Belsomra Tablet, Film Coated Uses, Dosage & Side Effects

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

BELSOMRA is contraindicated in patients with narcolepsy.

The following serious adverse reactions are discussed in greater detail in other sections:

• CNS Depressant Effects and Daytime Impairment [see Warnings and Precautions (5.1)]
• Worsening of Depression/Suicidal Ideation [see Warnings and Precautions (5.2)]
• Complex Sleep Behaviors [see Warnings and Precautions (5.3)]
• Sleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, Cataplexy-Like Symptoms [see Warnings and Precautions (5.4)]
• Patients with Compromised Respiratory Function [see Warnings and Precautions (5.5)]

• CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness (5.1).

• Worsening of Depression/Suicidal Ideation: Worsening of depression or suicidal thinking may occur. Risk increases with dose. Immediately evaluate any new behavioral changes (5.2).

• Complex Sleep Behaviors: Behaviors including sleep-walking, sleep-driving, and engaging in other activities while not fully awake may occur. Discontinue immediately if a complex sleep behavior occurs (5.3).

• Sleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, and Cataplexy-like Symptoms: May occur with the use of BELSOMRA. Risk increases with dose (5.4).

• Compromised Respiratory Function: Effect on respiratory function should be considered (5.5, 8.6).

• Need to Evaluate for Co-morbid Diagnoses: Reevaluate if insomnia persists after 7 to 10 days of treatment (5.6). 5.1 CNS Depressant Effects and Daytime Impairment

BELSOMRA is a central nervous system (CNS) depressant that 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 (i.e., less than formal testing of daytime wakefulness and/or psychomotor performance). 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. In a study of healthy adults, driving ability was impaired in some individuals taking 20 mg BELSOMRA

[see Clinical Studies (14.2)].

Although pharmacodynamic tolerance or adaptation to some adverse depressant effects of BELSOMRA may develop with daily use, patients using the 20 mg dose of BELSOMRA should be cautioned against next-day driving and other activities requiring full mental alertness. Patients taking lower doses of BELSOMRA should also be cautioned about the potential for driving impairment because there is individual variation in sensitivity to BELSOMRA.

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. Patients should be advised not to consume alcohol in combination with BELSOMRA because of additive effects [see Drug Interactions (7.1)]. Dosage adjustments of BELSOMRA and of 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

[see Dosage and Administration (2.3)].

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 the recommended dose is taken, if co-administered with other CNS depressants, or if co-administered with other drugs that increase blood levels of BELSOMRA. Patients should be cautioned against driving and other activities requiring complete mental alertness if BELSOMRA is taken in these circumstances.

Because BELSOMRA can cause drowsiness, patients, particularly the elderly, are at higher risk of falls. 5.2 Worsening of Depression/Suicidal Ideation

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 behavioral sign or symptom.

In primarily depressed patients treated with sedative-hypnotics, worsening of depression, and suicidal thoughts and actions (including completed suicides) 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.

The emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation. 5.3 Complex Sleep Behaviors

Complex sleep behaviors, including sleep-walking, sleep-driving, and engaging in other activities while not fully awake (e.g., 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 [see Drug Interactions (7.1)]. Discontinue BELSOMRA immediately if a patient experiences a complex sleep behavior. 5.4 Sleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, Cataplexy-Like Symptoms

Sleep paralysis, an inability to move or speak for up to several minutes during sleep-wake transitions, and hypnagogic/hypnopompic hallucinations, including vivid and disturbing perceptions by the patient, can occur with the use of BELSOMRA. Prescribers should explain the nature of these events to patients when prescribing 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 (e.g., laughter or surprise). 5.5 Patients with Compromised Respiratory Function

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)

[see Use in Specific Populations (8.6)]. 5.6 Need to Evaluate for Co-morbid Diagnoses

Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, treatment of insomnia should be initiated only after careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Worsening of insomnia or the emergence of new cognitive or behavioral abnormalities may be the result of an unrecognized underlying psychiatric or physical disorder and can emerge during the course of treatment with hypnotic drugs such as BELSOMRA.

When used with moderate CYP3A inhibitors, the recommended dosage of BELSOMRA is 5 mg taken no more than once per night (the dose generally should not exceed 10 mg). BELSOMRA is not recommended for use with strong CYP3A inhibitors [see Drug Interactions (7.2)].

1. 5 mg tablets are yellow, round, film-coated tablets with "5" on one side and plain on the other side.
2. 10 mg tablets are green, round, film-coated tablets with "33" on one side and plain on the other side.
3. 15 mg tablets are white, oval, film-coated tablets with the corporate logo on one side and "325" on the other side.
4. 20 mg tablets are white, round, film-coated tablets with the corporate logo and "335" on one side and plain on the other side.

• CYP3A inhibitors: Recommended dose is 5 mg when used with moderate CYP3A inhibitors. Dose can be increased to 10 mg once per night if the 5 mg dose is not effective. Not recommended for use in patients taking strong CYP3A inhibitors (2.4, 7.2).

• Strong CYP3A inducers: Efficacy may be reduced (7.2).

• Digoxin: Monitor digoxin concentrations (7.3). 7.1 CNS-Active Agents

When BELSOMRA was co-administered with alcohol, additive psychomotor impairment was demonstrated. There was no alteration in the pharmacokinetics of BELSOMRA

[see Warnings and Precautions (5.1, 5.3) and Clinical Pharmacology (12.3)]. 7.2 Effects of Other Drugs on BELSOMRA

Metabolism by CYP3A is the major elimination pathway for suvorexant. CYP3A Inhibitors

Concomitant use of BELSOMRA with strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin and conivaptan) is not recommended

[see Clinical Pharmacology (12.3)].

The recommended dose of BELSOMRA is 5 mg in subjects receiving moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil). The dose generally should not exceed 10 mg in patients receiving moderate CYP3A inhibitors

[see Clinical Pharmacology (12.3)]. CYP3A Inducers

Suvorexant exposure can be substantially decreased when co-administered with strong CYP3A inducers (e.g., rifampin, carbamazepine and phenytoin). The efficacy of BELSOMRA may be reduced

[see Clinical Pharmacology (12.3)]. 7.3 Effects of BELSOMRA on Other Drugs

Digoxin

Concomitant administration of BELSOMRA with digoxin slightly increased digoxin levels due to inhibition of intestinal P-gp. Digoxin concentrations should be monitored when co-administering BELSOMRA with digoxin

[see Clinical Pharmacology (12.3)].