled substances,[4] as it may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule III. The potential for psychological dependence is similar to that of zolpidem.[5] The drug became available in Japan in November 2014[6] and in the United States in February 2015.[7]

Medical uses[edit]

Suvorexant is used for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.[8]

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]

Side effects[edit]

The most common complaint about the drug is from users who report that it did not help them to sleep.[9] Some people reported that the drug caused a sleep disturbance such as a nightmare, sleep terror, or abnormal dream.[9][10] Others reported that the drug caused them to be more awake.[9]

Issues include sleepiness the next day and issues with driving.[10] Other concerns include thoughts of suicide.[10]

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 with the use of hypnotics such as suvorexant.[11]

Reasons to avoid[edit]

This drug is not recommended in people with liver impairment.[12] Suvorexant pregnancy category is currently classified as Category C.[13] 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.[12]

Suvorexant is contraindicated in people diagnosed with narcolepsy.[13]

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.[12][14] If suvorexant is used with a medication that moderately inhibits the liver enzyme CYP3A, like verapamil, erythromycin, diltiazem, or dronedarone, it is recommended that the dose of suvorexant be adjusted.[12][14]

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.[8] Animal studies report the binding affinities for OX1 (0.55 nM) and OX2 (0.35 nM).[15]

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.[13]

Abuse liability[edit]

According to the U.S. Drug Enforcement Administration (DEA), suvorexant produces similar reinforcing effects to those of zolpidem in humans and thus may have a similar abuse liability.[16] As such, suvorexant has been designated a schedule IV controlled substance in the U.S. under the Controlled Substances Act.[16]

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. 
  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. ^ "Schedules of Controlled Substances: Placement of Suvorexant into Schedule IV". federalregister.gov. Federal Register. February 13, 2014. Retrieved August 10, 2016. A Proposed Rule by the Drug Enforcement Administration on 02/13/2014 
  5. ^ "Rules - 2014 - Final Rule: Placement of Suvorexant into Schedule IV". www.deadiversion.usdoj.gov. Retrieved 2016-04-03. 
  6. ^ "New hypnotic drug without addiction to be released in Japan first". 
  7. ^ "Merck's Insomnia Medicine Belsomra C-IV Now Available in US". www.sleepreviewmag.com. Sleep Review. Retrieved 9 September 2015. 
  8. ^ a b "Highlights of prescribing information" (PDF). 
  9. ^ a b c Carr, Teresa (5 February 2016). "FDA Fields Complaints on Sleeping Pill Suvorexant". Consumer Reports. 
  10. ^ a b c 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. 
  11. ^ "Belsomra". drugs.com. Retrieved 20 February 2015. 
  12. ^ 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.
  13. ^ a b c Product Information: BELSOMRA(R) oral tablets, suvorexant oral tablets. Merck Sharp & Dohme Corp. (per manufacturer), Whitehouse Station, NJ, 2014.
  14. ^ 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.
  15. ^ "Suvorexant Advisory Committee Meeting Briefing Document" (PDF). May 22, 2013. Retrieved Feb 7, 2015. 
  16. ^ 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]