Tasimelteon

245.31700

245.32

612-059-5

SHS4PU80D9

DTXSID70209826

N05CH|N - Nervous system

38.33000

2.64210

1.145

442.553ºC at 760 mmHg

221.448ºC

1.564

1.1

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P312, P322, P330, P363, and P501|Aggregated GHS information provided by 2 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The most common adverse reactions are headache, increased alanine aminotransferase, nightmares or unusual dreams, and upper respiratory or urinary tract infections. There are currently no adequate or well-controlled studies that suggest that tasimelteon is safe to use during pregnancy. 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 greater than those used clinically. During clinical trials, rats did not self-administer tasimelteon, suggesting that the drug does not have a potential for abuse.

In several clinical trials, tasimelteon was found to be well tolerated. Serum enzyme elevations occurred in up to 10% of tasimelteon treated patients compared to 5% of placebo controls, but instances of clinically apparent liver injury were not reported. In a combined analysis of 6 trials of tasimelteon given for an average of 1 year, ALT elevations above 3 times the ULN arose in 6.5% of tasimelteon treated subjects, but no elevations were above 10 times ULN, and none were associated with symptoms or jaundice. Most elevations were single values and resolved spontaneously without dose reduction or discontinuation. Tasimelteon has been available for a limited period of time, but has not been linked to instances of clinically apparent liver injury. Tasimelteon is metabolized by the cytochrome P450 system (predominantly CYP 1A2 and CYP3A4), which can result in significant drug-drug interactions, strong inhibitors of the enzymes increasing serum concentrations of tasimelteon and strong inducers decreasing them.

At therapeutic concentrations, tasimelteon is about 90% bound to proteins.

Tasimelteon is indicated for the treatment of Non-24-Hour Sleep-Wake Disorder (N24HSWD).|FDA Label|Hetlioz is indicated for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24) in totally blind adults.|Treatment of non-24-hour sleep-wake disorder in the totally blind

Tasimelteon is a melatonin receptor agonist that is used for the treatment of non-24 hour sleep-wake disorder in blind individuals. Tasimelteon therapy is associated with a low rate of serum enzyme elevations, but has not been implicated in cases of clinically apparent liver injury.

Sedatives and Hypnotics

Following oral administration of radiolabeled tasimelteon, 80% of total radioactivity was excreted in urine and approximately 4% in feces, resulting in a mean recovery of 84%. Less than 1% of the dose was excreted in urine as the parent compound.|The apparent oral volume of distribution of tasimelteon at steady state in young healthy subjects is approximately 56 - 126 L.

Tasimelteon is extensively metabolized. Metabolism of tasimelteon consists primarily of oxidation at multiple sites and oxidative dealkylation resulting in opening of the dihydrofuran ring followed by further oxidation to give a carboxylic acid. CYP1A2 and CYP3A4 are the major isozymes involved in the metabolism of tasimelteon. Phenolic glucuronidation is the major phase II metabolic route.

The observed mean elimination half-life for tasimelteon is 1.3 ± 0.4 hours.

Tasimelteon is a selective dual agonist of the melatonin receptors MT1 and MT2.

BMS 214778

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