Suvorexant

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Suvorexant
Suvorexant.svg
Suvorexant-from-xtal-Mercury-3D-bs.png
Clinical data
Trade namesBelsomra
Other namesMK-4305
AHFS/Drugs.comMonograph
MedlinePlusa614046
License data
Routes of
administration		By mouth
Drug classOrexin antagonist
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: IV
Pharmacokinetic data
Bioavailability82% (at 10 mg)
Protein binding>99%
MetabolismHepatic (CYP3A, CYP2C19)
Elimination half-life12 hours[1]
ExcretionFeces (66%), urine (23%)
Identifiers
  • [(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
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.210.546 Edit this at Wikidata
Chemical and physical data
FormulaC23H23ClN6O2
Molar mass450.93 g·mol−1
3D model (JSmol)
  • Cc1ccc(-n2nccn2)c(C(=O)N2CCN(c3nc4cc(Cl)ccc4o3)CC[C@H]2C)c1
  • InChI=1S/C23H23ClN6O2/c1-15-3-5-20(30-25-8-9-26-30)18(13-15)22(31)29-12-11-28(10-7-16(29)2)23-27-19-14-17(24)4-6-21(19)32-23/h3-6,8-9,13-14,16H,7,10-12H2,1-2H3/t16-/m1/s1 ☒N
  • Key:JYTNQNCOQXFQPK-MRXNPFEDSA-N ☒N
 ☒NcheckY (what is this?)  

Suvorexant, sold under the trade name Belsomra, is a medication for the treatment of insomnia.[3] It is effective for insomnia, at least for four weeks and as compared to a placebo.[4]

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

The drug was initially released November 2014 in Japan,[8] then later reached the United States in February 2015,[9] Australia in November 2016, and Canada in November 2018[10]

Medical uses[]

Suvorexant is used for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.[1]

It is unclear how the medication compares to others used for insomnia as no comparisons have been done.[4] 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.[4]

Contraindications[]

Suvorexant is not recommended in people with liver impairment.[1] Suvorexant pregnancy category is classified as Category C.[1] 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.[1]

Suvorexant is contraindicated in people diagnosed with narcolepsy.[1]

Side effects[]

The most common complaint about the drug is from users who report that it did not help them to sleep.[11] Some people reported that the drug caused a sleep disturbance such as a nightmare, sleep terror, or abnormal dream.[11][12] Others reported that the drug caused them to be more awake.[11]

Issues include sleepiness the next day and issues with driving.[12] Other concerns include thoughts of suicide.[12]

Abuse liability[]

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

Interactions[]

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.[1][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.[1][14]

Pharmacology[]

Pharmacodynamics[]

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

Pharmacokinetics[]

The bioavailability of suvorexant is at 82%. It is highly protein-bound. Food delays the time to max concentration. The primary route of elimination is through the feces, with approximately 66% of radiolabeled dose recovered in the feces compared to 23% in the urine. The elimination half-life is reported to be 12 hours.[1]

References[]

  1. ^ a b c d e f g h i j "Belsomra- suvorexant tablet, film coated". DailyMed. 20 November 2019. Retrieved 30 January 2020.
  2. ^ "Suvorexant (Belsomra) Use During Pregnancy". Drugs.com. 9 September 2019. Retrieved 30 January 2020.
  3. ^ Baxter CA, Cleator E, Brands KM, Edwards JS, Reamer RA, Sheen FJ, et al. (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.
  4. ^ a b c Patel KV, Aspesi AV, Evoy KE (April 2015). "Suvorexant: a dual orexin receptor antagonist for the treatment of sleep onset and sleep maintenance insomnia". The Annals of Pharmacotherapy. 49 (4): 477–83. doi:10.1177/1060028015570467. PMID 25667197.
  5. ^ "FDA approves new type of sleep drug, Belsomra". U.S. Food and Drug Administration (FDA) (Press release). 13 August 2014. Archived from the original on 14 February 2017. Retrieved 30 January 2020.
  6. ^ "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
  7. ^ "Rules - 2014 - Final Rule: Placement of Suvorexant into Schedule IV". www.deadiversion.usdoj.gov. Retrieved 2016-04-03.
  8. ^ "New hypnotic drug without addiction to be released in Japan first".
  9. ^ "Merck's Insomnia Medicine Belsomra C-IV Now Available in US". www.sleepreviewmag.com. Sleep Review. Retrieved 9 September 2015.
  10. ^ "Regulatory Decision Summary - Belsomra - Health Canada". hpr-rps.hres.ca. Government of Canada. Retrieved 6 February 2020.
  11. ^ a b c Carr T (5 February 2016). "FDA Fields Complaints on Sleeping Pill Suvorexant". Consumer Reports.
  12. ^ a b c Jacobson LH, Callander GE, Hoyer D (November 2014). "Suvorexant for the treatment of insomnia". Expert Review of Clinical Pharmacology. 7 (6): 711–30. doi:10.1586/17512433.2014.966813. PMID 25318834.
  13. ^ a b "Schedules of controlled substances: placement of suvorexant into Schedule IV. Final rule" (PDF). Federal Register. 79 (167): 51243–7. August 2014. PMID 25167596.
  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.

External links[]

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