Events of clinical interest with BELSOMRA® (suvorexant)
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
(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
(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
(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
(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
- 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.
- 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.