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Suvorexant

Medically reviewed by Drugs.com. Last updated on Jul 23, 2020.

Pronunciation

(soo voe REX ant)

Index Terms

  • MK4305

Dosage Forms

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

Brand Names: U.S.

  • Belsomra

Pharmacologic Category

  • Hypnotic, Miscellaneous
  • Orexin Receptor Antagonist

Pharmacology

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.

Absorption

Decreased at higher doses

Distribution

Vd: ~49 L

Metabolism

Primarily hepatic by CYP3A with a minor contribution from CYP2C19; the hydroxy-suvorexant metabolite is inactive.

Excretion

Feces (~66%); urine (~23%)

Onset of Action

~30 minutes

Time to Peak

2 hours (range: 30 minutes to 6 hours); Delayed approximately 1.5 hours when administered with a meal.

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)

Protein Binding

>99%

Special Populations: 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.

Special Populations: 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).

Special Populations Note

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.

Use: Labeled Indications

Insomnia: Treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.

Contraindications

Narcolepsy.

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

Dosing: Adult

Insomnia: Oral: Note: Use the lowest effective dose for the patient. Usual dose: 10 mg once daily within 30 minutes of bedtime; may increase to a maximum of 20 mg once daily if the 10 mg dose is well tolerated but not effective. 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: Geriatric

Refer to adult dosing.

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: Obesity

Consider the increased risk of exposure-related adverse effects in obese women before increasing the dose.

Administration

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.

Dietary Considerations

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

Storage

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.

Drug Interactions

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

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

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

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). 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. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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. Consider therapy modification

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

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

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

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. Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Suvorexant. Avoid combination

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

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

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

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. 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. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

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

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

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. Consider therapy modification

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

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

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

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

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

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

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. Consider therapy modification

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

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

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

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

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. 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. Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

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

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

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

Oxybate Salt Products: Hypnotics (Nonbenzodiazepine) may enhance the CNS depressant effect of Oxybate Salt Products. 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. Consider therapy modification

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

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

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

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

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

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

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

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

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

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

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

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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. Consider therapy modification

Adverse Reactions

1% to 10%:

Gastrointestinal: Diarrhea (2%), xerostomia (2%; more common in females)

Nervous system: Headache (7%; more common in females), drowsiness (2% to 7%; more common in females), dizziness (3%), abnormal dreams (2%; 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 hallucination, sleep paralysis, suicidal ideation

Neuromuscular & skeletal: Lower extremity weakness (cataplexy-like symptoms)

Postmarketing:

Cardiovascular: Palpitations, tachycardia

Dermatologic: Pruritus

Nervous system: Anxiety, complex sleep-related disorder, psychomotor agitation

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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.

Monitoring Parameters

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

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies.

Patient Education

What is this drug used for?

• It is used to treat sleep problems.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Fatigue next day

• Headache

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Mood changes

• Behavioral changes

• Depression

• Suicidal ideation

• Confusion

• Sensing things that seem real but are not

• Trouble with memory

• Trouble moving

• Trouble speaking

• Muscle weakness

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.