|Trade names||Hetlioz, Hetlioz LQ|
|Drug class||Melatonin receptor agonist|
|Main uses||Non-24-hour sleep–wake disorder|
|Side effects||Headache, sleepiness, nausea, dizziness|
|Typical dose||20 mg OD|
|Bioavailability||not determined in humans|
|Metabolism||extensive liver, primarily CYP1A2 and CYP3A4-mediated|
|Elimination half-life||0.9–1.7 h / 0.8–5.9 h (terminal)|
|Excretion||80% in urine, 4% in feces|
|Chemical and physical data|
|Molar mass||245.322 g·mol−1|
|3D model (JSmol)|
Tasimelteon, sold under the brand name Hetlioz among others, is a medication used to treat non-24-hour sleep–wake disorder. It is taken by mouth, an hour before bedtime. Benefits may take months to occur.
Tasimelteon was approved for medical use in the United States in 2014 and Europe in 2015. In the United States it costs about 23,000 USD per month as of 2021. Despite being approved in Europe and available in Germany it is not sold in the United Kingdom as of 2021.
In the US, tasimelteon is used for the treatment of non-24-hour sleep–wake disorder (Non-24) in adults and for the treatment of nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) in people sixteen years of age and older. Tasimelteon oral suspension is indicated for the treatment of nighttime sleep disturbances in SMS in children from 3 to 15 years of age.
In Europe, tasimelteon capsules are indicated for the treatment of non-24-hour sleep–wake disorder (Non-24) in totally blind adults.
As a treatment for N24HSWD, as with melatonin or other melatonin derivatives, people may experience improved sleep timing while taking the drug. Reversion to baseline sleep performance occurs within a month of discontinuation.
The typical dose is 20 mg taken once per day.
The capsule and liquid suspension forms of tasimelteon are not interchangeable.
Mechanism of action
Tasimelteon is a selective agonist for the melatonin receptors MT1 and MT2, similar to other members of the melatonin receptor agonist class of which ramelteon (2005) and agomelatine (2009) were the first approved.
Tasimelteon (previously known as BMS-214,778) was developed for the treatment of insomnia and other sleep disorders. A phase II trial on circadian rhythm sleep disorders was concluded in March 2005. A phase III insomnia trial was conducted in 2006. A second phase III trial on insomnia, this time concerning primary insomnia, was completed in June 2008. In 2010, the FDA granted orphan drug status to tasimelteon, then regarded as an investigational medication, for use in totally blind adults with N24HSWD. (Through mechanisms such as easing the approval process and extending exclusivity periods, orphan drug status encourages development of drugs for rare conditions that otherwise might lack sufficient commercial incentive.)
On completion of Phase III trials, interpretations of the clinical trials by the research team concluded that the drug may have therapeutic potential for transient insomnia in circadian rhythm sleep disorders. A year-long (2011–2012) study at Harvard tested the use of tasimelteon in blind subjects with non-24-hour sleep-wake disorder. The drug has not been tested in children nor in any non-blind people.
In 2013, Vanda Pharmaceuticals submitted a New Drug Application to the Food and Drug Administration for the treatment of non-24-hour sleep–wake disorder in totally blind people. It was approved by the FDA on January 31, 2014 under the brand name Hetlioz. In the opinion of Public Citizen, an advocacy group, the FDA erroneously allowed it to be labelled without stating that it is only approved for use by totally blind people. However, FDA updated its press release on Oct. 2, 2014 to clarify the approved use of Hetlioz, which includes both sighted and blind individuals. The update did not change the drug labeling (prescribing information).
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In animal studies, administration of tasimelteon during pregnancy resulted in developmental toxicity (embryofetal mortality, neurobehavioral impairment, and decreased growth and development in offspring) at doses of up to 200 times greater than those used clinically.
- Vachharajani NN, Yeleswaram K, Boulton DW (April 2003). "Preclinical pharmacokinetics and metabolism of BMS-214778, a novel melatonin receptor agonist". Journal of Pharmaceutical Sciences. 92 (4): 760–72. doi:10.1002/jps.10348. PMID 12661062.
- Clinical trial number NCT00490945 for "Safety and Efficacy of VEC-162 on Circadian Rhythm in Healthy Adult Volunteers" at ClinicalTrials.gov
- Clinical trial number NCT00291187 for "VEC-162 Study in Healthy Adult Volunteers in a Model of Insomnia" at ClinicalTrials.gov
- Clinical trial number NCT00548340 for "VEC-162 Study in Adult Patients With Primary Insomnia" at ClinicalTrials.gov
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- Rajaratnam SM, Polymeropoulos MH, Fisher DM, Roth T, Scott C, Birznieks G, Klerman EB (February 2009). "Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials". Lancet. 373 (9662): 482–91. doi:10.1016/S0140-6736(08)61812-7. PMID 19054552. S2CID 36568291.
- Food and Drug Administration (January 31, 2014). "FDA approves Hetlioz: first treatment for non-24 hour sleep-wake disorder" (Press release). FDA. Archived from the original on February 2, 2014. Retrieved December 3, 2020.
- Carome M (1 July 2015). "Outrage of the Month: FDA Makes Major Blunder After Approving Drug for Rare Sleep Disorder". Huffington Post. Archived from the original on 4 July 2015. Retrieved 8 July 2015.
- Food and Drug Administration (January 31, 2014). "FDA NEWS RELEASE: FDA approves Hetlioz: first treatment for non-24 hour sleep–wake disorder in blind individuals". FDA. Archived from the original on February 2, 2014. Retrieved December 3, 2020.