Solriamfetol

Last updated

Solriamfetol
Solriamfetol.svg
Clinical data
Trade names Sunosi
Other namesSKL-N05, ADX-N05, ARL-N05, YKP10A, R228060, and JZP-110; (R)-2-amino-3-phenylpropylcarbamate hydrochloride
AHFS/Drugs.com Monograph
MedlinePlus a619040
License data
Routes of
administration
By mouth
Drug class Norepinephrine–dopamine reuptake inhibitors
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability ~95% [2]
Protein binding 13.3–19.4% [2]
Metabolism Minimal [2]
Elimination half-life ~7.1 hours [2]
Excretion Urine (95% unchanged)
Identifiers
  • (2R)-2-Amino-3-phenylpropyl carbamate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C10H14N2O2
Molar mass 194.234 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]

Contents

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] In addition to its approved indication of excessive sleepiness, solriamfetol is under development for certain other uses including the treatment of attention deficit hyperactivity disorder (ADHD), binge eating disorder, and circadian rhythm sleep disorders. [7]

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] It appears to be more effective in improving excessive daytime sleepiness associated with obstructive sleep apnea than certain other wakefulness-promoting agents including modafinil, armodafinil, and pitolisant. [8]

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]

Misuse potential

Solriamfetol at higher-than-approved doses—specifically doses of 300, 600, and 1,200 mg, which are 2 to 4 times the maximum recommended dose—produces drug-liking responses, including elevated mood and feelings of relaxation, that are similar in degree to those of phentermine (a Schedule IV controlled substance). [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] However, solriamfetol showed less misuse potential than Schedule II controlled stimulants like amphetamine and cocaine. [9] Consequently, the misuse potential of solriamfetol was rated as low and it was placed in the Schedule IV controlled substance category alongside phentermine. [9]

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 oral bioavailability of solriamfetol is approximately 95%. [2] The median time to peak levels of solriamfetol is 2 hours, with a range of 1.25 to 3.0 hours. [2] A high-fat meal has minimal influence on the peak and total concentrations of solriamfetol, but does delay time to peak levels by approximately 1 hour. [2] The apparent volume of distribution of solriamfetol is approximately 199 L. [2] The plasma protein binding of solriamfetol is 13.3% to 19.4% over a concentration range of 0.059 to 10.1 μg/mL. [2] Solriamfetol is minimally metabolized in humans. [2] It shows first-order elimination with oral administration and has an elimination half-life of about 7.1 hours. [2] The half-life of solriamfetol increases in the context of renal impairment. [2] Approximately 95% of a dose of solriamfetol is eliminated in urine as unchanged solriamfetol and 1% or less is eliminated as the minor inactive metabolite N-acetylsolriamfetol. [2]

Chemistry

Solriamfetol is derived from d-phenylalanine and its chemical name is (R)-2-amino-3-phenylpropylcarbamate. [10]

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 [11] 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] [12]

In 2019, solriamfetol was approved in the United States to improve wakefulness in adults with narcolepsy or obstructive sleep apnea (OSA). [13] [14] It was granted orphan drug designation. [15]

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). [13] The trials were conducted in Canada, Europe, and the United States. [13]

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. [16]

Society and culture

Names

During development it has been called SKL-N05, ADX-N05, ARL-N05, and JZP-110. [7]

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. [17] A prescription is required, and can only be refilled up to five times in a six-month period. [18] In countries of the European Union, a prescription is required. [3]

Research

Solriamfetol is under development for the treatment of attention deficit hyperactivity disorder (ADHD), binge eating disorder, and circadian rhythm sleep disorders. [7] [19] As of September 2023, it is in phase 3 clinical trials for ADHD and phase 2 clinical trials for binge eating disorder and circadian rhythm sleep disorders. [7] [19] A case report of solriamfetol for the treatment of ADHD has been published. [20] Solriamfetol was also under development for the treatment of depressive disorders, but development for this indication was discontinued. [7]

See also

Related Research Articles

<span class="mw-page-title-main">Modafinil</span> Eugeroic medication

Modafinil, sold under the brand name Provigil among others, is a wakefulness-promoting medication used primarily to treat narcolepsy. Modafinil is also approved for stimulating wakefulness in people with sleep apnea and shift work sleep disorder. It is taken by mouth. Modafinil is not approved by the US Food and Drug Administration (FDA) for use in people under age 17.

<span class="mw-page-title-main">Methylphenidate</span> Central nervous system stimulant

Methylphenidate, sold under the brand names Ritalin and Concerta among others, is a central nervous system (CNS) stimulant used medically to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, narcolepsy. It is a primary medication for ADHD ; it may be taken by mouth or applied to the skin, and different formulations have varying durations of effect, commonly ranging from 2–4 hours. For ADHD, the effectiveness of methylphenidate is comparable to atomoxetine but modestly lower than amphetamines.

A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission.

Upper airway resistance syndrome (UARS) is a sleep disorder characterized by the narrowing of the airway that can cause disruptions to sleep. The symptoms include unrefreshing sleep, fatigue, sleepiness, chronic insomnia, and difficulty concentrating. UARS can be diagnosed by polysomnograms capable of detecting Respiratory Effort-related Arousals. It can be treated with lifestyle changes, functional orthodontics, surgery, mandibular repositioning devices or CPAP therapy. UARS is considered a variant of sleep apnea, although some scientists and doctors believe it to be a distinct disorder.

<span class="mw-page-title-main">Reboxetine</span> NRI antidepressant drug

Reboxetine, sold under the brand name Edronax among others, is a drug of the norepinephrine reuptake inhibitor (NRI) class, marketed as an antidepressant by Pfizer for use in the treatment of major depression, although it has also been used off-label for panic disorder and attention deficit hyperactivity disorder (ADHD). It is approved for use in many countries worldwide, but has not been approved for use in the United States. Although its effectiveness as an antidepressant has been challenged in multiple published reports, its popularity has continued to increase.

<span class="mw-page-title-main">Pemoline</span> Stimulant, used in the treatment of ADHD

Pemoline, sold under the brand name Cylert among others, is a stimulant medication which has been used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. It has been discontinued in most countries due to rare but serious problems with liver toxicity. The medication was taken by mouth.

<span class="mw-page-title-main">Viloxazine</span> Medication used to treat ADHD

Viloxazine, sold under the brand name Qelbree and formerly as Vivalan among others, is a selective norepinephrine reuptake inhibitor medication which is used in the treatment of attention deficit hyperactivity disorder (ADHD) in children and adults. It was marketed for almost 30 years as an antidepressant for the treatment of depression before being discontinued and subsequently repurposed as a treatment for ADHD. Viloxazine is taken orally. It was used as an antidepressant in an immediate-release form and is used in ADHD in an extended-release form.

<span class="mw-page-title-main">Armodafinil</span> Eugeroic medication

Armodafinil (trade name Nuvigil) is the enantiopure compound of the eugeroic modafinil (Provigil). It consists of only the (R)-(−)-enantiomer of the racemic modafinil. Armodafinil is produced by the pharmaceutical company Cephalon Inc. and was approved by the U.S. Food and Drug Administration (FDA) in June 2007. In 2016, the FDA granted Mylan rights for the first generic version of Cephalon's Nuvigil to be marketed in the U.S.

Christian Guilleminault was a French physician and researcher in the field of sleep medicine who played a central role in the early discovery of obstructive sleep apnea and made seminal discoveries in many other areas of sleep medicine.

<span class="mw-page-title-main">Narcolepsy</span> Human sleep disorder that involves an excessive urge to sleep and other neurological features

Narcolepsy is a chronic neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. Narcolepsy paired with cataplexy is evidenced to be an autoimmune disorder. These experiences of cataplexy can be brought on by strong emotions. Less commonly, there may be vivid hallucinations or an inability to move while falling asleep or waking up. People with narcolepsy tend to sleep about the same number of hours per day as people without it, but the quality of sleep tends to be lessened.

Pitolisant, sold under the brand name Wakix among others, is a medication used for the treatment of excessive daytime sleepiness in adults with narcolepsy. It is a histamine 3 (H3) receptor antagonist/inverse agonist (an antihistamine drug specific to that kind of receptors). It represents the first commercially available medication in its class, so that the US Food and Drug Administration (FDA) declares it a first-in-class medication. Pitolisant enhances the activity of histaminergic neurons in the brain that function to improve a person's wakefulness.

<span class="mw-page-title-main">NS-2359</span> Chemical compound

NS-2359 (GSK-372,475) is a serotonin-norepinephrine-dopamine reuptake inhibitor. It was under development by GlaxoSmithKline (GSK) as an antidepressant, but was discontinued in 2009 when phase II clinical trials showed the drug was not effective and not well tolerated. The results did not support further effort by the company. NS-2359 was also in clinical trials for the treatment of ADHD, phase II having been completed in 2007. A phase I clinical trial exploring the effect of NS-2359 on cocaine-dependent individuals was completed in 2002.

<span class="mw-page-title-main">Dasotraline</span> Chemical compound

Dasotraline is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) that was under development by Sunovion for the treatment of attention-deficit hyperactivity disorder (ADHD) and binge eating disorder (BED). Structurally, dasotraline is a stereoisomer of desmethylsertraline (DMS), which is an active metabolite of the marketed selective serotonin reuptake inhibitor (SSRI) antidepressant sertraline (Zoloft).

<span class="mw-page-title-main">Norepinephrine releasing agent</span> Catecholaminergic type of drug

A norepinephrine releasing agent (NRA), also known as an adrenergic releasing agent, is a catecholaminergic type of drug that induces the release of norepinephrine (noradrenaline) and epinephrine (adrenaline) from the pre-synaptic neuron into the synapse. This in turn leads to increased extracellular concentrations of norepinephrine and epinephrine therefore an increase in adrenergic neurotransmission.

<span class="mw-page-title-main">Eugeroic</span> Drugs for wakefulness and alertness

Eugeroics, also known as wakefulness-promoting agents and wakefulness-promoting drugs, are a class of drugs that promote wakefulness and alertness. They are medically indicated for the treatment of certain sleep disorders including excessive daytime sleepiness (EDS) in narcolepsy or obstructive sleep apnea (OSA). Eugeroics are also often prescribed off-label for the treatment of EDS in idiopathic hypersomnia. In contrast to classical psychostimulants, such as methylphenidate and amphetamine, which are also used in the treatment of these disorders, eugeroics typically do not produce marked euphoria, and, consequently, have a lower addictive potential.

<span class="mw-page-title-main">Norepinephrine–dopamine reuptake inhibitor</span> Drug that inhibits the reuptake of norepinephrine and dopamine

A norepinephrine–dopamine reuptake inhibitor (NDRI) is a drug used for the treatment of clinical depression, attention deficit hyperactivity disorder (ADHD), narcolepsy, and the management of Parkinson's disease. The drug acts as a reuptake inhibitor for the neurotransmitters norepinephrine and dopamine by blocking the action of the norepinephrine transporter (NET) and the dopamine transporter (DAT), respectively. This in turn leads to increased extracellular concentrations of both norepinephrine and dopamine and, therefore, an increase in adrenergic and dopaminergic neurotransmission.

Idiopathic hypersomnia(IH) is a neurological disorder which is characterized primarily by excessive sleep and excessive daytime sleepiness (EDS). Idiopathic hypersomnia was first described in 1976, and it can be divided into two forms: polysymptomatic and monosymptomatic. The condition typically becomes evident in early adulthood and most patients diagnosed with IH will have had the disorder for many years prior to their diagnosis. As of August 2021, an FDA-approved medication exists for IH called Xywav, which is oral solution of calcium, magnesium, potassium, and sodium oxybates; in addition to several off-label treatments (primarily FDA-approved narcolepsy medications).

Selective norepinephrine reuptake inhibitors (sNRIs) are a class of drugs that have been marketed as antidepressants and are used for various mental disorders, mainly depression and attention-deficit hyperactivity disorder (ADHD). The norepinephrine transporter (NET) serves as the fundamental mechanism for the inactivation of noradrenergic signaling because of the NET termination in the reuptake of norepinephrine (NE). The selectivity and mechanism of action for the NRI drugs remain mostly unresolved and, to date, only a limited number of NRI-selective inhibitors are available. The first commercially available selective NRI was the drug reboxetine (Edronax), developed as a first-line therapy for major depressive disorder. Atomoxetine (Strattera) is another potent and selective NRI which is also effective and well tolerated for the treatment of ADHD in adults; it may also be a new treatment option for adults with ADHD, particularly for those patients at risk of substance abuse.

References

  1. "Summary Basis of Decision (SBD) for Sunosi". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 "Sunosi – solriamfetol tablet, film coated". DailyMed . 16 October 2019. Retrieved 24 November 2019.
  3. 1 2 3 "Sunosi EPAR". European Medicines Agency (EMA). 12 November 2019. Retrieved 26 September 2020.
  4. 1 2 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. 1 2 3 Ji-young S (5 March 2018). "SK Biopharmaceuticals' narcolepsy drug on track to hitting US market". The Korea Herald.
  7. 1 2 3 4 5 "Solriamfetol – Jazz Pharmaceuticals/SK Biopharmaceuticals". AdisInsight. Retrieved 13 October 2023.
  8. Pitre T, Mah J, Roberts S, Desai K, Gu Y, Ryan C, Busse JW, Zeraatkar D (May 2023). "Comparative Efficacy and Safety of Wakefulness-Promoting Agents for Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnea : A Systematic Review and Network Meta-analysis". Ann Intern Med. 176 (5): 676–684. doi:10.7326/M22-3473. PMID   37155992. S2CID   258558603.
  9. 1 2 "Federal Register :: Request Access".
  10. 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.
  11. 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.
  12. Garde D (14 January 2014). "Jazz bets up to $397M on Aerial's narcolepsy drug". FierceBiotech.
  13. 1 2 3 "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.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  14. "Drug Approval Package: Sunosi". U.S. Food and Drug Administration (FDA). 29 April 2019. Retrieved 24 November 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  15. "Solriamfetol Orphan Drug Approval". U.S. Food and Drug Administration (FDA). Retrieved 24 November 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  16. "Axsome To Buy Sunosi From Jazz". NASDAQ . Retrieved 28 March 2022.
  17. 21 U.S.C.   § 812 – Schedules of controlled substances
  18. "Manuals – Practitioner's Manual – Section V". Archived from the original on 7 January 2014. Retrieved 30 May 2021. Retrieved 2014-01-07
  19. 1 2 Surman CB, Walsh DM, Horick N, DiSalvo M, Vater CH, Kaufman D (October 2023). "Solriamfetol for Attention-Deficit/Hyperactivity Disorder in Adults: A Double-Blind Placebo-Controlled Pilot Study". J Clin Psychiatry. 84 (6). doi:10.4088/JCP.23m14934. PMID   37819836. S2CID   263715808.
  20. Naguy A, El-Sheshaie A, Elsori DH, Alamiri B (April 2021). "Solriamfetol for attention deficit hyperactivity disorder". CNS Spectr. 27 (6): 662–663. doi: 10.1017/S1092852921000328 . PMID   33870884.