Insomnia: Very limited data available; efficacy results variable:
Children ≥10 years and Adolescents: Oral: 10 to 20 mg once daily at bedtime; use of the lowest effective dose is recommended in adult experience; tablets are available starting at 5 mg; maximum daily dose: 20 mg/day.
Dosing based on an open-label trial (Ref) and a single case report (Ref). In an open-label trial of 30 children and adolescents (age: 15.7 ± 2.4 years; range: 10 to 20 years), most of whom had concomitant psychiatric disorder, all patients received 20 mg. Clinical Global Impression sleep scores were significantly improved from baseline when measured at 6 months of therapy in the 17 patients who continued therapy for the duration of the study; however, sleep quality scores were higher in patients who had discontinued therapy as compared to those still taking suvorexant at 6 months; a single patient experienced excessive sleep and daytime sleepiness, and 2 patients discontinued therapy due to abnormal dreams (Ref). Although this study used a fixed dose of 20 mg, based on experience in adults, the lowest effective dose is recommended in adolescents. A case report describes use in a 16-year-old with bipolar 1 disorder and sleep cycle dysregulation; suvorexant 10 mg/day resulted in improved sleep duration and quality; daytime irritability and aggression were subsequently reduced (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no pediatric-specific recommendations; based on extrapolation of adult data, no dosage adjustment necessary.
There are no pediatric-specific recommendations; based on extrapolation of adult data, no dosage adjustment is necessary for mild or moderate impairment; use is not recommended with severe impairment.
(For additional information see "Suvorexant: Drug information")
Insomnia, sleep onset or sleep maintenance:
Note: In general, limit long-term use (>4 weeks) of insomnia medications to cases for which nonpharmacologic treatments are unavailable or ineffective and benefits are felt to outweigh risks (Ref). In one study, suvorexant was well tolerated and provided sustained efficacy over the course of 1 year (Ref).
Oral: Initial: 10 mg once daily, as needed, within 30 minutes of bedtime and at least 7 hours before planned time of awakening; may increase up to 20 mg based on response and tolerability. Maximum daily dose: 20 mg.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
Mild or moderate impairment: No dosage adjustment necessary.
Severe impairment: Use is not recommended (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Gastrointestinal: Diarrhea (2%), xerostomia (2%; more common in females)
Nervous system: Abnormal dreams (2%; more common in females), dizziness (3%), drowsiness (2% to 7%; more common in females), headache (7%; more common in females)
Respiratory: Cough (2%; more common in females), upper respiratory tract infection (2%; more common in females)
Frequency not defined:
Endocrine & metabolic: Increased serum cholesterol
Nervous system: Central nervous system depression, daytime sedation, exacerbation of depression, hypnogenic hallucinations, sleep paralysis, suicidal ideation
Neuromuscular & skeletal: Lower extremity weakness (cataplexy-like symptoms)
Postmarketing:
Cardiovascular: Palpitations, tachycardia
Dermatologic: Pruritus
Gastrointestinal: Nausea, vomiting
Nervous system: Anxiety, complex sleep-related disorder, psychomotor agitation
Narcolepsy.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to suvorexant or any component of the formulation.
Concerns related to adverse effects:
• Abnormal thinking/behavioral changes: Hypnotics have been associated with abnormal thinking and behavior changes (eg, amnesia, anxiety, hallucinations).
• CNS depression: May cause CNS depression impairing physical and mental capabilities; patients must be cautioned about performing tasks which require mental alertness (operating machinery or driving). Suvorexant should only be administered when the patient is able to stay in bed a full night (≥7 hours) before being active again. Discontinue or decrease the dose in patients who drive if daytime somnolence occurs.
• Complex sleep behaviors: Complex sleep behaviors, including sleep-walking, sleep-driving, and engaging in other activities while not fully awake, may occur following use of suvorexant. Other complex sleep behaviors (eg, preparing and eating food, making phone calls, having sex) while asleep have also been reported. Patients usually do not remember these events. May occur with first use or any subsequent use with or without the use of alcohol or other CNS depressants. Discontinue immediately if a patient experiences a complex sleep behavior.
• REM sleep effects: Sleep paralysis (inability to move or speak for up to several minutes during sleep-wake transitions), hypnagogic/hypnopompic hallucinations, and mild cataplexy may occur. Cataplexy symptoms may 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 a triggering event (eg, laughter, surprise).
Disease-related concerns:
• Depression: Use with caution in patients with depression; worsening of depression, including suicide or suicidal ideation has been reported with the use of hypnotics. Intentional overdose may be an issue in this population. The minimum dose that will effectively treat the individual patient should be used. Prescriptions should be written for the smallest quantity consistent with good patient care.
• Drug abuse: Use with caution in patients with a history of drug dependence. Risk of abuse is increased with prolonged use of suvorexant, in patients with a history of drug abuse, or those who use suvorexant in combination with alcohol or other abused drugs.
• Hepatic impairment: Use is not recommended in patients with severe hepatic impairment (has not been studied).
• Respiratory disease: Use with caution in patients with respiratory compromise; has not been studied in patients with severe chronic obstructive pulmonary disease or severe obstructive sleep apnea.
Special populations:
• Female patients: Exposure is increased in females compared to males. Consider the increased risk of exposure-related adverse effects, particularly in obese females, before increasing the dose.
• Obese patients: Exposure is increased in obese compared to nonobese patients. Consider the increased risk of exposure-related adverse effects, particularly in obese females, before increasing the dose.
Other warnings/precautions:
• Appropriate use: Symptomatic treatment of insomnia should be initiated only after careful evaluation of potential causes of sleep disturbance. Failure of sleep disturbance to resolve after 7 to 10 days may indicate the need for psychiatric and/or medical illness reevaluation.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Belsomra: 5 mg
Belsomra: 10 mg [contains fd&c blue #1 (brill blue) aluminum lake]
Belsomra: 15 mg, 20 mg
No
Tablets (Belsomra Oral)
5 mg (per each): $17.77
10 mg (per each): $18.62
15 mg (per each): $18.62
20 mg (per each): $18.62
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
C-IV
Oral: Administer within 30 minutes of bedtime with at least 7 hours remaining before planned time of awakening. Onset is delayed when taken with a meal.
Oral: Administer within 30 minutes of bedtime with ≥7 hours remaining before planned time of awakening. May be administered with or without food; onset may be delayed if taken with or immediately after food.
Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Protect from light and moisture.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/204569s008lbl.pdf#page=23 , must be dispensed with this medication.
Treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance (FDA approved in adults).
Substrate of CYP2C19 (Minor), CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Alcohol (Ethyl): May increase CNS depressant effects of Suvorexant. Risk X: Avoid
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification
Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CNS Depressants: May increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
CYP3A4 Inducers (Moderate): May decrease serum concentration of Suvorexant. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Suvorexant. Risk C: Monitor
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Strong): May increase serum concentration of Suvorexant. Risk X: Avoid
Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Grapefruit Juice: May increase serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients who consume grapefruit juice, a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy. Risk D: Consider Therapy Modification
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Melatonin: May increase sedative effects of Hypnotics (Nonbenzodiazepine). Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification
Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: Hypnotics (Nonbenzodiazepine) may increase CNS depressant effects of Oxybate Salt Products. Risk X: Avoid
OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification
ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Suvorexant serum concentrations may be increased when taken with grapefruit juice. Management: Reduce initial dose.
For faster sleep onset, do not administer with (or immediately after) a meal.
Adverse events have been observed in some animal reproduction studies.
Daytime alertness; respiratory rate; behavior profile; tolerance, abuse, dependence.
Suvorexant blocks the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R, which is thought to suppress wake drive. Antagonism of orexin receptors may also underlie potential adverse effects such as signs of narcolepsy/cataplexy.
Onset of action: ~30 minutes
Absorption: Decreased at higher doses
Distribution: Vd: ~49 L
Protein binding: >99%
Metabolism: Primarily hepatic by CYP3A with a minor contribution from CYP2C19; the hydroxy-suvorexant metabolite is inactive.
Bioavailability: 82%
Half-life elimination: ~12 hours
Half-life terminal: ~15 hours (healthy subjects, range: 10 to 22 hours), ~19 hours (moderate hepatic disease, range: 11 to 49 hours)
Time to peak: 2 hours (range: 30 minutes to 6 hours); Delayed ~1.5 hours when administered with a meal
Excretion: Feces (~66%); urine (~23%)
Hepatic function impairment: The apparent terminal half-life of suvorexant increased from ~15 hours (range: 10 to 22 hours) in healthy subjects to ~19 hours (range: 11 to 49 hours) in patients with moderate hepatic insufficiency.
Sex: In females, the AUC and Cmax increased by 17% and 9%, respectively, following administration of suvorexant 40 mg. The average concentration 9 hours after dosing is 5% higher for females across the dose range studied (10 to 40 mg).
Obesity: The AUC and Cmax increases by 31% and 17%, respectively. The average concentration ~9 hours after a 20 mg dose is 15% higher in obese patients (BMI >30 kg/m2) relative to those with a normal BMI (BMI ≤25 kg/m2). In obese females, the AUC and Cmax increase by 46% and 25%, respectively.