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Solriamfetol

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Solriamfetol
Clinical data
Trade namesSunosi
Other namesSKL-N05, ADX-N05, ARL-N05, YKP10A, R228060, and JZP-110; (R)-2-amino-3-phenylpropylcarbamate hydrochloride
AHFS/Drugs.comMonograph
MedlinePlusa619040
License data
Routes of
administration		By mouth
Drug classNorepinephrine–dopamine reuptake inhibitors
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability~95%[2]
Protein binding13.3–19.4%[2]
MetabolismMinimal[2]
Elimination half-life~7.1 hours[2]
ExcretionUrine (95% unchanged)
Identifiers
  • (2R)-2-Amino-3-phenylpropyl carbamate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC10H14N2O2
Molar mass194.234 g·mol−1
3D model (JSmol)
  • C1=CC=C(C=C1)C[C@H](COC(=O)N)N
  • InChI=1S/C10H14N2O2/c11-9(7-14-10(12)13)6-8-4-2-1-3-5-8/h1-5,9H,6-7,11H2,(H2,12,13)/t9-/m1/s1
  • Key:UCTRAOBQFUDCSR-SECBINFHSA-N

Solriamfetol, sold under the brand name Sunosi, is a wakefulness-promoting medication used in the treatment of excessive sleepiness related to narcolepsy and sleep apnea.[2][4][5] It is taken by mouth.[2]

Common side effects of solriamfetol include headache, nausea, anxiety, and trouble sleeping.[2] It is a norepinephrine–dopamine reuptake inhibitor (NDRI) and is thought to work by increasing levels of the neurotransmitters norepinephrine and dopamine in the brain.[2][4]

The drug was discovered by a subsidiary of SK Group, which licensed rights outside of eleven countries in Asia to Aerial Pharma in 2011.[6]

Medical uses

Solriamfetol is used to promote wakefulness in the treatment of excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea in adults.[2]

Available forms

Solriamfetol is available in the form of 75 and 150 mg oral tablets.[2]

Side effects

Side effects of solriamfetol include headache, nausea, decreased appetite, insomnia, anxiety, irritability, feeling jittery, dizziness, chest discomfort, heart palpitations, dry mouth, increased sweating, abdominal pain, constipation, and diarrhea.[2]

Solriamfetol at higher-than-approved doses (300, 600, and 1,200 mg—two to four times the maximum recommended dose) produces drug-liking responses, including elevated mood and feelings of relaxation, similar in degree to those of phentermine.[2] Elevated mood occurred in 2.4% with placebo, 8 to 24% with solriamfetol, and 10 to 18% with phentermine, while feelings of relaxation occurred in 5% with placebo, 5 to 19% with solriamfetol, and 15 to 20% with phentermine.[2] As such, solriamfetol has significant misuse potential and is a controlled substance in the United States.[2]

Pharmacology

Pharmacodynamics

Solriamfetol is a norepinephrine–dopamine reuptake inhibitor (NDRI).[2] It binds to the dopamine transporter and the norepinephrine transporter with affinities (Ki) of 14.2 μM and 3.7 μM, respectively).[2] It inhibits the reuptake of dopamine and norepinephrine with IC50 values of 2.9 μM and 4.4 μM, respectively.[2] It has weak affinity for the serotonin transporter (Ki = 81.5 μM) and does not appreciably inhibit serotonin reuptake (IC50 > 100 μM).[2] Solriamfetol has no appreciable affinity for a variety of other targets, including the dopamine, serotonin, adrenergic, GABA, adenosine, histamine, orexin, benzodiazepine, and acetylcholine receptors.[2]

Pharmacokinetics

The time to peak levels of solriamfetol is about 2 hours (range 1.25–3.0 hours).[2] Solriamfetol is minimally metabolized in humans.[2] Its elimination half-life is about 7.1 hours.[2]

Chemistry

Solriamfetol is derived from d-phenylalanine and its chemical name is (R)-2-amino-3-phenylpropylcarbamate.[7]

History

The drug was discovered by a subsidiary of SK Group, which licensed rights outside of eleven countries in Asia to Aerial Pharma in 2011.[6] Aerial ran two Phase II trials of the drug in narcolepsy[8] before selling the license to solriamfetol to Jazz in 2014; Jazz Pharmaceuticals paid Aerial $125 million up front and will pay Aerial and SK up to $272 million in milestone payments, and will pay double-digit royalties to SK.[6][9]

In 2019, solriamfetol was approved in the United States to improve wakefulness in adults with narcolepsy or obstructive sleep apnea (OSA).[10][11] It was granted orphan drug designation.[12]

The U.S. Food and Drug Administration (FDA) approved solriamfetol based primarily on evidence from five clinical trials (Trial 1/NCT02348593, Trial 2/NCT02348606, Trial 3/NCT02348619, Trial 4/NCT02348632, Trial 5 NCT01681121) of 622 patients with narcolepsy or obstructive sleep apnea (OSA).[10] The trials were conducted in Canada, Europe, and the United States.[10]

Solriamfetol was approved for medical use in the European Union in January 2020.[3]

In March 2022, it was announced that Axsome Therapeutics would be acquiring Solriamfetol, under the brand name Sunosi, from Jazz Pharmaceuticals, for an upfront sum of $53 million. Jazz will receive a high single-digit royalty on Axsome's U.S. net sales of Sunosi in the current indication, and a mid-single-digit royalty in the future indications. Axsome will also assume the commitments of Jazz to SK Biopharmaceuticals and Aerial Biopharma.[13]

Society and culture

Names

During development it has been called SKL-N05, ADX-N05, ARL-N05, and JZP-110.[14]

In the United States, solriamfetol is a Schedule IV controlled substance,[2] meaning that it has an accepted medical use and a low potential for abuse, but that abuse may lead to physical or psychological dependence.[15] A prescription is required, and can only be refilled up to five times in a six-month period.[16] In countries of the European Union, a prescription is required.[3]

Research

Attention deficit hyperactivity disorder

A case report of solriamfetol for the treatment of attention deficit hyperactivity disorder (ADHD) exists.[17]

References

  1. ^ "Summary Basis of Decision (SBD) for Sunosi". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  2. ^ a b c d e f g h i j k l m n o p q r s t u v w x "Sunosi – solriamfetol tablet, film coated". DailyMed. 16 October 2019. Retrieved 24 November 2019.
  3. ^ a b c "Sunosi EPAR". European Medicines Agency (EMA). 12 November 2019. Retrieved 26 September 2020.
  4. ^ a b Powell J, Piszczatoski C, Garland S (October 2020). "Solriamfetol for Excessive Sleepiness in Narcolepsy and Obstructive Sleep Apnea". Ann Pharmacother. 54 (10): 1016–1020. doi:10.1177/1060028020915537. PMID 32270686. S2CID 215605290.
  5. ^ Abad VC, Guilleminault C (December 2018). "Solriamfetol for the treatment of daytime sleepiness in obstructive sleep apnea". Expert Rev Respir Med. 12 (12): 1007–1019. doi:10.1080/17476348.2018.1541742. PMID 30365900. S2CID 53106520.
  6. ^ a b c Ji-young S (5 March 2018). "SK Biopharmaceuticals' narcolepsy drug on track to hitting US market". The Korea Herald.
  7. ^ Abad VC, Guilleminault C (2017). "New developments in the management of narcolepsy". Nature and Science of Sleep. 9: 39–57. doi:10.2147/NSS.S103467. PMC 5344488. PMID 28424564.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  8. ^ Sullivan SS, Guilleminault C (2015). "Emerging drugs for common conditions of sleepiness: obstructive sleep apnea and narcolepsy". Expert Opinion on Emerging Drugs. 20 (4): 571–82. doi:10.1517/14728214.2015.1115480. PMID 26558298. S2CID 7951307.
  9. ^ Garde D (14 January 2014). "Jazz bets up to $397M on Aerial's narcolepsy drug". FierceBiotech.
  10. ^ a b c "Drug Trials Snapshots: Sunosi". U.S. Food and Drug Administration (FDA). 16 April 2019. Archived from the original on 28 September 2019. Retrieved 24 November 2019. Public Domain This article incorporates text from this source, which is in the public domain.
  11. ^ "Drug Approval Package: Sunosi". U.S. Food and Drug Administration (FDA). 29 April 2019. Retrieved 24 November 2019. Public Domain This article incorporates text from this source, which is in the public domain.
  12. ^ "Solriamfetol Orphan Drug Approval". U.S. Food and Drug Administration (FDA). Retrieved 24 November 2019. Public Domain This article incorporates text from this source, which is in the public domain.
  13. ^ "Axsome To Buy Sunosi From Jazz". NASDAQ. Retrieved 28 March 2022.
  14. ^ "Solriamfetol – Jazz Pharmaceuticals/SK Biopharmaceuticals". AdisInsight. Retrieved 15 April 2018.
  15. ^ 21 U.S.C. § 812 – Schedules of controlled substances
  16. ^ "Manuals – Practitioner's Manual – Section V". Retrieved 2014-01-07
  17. ^ Naguy A, El-Sheshaie A, Elsori DH, Alamiri B (April 2021). "Solriamfetol for attention deficit hyperactivity disorder". CNS Spectr: 1–2. doi:10.1017/S1092852921000328. PMID 33870884.
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