BELSOMRA®

(suvorexant) 5, 10, 15, 20 mg tablets, for oral use, C-IV

Safety

Events of Clinical Interest

Prespecified events of clinical interest (ECIs) in clinical trials with BELSOMRA

ECIs were selected for prospective assessment based on1:

  • Safety concerns observed with sedative-hypnotic treatments
  • Theoretical safety concerns given the orexin receptor antagonist mechanism of action of BELSOMRA

PERCENTAGE OF PATIENTS WITH ECIs DURING 3 MONTHS OF TREATMENT IN CLINICAL TRIALS (POOLED DATA)1

Events of clinical interest in patients taking BELSOMRA vs placebo
  PLACEBO  (n=1025)a BELSOMRA (20 mg in patients aged <65 years, or 15 mg in patients aged ≥65 years)  (n=493)
 
Suicidal ideation and/or behaviors 0.1 0.2
Adverse events with potential for abuse liabilityb 2.2 3.2
Complex sleep-related behaviorsc 0.0 0.0
Hypnagogic/hypnopompic hallucinations 0.0 0.4
Excessive daytime sleepiness (EDS)d 0.2 0.6
Sleep paralysis 0.0 0.2
Sleep onset paralysise 0.0 0.0
Cataplexye 0.0 0.0
Fallsf 0.9 0.8

(a) This n includes patients from an additional safety study treated at higher than recommended doses.

(b) All events in this category were instances of drug maladministration.1

(c) Complex sleep-related behaviors are events characterized as engaging in specific activities while asleep (eg, eating, drinking, preparing meals, making phone calls, having sex, driving, and sleepwalking).1

(d) EDS is distinguished from somnolence by a more persistent sleepiness that could occur intermittently over the course of a day or for multiple consecutive days, and is often associated with impairment in daytime function, despite the patient having had adequate sleep during the preceding night(s).1

(e) Confirmed by adjudication.1

(f) Falls were adjudicated to determine whether they were suggestive of cataplexy; all falls were associated with circumstances which contributed to or triggered the fall and were not related to residual somnolence or impaired coordination.1

Prespecified events of clinical interest (ECIs) for patients ≥65 years taking BELSOMRA 15 mg in the same 2 clinical trials

ECIs were selected for prospective assessment based on1,2:

  • Safety concerns observed with sedative-hypnotic treatments
  • Theoretical safety concerns given the orexin receptor antagonist mechanism of action of BELSOMRA

Patients were mostly 65–74 years of age (~80%). Patients were usually in good general health, and had a diagnosis consistent with DSM-IV for primary insomnia. Patients with major depression or sleep-related breathing disorders, among others, were excluded.2

PERCENTAGE OF PATIENTS ≥65 YEARS OF AGE WITH ECIs DURING 3 MONTHS OF TREATMENT IN CLINICAL TRIALS (POOLED DATA)2

  PLACEBO  (n=469)a BELSOMRA (15 mg in patients aged ≥65 years)  (n=202)
 
Suicidal ideation and/or behaviors 0.0 0.0
Events suggestive of abuse potentialb 2.1 0.5
Complex sleep-related behaviors 0.0 0.0
Hypnagogic hallucinations 0.0 0.0
Hypnopompic hallucinations 0.0 0.5
Excessive daytime sleepiness (EDS)c 0.0 0.5
Sleep paralysis 0.0 0.0
Sleep onset paralysisd 0.0 0.0
Fallse 1.5 1.5

(a) This n includes patients from an additional safety study treated at higher than recommended doses.2

(b) All events in this category were instances of drug maladministration.2

(c) EDS defined as more persistent sleepiness than typical next-day residual somnolence.2

(d) Confirmed by adjudication.2

(e) Falls were adjudicated to determine whether they were suggestive of cataplexy.2

Safety Information Related to Prespecified Events of Clinical Interest

  • Because BELSOMRA can cause drowsiness, patients, particularly the elderly, are at higher risk of falls.
  • In clinical studies, a dose-dependent increase in suicidal ideation was observed in patients taking BELSOMRA, as assessed by questionnaire. Immediately evaluate patients with suicidal ideation or any new onset behavioral changes. In primarily depressed patients treated with sedative-hypnotics, worsening of depression or suicidal thinking, including suicidal thoughts and actions (including completed suicide), have been reported. Suicidal tendencies may be present in such patients and protective measures may be required. Intentional overdose is more common in this group of patients; therefore, the lowest number of tablets that is feasible should be prescribed for the patient at any one time.
  • Complex sleep behaviors, including sleep-walking, sleep-driving, and engaging in other activities while not fully awake (eg, preparing and eating food, making phone calls, having sex), have been reported to occur with the use of hypnotics such as BELSOMRA. These events can occur in hypnotic-naive as well as in hypnotic-experienced persons. Patients usually do not remember these events. Complex sleep behaviors may occur following the first or any subsequent use of BELSOMRA, with or without the concomitant use of alcohol and other CNS depressants. Discontinue BELSOMRA immediately if a patient experiences a complex sleep behavior.
  • Sleep paralysis, an inability to move or speak for up to several minutes during sleep-wake transitions, and hypnagogic/hypnopompic hallucinations, including vivid perceptions by the patient, can occur with use of BELSOMRA.
  • Symptoms similar to mild cataplexy can occur, with risk increasing with the dose of BELSOMRA. Such symptoms can include periods of leg weakness lasting from seconds to a few minutes, can occur both at night and during the day, and may not be associated with an identified triggering event (eg, laughter or surprise).
  • BELSOMRA contains suvorexant, a Schedule IV controlled substance.
  • Because individuals with a history of abuse or addiction to alcohol or other drugs may be at increased risk for abuse and addiction to BELSOMRA, health care providers should follow such patients carefully when those patients are receiving BELSOMRA.

References

1. Data available on request from Merck Professional Services-DAP, WP1, PO Box 4, West Point, PA 19486-0004. Please specify information package US-IMA-01365.

2. Herring WJ, Connor KM, Snyder E, et al. Suvorexant in elderly patients with insomnia: pooled analyses of data from phase III randomized controlled clinical trials. Am J Geriatr Psychiatry. 2017;25:791-802.

Indications and Usage

BELSOMRA® (suvorexant) is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.

Selected Safety Information

  • BELSOMRA is contraindicated in patients with narcolepsy.
  • BELSOMRA is a central nervous system (CNS) depressant and can impair daytime wakefulness even when used as prescribed. Prescribers should monitor for somnolence and CNS depressant effects, but impairment can occur in the absence of symptoms, and may not be reliably detected by ordinary clinical exam. CNS depressant effects may persist in some patients for up to several days after discontinuing BELSOMRA.
  • BELSOMRA can impair driving skills and may increase the risk of falling asleep while driving. Discontinue or decrease the dose in patients who drive if daytime somnolence develops. Caution patients taking BELSOMRA 20 mg against next-day driving and other activities requiring full mental alertness. Caution patients taking lower doses of BELSOMRA as well, because there is individual variation in sensitivity to BELSOMRA.
  • Coadministration with other CNS depressants (eg, benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. Patients should be advised not to consume alcohol in combination with BELSOMRA due to additive effects. Dosage adjustments of BELSOMRA and of other concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of BELSOMRA with other drugs to treat insomnia is not recommended.
  • The risk of next-day impairment, including impaired driving, is increased if BELSOMRA is taken with less than a full night of sleep remaining, if a higher than recommended dose is taken, if coadministered with other CNS depressants, or if coadministered with other drugs that increase blood levels of BELSOMRA. Patients should be cautioned against driving and other activities requiring complete mental alertness if taken in these circumstances.
  • Because BELSOMRA can cause drowsiness, patients, particularly the elderly, are at higher risk of falls.
  • In clinical studies, a dose-dependent increase in suicidal ideation was observed in patients taking BELSOMRA, as assessed by questionnaire. Immediately evaluate patients with suicidal ideation or any new onset behavioral changes. In primarily depressed patients treated with sedative-hypnotics, worsening of depression or suicidal thinking, including suicidal thoughts and actions (including completed suicide), have been reported. Suicidal tendencies may be present in such patients and protective measures may be required. Intentional overdose is more common in this group of patients; therefore, the lowest number of tablets that is feasible should be prescribed for the patient at any one time.
  • Complex sleep behaviors, including sleep-walking, sleep-driving, and engaging in other activities while not fully awake (eg, preparing and eating food, making phone calls, having sex), have been reported to occur with the use of hypnotics such as BELSOMRA. These events can occur in hypnotic-naïve as well as in hypnotic-experienced persons. Patients usually do not remember these events. Complex sleep behaviors may occur following the first or any subsequent use of BELSOMRA, with or without the concomitant use of alcohol and other CNS depressants. Discontinue BELSOMRA immediately if a patient experiences a complex sleep behavior.
  • Sleep paralysis, an inability to move or speak for up to several minutes during sleep-wake transitions, and hypnagogic/hypnopompic hallucinations, including vivid perceptions by the patient, can occur with use of BELSOMRA.
  • Symptoms similar to mild cataplexy can occur, with risk increasing with the dose of BELSOMRA. Such symptoms can include periods of leg weakness lasting from seconds to a few minutes, can occur both at night and during the day, and may not be associated with an identified triggering event (eg, laughter or surprise).
  • The effect of BELSOMRA on respiratory function should be considered if prescribed to patients with compromised respiratory function. BELSOMRA has not been studied in patients with severe obstructive sleep apnea (OSA) or severe chronic obstructive pulmonary disease (COPD).
  • Symptomatic treatment of insomnia should be initiated only after careful evaluation of the patient. Reevaluate for comorbid conditions if insomnia persists after 7 to 10 days of treatment.
  • In pivotal clinical studies, the most common adverse reaction (reported in 5% or more of patients treated with 15 mg or 20 mg of BELSOMRA and at least twice the placebo rate) was somnolence (BELSOMRA 7%, placebo 3%).
  • In clinical studies, during the first 3 months of treatment, the adverse reactions reported in ≥2% of elderly patients treated with 15 mg or non-elderly patients treated with 20 mg of BELSOMRA and more commonly than in patients treated with placebo, were: diarrhea (BELSOMRA 2%, placebo 1%), dry mouth (2%, 1%), upper respiratory tract infection (2%, 1%), headache (7%, 6%), somnolence (7%, 3%), dizziness (3%, 2%), abnormal dreams (2%, 1%), and cough (2%, 1%).
  • At doses of 15 mg or 20 mg, the incidence of somnolence was higher in females (8%) than in males (3%). The incidence of headache, abnormal dreams, dry mouth, cough, and upper respiratory tract infection occurred in women at least twice that in men.
  • In the insomnia study in patients with mild to moderate Alzheimer’s disease receiving BELSOMRA, the adverse reactions occurring ≥2% and greater than placebo were somnolence (4% compared to 1% placebo), dry mouth (2% compared to 1% placebo), and falls (2% compared to 0% placebo).
  • When BELSOMRA was coadministered with alcohol, additive psychomotor impairment was demonstrated.
  • Concomitant use of BELSOMRA with strong inhibitors of CYP3A (eg, ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin, conivaptan) is not recommended.
  • The recommended dose of BELSOMRA is 5 mg in subjects receiving moderate CYP3A inhibitors (eg, amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil). The dose generally should not exceed 10 mg in patients receiving moderate CYP3A4 inhibitors.
  • The efficacy of BELSOMRA may be reduced when coadministered with strong CYP3A inducers (eg, rifampin, carbamazepine, phenytoin).
  • Slightly increased levels of digoxin were seen with coadministration of BELSOMRA. Digoxin levels should be monitored when coadministering BELSOMRA with digoxin.
  • Available data from postmarketing reports with BELSOMRA use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.
  • There are no data on the presence of suvorexant in human milk, the effects on the breastfed infant or the effects on milk production. Infants exposed to BELSOMRA through breastmilk should be monitored for excessive sedation. The benefits of breastfeeding should be considered along with the mother’s clinical need for BELSOMRA and any potential adverse effects on the breastfed infant.
  • Safety and effectiveness of BELSOMRA in pediatric patients have not been established.
  • Because BELSOMRA can increase drowsiness, patients, particularly the elderly, are at a higher risk of falls.
  • BELSOMRA contains suvorexant, a Schedule IV controlled substance.
  • Because individuals with a history of abuse or addiction to alcohol or other drugs may be at increased risk for abuse and addiction to BELSOMRA, health care providers should follow such patients carefully when those patients are receiving BELSOMRA.
  • Use the lowest dose effective for the patient.
  • The recommended dose for BELSOMRA is 10 mg, taken no more than once per night, and within 30 minutes of going to bed, with at least 7 hours remaining before the planned time of awakening. If the 10-mg dose is well tolerated but not effective, the dose can be increased. The maximum recommended dose of BELSOMRA is 20 mg taken no more than once per night.
  • Exposure to BELSOMRA is increased in obese compared to non-obese patients, and in women compared to men. Particularly in obese women, the increased risk of exposure-related adverse effects should be considered before increasing the dose.
  • When BELSOMRA is combined with other CNS depressant drugs, dosage reduction of BELSOMRA and/or the other drug(s) may be necessary because of potentially additive effects. The recommended dosage of BELSOMRA is 5 mg taken no more than once per night when used with moderate CYP3A inhibitors (the dose generally should not exceed 10 mg).
  • BELSOMRA is not recommended for use with strong CYP3A inhibitors.
  • Time to effect of BELSOMRA may be delayed if taken with or soon after a meal.
  • No dose adjustment is required in patients with mild and moderate hepatic impairment. BELSOMRA has not been studied in patients with severe hepatic impairment and is not recommended for these patients.

Before prescribing BELSOMRA, please read the Prescribing Information. The Medication Guide also is available.

US-IMA-0177101/22