Suvorexant (Monograph)

Brand name: Belsomra
Drug class: Orexin Receptor Antagonists
Chemical name: [(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
Molecular formula: C₂₃H₂₃ClN₆O₂
CAS number: 1030377-33-3

Medically reviewed by Drugs.com on Jul 25, 2022. Written by ASHP.

Introduction

Hypnotic; orexin receptor antagonist.

Uses for Suvorexant

Insomnia

Management of insomnia characterized by difficulty with sleep onset and/or sleep maintenance.

Decreases sleep latency and improves sleep maintenance.

Suvorexant Dosage and Administration

General

Pretreatment Screening

• Because sleep disturbances may be a manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after careful evaluation of the patient.

Patient Monitoring

• Monitor for somnolence and CNS depressant effects.

Administration

Oral Administration

Administer no more than once per night, within 30 minutes of bedtime.

May administer without regard to meals; however, administration with or immediately after a meal decreases rate of absorption and may delay onset of effect.

Use only if ≥7 hours remain before planned time of awakening.

Dosage

Use smallest effective dosage.

Adults

Insomnia

Oral

10 mg no more than once per night. If 10 mg is well tolerated but ineffective, may increase dosage, but do not exceed 20 mg once per night.

When used concomitantly with a moderate CYP3A inhibitor, recommended dosage of suvorexant is 5 mg taken no more than once per night; dosage should generally not exceed 10 mg once per night. Concomitant use of strong CYP3A inhibitors is not recommended.

When used concomitantly with other CNS depressants, dosage adjustment of suvorexant or the other CNS depressant may be necessary because of potential additive effects.

Prescribing Limits

Adults

Insomnia

Oral

Maximum 20 mg once per night.

Special Populations

Hepatic Impairment

No dosage adjustment necessary in patients with mild to moderate hepatic impairment.

Not adequately studied in patients with severe hepatic impairment; use not recommended.

Renal Impairment

Dosage adjustment not necessary.

Geriatric Patients

Dosage adjustment not necessary based solely on age.

Obese Patients and Women

Systemic exposure is increased in obese patients (BMI >30 kg/m²) compared with nonobese patients, and in women compared with men.

Manufacturer states that the increased risk of exposure-related adverse effects should be considered before increasing dosage of suvorexant, particularly in obese women.

Related/similar drugs

lorazepam, zolpidem, diphenhydramine, melatonin, Ativan, Ambien

Cautions for Suvorexant

Contraindications

• Narcolepsy.

Warnings/Precautions

CNS Depressant Effects and Daytime Impairment

CNS depressant; may impair daytime wakefulness even when used as prescribed. May increase risk of falls, particularly in geriatric patients.

May impair ability to drive a motor vehicle and may increase risk of falling asleep while driving. Patients receiving the 20-mg dose should avoid driving or engaging in other activities that require complete mental alertness the day after use. Driving impairment also possible in patients receiving lower dosages. If daytime somnolence develops in patients who drive, discontinue drug or decrease dosage.

Risk of daytime impairment is increased if drug is administered with less than a full night of sleep remaining, if a higher than recommended dose is administered, or if used concomitantly with other CNS depressants or with drugs capable of increasing suvorexant concentrations.

Monitor patients for excessive somnolence and CNS depression; however, impairment may occur in the absence of symptoms and may not be reliably detected by ordinary clinical examination (i.e., formal psychomotor testing may be required). CNS depressant effects may persist for up to several days after discontinuance.

Concomitant use with other CNS depressants (e.g., alcohol, benzodiazepines, opiates, tricyclic antidepressants) increases the risk of CNS depression.

Worsening of Depression and Suicidal Ideation

Dose-dependent increase in suicidal ideation observed in clinical studies.

Worsening of depression and suicidal thoughts and actions (including completed suicides) reported in primarily depressed patients receiving sedative and hypnotic agents. Suicidal tendencies may be present; intentional overdosage more frequent in such patients. Protective measures may be required. Prescribe and dispense drug in the smallest feasible quantity.

Evaluate patient immediately if emergence of suicidality or any new behavioral abnormalities occurs.

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) with no memory of the event reported.

Can occur in hypnotic agent-naive or -experienced patients, following the first dose or at any time during treatment, or with or without concomitant use of alcohol or other CNS depressants.

Discontinue suvorexant immediately if a complex sleep behavior occurs.

Sleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, and Cataplexy-like Symptoms

Sleep paralysis (inability to move or speak for up to several minutes during sleep-wake transition) and hypnagogic/hypnopompic hallucinations reported. Dose-related symptoms similar to mild cataplexy (e.g., leg weakness lasting from seconds to a few minutes) may occur at night and/or during the day; may not be associated with an identified triggering event (e.g., laughter, surprise).

Patients with Compromised Respiratory Function

If used in patients with compromised respiratory function, consider possible effects on respiratory function. Respiratory depressant effects in patients with mild to moderate obstructive sleep apnea (OSA) or COPD cannot be excluded; not studied in patients with severe OSA or COPD.

No respiratory depressant effect observed in healthy individuals with normal respiratory function after single doses up to 150 mg.

Adequate Patient Evaluation

Insomnia may be a manifestation of an underlying physical and/or psychiatric disorder; carefully evaluate patient before providing symptomatic treatment.

Failure of insomnia to remit after 7–10 days of treatment, worsening of insomnia, or emergence of new cognitive or behavioral abnormalities may indicate the presence of an underlying psychiatric, physical, and/or medical condition that requires evaluation.

Abuse Potential and Dependence

Abuse potential of high suvorexant doses (40–150 mg) appears to be similar to that of high zolpidem tartrate doses (15–30 mg). Patients with a history of drug or alcohol abuse or addiction are at increased risk of abuse and addiction; use only with careful surveillance in such patients.

Discontinuance following chronic administration did not produce withdrawal symptoms or clear evidence of rebound insomnia. Does not appear to produce physical dependence.

Specific Populations

Pregnancy

No adequate data in humans. In animal reproduction studies, no adverse fetal or developmental toxicities observed at dosages resulting in up to 25 times the exposures achieved with the maximum recommended human dosage. Decreased maternal and fetal weight gain observed at higher exposures.

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Effects on milk production or on breast-fed infant also not known. Consider benefits of breast-feeding and importance of the drug to the woman; also consider potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

At recommended dosages, no overall differences in safety or efficacy relative to younger adults.

Balance impairment observed when geriatric individuals were awakened 90 minutes after a 30-mg dose; no memory impairment observed when awakened 4 hours after the dose.

Geriatric patients particularly are at higher risk of falls.

Hepatic Impairment

Dosage adjustment not necessary in patients with mild or moderate hepatic impairment.

Not adequately studied in patients with severe hepatic impairment; use not recommended.

Renal Impairment

Dosage adjustment not necessary in patients with renal impairment.

Gender

Somnolence, headache, abnormal dreams, dry mouth, cough, and upper respiratory infection are at least twice as common in women as in men.

Systemic exposure and peak plasma concentration are higher in women compared with men.

Obesity

Systemic exposure and peak plasma concentration are higher in obese patients (BMI >30 kg/m²) compared with nonoverweight patients (BMI ≤25 kg/m²).

Common Adverse Effects

Somnolence.

Drug Interactions

Metabolized principally by CYP3A and, to a lesser extent, by CYP2C19.

May potentially inhibit CYP3A and intestinal P-glycoprotein (P-gp). Does not appear to inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19, or 2D6.

Not expected to cause clinically important inhibition of organic anion-transporting polypeptide (OATP) 1B1, breast cancer resistance protein (BCRP), or organic cation transporter (OCT) 2.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A: Potential increased exposure to suvorexant. Avoid concomitant use with a potent CYP3A inhibitor. If used concomitantly with a moderate CYP3A inhibitor, recommended initial suvorexant dose is 5 mg; may increase dosage if necessary, but generally do not exceed 10 mg once daily.

Potent inducers of CYP3A: Potential decreased exposure to and efficacy of suvorexant, but do not exceed maximum recommended suvorexant dosage (20 mg once daily).

Specific Drugs and Foods

Suvorexant Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations attained in approximately 2 hours (range: 0.5–6 hours) after oral administration in fasted state.

Absolute oral bioavailability is 82%.

Food

High-fat meal prolongs time to peak plasma concentration by approximately 1.5 hours but does not substantially affect peak plasma concentration and AUC.

Special Populations

Peak plasma concentration, mean concentration at 9 hours postdose, and AUC are increased by 9, 5, and 17%, respectively, in women compared with men.

In obese patients (BMI >30 kg/m²), peak plasma concentration, mean concentration at 9 hours postdose, and AUC are increased by 17, 15, and 31%, respectively, compared with nonoverweight patients (BMI <25 kg/m²). In obese women, peak plasma concentration and AUC are increased by 25 and 46%, respectively, compared with nonobese women.

In patients with moderate hepatic impairment (Child-Pugh score 7–9), systemic exposure after single dose is unchanged but half-life is increased. (See Elimination: Special Populations, under Pharmacokinetics.)

Severe renal impairment (Cl_cr <30 mL/minute) does not substantially alter systemic exposure.

Distribution

Plasma Protein Binding

>99%; binds to albumin and α₁-acid glycoprotein.

Elimination

Metabolism

Metabolized principally by CYP3A and, to a lesser extent, by CYP2C19; major circulating metabolite (hydroxy derivative) is not expected to be active.

Elimination Route

Excreted in feces (66%) and urine (23%).

Half-life

Approximately 12 hours.

Special Populations

Clearance is inversely related to BMI. (See Absorption: Special Populations, under Pharmacokinetics.)

In patients with moderate hepatic impairment (Child-Pugh score 7–9), half-life is approximately 19 hours (versus 15 hours in healthy individuals).

Age and race predicted to have no clinically important effect on suvorexant pharmacokinetics.

Stability

Storage

Oral

Tablets

20–25°C (may be exposed to 15–30°C). Store in original package until use to protect from light and moisture.

Actions

• Antagonist at orexin-1 and orexin-2 receptors. Blockade of the actions of neuropeptides orexin A and B at these receptors is thought to suppress wake drive and promote sleep.

• The orexin neuropeptide signaling system plays a role in promoting and maintaining wakefulness. Loss of orexin-producing neurons and decreased CSF orexin concentrations are associated with narcolepsy with cataplexy , while increased orexin activity may be associated with insomnia.

Advice to Patients

• Importance of reading the manufacturer's medication guide.

• Importance of taking suvorexant only once per night within 30 minutes of going to bed and only when able to stay in bed for ≥7 hours before being active again. Taking suvorexant with or immediately after a meal may delay its effect.

• Importance of taking suvorexant only as prescribed and of not increasing the dose unless otherwise instructed by a clinician.

• Importance of not taking suvorexant if alcohol has been consumed in the evening or before bedtime.

• Importance of avoiding activities requiring complete mental alertness or physical coordination (e.g., driving a motor vehicle) for ≥8 hours after a dose.

• Risk of daytime impairment. In patients receiving the 20-mg dose, importance of avoiding driving or engaging in other activities that require complete mental alertness the day after use.

• Risk of complex sleep behaviors, including sleep-walking, sleep-driving, preparing and eating food, making phone calls, or having sex while not being fully awake. Importance of immediately contacting a clinician if a complex sleep behavior occurs.

• Importance of being alert to and immediately reporting worsening depression or suicidal ideation.

• Importance of informing patients and their families that sleep paralysis, hypnagogic/hypnopompic hallucinations, and mild cataplexy-like symptoms may occur.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant or past illnesses (e.g., depression, substance abuse).

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.

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