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  • CLASSES

    Sedatives, Other

    DEA CLASS

    Rx, schedule IV

    DESCRIPTION

    Orexin receptor antagonist.
    Used for the treatment of insomnia in adults.
    Novel mechanism of action which alters the signaling of neurotransmitters called orexins that regulate the sleep-wake cycle.

    COMMON BRAND NAMES

    Belsomra

    HOW SUPPLIED

    Belsomra Oral Tab: 5mg, 10mg, 15mg, 20mg

    DOSAGE & INDICATIONS

    For the treatment of insomnia characterized by difficulties with sleep onset or sleep maintenance.
    Oral dosage
    Adults

    10 mg PO taken once per night within 30 minutes of going to bed, and with at least 7 hours remaining before the planned time of awakening. If needed, the dose may be increased to the maximum dose of 20 mg once per night; however, it should be noted that the risk of next-day impairment is increased with use of the higher dose. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Geriatric Adults

    10 mg PO taken once per night within 30 minutes of going to bed, and with at least 7 hours remaining before the planned time of awakening. If needed, the dose may be increased to the maximum dose of 20 mg once per night; however, it should be noted that the risk of next-day impairment is increased with use of the higher dose. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of sedative and hypnotics in long-term care facility (LTCF) residents. Specific dosage thresholds for suvorexant are not available; use in accordance with approved product labeling. If the sleep agent is used routinely and is beyond the manufacturer's recommendations for duration of use, the facility should attempt a quarterly taper unless clinically contraindicated as defined in the OBRA guidelines.

    MAXIMUM DOSAGE

    Adults

    20 mg/day PO.

    Geriatric

    20 mg/day PO.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Not indicated.

    Neonates

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Suvorexant is not recommended in patients with severe hepatic impairment. No dosage adjustment is required in patients with mild to moderate hepatic impairment.

    Renal Impairment

    No dosage adjustments are required in patients with renal impairment.

    ADMINISTRATION

    Oral Administration

    Administer 30 minutes prior to bedtime.
    The time to effect of suvorexant may be delayed if taken with or soon after a meal. For the fastest effect, take on an empty stomach.

    STORAGE

    Belsomra:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in original package until time of use

    CONTRAINDICATIONS / PRECAUTIONS

    Narcolepsy

    Suvorexant is contraindicated for use in patients with narcolepsy. Sleep paralysis (an inability to move or speak for up to several minutes during sleep-wake transitions), hypnagogic/hypnopompic hallucinations (vivid and disturbing perceptions by the patient), and cataplexy-like symptoms (periods of leg weakness lasting from seconds to a few minutes) can occur during use of suvorexant. The mechanism by which suvorexant exerts its therapeutic effect (i.e., antagonism of orexin receptors) may account for its ability to produce signs of narcolepsy/cataplexy.

    Behavioral changes, depression, suicidal ideation

    Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, treatment of insomnia with suvorexant should be initiated only after careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Worsening of insomnia or the emergence of new cognitive or behavioral changes may be the result of an unrecognized underlying psychiatric or physical disorder, and can emerge during the course of treatment with hypnotic drugs such as suvorexant. A variety of cognitive and behavioral changes (e.g., amnesia, anxiety, hallucinations and other neuro-psychiatric symptoms) have been reported to occur in association with the use of hypnotics such as suvorexant. In clinical studies, a dose-dependent increase in suicidal ideation was observed in patients taking suvorexant 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. Suvorexant should be prescribed in the smallest quantity consistent with good patient management to reduce the risk of overdose.

    Coadministration with other CNS depressants, driving or operating machinery, ethanol ingestion, sleep-related behaviors

    Suvorexant should only be administered immediately prior to retiring. Patients should be instructed to avoid driving or operating machinery or performing other tasks requiring mental alertness after taking their dose. In a study of healthy adults, driving ability was impaired in some subjects receiving the 20-mg dose of suvorexant. Therefore, patients receiving the 20-mg dose should be advised against next-day driving or other activities requiring full alertness, even if the patient feels fully awake. Because individual sensitivity to sleep medications may vary, patients receiving the 10-mg dose should also be cautioned about the potential for next-day impairment. The risk for next-morning impairment is higher if suvorexant is taken with less than a full night of sleep remaining, if a higher than the recommended dose is taken. Risk is also increased during the coadministration with other CNS depressants or with medications that increase suvorexant blood concentrations. Patients should not take suvorexant with other sedative-hypnotics. Additive effects may occur with alcohol, and patients should avoid ethanol ingestion while taking suvorexant. Lower dosages of suvorexant should be considered in patients taking other CNS-depressant medications. Sedative-hypnotic medications, including suvorexant, have the potential to cause sleep-related behaviors such as sleep-driving, a state of driving after ingestion of a sedative-hypnotic while not fully awake and having no memory of the event. Other sleep-related behaviors may include making phone calls or eating while asleep. The exact incidences among various sedative products are unknown; however patients should be informed of the risks prior to receiving any medication from this class.

    Chronic obstructive pulmonary disease (COPD), pulmonary disease, respiratory depression, sleep apnea

    Sedative-hypnotics have the potential to cause respiratory depression or oxygen desaturation, particularly in patients with pre-existing pulmonary disease. Suvorexant has not been formally evaluated in patients with severe obstructive sleep apnea (OSA) or severe chronic obstructive pulmonary disease (COPD). Evaluation of suvorexant in patients with mild to moderate OSA or COPD resulted in a wide variation of effects, suggesting that clinically meaningful effects on respiratory function are possible in some individuals. Therefore, the benefits of treatment should be weighed against the potential for adverse respiratory effects prior to using suvorexant in patients with pulmonary disease.

    Hepatic disease

    Suvorexant is not recommended in patients with severe hepatic disease (Child Pugh score more than 9) since the drug has not been studied in this patient population. No dosage adjustment is required in patients with mild to moderate hepatic impairment.

    Sleep paralysis

    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 suvorexant. Prescribers should explain the nature of these events to patients when prescribing suvorexant. Symptoms similar to mild cataplexy can occur, and the risk is dose-related. 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).

    Geriatric

    There were no clinically meaningful differences in safety and efficacy between geriatric adults and younger adults during clinical trials of suvorexant. However, dose selection should generally be cautious in the geriatric population since these patients may be more likely to experience confusion and oversedation from sedative hypnotics. According to the Beers Criteria, sedative hypnotics are considered potentially inappropriate medications (PIMs) in geriatric patients with delirium or at high risk of delirium and should be avoided because new-onset or worsening delirium may occur. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to the OBRA guidelines, factors potentially causing insomnia should be evaluated before initiating a sedative (e.g., sleep environment, inadequate physical activity, provision of care disruptions, caffeine or medications, pain and discomfort, or other underlying conditions that cause insomnia). Most cases of insomnia are associated with other underlying conditions. It is expected that non-pharmacologic interventions and maximized treatment of underlying conditions (if applicable) are implemented to address the causative factor(s). Initiation of sleep induction or maintenance medication should be preceded or accompanied by other interventions to attempt sleep improvement. All sleep medications should be used in accordance with approved product labeling. The use of sedating medications for individuals with diagnosed sleep apnea requires careful assessment, documented clinical rationale, and close monitoring. Exceptions to the OBRA provisions include: single dose sedative use for a dental or medical procedure or short-term sedative use during initiation of treatment for depression, pain, or other comorbid condition until symptoms improve or the underlying causative factor can be identified and/or effectively treated. OBRA provides dosing guidance for most sedatives; however, specific guidance for suvorexant is not available. When a drug is being used to induce sleep or treat a sleep disorder, the facility should attempt periodic tapering of the medication or provide documentation of medical necessity in accordance with OBRA guidelines.

    Labor, obstetric delivery, pregnancy

    There are no adequate or well-controlled studies of suvorexant in pregnant women. Suvorexant should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Administration of doses exceeding the maximum recommended human dose during animal studies resulted in reduced body weight in the offspring. There are case reports of withdrawal symptoms, severe neonatal respiratory depression, and possible neonatal flaccidity in neonates born to mothers taking other sedative-hypnotics. Suvorexant has no established use during labor or obstetric delivery.

    Breast-feeding

    It is not known if suvorexant is excreted into human milk, and caution should be used when the drug is administered to a woman who is breast-feeding. Suvorexant and a hydroxyl-suvorexant metabolite were excreted in rat milk at levels higher (9 and 1.5 times, respectively) than that in maternal plasma.

    Children, infants

    The safety and efficacy of suvorexant in children and adolescents less than 18 years of age has not been established. There is no known use for this drug in infants.

    Alcoholism, substance abuse

    Suvorexant should be used in patients with a history of substance abuse only if the benefit justifies the potential risk of psychological dependence, misuse, and/or abuse. If treatment with suvorexant is deemed necessary in such patients, careful monitoring is recommended.In an abuse liability study of recreational polydrug users, suvorexant produced similar subjective measures of abuse liability (e.g., drug liking) as zolpidem. Prolonged use of suvorexant did not demonstrate evidence of physical dependence. There were no reported withdrawal symptoms after discontinuation of suvorexant. Abuse of suvorexant is associated with an increased risk of somnolence, daytime drowsiness, impaired reaction time, and impaired driving skills. Conditions that may increase the risk for abuse include prolonged use, a history of drug abuse or alcoholism, and those who use suvorexant in combination with alcohol or other abused drugs.

    ADVERSE REACTIONS

    Severe

    suicidal ideation / Delayed / Incidence not known

    Moderate

    memory impairment / Delayed / Incidence not known
    depression / Delayed / Incidence not known
    sleep-related behaviors / Early / Incidence not known
    amnesia / Delayed / Incidence not known
    cataplexy / Delayed / Incidence not known
    myasthenia / Delayed / Incidence not known
    sleep paralysis / Delayed / Incidence not known
    hallucinations / Early / Incidence not known
    palpitations / Early / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    psychological dependence / Delayed / Incidence not known

    Mild

    drowsiness / Early / 7.0-7.0
    headache / Early / 7.0-7.0
    dizziness / Early / 3.0-3.0
    abnormal dreams / Early / 2.0-2.0
    xerostomia / Early / 2.0-2.0
    diarrhea / Early / 2.0-2.0
    infection / Delayed / 0-2.0
    cough / Delayed / 2.0-2.0
    hyperactivity / Early / Incidence not known
    anxiety / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking medications for sleep, such as suvorexant, eszopiclone, zaleplon, or zolpidem should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
    Acetaminophen; Butalbital: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness.
    Acetaminophen; Butalbital; Caffeine: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness. (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking medications for sleep, such as suvorexant, eszopiclone, zaleplon, or zolpidem should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness. (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking medications for sleep, such as suvorexant, eszopiclone, zaleplon, or zolpidem should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
    Acetaminophen; Caffeine; Dihydrocodeine: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking medications for sleep, such as suvorexant, eszopiclone, zaleplon, or zolpidem should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking medications for sleep, such as suvorexant, eszopiclone, zaleplon, or zolpidem should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking medications for sleep, such as suvorexant, eszopiclone, zaleplon, or zolpidem should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
    Acetaminophen; Pentazocine: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed. These agents include mixed opiate agonists/antagonists.
    Acetaminophen; Tramadol: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
    Alprazolam: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines.
    Amiodarone: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with amiodarone. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and amiodarone is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
    Amitriptyline; Chlordiazepoxide: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines.
    Amobarbital: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Coadministration of suvorexant and clarithromycin is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Clarithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Coadministration of suvorexant and clarithromycin is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Clarithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Amprenavir: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with amprenavir. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and amprenavir is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhbitor increased the suvorexant AUC by 2-fold.
    Anxiolytics; Sedatives; and Hypnotics: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. Use cautiously with any anxiolytics; use with other sedatives and hypnotics should generally be avoided due to duplication of treatments.
    Apalutamide: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with apalutamide is necessary. Suvorexant is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%.
    Aprepitant, Fosaprepitant: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with aprepitant or fosaprepitant. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate. When administered as a 3-day oral regimen (125 mg/80 mg/80 mg), aprepitant is a moderate CYP3A4 inhibitor. When administered as a single oral or single intravenous dose, the inhibitory effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive substrate.
    Aripiprazole: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness. (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking medications for sleep, such as suvorexant, eszopiclone, zaleplon, or zolpidem should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness. (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking medications for sleep, such as suvorexant, eszopiclone, zaleplon, or zolpidem should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking medications for sleep, such as suvorexant, eszopiclone, zaleplon, or zolpidem should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
    Atazanavir: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with atazanavir. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and atazanavir is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
    Atazanavir; Cobicistat: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with atazanavir. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and atazanavir is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold. (Major) Coadministration of suvorexant and cobicistat is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness.
    Barbiturates: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness.
    Benzodiazepines: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines.
    Boceprevir: (Major) Coadministration of suvorexant and boceprevir is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Boceprevir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Buprenorphine: (Moderate) If concurrent use of suvorexant and buprenorphine is necessary, consider a dose reduction of one or both drugs because of the potential for additive pharmacological effects. Sedation, coma, or respiratory depression may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
    Buprenorphine; Naloxone: (Moderate) If concurrent use of suvorexant and buprenorphine is necessary, consider a dose reduction of one or both drugs because of the potential for additive pharmacological effects. Sedation, coma, or respiratory depression may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
    Butabarbital: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness.
    Caffeine: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking medications for sleep, such as suvorexant, eszopiclone, zaleplon, or zolpidem should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
    Caffeine; Ergotamine: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking medications for sleep, such as suvorexant, eszopiclone, zaleplon, or zolpidem should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
    Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and suvorexant. CNS depressants can potentiate the effects of cannabidiol.
    Carbamazepine: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with carbamazepine is necessary. Suvorexant is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%.
    Carbidopa; Levodopa; Entacapone: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
    Cariprazine: (Moderate) Due to the CNS effects of cariprazine, caution should be used when cariprazine is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics like suvorexant.
    Ceritinib: (Moderate) Monitor for suvorexant-related adverse reactions if coadministration with ceritinib is possible; a dose adjustment may be necessary. Patients should not drive or engage in other activities requiring full alertness within 8 hours of taking suvorexant. Ceritinib is a CYP3A4 inhibitor and suvorexant is primarily metabolized by CYP3A4. Coadministration with a strong CYP3A4 inhibitor increased suvorexant exposure 3-fold, while concomitant use of a moderate CYP3A4 inhibitor increased exposure 1.36-fold to 2.05-fold. The manufacturer of suvorexant recommends avoiding coadministration with strong CYP3A4 inhibitors and dosing at 5 mg (maximum, 10 mg) for patients taking moderate CYP3A4 inhibitors. The degree of CYP3A4 inhibition by ceritinib is unknown.
    Chloral Hydrate: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. Use cautiously with any anxiolytics; use with other sedatives and hypnotics should generally be avoided due to duplication of treatments.
    Chloramphenicol: (Major) Coadministration of suvorexant and chloramphenicol is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Chlordiazepoxide: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines.
    Chlordiazepoxide; Clidinium: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines.
    Ciprofloxacin: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with ciprofloxacin. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
    Clarithromycin: (Major) Coadministration of suvorexant and clarithromycin is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Clarithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Clonazepam: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines.
    Clorazepate: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines.
    Cobicistat: (Major) Coadministration of suvorexant and cobicistat is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration of suvorexant and cobicistat is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of suvorexant and cobicistat is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Conivaptan: (Major) Coadministration of suvorexant and conivaptan is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Conivaptan is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold. Conivaptan elimination occurs over several days. Subsequent treatment with CYP3A substrates such as suvorexant may be initiated no sooner than 1 week after a conivaptan infusion is completed.
    Crizotinib: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with crizotinib. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and crizotinib is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
    Cyclobenzaprine: (Moderate) Cyclobenzaprine may cause additive CNS depression if used concomitantly with other CNS depressants, such as anxiolytics, sedatives, and hypnotics. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary.
    Cyclosporine: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with cyclosporine. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and cyclosporine is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
    Dalfopristin; Quinupristin: (Major) Coadministration of suvorexant and dalfopristin; quinupristin is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Quinupristin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Darunavir: (Major) Coadministration of suvorexant and darunavir is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Darunavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Darunavir; Cobicistat: (Major) Coadministration of suvorexant and cobicistat is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold. (Major) Coadministration of suvorexant and darunavir is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Darunavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of suvorexant and cobicistat is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold. (Major) Coadministration of suvorexant and darunavir is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Darunavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Coadministration of suvorexant and ritonavir is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Ritonavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Delavirdine: (Major) Coadministration of suvorexant and delavirdine is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Delavirdine is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Deutetrabenazine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as suvorexant, may have additive effects and worsen drowsiness or sedation.
    Diazepam: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines.
    Digoxin: (Major) Digoxin concentrations should be monitored during use with suvorexant. In one evaluation, concomitant administration of digoxin and suvorexant slightly increased digoxin levels presumably due to inhibition of intestinal P-glycoprotein (P-gp) by suvorexant.
    Diltiazem: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with diltiazem. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and diltiazem is a moderate CYP3A4 inhibitor. Coadministration with diltiazem increased the suvorexant AUC by 2-fold.
    Dronabinol: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
    Dronedarone: (Major) Suvorexant is primarily metabolized by CYP3A, and the manufacturer recommends a dose reduction to 5 mg of suvorexant during concurrent use with moderate CYP3A inhibitors and a maximum recommended dose of 10 mg/day. Dronedarone is a moderate CYP3A4 inhibitor, and increased plasma concentrations of suvorexant are possible during concurrent use of these drugs.
    Droperidol: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
    Efavirenz: (Major) Suvorexant is primarily metabolized by CYP3A, and decreased systemic exposure of suvorexant may occur during concurrent use with strong CYP3A inducers such as efavirenz. Patients should be monitored for a reduction in efficacy if this combination is necessary.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Suvorexant is primarily metabolized by CYP3A, and decreased systemic exposure of suvorexant may occur during concurrent use with strong CYP3A inducers such as efavirenz. Patients should be monitored for a reduction in efficacy if this combination is necessary.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Suvorexant is primarily metabolized by CYP3A, and decreased systemic exposure of suvorexant may occur during concurrent use with strong CYP3A inducers such as efavirenz. Patients should be monitored for a reduction in efficacy if this combination is necessary.
    Elbasvir; Grazoprevir: (Moderate) Administering suvorexant with elbasvir; grazoprevir may result in elevated suvorexant plasma concentrations. Suvorexant is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Entacapone: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
    Enzalutamide: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with enzalutamide is necessary. Suvorexant is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%.
    Erythromycin: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with erythromycin. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
    Erythromycin; Sulfisoxazole: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with erythromycin. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
    Estazolam: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines.
    Eszopiclone: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. Use cautiously with any anxiolytics; use with other sedatives and hypnotics should generally be avoided due to duplication of treatments.
    Ethanol: (Major) Patients should be advised not to consume alcohol in combination with suvorexant because of additive effects. When suvorexant was co-administered with alcohol, additive psychomotor impairment was demonstrated. There was no alteration in the pharmacokinetics of suvorexant.
    Fluconazole: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with fluconazole. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and fluconazole is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
    Flurazepam: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines.
    Fosamprenavir: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with fosamprenavir. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and fosamprenavir is a CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
    Fosphenytoin: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with fosphenytoin is necessary. Suvorexant is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%.
    General anesthetics: (Moderate) CNS depressant drugs, including general anesthetics, may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of either suvorexant or the CNS depressant may be needed in some cases.
    Grapefruit juice: (Major) Suvorexant is primarily metabolized by CYP3A, and the manufacturer recommends a dose reduction to 5 mg/day initially of suvorexant, with an increase to 10 mg/day if clinically warranted, during concurrent use with moderate CYP3A inhibitors. A dose reduction should be considered in patients who regularly consume grapefruit juice, a moderate CYP3A inhibitor with the potential to increase suvorexant exposure.
    Idelalisib: (Major) Coadministration of suvorexant and idelalisib is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Idelalisib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Imatinib: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with imatinib. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
    Indinavir: (Major) Coadministration of suvorexant and indinavir is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Indinavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Isavuconazonium: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with isavuconazonium. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate. Isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of CYP3A4.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with rifampin is necessary. Suvorexant is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased suvorexant exposure by 77% to 88%.
    Isoniazid, INH; Rifampin: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with rifampin is necessary. Suvorexant is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased suvorexant exposure by 77% to 88%.
    Itraconazole: (Major) Coadministration of suvorexant and itraconazole is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Itraconazole is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Kava Kava, Piper methysticum: (Major) Any substance that acts on the CNS may interact with certain herbal products including kava kava, Piper methysticum. These interactions are probably pharmacodynamic in nature, or result from additive mechanisms of action. The possibility of pharmacodynamic interactions at normal prescription dosages of suvorexant signals the need for patients to avoid concomitant administration of dietary supplements promoted for sleep and relaxation.
    Ketoconazole: (Major) Coadministration of suvorexant and ketoconazole is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole increased the suvorexant AUC by 2.8-fold.
    Lapatinib: (Major) Suvorexant is primarily metabolized by CYP3A, and the manufacturer recommends a dose reduction to 5 mg of suvorexant during concurrent use with moderate CYP3A inhibitors and a maximum recommended dose of 10 mg/day. Lapatinib is a moderate CYP3A4 inhibitor, and increased plasma concentrations of suvorexant are possible during concurrent use of these drugs.
    Letermovir: (Major) The recommended dose of suvorexant is 5 mg and may be increased to a maximum of 10 mg if necessary for efficacy when coadministered with letermovir. Concurrent use is not recommended in patients also receiving cyclosporine, because the magnitude of the interaction may be amplified. Suvorexant is a CYP3A4 substrate. A clinically relevant increase in the plasma concentration of suvorexant may occur if given with letermovir. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates is similar to a strong CYP3A4 inhibitor.
    Lofexidine: (Moderate) Monitor for additive sedation during coadministration of lofexidine and suvorexant. Lofexidine can potentiate the effects of CNS depressants. Patients should be advised to avoid driving or performing any other tasks requiring mental alertness until the effects of the combination are known.
    Lopinavir; Ritonavir: (Major) Coadministration of suvorexant and lopinavir; ritonavir is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Lopinavir; ritonavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold. (Major) Coadministration of suvorexant and ritonavir is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Ritonavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Lorazepam: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines.
    Lumacaftor; Ivacaftor: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with lumacaftor; ivacaftor is necessary. Suvorexant is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%.
    Lurasidone: (Moderate) Drugs that can cause CNS depression, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
    Melatonin: (Major) Pharmacodynamic interactions often occur when sedative agents are used together. Until more data are available, avoid combining melatonin with other hypnotics, including suvorexant. In a clinical trial, there was clear evidence for a transitory pharmacodynamic interaction between melatonin and another hypnotic agent one hour following co-dosing. Concomitant administration resulted in increased impairment of attention, memory and co-ordination compared to the hypnotic agent alone. Use of more than one agent for hypnotic purposes may increase the risk for over-sedation, CNS effects, or sleep-related behaviors. Be alert for unusual changes in moods or behaviors. Patients reporting unusual sleep-related behaviors likely should discontinue melatonin use.
    Mephobarbital: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness.
    Meprobamate: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. Use cautiously with any anxiolytics; use with other sedatives and hypnotics should generally be avoided due to duplication of treatments.
    Methohexital: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness.
    Metyrapone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as suvorexant, should be used with caution. Additive drowsiness and/or dizziness is possible.
    Midazolam: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines.
    Mifepristone: (Major) Coadministration of suvorexant and chronic mifepristone therapy is not recommended due to the potential for significantly increased suvorexant exposure. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Suvorexant is a CYP3A4 substrate. Mifepristone is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Mirtazapine: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
    Mitotane: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with mitotane is necessary. Suvorexant is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%.
    Nabilone: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
    Nalbuphine: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed. These agents include mixed opiate agonists/antagonists.
    Nefazodone: (Major) Coadministration of suvorexant and nefazodone is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Nefazodone is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Nelfinavir: (Major) Coadministration of suvorexant and nelfinavir is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Nelfinavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Netupitant, Fosnetupitant; Palonosetron: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with netupitant; palonosetron. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and netupitant is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
    Nicardipine: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with nicardipine. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and nicardipine is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
    Nilotinib: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with nilotinib. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and nilotinib is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Coadministration of suvorexant and ritonavir is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Ritonavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Opiate Agonists: (Major) Concomitant use of opioid agonists with suvorexant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with suvorexant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opioid agonist is initiated in a patient taking suvorexant, reduce initial dosage and titrate to clinical response. If suvorexant is prescribed in a patient taking an opioid agonist, use a lower initial dose of suvorexant and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Oxazepam: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines.
    Pentazocine: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed. These agents include mixed opiate agonists/antagonists.
    Pentazocine; Naloxone: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed. These agents include mixed opiate agonists/antagonists.
    Pentobarbital: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness.
    Phenobarbital: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness.
    Phenytoin: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with phenytoin is necessary. Suvorexant is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%.
    Posaconazole: (Major) Coadministration of suvorexant and posaconazole is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Posaconazole is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Pramipexole: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
    Pregabalin: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
    Primidone: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness.
    Quazepam: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines.
    Quinine: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with quinine. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and quinine is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
    Ramelteon: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. These agents include any other sedatives and hypnotics. Ramelteon and suvorexant would be considered duplicate treatments and use together should generally be avoided.
    Ribociclib: (Major) Coadministration of suvorexant and ribociclib is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Ribociclib; Letrozole: (Major) Coadministration of suvorexant and ribociclib is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Rifampin: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with rifampin is necessary. Suvorexant is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased suvorexant exposure by 77% to 88%.
    Ritonavir: (Major) Coadministration of suvorexant and ritonavir is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Ritonavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Ropinirole: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
    Safinamide: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as suvorexant.
    Saquinavir: (Major) Coadministration of suvorexant and saquinavir is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Saquinavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Secobarbital: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness.
    Sedating H1-blockers: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
    St. John's Wort, Hypericum perforatum: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with St. John's Wort is necessary. Suvorexant is a CYP3A4 substrate and St. John's Wort is a strong CYP3A4 inducer. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%.
    Streptogramins: (Major) Coadministration of suvorexant and dalfopristin; quinupristin is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Quinupristin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Tasimelteon: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. These agents include any other sedatives and hypnotics. Tasimelteon and suvorexant would be considered duplicate treatments and use together should generally be avoided.
    Telaprevir: (Major) Coadministration of suvorexant and telaprevir is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Telaprevir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Telithromycin: (Major) Coadministration of suvorexant and telithromycin is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Telithromycin is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Temazepam: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines.
    Thiopental: (Moderate) Monitor for decreased efficacy of suvorexant if coadministration with a barbiturate is necessary. Suvorexant is a CYP3A4 substrate and barbiturates are strong CYP3A4 inducers. Coadministration with another strong CYP3A inducer decreased suvorexant exposure by 77% to 88%. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia is not recommended. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should be cautioned against driving and other activities requiring complete mental alertness.
    Tipranavir: (Major) Coadministration of suvorexant and tipranavir is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Tipranavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Tolcapone: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
    Tramadol: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
    Trandolapril; Verapamil: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with verapamil. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
    Trazodone: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
    Triazolam: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines.
    Tricyclic antidepressants: (Moderate) The use of suvorexant with other CNS depressants (e.g., tricyclic antidepressants) increases the risk of CNS depression. Dosage adjustments of suvorexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of suvorexant with other drugs to treat insomnia, such as tricyclic antidepressants used for insomnia, is not recommended.
    Valerian, Valeriana officinalis: (Major) Any substance that acts on the CNS may interact with certain herbal products including valerian, Valeriana officinalis. These interactions are probably pharmacodynamic in nature, or result from additive mechanisms of action. The possibility of pharmacodynamic interactions at normal prescription dosages of suvorexant signals the need for patients to avoid concomitant administration of dietary supplements promoted for sleep and relaxation.
    Verapamil: (Major) A dose reduction to 5 mg of suvorexant is recommended during concurrent use with verapamil. The suvorexant dose may be increased to 10 mg if needed for efficacy. Suvorexant is a CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased the suvorexant AUC by 2-fold.
    Voriconazole: (Major) Coadministration of suvorexant and voriconazole is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Voriconazole is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
    Zafirlukast: (Major) Suvorexant is primarily metabolized by CYP3A, and the manufacturer recommends a dose reduction to 5 mg of suvorexant during concurrent use with moderate CYP3A inhibitors and a maximum recommended dose of 10 mg/day. Zafirlukast is a moderate CYP3A4 inhibitor, and increased plasma concentrations of suvorexant are possible during concurrent use of these drugs.
    Zaleplon: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. Use cautiously with any anxiolytics; use with other sedatives and hypnotics should generally be avoided due to duplication of treatments.
    Zolpidem: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. Use cautiously with any anxiolytics; use with other sedatives and hypnotics should generally be avoided due to duplication of treatments.

    PREGNANCY AND LACTATION

    Pregnancy

    It is not known if suvorexant is excreted into human milk, and caution should be used when the drug is administered to a woman who is breast-feeding. Suvorexant and a hydroxyl-suvorexant metabolite were excreted in rat milk at levels higher (9 and 1.5 times, respectively) than that in maternal plasma.

    MECHANISM OF ACTION

    The mechanism by which suvorexant exerts its therapeutic effect in treating insomnia is thought to occur through its antagonism of orexin receptors. Suvorexant blocks the binding of wake-promoting neuropeptides orexin A and orexin B to the OX1R and OX2R receptors, subsequently suppressing the wake drive.

    PHARMACOKINETICS

    Suvorexant is administered orally. The kinetics of suvorexant are similar in healthy subjects and patients with insomnia. The mean volume of distribution is about 49 liters. Suvorexant is highly protein bound (> 99%) to both serum albumin and alpha-1 acid glycoprotein. Suvorexant is primarily metabolized by CYP3A, with minor involvement of CYP2C19, to form the inactive metabolite hydroxy-suvorexant. The mean half-life of suvorexant is about 12 hours. Elimination occurs primarily through the feces (66%), and to a lesser extent in the urine (23%).
     
    Affected Cytochrome P450 enzymes and drug transporters: CYP3A, P-glycoprotein (P-gp)
    Suvorexant is primarily metabolized by CYP3A, and drugs which inhibit or induce CYP3A may have a significant effect on suvorexant exposure. Suvorexant presumably inhibits P-gp, and may alter the exposure to drugs which are dependent on intestinal P-gp transport (e.g., digoxin).

    Oral Route

    After oral administration, peak concentrations occur at a median Tmax of 2 hours (range: 30 minutes to 6 hours) under fasting conditions. The Tmax is delayed by about 1.5 hours when suvorexant is administered with a high-fat meal, but there are no meaningful changes in AUC or Cmax. For fastest sleep onset, suvorexant should not be administered with or soon after a meal. The mean absolute bioavailability of the 10 mg dose is 82%. Suvorexant exposure increases in a less than dose-proportional manner over a range of 10 to 80 mg because of decreased absorption at higher doses.