Belsomra
Suvorexant · Tablet, Film Coated · Oral
Uses
1 INDICATIONS AND USAGE BELSOMRA ® (suvorexant) is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance. BELSOMRA is an orexin receptor antagonist indicated for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance ( 1 ).
Dosage and administration
Use the lowest dose effective for the patient ( 2.1 ). Recommended dose is 10 mg, no more than once per night taken 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, not to exceed 20 mg once daily ( 2.1 , 2.2 ). Time to effect may be delayed if taken with or soon after a meal ( 2.1 ). 2.1 Dosing Information Use the lowest dose effective for the patient. For all BELSOMRA doses, take no more than once per night within 30 minutes of going to bed (with at least 7 hours remaining prior to planned awakening). Time to effect of BELSOMRA may be delayed if taken with or soon after a meal [see Clinical Pharmacology (12.3) ]. The recommended dose for BELSOMRA is 10 mg, taken no more than once per night. 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. 2.2 Special Populations 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 [see Clinical Pharmacology (12.3) ] . 2.3 Use with CNS Depressants 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 [see Warnings and Precautions (5.1) ] . 2.4 Dosage Adjustments with CYP3A Inhibitors 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) ] .
Dosage forms and strengths
5 mg tablets are yellow, round, film-coated tablets with "5" on one side and plain on the other side. 10 mg tablets are green, round, film-coated tablets with "33" on one side and plain on the other side. 15 mg tablets are white, oval, film-coated tablets with the corporate logo on one side and "325" on the other side. 20 mg tablets are white, round, film-coated tablets with the corporate logo and "335" on one side and plain on the other side. Tablets, 5 mg, 10 mg, 15 mg, 20 mg ( 3 ).
Contraindications
4 CONTRAINDICATIONS BELSOMRA is contraindicated in patients with narcolepsy. BELSOMRA is contraindicated in patients with narcolepsy ( 4 ).
Warnings and precautions
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.
Side effects
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) ] The most common adverse reaction (reported in 5% or more of patients treated with BELSOMRA and at least twice the placebo rate) with BELSOMRA was somnolence ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In 3-month controlled efficacy trials (Study 1 and Study 2), 1263 patients were exposed to BELSOMRA including 493 patients who received BELSOMRA 15 mg or 20 mg (see Table 1 ). In a long-term study, additional patients (n=521) were treated with BELSOMRA at higher than recommended doses, including a total of 160 patients who received BELSOMRA for at least one year. Table 1: Patient Exposure to BELSOMRA 15 mg or 20 mg in Study 1 and Study 2 Patients Treated BELSOMRA 15 mg BELSOMRA 20 mg For ≥ 1 Day (n) 202 291 Men (n) 69 105 Women (n) 133 186 Mean Age (years) 70 45 For ≥ 3 Months (n) 118 172 The pooled safety data described below (see Table 2 ) reflect the adverse reaction profile during the first 3 months of treatment. Adverse Reactions Resulting in Discontinuation of Treatment The incidence of discontinuation due to adverse reactions for patients treated with 15 mg or 20 mg of BELSOMRA was 3% compared to 5% for placebo. No individual adverse reaction led to discontinuation at an incidence ≥1%. Most Common Adverse Reactions In clinical trials of patients with insomnia treated with BELSOMRA 15 mg or 20 mg, the most common adverse reaction (reported in 5% or more of patients treated with BELSOMRA and at least twice the placebo rate) was somnolence (BELSOMRA 7%; placebo 3%). Table 2 shows the percentage of patients with adverse reactions during the first three months of treatment, based on the pooled data from 3-month controlled efficacy trials (Study 1 and Study 2). At doses of 15 or 20 mg, the incidence of somnolence was higher in females (8%) than in males (3%). Of the adverse reactions reported in Table 2, the following occurred in women at an incidence of at least twice that in men: headache, abnormal dreams, dry mouth, cough, and upper respiratory tract infection. The adverse reaction profile in elderly patients was generally consistent with non-elderly patients. The adverse reactions reported during long-term treatment up to 1 year were generally consistent with those observed during the first 3 months of treatment. Table 2: Percentage of Patients with Adverse Reactions Incidence ≥2% and Greater than Placebo in 3-Month Controlled Efficacy Trials (Study 1 and Study 2) Placebo BELSOMRA (20 mg in non-elderly or 15 mg in elderly patients) n=767 n=493 Gastrointestinal Disorders Diarrhea 1 2 Dry mouth 1 2 Infections and Infestations Upper respiratory tract infection 1 2 Nervous System Disorders Headache 6 7 Somnolence 3 7 Dizziness 2 3 Psychiatric Disorders Abnormal dreams 1 2 Respiratory, Thoracic and Mediastinal Disorders Cough 1 2 Dose Relationship for Adverse Reactions There is evidence of a dose relationship for many of the adverse reactions associated with BELSOMRA use, particularly for certain CNS adverse reactions. In a placebo-controlled crossover study (Study 3), non-elderly adult patients were treated for up to one month with BELSOMRA at doses of 10 mg, 20 mg, 40 mg (2 times the maximum recommended dose) or 80 mg (4 times the maximum recommended dose). In patients treated with BELSOMRA 10 mg (n=62), the types of adverse reactions observed were similar to those observed in patients treated with BELSOMRA 20 mg. BELSOMRA was associated with a dose-related increase in somnolence: 2% at the 10 mg dose, 5% at the 20 mg dose, 12% at the 40 mg dose, and 11% at the 80 mg dose, compared to <1% for placebo. BELSOMRA was also associated with a dose-related increase in serum cholesterol: 1 mg/dL at the 10 mg dose, 2 mg/dL at the 20 mg dose, 3 mg/dL at the 40 mg dose, and 6 mg/dL at the 80 mg dose after 4 weeks of treatment, compared to a 4 mg/dL decrease for placebo. Insomnia Study in Patients with Mild to Moderate Alzheimer's Disease In a 4-week insomnia study of BELSOMRA in 285 patients (BELSOMRA n=142; placebo n=143) with mild to moderate Alzheimer's Disease, the adverse reactions occurring ≥2% and greater than placebo were somnolence (4% compared to 1% for placebo), dry mouth (2% compared to 1% for placebo), and falls (2% compared to 0% for placebo) [see Clinical Studies (14.1) ] . 6.2 Post-Marketing Experience The following adverse reactions have been identified during post-approval use of BELSOMRA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac disorders : palpitations, tachycardia Gastrointestinal disorders: nausea, vomiting Nervous system disorders : psychomotor hyperactivity Psychiatric disorders : anxiety Skin and subcutaneous tissue disorders : pruritus
Drug interactions
7 DRUG INTERACTIONS 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) ].
Use in specific populations
Patients with severe hepatic impairment: Not recommended ( 8.7 ). 8.1 Pregnancy Risk Summary 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. In animal reproduction studies, oral administration of suvorexant to pregnant rats and rabbits during the period of organogenesis decreased maternal body weight and/or weight gain at doses ≥ 30 and 28 times the maximum recommended human dose (MRHD) of 20 mg based on AUC in the rat and rabbit, respectively. Suvorexant caused decreased fetal weight at doses ≥ 86 times the MRHD based on AUC in the rat and did not cause significant fetal toxicity at doses up to 28 times the MRHD based on AUC in the rabbit. The no observed adverse effect levels (NOAELs) for fetal toxicity are 25 and 28 times the MRHD based on AUC in the rat and rabbit, respectively. Oral administration of suvorexant to pregnant rats during pregnancy and lactation caused decreased maternal and pup body weight or weight gain at approximately 48 times the MRHD based on AUC. The NOAEL for development toxicity in the rat is 25 times the MRHD based on AUC (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Suvorexant was administered orally to pregnant rats during the period of organogenesis in two separate studies at doses of 30, 150, and 1000 mg/kg/day or 30, 80, and 325 mg/kg/day, which are approximately 3 to 93 times the MRHD based on AUC. Suvorexant decreased maternal weights at doses ≥ 150 mg/kg/day and fetal weights at doses ≥ 325 mg/kg/day. The NOAEL for both maternal and fetal toxicity is 80 mg/kg/day, which is approximately 25 times the MRHD based on AUC. Suvorexant was administered orally to pregnant rabbits during the period of organogenesis in two separate studies at doses of 40, 100, and 300 mg/kg/day or 50, 150, and 325 mg/kg/day, which are approximately 3 to 70 times the MRHD based on AUC. Suvorexant decreased maternal body weight or weight gain at doses ≥ 150 mg/kg/day. Suvorexant caused excessive maternal toxicity that led to premature deaths at 325 mg/kg/day, which precluded fetal evaluation. Suvorexant did not cause significant fetal toxicity at doses up to 300 mg/kg/day. The NOAELs for maternal and fetal toxicities are 100 mg/kg/day and 300 mg/kg/day, respectively, which are approximately 10 and 28 times the MRHD based on AUC, respectively. Suvorexant was administered orally to pregnant rats during pregnancy and lactation at doses of 30, 80, and 200 mg/kg/day, which are approximately 8 to 48 times the MRHD based on AUC. Suvorexant caused maternal toxicity of decreased body weight and weight gain and food consumption at 200 mg/kg/day. At this maternally toxic dose, suvorexant caused decreased weight gain in offspring pups. The NOAEL for maternal and developmental toxicity is 80 mg/kg/day, which is approximately 25 times the MRHD based on AUC. 8.2 Lactation Risk Summary Suvorexant and its metabolite, hydroxy suvorexant, are present in low concentrations in breast milk with a relative infant dose of less than 1% following maternal oral administration (see Data ) . There are no data on the effects of suvorexant on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BELSOMRA and any potential adverse effects on the breastfed infant from BELSOMRA or from the underlying maternal condition. Data A single dose (20 mg) milk and plasma lactation study was conducted in 12 healthy lactating women. The mean amount of suvorexant recovered in breast milk was 0.011 mg following a 20 mg maternal dose. The calculated mean daily infant dose was 0.002 mg/kg/day based on the actual infant body weight (i.e., 6.2 kg). The relative infant dose is less than 1% of the maternal dose. Approximately 82% of the amount of suvorexant excreted in breast milk was excreted by 24 hours after a single maternal dose administration. Suvorexant and its metabolite, hydroxy suvorexant, are present in breast milk and the transfer of hydroxy suvorexant into breast milk is lower than suvorexant (metabolite/parent: 0.13). 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Of the total number of patients treated with BELSOMRA (n=1784) in controlled clinical safety and efficacy studies, 829 patients were 65 years and over, and 159 patients were 75 years and over. No clinically meaningful differences in safety or effectiveness were observed between these patients and younger patients at the recommended doses [see Clinical Pharmacology (12.3) and Clinical Studies (14) ] . Because BELSOMRA can increase drowsiness, patients, particularly the elderly, are at a higher risk of falls [see Warnings and Precautions (5.1) ] . 8.6 Patients with Compromised Respiratory Function Effects of BELSOMRA on respiratory function should be considered if prescribed to patients with compromised respiratory function. Obstructive Sleep Apnea The respiratory depressant effect of BELSOMRA was evaluated after one night and after four consecutive nights of treatment in a randomized, placebo-controlled, 2-period crossover study in patients (n=26) with mild to moderate obstructive sleep apnea.
Pregnancy
8.1 Pregnancy Risk Summary 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. In animal reproduction studies, oral administration of suvorexant to pregnant rats and rabbits during the period of organogenesis decreased maternal body weight and/or weight gain at doses ≥ 30 and 28 times the maximum recommended human dose (MRHD) of 20 mg based on AUC in the rat and rabbit, respectively. Suvorexant caused decreased fetal weight at doses ≥ 86 times the MRHD based on AUC in the rat and did not cause significant fetal toxicity at doses up to 28 times the MRHD based on AUC in the rabbit. The no observed adverse effect levels (NOAELs) for fetal toxicity are 25 and 28 times the MRHD based on AUC in the rat and rabbit, respectively. Oral administration of suvorexant to pregnant rats during pregnancy and lactation caused decreased maternal and pup body weight or weight gain at approximately 48 times the MRHD based on AUC. The NOAEL for development toxicity in the rat is 25 times the MRHD based on AUC (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Suvorexant was administered orally to pregnant rats during the period of organogenesis in two separate studies at doses of 30, 150, and 1000 mg/kg/day or 30, 80, and 325 mg/kg/day, which are approximately 3 to 93 times the MRHD based on AUC. Suvorexant decreased maternal weights at doses ≥ 150 mg/kg/day and fetal weights at doses ≥ 325 mg/kg/day. The NOAEL for both maternal and fetal toxicity is 80 mg/kg/day, which is approximately 25 times the MRHD based on AUC. Suvorexant was administered orally to pregnant rabbits during the period of organogenesis in two separate studies at doses of 40, 100, and 300 mg/kg/day or 50, 150, and 325 mg/kg/day, which are approximately 3 to 70 times the MRHD based on AUC. Suvorexant decreased maternal body weight or weight gain at doses ≥ 150 mg/kg/day. Suvorexant caused excessive maternal toxicity that led to premature deaths at 325 mg/kg/day, which precluded fetal evaluation. Suvorexant did not cause significant fetal toxicity at doses up to 300 mg/kg/day. The NOAELs for maternal and fetal toxicities are 100 mg/kg/day and 300 mg/kg/day, respectively, which are approximately 10 and 28 times the MRHD based on AUC, respectively. Suvorexant was administered orally to pregnant rats during pregnancy and lactation at doses of 30, 80, and 200 mg/kg/day, which are approximately 8 to 48 times the MRHD based on AUC. Suvorexant caused maternal toxicity of decreased body weight and weight gain and food consumption at 200 mg/kg/day. At this maternally toxic dose, suvorexant caused decreased weight gain in offspring pups. The NOAEL for maternal and developmental toxicity is 80 mg/kg/day, which is approximately 25 times the MRHD based on AUC.
Pediatric use
8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Geriatric use
8.5 Geriatric Use Of the total number of patients treated with BELSOMRA (n=1784) in controlled clinical safety and efficacy studies, 829 patients were 65 years and over, and 159 patients were 75 years and over. No clinically meaningful differences in safety or effectiveness were observed between these patients and younger patients at the recommended doses [see Clinical Pharmacology (12.3) and Clinical Studies (14) ] . Because BELSOMRA can increase drowsiness, patients, particularly the elderly, are at a higher risk of falls [see Warnings and Precautions (5.1) ] .
Overdosage
There is limited premarketing clinical experience with an overdosage of BELSOMRA. In clinical pharmacology studies, healthy subjects who were administered morning doses of up to 240 mg of suvorexant showed dose-dependent increases in the frequency and duration of somnolence. General symptomatic and supportive measures should be used, along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. As in all cases of drug overdose, vital signs should be monitored and general supportive measures employed. The value of dialysis in the treatment of overdosage has not been determined. As suvorexant is highly protein-bound, hemodialysis is not expected to contribute to elimination of suvorexant. As with the management of all overdosage, the possibility of multiple drug ingestion should be considered. Consider contacting a poison control center for up-to-date information on the management of hypnotic drug product overdosage.
Description
11 DESCRIPTION BELSOMRA tablets contain suvorexant, an orexin receptor antagonist. Suvorexant is described chemically as: [(7R)-4-(5-chloro-2-benzoxazolyl) hexahydro-7-methyl-1H-1,4-diazepin-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone Its empirical formula is C 23 H 23 ClN 6 O 2 and the molecular weight is 450.92. Its structural formula is: Suvorexant is a white to off-white powder that is insoluble in water. Each film coated tablet contains 5 mg, 10 mg, 15 mg, or 20 mg of suvorexant and the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and polyvinylpyrrolidone/vinyl acetate copolymer (copovidone). In addition, the film coating contains the following inactive ingredients: hypromellose, lactose monohydrate, titanium dioxide, and triacetin. The film coating for the 5 mg tablets also contains iron oxide black and iron oxide yellow, and the film coating for the 10 mg tablets also contains FD&C Blue #1/Brilliant Blue FCF Aluminum Lake and iron oxide yellow. Chemical Structure
Mechanism of action
12.1 Mechanism of Action The mechanism of action of suvorexant in the treatment of insomnia is presumed to be through antagonism of orexin receptors. The orexin neuropeptide signaling system plays a role in wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive.
How supplied
16.1 How Supplied BELSOMRA tablets, 5 mg, are yellow, round, film-coated tablets, with "5" on one side and plain on the other side. They are supplied as follows: NDC 0006-0005-30 unit-of-use blisters of 30 BELSOMRA tablets, 10 mg, are green, round, film-coated tablets, with "33" on one side and plain on the other side. They are supplied as follows: NDC 0006-0033-30 unit-of-use blisters of 30 BELSOMRA tablets, 15 mg, are white, oval, film-coated tablets with the corporate logo on one side and "325" on the other side. They are supplied as follows: NDC 0006-0325-30 unit-of-use blisters of 30 BELSOMRA tablets, 20 mg, are white, round, film-coated tablets with the corporate logo and "335" on one side and plain on the other side. They are supplied as follows: NDC 0006-0335-30 unit-of-use blisters of 30 16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F), [see USP Controlled Room Temperature]. Store in the original package until use to protect from light and moisture.
Storage
16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F), [see USP Controlled Room Temperature]. Store in the original package until use to protect from light and moisture.
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). CNS Depressant Effects and Next-Day Impairment Tell patients that BELSOMRA has the potential to cause next-day impairment, and that this risk is increased with higher doses or if dosing instructions are not carefully followed. Patients using the 20 mg dose should be cautioned against next-day driving and other activities requiring full mental alertness as this dose is associated with a higher risk of impaired driving. Patients taking lower doses should also be cautioned about the potential for driving impairment because there is individual variation in sensitivity to BELSOMRA. Patients should not drive or engage in other activities requiring full alertness within 8 hours of dosing of BELSOMRA. Advise patients that increased drowsiness may increase the risk of falls in some patients [see Warnings and Precautions (5.1) ] . Sleep-Driving and Other Complex Behaviors Instruct patients to inform their families that BELSOMRA has been associated with getting out of bed while not being fully awake, and tell patients and their families to call their healthcare providers if this occurs. Hypnotics, like BELSOMRA, have been associated with "sleep-driving" and other complex behaviors while not being fully awake (preparing and eating food, making phone calls, or having sex). Tell patients and their families to call their healthcare providers if they develop any of these symptoms. Suicide Tell patients to report any worsening of depression or suicidal thoughts immediately. Alcohol and Other Drugs Ask patients about alcohol consumption, prescription medicines they are taking, and drugs they may be taking without a prescription. Advise patients not to use BELSOMRA if they drank alcohol that evening or before bed. Tolerance, Abuse, and Dependence Tell patients not to increase the dose of BELSOMRA on their own, and to inform you if they believe the drug "does not work." Administration Instructions Advise patients to take BELSOMRA only when preparing for or getting into bed and only if they can stay in bed for a full night before being active again. Advise patients to report all of their prescription and nonprescription medicines, vitamins and herbal supplements to the prescriber.
Label text from the FDA structured product label by Merck Sharp & Dohme LLC (revised Mar 10, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Suvorexant in 4 products
Belsomra NDC products (4)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0006-0005 | Suvorexant 5 mg/1 Tablet, Film Coated | Merck Sharp & Dohme LLC | NDA · DEA CIV |
| 0006-0033 | Suvorexant 10 mg/1 Tablet, Film Coated | Merck Sharp & Dohme LLC | NDA · DEA CIV |
| 0006-0325 | Suvorexant 15 mg/1 Tablet, Film Coated | Merck Sharp & Dohme LLC | NDA · DEA CIV |
| 0006-0335 | Suvorexant 20 mg/1 Tablet, Film Coated | Merck Sharp & Dohme LLC | NDA · DEA CIV |
Belsomra recalls
- D-0584-2025 Aug 20, 2025 · Class II · Ongoing
Failed Dissolution Specifications: potential for delayed dissolution of the dose after administration which may result in delayed release of the drug, delaying onset of sleep. - D-0523-2021 Jun 2, 2021 · Class II · Terminated
CGMP Deviations: Intermittent exposure to temperature excursion during storage.
Frequently asked questions
What is Belsomra used for?
1 INDICATIONS AND USAGE BELSOMRA ® (suvorexant) is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance. BELSOMRA is an orexin receptor antagonist indicated for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance ( 1 ).
What are the side effects of Belsomra?
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 the full label for the complete list.
Who makes Belsomra?
Belsomra is listed by 1 labeler in the FDA NDC directory, including Merck Sharp & Dohme LLC.
Has Belsomra been recalled?
The FDA enforcement database lists 2 recalls for Belsomra, most recently D-0584-2025 (class ii): Failed Dissolution Specifications: potential for delayed dissolution of the dose after administration which may result in delayed release of the drug, delaying…