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Suvorexant: Pediatric drug information

Suvorexant: Pediatric drug information
(For additional information see "Suvorexant: Drug information" and see "Suvorexant: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Belsomra
Brand Names: Canada
  • Belsomra [DSC]
Therapeutic Category
  • Hypnotic, Miscellaneous;
  • Orexin Receptor Antagonist
Dosing: Pediatric

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 (Kawabe 2017) and a single case report (Prieto 2019). 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 (Kawabe 2017). 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 (Prieto 2019).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no pediatric-specific recommendations; based on extrapolation of adult data, no dosage adjustment necessary.

Dosing: Hepatic Impairment: Pediatric

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.

Dosing: Adult

(For additional information see "Suvorexant: Drug information")

Note: Intended for short-term use (≤4 to 8 weeks), preferably in conjunction with nonpharmacologic therapies (ACP [Qaseem 2016]; ESRS [Riemann 2017]; Winkelman 2021). Limit long-term use to cases for which nonpharmacologic treatments are not available or not effective and benefits are felt to outweigh risks (AASM [Sateia 2017]).

Insomnia, sleep onset or sleep maintenance: 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.

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

Mild or moderate impairment: No dosage adjustment necessary.

Severe impairment: Use is not recommended (has not been studied).

Dosage Forms: US

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 aluminum lake]

Belsomra: 15 mg, 20 mg

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Belsomra: 10 mg [DSC] [contains fd&c blue #1 aluminum lake]

Belsomra: 15 mg [DSC], 20 mg [DSC]

Controlled Substance

C-IV

Medication Guide and/or Vaccine Information Statement (VIS)

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.

Administration: Pediatric

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.

Administration: Adult

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.

Storage/Stability

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.

Use

Treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance (FDA approved in adults).

Adverse Reactions

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

Contraindications

Narcolepsy.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to suvorexant or any component of the formulation.

Warnings/Precautions

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.

Metabolism/Transport Effects

Substrate of CYP2C19 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Alcohol (Ethyl): May enhance the CNS depressant effect of Suvorexant. Risk X: Avoid combination

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect 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

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect 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 enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CNS Depressants: May enhance the CNS depressant effect 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 the serum concentration of Suvorexant. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Suvorexant. Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the 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 the serum concentration of Suvorexant. Risk X: Avoid combination

Daridorexant: May enhance the CNS depressant effect 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

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect 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

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect 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 the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lemborexant: May enhance the CNS depressant effect 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

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Melatonin: May enhance the sedative effect of Hypnotics (Nonbenzodiazepine). Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect 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 enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: Hypnotics (Nonbenzodiazepine) may enhance the CNS depressant effect of Oxybate Salt Products. Risk X: Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect 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 enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect 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

Food Interactions

Suvorexant serum concentrations may be increased when taken with grapefruit juice. Management: Reduce initial dose.

Dietary Considerations

For faster sleep onset, do no administer with (or immediately after) a meal.

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies.

Monitoring Parameters

Daytime alertness; respiratory rate; behavior profile; tolerance, abuse, dependence.

Mechanism of Action

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.

Pharmacokinetics (Adult data unless noted)

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%)

Pharmacokinetics: Additional Considerations

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.

Gender: 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.

Pricing: US

Tablets (Belsomra Oral)

5 mg (per each): $16.13

10 mg (per each): $16.13

15 mg (per each): $16.13

20 mg (per each): $16.13

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Brand Names: International
  • Belsomra (AU, JP)


For country abbreviations used in Lexicomp (show table)

REFERENCES

  1. Belsomra (suvorexant) [prescribing information]. Whitehouse Station, NJ: Merck, Sharpe & Dohme Corp; March 2021.
  2. Belsomra (suvorexant) [product monograph]. Kirkland, Quebec, Canada: Merck Canada Inc; March 2021.
  3. Kawabe K, Horiuchi F, Ochi M, Nishimoto K, Ueno SI, Oka Y. Suvorexant for the treatment of insomnia in adolescents. J Child Adolesc Psychopharmacol. 2017;27(9):792-795. [PubMed 28520464]
  4. Prieto DI, Zehgeer AA, Connor DF. Use of suvorexant for sleep regulation in an adolescent with early-onset bipolar disorder. J Child Adolesc Psychopharmacol. 2019;29(5):395. [PubMed 31033344]
  5. Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Management of chronic insomnia disorder in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016;165(2):125-133. doi:10.7326/M15-2175 [PubMed 27136449]
  6. Riemann D, Baglioni C, Bassetti C, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017;26(6):675-700. doi:10.1111/jsr.12594 [PubMed 28875581]
  7. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(2):307-349. doi:10.5664/jcsm.6470 [PubMed 27998379]
  8. Winkelman JW. Overview of the treatment of insomnia in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 10, 2021.
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