Pharmacology Update: Tasimelteon Capsules (Hetlioz™)

Pharmacology Update: Tasimelteon Capsules (Hetlioz™)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA

Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The fda has approved the first drug for the treatment of chronic circadian rhythm disorder known as non-24 sleep-wake disorder (non-24). This condition occurs in individuals who are completely blind and have abnormal synchronization with 24-hour light/dark cycles. Tasimelteon is a melatonin (MT1 and MT2) receptor agonist. It is marketed by Vanda Pharmaceuticals as Hetlioz.

Indications

Tasimelteon is indicated for the treatment of non-24 sleep-wake disorder.¹

Dosage

Tasimelteon is taken at the same time every night.¹ It should be taken without food. It is available as a 20 mg capsule.

Potential Advantages

Tasimelteon is the first drug approved for non-24 disorder. It improved nighttime sleep and reduced daytime naps in patients with non-24.¹

Potential Disadvantages

Tasimelteon may cause somnolence and reduce mental alertness.¹ Headache, increased alanine aminotransferase, nightmares, or unusual dreams may occur. The frequency varies from 10-17% compared to 0-7% for placebo.¹ Concomitant use of strong CYP1A2 inhibitors or CYUP3A4 inducers should be avoided.

Comments

The endogenous circadian pacemaker, or biological clock, is mainly synchronized by light. Since light perception is lacking in completely blind individuals, their biological clock is not synchronized to the 24-hour day.^2,3 As a result, their sleep-wake patterns may drift in and out of sync with the conventional sleep-wake schedule. Common complaints include insomnia, difficulty waking in the morning, and excessive daytime sleepiness. The effectiveness of tasimelteon was evaluated in two randomized, placebo-controlled studies. In the first study, totally blind subjects (n = 82) were randomized to 20 mg of tasimelteon or placebo taken 1 hour before bedtime for up to 6 months. Efficacy endpoints were the total sleep time at night and daytime nap duration based on 25% of nights with the least nighttime sleep and 25% of days with the most daytime naps. Data were captured via patient-recorded diaries. In the first study, diaries were recorded for an average of 88 days during screening and 133 days during randomization. Tasimelteon improved nighttime sleep duration by 50 minutes (baseline 195 minutes) compared to 22 minutes for placebo. Daytime naps were reduced by 49 minutes (baseline 137 minutes) compared to -22 minutes for placebo. The second study was for 12 weeks. Subjects were treated for 12 weeks with tasimelteon and those with calculated time of peak melatonin level occurring at approximately the same time of day were randomized to continue with tasimelteon or placebo. Those randomized to tasimelteon showed a 7-minute decrease in nighttime sleep time and a 9-minute decrease in daytime nap time compared to -74 minutes and +50 minutes with placebo.¹ Less than one-third of subjects treated were considered as responders, defined as at least 45 minutes increase in nighttime sleep and = 45 minutes reduction of daytime nap time.

Clinical Implications

Approximately 50% of blind people are affected by non-24 disorder.² Within non-24, there appears to be significant physiological presentation. Current treatment includes the combination of good sleep hygiene, structured daily schedules, and low-dose melatonin (0.5 mg).³ Tasimelteon offers the first FDA-approved pharmacological treatment with about 30% of users achieving meaningful improvement. There are no published comparative studies between melatonin and tasimelteon. The cost for tasimelteon was not available at the time of this review.

References

1. Hetlioz Prescribing Information. Washington, DC: Vanda Pharmaceuticals; January 2014.
2. Zhu L, Zee PC. Circadian rhythm sleep disorders. Neurol Clin 2012;30:1167-1191.
3. Emens JS, et al. Non-24-hour disorder in blind individuals revisited: Variability and the influence of environmental time cues. Sleep 2013;36:1091-1100.