JULY 10, 2015
Monica Holmberg, PharmD, BCPS
The FDA has approved Merck’s Belsomra (suvorexant), a Schedule IV substance, for the treatment of insomnia, as characterized by difficulties with sleep onset and/or sleep maintenance.1 Belsomra is an orexin receptor antagonist and the first medication in its class.2 It is available as 5-mg, 10-mg, 15-mg, and 20-mg tablets.1

Pharmacology and Pharmacokinetics
The orexin neuropeptide signaling system is a central promoter of wakefulness. Belsomra is believed to exert its effect by blocking the binding of orexin to its receptors, resulting in a suppression of the wake drive. Under fasting conditions, the median time to maximum effect of Belsomra is 2 hours; a high-fat meal may delay this by approximately 1.5 hours. Belsomra’s metabolism is primarily through CYP3A with a minor contribution by CYP2C19.1

Dosage and Administration
Patients should use the lowest possible dose that will be effective for them. The recommended dose is 10 mg taken once nightly within 30 minutes of going to bed, with at least 7 hours remaining before the patient plans to wake up. If the 10-mg dose is tolerated but not effective, the dose can be increased to a maximum of 20 mg once daily. If taken with or soon after a meal, the time to effect of Belsomra may be delayed.

Clinical Trials
Belsomra was evaluated in 3 clinical trials of patients with insomnia, as characterized by difficulties with sleep onset and/or sleep maintenance. Studies 1 and 2 were 3-month, randomized, double-blind, placebo-controlled, parallel-group studies. Patients were randomized to receive either Belsomra (20 mg for nonelderly patients; 15 mg for elderly patients) or placebo. In these trials, both doses of Belsomra were found to be superior to placebo for sleep latency and sleep maintenance, as assessed objectively by polysomnography and subjectively by patient estimations. Doses of 30 mg and 40 mg were also evaluated, and although they were found to have similar efficacy to lower doses, there were significantly more adverse reactions.

Study 3 was a 1-month crossover study of nonelderly adults who were treated with placebo and Belsomra at doses of 10 or 20 mg, or up to 80 mg. The 10-mg and 20-mg doses were found to be superior to placebo for sleep latency and sleep maintenance, as assessed objectively by polysomnography.1

Contraindications, Warnings, and Precautions
Even when used as prescribed, Belsomra can impair daytime wakefulness and driving skills and may increase the risk of falling asleep while driving. Patients using the 20-mg strength should be cautioned against next-day driving or activities that require full mental alertness.1 Patients using lower doses should also be made aware of the potential for next-day driving impairment, as each individual’s reaction to the medication will vary in sensitivity.2 If insomnia persists longer than 7 to 10 days after starting treatment with Belsomra, the patient should be evaluated for comorbid conditions.

Nighttime sleep-driving and other complex behaviors have been reported in patients using hypnotics such as Belsomra. This risk increases with dose, the use of central nervous system depressants, and alcohol consumption. Worsening depression or suicidal thinking may occur; this risk increases with dosage strength. Any new behavioral changes should be evaluated immediately. Belsomra has not been studied in patients with severe obstructive sleep apnea or severe chronic obstructive pulmonary disease. The risk of sleep paralysis, hypnagogic/ hypnopompic hallucinations, and cataplexy-like symptoms increases with dose. Treatment with Belsomra is contraindicated in patients with narcolepsy. The most commonly reported adverse reaction (≥5%) was somnolence.1

Patients concomitantly using a moderate CYP3A inhibitor should begin treatment with Belsomra at the 5-mg dose, with an increase to 10 mg if needed. Patients using a strong CYP3A inducer should also not take Belsomra because its efficacy may be reduced. Patients using digoxin should have their levels monitored while taking Belsomra. Belsomra is Pregnancy Category C. It should not be used in patients with severe hepatic impairment.

Dr. Holmberg earned her PharmD from the University of Connecticut and completed an ambulatory care residency in the Phoenix VA Healthcare System. Her practice has also included pediatrics and inpatient mental health. She resides in Phoenix, Arizona.

  1. Belsomra [prescribing information]. Whitehouse Station, NJ: Merck; 2014. Updated August 2014. Accessed May 2015.
  2. FDA approves new type of sleep drug, Belsomra [press release]. Silver Spring, MD: US Food and Drug Administration; August 13, 2014. Updated August 18, 2014. Accessed May 2015.