Hetlioz (tasimelteon)

Hetlioz is indicated for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24).

The precise mechanism by which tasimelteon exerts its therapeutic effect in patients with Non24 is not known. Tasimelteon is an agonist at melatonin MT1 and MT2 receptors. These receptors are thought to be involved in the control of circadian rhythms.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

A total of 1346 subjects were treated with at least one dose of Hetlioz, of which 139 were treated for > 26 weeks and 93 were treated for > 1 year.

A 26-week, parallel-arm placebo-controlled study (Study 1) evaluated Hetlioz (n=42) compared to placebo (n=42) in patients with Non-24. A randomized-withdrawal, placebo-controlled study of 8 weeks duration (Study 2) also evaluated Hetlioz (n=10), compared to placebo (n=10), in patients with Non-24.

In placebo-controlled studies, 6% of patients exposed to Hetlioz discontinued treatment due to an adverse event, compared with 4% of patients who received placebo.

Table 1 shows the incidence of adverse reactions from Study 1.

Table 1: Adverse Reactions in Study 1

Controlled Substance

Tasimelteon is not a controlled substance under the Controlled Substances Act.

Abuse

Tasimelteon did not produce any abuse-related signals in animal behavioral studies. Rats did not self-administer tasimelteon, suggesting that the drug does not have rewarding properties. There were also no signs or symptoms indicative of abuse potential in clinical studies with Hetlioz.

Dependence

Discontinuation of Hetlioz in humans following chronic administration did not produce withdrawal signs. Hetlioz does not appear to produce physical dependence.

The recommended dosage of Hetlioz is 20 mg per day taken before bedtime, at the same time every night.

Because of individual differences in circadian rhythms, drug effect may not occur for weeks or months.

Hetlioz should be taken without food.

Dosage Forms And Strengths

Capsules: 20 mg size 1 dark blue opaque, hard gelatin capsules printed with “Vanda 20 mg” in white.

Strong CYP1A2 Inhibitors (e.g., fluvoxamine)

Avoid use of Hetlioz in combination with fluvoxamine or other strong CYP1A2 inhibitors because of a potentially large increase in tasimelteon exposure and greater risk of adverse reactions.

Strong CYP3A4 Inducers (e.g., rifampin)

Avoid use of Hetlioz in combination with rifampin or other CYP3A4 inducers because of a potentially large decrease in tasimelteon exposure with reduced efficacy.

Smokers

Smoking causes induction of CYP1A2 levels. The exposure of tasimelteon in smokers was lower than in non-smokers and therefore the efficacy of Hetlioz may be reduced in smokers.

There are no adequate and well-controlled studies of Hetlioz in pregnant women. 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. Hetlioz should be used during pregnancy only if the potential benefit justifies the potential risks.

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Hetlioz is administered to a nursing woman.