Lemborexant is an oral dual orexin receptor antagonist (DORA) indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults. Lemborexant alters the signaling of neurotransmitters called orexins, which are responsible for regulating the sleep-wake cycle. Similar to other hypnotics, lemborexant may cause worsening of depression or suicidality, primarily in patients with pre-existing depression. In addition, complex sleep-related behaviors such as sleep-walking, sleep talking, or engagement in other activities while not fully awake are also possible. Patients should be informed of the potential for worsening depression, suicidality, or complex sleep-related behaviors prior to initiating treatment with lemborexant and be advised to seek medical attention immediately if any of these adverse effects occur during treatment with lemborexant.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Only administer immediately before going to bed or when getting into bed, and only when there is at least 7 hours remaining before the planned time of awakening.
-Time to sleep onset may be delayed if taken with or soon after a meal.
During premarketing controlled trials of lemborexant for insomnia in adults, the following centrally-mediated adverse effects occurred in at least 2% of lemborexant-treated patients and more frequently than in placebo-treated patients: somnolence/drowsiness or fatigue (6.9% to 9.6%), headache (4.5% to 5.9%), and nightmares or abnormal dreams (0.9% to 2.2%). In a pooled analysis, the incidence of somnolence was higher in geriatric patients than younger adults receiving the 10 mg dose of lemborexant; therefore, caution is recommended when using doses higher than 5 mg in geriatric patients. Because hypnotics such as lemborexant can cause drowsiness, there is a higher risk of falls, particularly in the elderly. Next-day impairment is possible, especially when lemborexant is taken with less than a full night of sleep remaining, if a higher than recommended dose is taken, if other CNS depressants are coadministered, or during use of medications that increase systemic exposure to lemborexant. Prescribers should caution patients against driving or other activities requiring complete mental alertness if lemborexant is taken with less than a full night of sleep remaining or if a higher than recommended dose is taken. During premarketing evaluation, lemborexant was associated with a dose-dependent worsening on measures of attention and memory impairment compared to placebo during middle-of-the-night awakenings (4 hours post-dose); there were no meaningful effects on the ability to awaken to sound (postural stability). Overall, there were no meaningful effects on next-day postural stability, memory, or driving performance, although some patients receiving the 10-mg dose experienced impairment of next-morning driving ability. Patients should be cautioned about middle-of-the-night attention and memory impairment, the potential for postural instability, and the possibility for next-morning driving impairment with the 10-mg dose of lemborexant. Lower dosages of lemborexant should be considered in patients taking other CNS depressants and the use of other hypnotics should be avoided. Concomitant use of alcohol increased systemic exposure of lemborexant and produced a greater impact on postural stability and memory compared with alcohol alone at 2 hours post-dose; therefore, alcohol consumption should be avoided.
Symptoms consistent with narcolepsy have occurred during use of orexin receptor antagonists such as lemborexant. During premarketing evaluation of lemborexant for insomnia in adults, sleep paralysis was reported in 1.6% of patients receiving 10 mg of lemborexant, 1.3% of patients receiving 5 mg of lemborexant, and no patients receiving placebo. Hypnagogic hallucinations were reported in 0.7% and 0.1% of patients receiving lemborexant 10 mg and 5 mg, respectively. Symptoms similar to mild cataplexy can occur with lemborexant (e.g., periods of leg weakness lasting from seconds to a few minutes) either at night or during the day, which may not be associated with an identified triggering event (e.g., laughter or surprise). Prescribers should explain the nature of these events to patients when prescribing lemborexant.
Complex sleep-related behaviors, which includes sleepwalking (somnambulism), sleep-driving, and completing activities while not fully awake (such as making phone calls, having sex, or preparing and eating food) can occur with the use of hypnotic medications, including lemborexant. Patients often have no recollection of these events. These activities can occur at any point in treatment and in both hypnotic-naive and experienced patients. They may also occur with or without concomitant use of alcohol or other CNS depressants. Patients should discontinue use of lemborexant immediately if any of these complex sleep-related behaviors occur and contact their health care provider about the events.
Worsening of depression, including suicidal ideation and completed suicides, have been reported during the use of hypnotics, primarily in patients with pre-existing depression. Immediately evaluate patients with worsening depression, emergent suicidal ideation, or other new or worsening adverse behaviors during treatment with lemborexant. Because intentional overdose is more common in patients with pre-existing depression, lemborexant should be prescribed in the smallest quantity consistent with good patient management to reduce the risk of overdose.
Because lemborexant is a controlled substance, psychological dependence is possible. In an abuse potential study of recreational sedative abusers receiving lemborexant doses of 10 mg to 30 mg, lemborexant produced similar subjective measures of abuse liability (e.g., "drug liking") as zolpidem 30 mg and suvorexant 40 mg and a statistically greater response than the placebo group. Abuse of lemborexant can be 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, use of higher than recommended doses, alcohol consumption, or combined use with other abused drugs. Animal studies and clinical trials showed that chronic administration of lemborexant did not result in physiologic or withdrawal symptoms upon drug discontinuation. This suggests that lemborexant does not produce physical dependence; however, the potential for physical dependence cannot be excluded and further studies are needed to confirm this finding. During premarketing evaluation, discontinuation of lemborexant was not associated with rebound insomnia.
Lemborexant 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 lemborexant. Prescribers should explain the nature of these events to patients when prescribing lemborexant.
Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, treatment of insomnia with lemborexant 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. 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.
Worsening of depression, including suicidal ideation and completed suicides, have been reported during the use of hypnotics, primarily in patients with pre-existing depression. Immediately evaluate patients with worsening depression, emergent suicidal ideation, or other new or worsening adverse behaviors during treatment with lemborexant. Because intentional overdose is more common in patients with pre-existing depression, lemborexant should be prescribed in the smallest quantity consistent with good patient management to reduce the risk of overdose.
Lemborexant should only be administered immediately before going to bed. Patients should be instructed to avoid driving or operating machinery or performing other tasks requiring mental alertness after taking their dose. Next-day impairment is possible, particularly when lemborexant is taken with less than a full night of sleep remaining or if a higher than the recommended dose is taken. The risk is also increased during coadministration with other CNS depressants or with medications that increase systemic exposure to lemborexant. Prescribers should advise patients about the potential for next-day somnolence. Additive adverse effects on postural stability and memory occur when alcohol is coadministered with lemborexant; therefore, ethanol ingestion should be avoided while taking lemborexant. Lower dosages of lemborexant should be considered in patients taking other CNS depressants, and concurrent use of other hypnotics should be avoided. Hypnotics, including lemborexant, have the potential to cause complex sleep-related behaviors (e.g., sleep-driving, preparing food, having sex) while not fully awake and frequently having no memory of the event. Patients should be informed of the risks prior to receiving a hypnotic. If a complex sleep behavior occurs, lemborexant should be discontinued immediately. Because lemborexant can cause drowsiness, the risk of falls is increased.
Consider the benefits of treatment against the potential for adverse respiratory effects before using lemborexant in patients with compromised respiratory function. Hypnotics have the potential to cause respiratory depression or oxygen desaturation, particularly in patients with preexisting pulmonary disease, such as sleep apnea or chronic obstructive pulmonary disease (COPD). The respiratory depressant effects of lemborexant have been evaluated in patients with mild to severe obstructive sleep apnea (OSA) and in those with moderate to severe COPD (i.e., FEV1 30% to 79% of predicted). In a randomized, placebo-controlled, 2-period crossover study of 37 patients with mild OSA (apnea-hypopnea index less than 15 events/hour of sleep) receiving lemborexant 10 mg/night for 8 consecutive nights, the mean treatment difference (lemborexant-placebo) on Day 8 for the apnea-hypopnea index was -0.06 (95% CI -19.5 to 1.83). In another study of same design (n= 33 patients with moderate to severe OSA with an apnea-hypopnea index of 15 events or more per hour of sleep), the mean treatment difference on Day 8 for the apnea-hypopnea index was 0.80 (95% CI, -4.88 to 3.29). Similarly, respiratory effects were also examined in a randomized, placebo-controlled 2-period crossover study of 30 patients with moderate to severe COPD. Following lemborexant 10 mg/night, the mean treatment difference (lemborexant-placebo) on Day 8 for the mean peripheral capillary oxygen saturation during sleep was 0.47 (95% CI: 0.07 to 0.87). Lemborexant has not been studied in very severe COPD (FEV1 less than 30% of predicted). Due to study limitations and the short duration of the studies performed, clinically meaningful respiratory effects of lemborexant in patients with OSA, COPD, or other compromised respiratory function cannot be excluded.
Lemborexant is a controlled substance and patients with a history of substance abuse who require lemborexant should be carefully monitored. In an abuse potential study of recreational sedative abusers receiving lemborexant doses of 10 mg to 30 mg, lemborexant produced similar subjective measures of abuse liability (e.g., drug liking) as zolpidem 30 mg and suvorexant 40 mg and a statistically greater response than the placebo group. Abuse of lemborexant can be 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, use of higher than recommended doses, and those who use lemborexant in combination with alcohol or other abused drugs.
Lemborexant is not recommended in patients with severe hepatic disease (Child-Pugh class C) because the drug has not been studied in this patient population. Because systemic exposure to lemborexant is increased in patients with moderate hepatic impairment (Child-Pugh class B), the recommended maximum daily dose in this population is 5 mg. The effect of mild hepatic impairment on lemborexant kinetics does not require a dosage adjustment; however, patients with mild hepatic impairment may experience an increased risk of somnolence.
During clinical trials of lemborexant, efficacy was similar between younger and geriatric adults aged 65 years and older. In a pooled analysis, the incidence of somnolence was higher in geriatric versus younger adults with the 10 mg dosage of lemborexant. Therefore, caution is recommended if the daily dosage is more than 5 mg in geriatric individuals. The U.S. Omnibus Budget Reconciliation Act (OBRA) regulates the use of sedative/hypnotic agents for residents of long-term care facilities (LTCFs); when a drug is being used to induce sleep or treat a sleep disorder, the facility should attempt periodic tapering of the medication as stated in the OBRA guidelines or provide documentation of continued medical necessity.
There are no available data on lemborexant use in pregnant women to evaluate for drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Neonates born to mothers using other hypnotics late in the third trimester of pregnancy have been reported to experience respiratory depression and sedation. Administration of doses exceeding the maximum recommended human dose of lemborexant during animal studies resulted in maternal and non-teratogenic fetal toxicities. There is a pregnancy exposure registry that monitors pregnancy outcomes in women who are exposed to lemborexant during pregnancy. Health care providers are encouraged to register patients in the Dayvigo Pregnancy Registry by calling 1-888-274-2378.
If the use of lemborexant is required during breast-feeding, the breastfed infant should be monitored for excessive sedation. In a single dose study of 8 lactating women, small amounts of lemborexant transferred into breast milk. There are no data on the effects of lemborexant on the breastfed infant or on milk production. Following a 10 mg maternal dose, the mean amount of lemborexant recovered was 0.0174 mg. The mean calculated daily infant dose was 0.0029 mg/kg/day based on nominal infant body weight of 6 kg, a relative infant dose of less than 2% of the maternal dose. Approximately 70% of the total amount of lemborexant that was excreted in milk was excreted by 24 hours after the single dose administration. When considering the use of lemborexant during breast-feeding, assess the developmental and health benefits of breast-feeding, along with the potential risks of infant drug exposure, and the risk of an untreated or inadequately treated maternal condition.
For the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance:
Oral dosage:
Adults: 5 mg PO immediately before bedtime and with at least 7 hours remaining before the planned time of awakening. May increase if needed; use lowest effective dose. Max: 10 mg/night. Use caution when using a dose greater than 5 mg/night in those 65 years of age and older. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Maximum Dosage Limits:
-Adults
10 mg/day PO.
-Geriatric
10 mg/day PO.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Child-Pugh class A: No dosage adjustments are needed.
Child-Pugh class B: The initial and maximum recommended dose is 5 mg/night PO.
Child-Pugh class C: Use is not recommended.
Patients with Renal Impairment Dosing
Dosage adjustments are not needed in patients with mild, moderate, or severe renal impairment; however, patients with severe renal impairment may have an increased risk of somnolence.
Intermittent hemodialysis
Because lemborexant is highly protein-bound, hemodialysis is not expected to contribute to elimination of the drug.
*non-FDA-approved indication
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with lemborexant may cause excessive sedation and somnolence. Limit the use of dihydrocodeine with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression. Avoid prescribing dihydrocodeine cough medicine in patients taking lemborexant.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Acetaminophen; Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with lemborexant may cause excessive sedation and somnolence. Limit the use of codeine with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression. Avoid prescribing codeine cough medicine in patients taking lemborexant.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Acetaminophen; Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with lemborexant may cause excessive sedation and somnolence. Limit the use of hydrocodone with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression. Avoid prescribing hydrocodone cough medicine in patients taking lemborexant.
Acetaminophen; Oxycodone: (Moderate) Concomitant use of oxycodone with lemborexant may cause excessive sedation and somnolence. Limit the use of oxycodone with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Acrivastine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Adagrasib: (Major) Avoid coadministration of lemborexant and adagrasib as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; adagrasib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the lemborexant overall exposure by up to 4.5-fold.
Alfentanil: (Moderate) Concomitant use of alfenatanil with lemborexant may cause excessive sedation and somnolence. Limit the use of alfenatanil with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Alprazolam: (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Amiodarone: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with amiodarone as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; amiodarone is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Amitriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and tricyclic antidepressants. Dosage adjustments of lemborexant and the tricyclic antidepressant may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Amobarbital: (Major) Avoid coadministration of lemborexant and amobarbital as concurrent use may decrease lemborexant exposure which may reduce efficacy. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Lemborexant is a CYP3A4 substrate; amobarbital sodium is a moderate CYP3A4 inducer.
Amoxapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and amoxapine. Dosage adjustments of lemborexant and amoxapine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of lemborexant and clarithromycin as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Use of lemborexant with other sedatives and hypnotics should generally be avoided due to duplication of treatments and due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed.
Apalutamide: (Major) Avoid coadministration of lemborexant and apalutamide as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; apalutamide is a strong CYP3A4 inducer.
Apomorphine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and apomorphine. Dosage adjustments of lemborexant and apomorphine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Aprepitant, Fosaprepitant: (Major) Avoid coadministration of lemborexant and aprepitant as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; aprepitant is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Aripiprazole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Asciminib: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with asciminib as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; asciminib is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Asenapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid coadministration of lemborexant and butalbital as concurrent use may decrease lemborexant exposure which may reduce efficacy. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Lemborexant is a CYP3A4 substrate; butalbital is a moderate CYP3A4 inducer.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and orphenadrine. Dosage adjustments of lemborexant and orphenadrine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with lemborexant may cause excessive sedation and somnolence. Limit the use of codeine with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression. Avoid prescribing codeine cough medicine in patients taking lemborexant. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and carisoprodol. Dosage adjustments of lemborexant and carisoprodol may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of oxycodone with lemborexant may cause excessive sedation and somnolence. Limit the use of oxycodone with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Atazanavir: (Major) Avoid coadministration of lemborexant and atazanavir as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong/moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Atazanavir; Cobicistat: (Major) Avoid coadministration of lemborexant and atazanavir as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong/moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold. (Major) Avoid coadministration of lemborexant and cobicistat as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Atropine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atropine. Dosage adjustments of lemborexant and atropine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Atropine; Difenoxin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atropine. Dosage adjustments of lemborexant and atropine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
atypical antipsychotic: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Avacopan: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with avacopan as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; avacopan is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Azelastine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and azelastine. Dosage adjustments of lemborexant and azelastine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Azelastine; Fluticasone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and azelastine. Dosage adjustments of lemborexant and azelastine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Baclofen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and baclofen. Dosage adjustments of lemborexant and baclofen may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Belladonna; Opium: (Moderate) Concomitant use of opium with lemborexant may cause excessive sedation and somnolence. Limit the use of opium with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Belumosudil: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with belumosudil as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; belumosudil is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Benzhydrocodone; Acetaminophen: (Moderate) Concomitant use of benzhydrocodone with lemborexant may cause excessive sedation and somnolence. Limit the use of benzhydrocodone with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Benzodiazepines: (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Berotralstat: (Major) Avoid coadministration of lemborexant and berotralstat as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; berotralstat is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Bexarotene: (Major) Avoid coadministration of lemborexant and bexarotene as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; bexarotene is a moderate CYP3A4 inducer.
Bicalutamide: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with bicalutamide as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; bicalutamide is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Bosentan: (Major) Avoid coadministration of lemborexant and bosentan as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; bosentan is a moderate CYP3A4 inducer.
Brexpiprazole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Brompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Brompheniramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Brompheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Buprenorphine: (Moderate) Concomitant use of opiate agonists-antagonists with lemborexant may cause excessive sedation and somnolence. Limit the use of the opiate agonists-antagonist with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Buprenorphine; Naloxone: (Moderate) Concomitant use of opiate agonists-antagonists with lemborexant may cause excessive sedation and somnolence. Limit the use of the opiate agonists-antagonist with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Bupropion: (Moderate) Monitor for loss of efficacy of bupropion during coadministration of lemborexant as concurrent use may decrease bupropion exposure. A bupropion dose adjustment may be necessary; do not exceed maximum dose for the specific product prescribed. Bupropion is a sensitive substrate of CYP2B6; lemborexant is a weak CYP2B6 inducer.
Bupropion; Naltrexone: (Moderate) Monitor for loss of efficacy of bupropion during coadministration of lemborexant as concurrent use may decrease bupropion exposure. A bupropion dose adjustment may be necessary; do not exceed maximum dose for the specific product prescribed. Bupropion is a sensitive substrate of CYP2B6; lemborexant is a weak CYP2B6 inducer.
Butalbital; Acetaminophen: (Major) Avoid coadministration of lemborexant and butalbital as concurrent use may decrease lemborexant exposure which may reduce efficacy. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Lemborexant is a CYP3A4 substrate; butalbital is a moderate CYP3A4 inducer.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid coadministration of lemborexant and butalbital as concurrent use may decrease lemborexant exposure which may reduce efficacy. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Lemborexant is a CYP3A4 substrate; butalbital is a moderate CYP3A4 inducer.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid coadministration of lemborexant and butalbital as concurrent use may decrease lemborexant exposure which may reduce efficacy. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Lemborexant is a CYP3A4 substrate; butalbital is a moderate CYP3A4 inducer. (Moderate) Concomitant use of codeine with lemborexant may cause excessive sedation and somnolence. Limit the use of codeine with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression. Avoid prescribing codeine cough medicine in patients taking lemborexant.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid coadministration of lemborexant and butalbital as concurrent use may decrease lemborexant exposure which may reduce efficacy. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Lemborexant is a CYP3A4 substrate; butalbital is a moderate CYP3A4 inducer. (Moderate) Concomitant use of codeine with lemborexant may cause excessive sedation and somnolence. Limit the use of codeine with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression. Avoid prescribing codeine cough medicine in patients taking lemborexant.
Butorphanol: (Moderate) Concomitant use of opiate agonists-antagonists with lemborexant may cause excessive sedation and somnolence. Limit the use of the opiate agonists-antagonist with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Contraindicated) Coadministration of sodium oxybate with other sedative hypnotic drugs, such as lemborexant, is contraindicated. The concurrent use of sodium oxybate and other CNS depressants may increase the risk of respiratory depression, hypotension, profound sedation, syncope, and death.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and cannabidiol. Dosage adjustments of lemborexant and cannabidiol may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Capivasertib: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with capivasertib as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; capivasertib is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Capsaicin; Metaxalone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and metaxalone. Dosage adjustments of lemborexant and metaxalone may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Carbamazepine: (Major) Avoid coadministration of lemborexant and carbamazepine as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Additive CNS effects are also possible; monitor for sedation or other potential impairment.
Carbidopa; Levodopa: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and levodopa. Dosage adjustments of lemborexant and levodopa may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Carbidopa; Levodopa; Entacapone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and entacapone. Dosage adjustments of lemborexant and entacapone may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and levodopa. Dosage adjustments of lemborexant and levodopa may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Carbinoxamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Cariprazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Carisoprodol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and carisoprodol. Dosage adjustments of lemborexant and carisoprodol may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Celecoxib; Tramadol: (Moderate) Concomitant use of tramadol with lemborexant may cause excessive sedation and somnolence. Limit the use of tramadol with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Cenobamate: (Major) Avoid coadministration of lemborexant and cenobamate as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; cenobamate is a moderate CYP3A4 inducer. Additive CNS effects, such as sedation and psychomotor impairment, are also possible.
Ceritinib: (Major) Avoid coadministration of lemborexant and ceritinib as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration of lemborexant with a strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Cetirizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and cetirizine. Dosage adjustments of lemborexant and cetirizine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Cetirizine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and cetirizine. Dosage adjustments of lemborexant and cetirizine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Chlophedianol; Dexbrompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Chloramphenicol: (Major) Avoid coadministration of lemborexant and chloramphenicol as concurrent use may significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Chlorcyclizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Chlordiazepoxide: (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Chlordiazepoxide; Amitriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and tricyclic antidepressants. Dosage adjustments of lemborexant and the tricyclic antidepressant may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Chlordiazepoxide; Clidinium: (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with lemborexant may cause excessive sedation and somnolence. Limit the use of codeine with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression. Avoid prescribing codeine cough medicine in patients taking lemborexant. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with lemborexant may cause excessive sedation and somnolence. Limit the use of hydrocodone with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression. Avoid prescribing hydrocodone cough medicine in patients taking lemborexant. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Chlorpheniramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Chlorpheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Chlorpromazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and phenothiazines. Dosage adjustments of lemborexant and the phenothiazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Chlorzoxazone: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with chlorzoxazone as concurrent use may increase lemborexant exposure and the risk of adverse effects. Additionally, monitor for excessive sedation and somnolence during coadministration as additive CNS effects are possible. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Lemborexant is a CYP3A4 substrate; chlorzoxazone is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Cimetidine: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with cimetidine as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; cimetidine is a weak CYP3A4 inhibitor. Consider if an alternative to cimetidine would be appropriate for the patient. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Ciprofloxacin: (Major) Avoid coadministration of lemborexant and ciprofloxacin as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; ciprofloxacin is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Clarithromycin: (Major) Avoid coadministration of lemborexant and clarithromycin as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Clemastine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Clobazam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and clobazam. Dosage adjustments of lemborexant and clobazam may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Clofazimine: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with clofazimine as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; clofazimine is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Clomipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and tricyclic antidepressants. Dosage adjustments of lemborexant and the tricyclic antidepressant may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Clonazepam: (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Clonidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and clonidine. Dosage adjustments of lemborexant and clonidine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Clorazepate: (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Clozapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Cobicistat: (Major) Avoid coadministration of lemborexant and cobicistat as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Cocaine: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with cocaine systemically as concurrent use may increase lemborexant exposure and the risk of adverse effects. The relatively low plasma concentrations of cocaine resulting from topical or nasal solutions are not expected to raise significant drug-drug interaction concerns. Recreational use of cocaine, however, should be avoided by the patient. Lemborexant is a CYP3A4 substrate; cocaine is reported to be a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Codeine: (Moderate) Concomitant use of codeine with lemborexant may cause excessive sedation and somnolence. Limit the use of codeine with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression. Avoid prescribing codeine cough medicine in patients taking lemborexant.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with lemborexant may cause excessive sedation and somnolence. Limit the use of codeine with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression. Avoid prescribing codeine cough medicine in patients taking lemborexant.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with lemborexant may cause excessive sedation and somnolence. Limit the use of codeine with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression. Avoid prescribing codeine cough medicine in patients taking lemborexant.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with lemborexant may cause excessive sedation and somnolence. Limit the use of codeine with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression. Avoid prescribing codeine cough medicine in patients taking lemborexant. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and phenothiazines. Dosage adjustments of lemborexant and the phenothiazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with lemborexant may cause excessive sedation and somnolence. Limit the use of codeine with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression. Avoid prescribing codeine cough medicine in patients taking lemborexant. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and phenothiazines. Dosage adjustments of lemborexant and the phenothiazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Conivaptan: (Major) Avoid coadministration of lemborexant and conivaptan as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; conivaptan is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the lemborexant AUC by up to 4.5-fold.
Crizotinib: (Major) Avoid coadministration of lemborexant and crizotinib as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; crizotinib is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Cyclobenzaprine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and cyclobenzaprine. Dosage adjustments of lemborexant and cyclobenzaprine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Cyclosporine: (Major) Avoid coadministration of lemborexant and cyclosporine as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; cyclosporine is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Cyproheptadine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Dabrafenib: (Major) Avoid coadministration of lemborexant and dabrafenib as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; dabrafenib is a moderate CYP3A4 inducer.
Dalfopristin; Quinupristin: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with streptogramins such as quinupristin as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; quinupristin inhibits CYP3A4. It is reasonable to expect that the concomitant administration may likely result in increased plasma concentrations of lemborexant. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Danazol: (Major) Avoid coadministration of lemborexant and danazol as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Dantrolene: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and dantrolene. Dosage adjustments of lemborexant and dantrolene may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Daridorexant: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with daridorexant as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; daridorexant is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold. Use together is not recommended as both are in the same class and used to treat insomnia.
Darunavir: (Major) Avoid coadministration of lemborexant and darunavir as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Darunavir; Cobicistat: (Major) Avoid coadministration of lemborexant and cobicistat as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold. (Major) Avoid coadministration of lemborexant and darunavir as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of lemborexant and cobicistat as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold. (Major) Avoid coadministration of lemborexant and darunavir as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Delavirdine: (Major) Avoid coadministration of lemborexant and delavirdine as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Desipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and tricyclic antidepressants. Dosage adjustments of lemborexant and the tricyclic antidepressant may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Deutetrabenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and deutetrabenazine. Dosage adjustments of lemborexant and deutetrabenazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Dexbrompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Dexchlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Dexmedetomidine: (Moderate) Although CNS depression is a desired effect of dexmedetomidine, patients also receiving lemborexant should be closely monitored for additive effects that may prolong recovery after administration of dexmedetomidine.
Dextromethorphan; Bupropion: (Moderate) Monitor for loss of efficacy of bupropion during coadministration of lemborexant as concurrent use may decrease bupropion exposure. A bupropion dose adjustment may be necessary; do not exceed maximum dose for the specific product prescribed. Bupropion is a sensitive substrate of CYP2B6; lemborexant is a weak CYP2B6 inducer.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Diazepam: (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Diltiazem: (Major) Avoid coadministration of lemborexant and diltiazem as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; diltiazem is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Dimenhydrinate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Diphenhydramine; Ibuprofen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Diphenhydramine; Naproxen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Diphenhydramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Diphenoxylate; Atropine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atropine. Dosage adjustments of lemborexant and atropine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Doxepin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and tricyclic antidepressants. Dosage adjustments of lemborexant and the tricyclic antidepressant may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Doxylamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Doxylamine; Pyridoxine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Dronabinol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and dronabinol. Dosage adjustments of lemborexant and dronabinol may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Dronedarone: (Major) Avoid coadministration of lemborexant and dronedarone as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; dronedarone is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Droperidol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and droperidol. Dosage adjustments of lemborexant and droperidol may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Duvelisib: (Major) Avoid coadministration of lemborexant and duvelisib as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Efavirenz: (Major) Avoid coadministration of lemborexant and efvirenz as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; efavirenz is a moderate CYP3A4 inducer.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of lemborexant and efvirenz as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; efavirenz is a moderate CYP3A4 inducer.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of lemborexant and efvirenz as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; efavirenz is a moderate CYP3A4 inducer.
Elagolix: (Major) Avoid coadministration of lemborexant and elagolix as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; elagolix is a moderate CYP3A4 inducer.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid coadministration of lemborexant and elagolix as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; elagolix is a moderate CYP3A4 inducer.
Elbasvir; Grazoprevir: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with grazoprevir as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; grazoprevir is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Elexacaftor; tezacaftor; ivacaftor: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with ivacaftor as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; ivacaftor is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Eluxadoline: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with eluxadoline as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; eluxadoline is reported to be a weak CYP3A4 inhibitor, but clinically relevant drug-drug interactions with eluxadoline are not certain. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of lemborexant and cobicistat as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of lemborexant and cobicistat as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Encorafenib: (Major) Avoid coadministration of lemborexant and encorafenib as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A substrate; encorafenib is a strong CYP3A inducer.
Entacapone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and entacapone. Dosage adjustments of lemborexant and entacapone may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Enzalutamide: (Major) Avoid coadministration of lemborexant and enzalutamide as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; enzalutamide is a strong CYP3A4 inducer.
Erythromycin: (Major) Avoid coadministration of lemborexant and erythromycin as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; erythromycin is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Eslicarbazepine: (Major) Avoid coadministration of lemborexant and eslicarbazepine as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; eslicarbazepine is a moderate CYP3A4 inducer.
Estazolam: (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Eszopiclone: (Moderate) Use of lemborexant with other sedatives and hypnotics should generally be avoided due to duplication of treatments and due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed.
Ethanol: (Major) Advise patients to avoid the use of alcohol with lemborexant as concurrent use increases lemborexant exposure and the risk for additive CNS depression and impairment, including daytime impairment. Use of alcohol with lemborexant increased the lemborexant AUC by 1.5- to 2-fold.
Etomidate: (Moderate) Although CNS depression is a desired effect of general anesthetics, monitor patients also receiving lemborexant closely for additive CNS depression that may prolong recovery after administration of a general anesthetic.
Etravirine: (Major) Avoid coadministration of lemborexant and etravirine as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; etravirine is a moderate CYP3A4 inducer.
Everolimus: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with everolimus as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; everolimus is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Fedratinib: (Major) Avoid coadministration of lemborexant and fedratinib as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; fedratinib is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and lemborexant. Concurrent use may result in additive CNS depression.
Fentanyl: (Moderate) Concomitant use of fentanyl with lemborexant may cause excessive sedation and somnolence. Limit the use of fentanyl with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Fexinidazole: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with fexinidazole as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; fexinidazole is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Flibanserin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and flibanserin. Dosage adjustments of lemborexant and flibanserin may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Fluconazole: (Major) Avoid coadministration of lemborexant and fluconazole as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; fluconazole is a moderate CYP3A4 inhibitor. In a drug interaction study, fluconazole increased the lemborexant AUC by up to 4.5-fold.
Fluoxetine: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with fluoxetine as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; fluoxetine is a weak CYP3A4 inhibitor and one metabolite, norfluoxetine, is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Fluphenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and phenothiazines. Dosage adjustments of lemborexant and the phenothiazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Flurazepam: (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Fluvoxamine: (Major) Avoid coadministration of lemborexant and fluvoxamine as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; fluvoxamine maleate is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Fosamprenavir: (Major) Avoid coadministration of lemborexant and fosamprenavir as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the lemborexant overall exposure by up to 4.5-fold.
Fosphenytoin: (Major) Avoid coadministration of lemborexant and fosphenytoin as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; fosphenytoin is a strong CYP3A4 inducer. Additive CNS effects, such as sedation or impairment, may also be possible.
Fostamatinib: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with fostamatinib as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; fostamatinib is a weak CYP3A4 inhibitor. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and gabapentin. Dosage adjustments of lemborexant and gabapentin may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
General anesthetics: (Moderate) Although CNS depression is a desired effect of general anesthetics, monitor patients also receiving lemborexant closely for additive CNS depression that may prolong recovery after administration of a general anesthetic.
Grapefruit juice: (Major) It is advisable to have patients avoid grapefruit juice and grapefruit during treatment with lemborexant due to an expected significant increase in lemborexant exposure and risk for side effects. Lemborexant is a CYP3A4 substrate; grapefruit juice is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Guanfacine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and guanfacine. Dosage adjustments of lemborexant and guanfacine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with lemborexant may cause excessive sedation and somnolence. Limit the use of hydrocodone with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression. Avoid prescribing hydrocodone cough medicine in patients taking lemborexant.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with lemborexant may cause excessive sedation and somnolence. Limit the use of hydrocodone with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression. Avoid prescribing hydrocodone cough medicine in patients taking lemborexant.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with lemborexant may cause excessive sedation and somnolence. Limit the use of hydrocodone with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression. Avoid prescribing hydrocodone cough medicine in patients taking lemborexant.
Hydromorphone: (Moderate) Concomitant use of hydromorphone with lemborexant may cause excessive sedation and somnolence. Limit the use of hydromorphone with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Hydroxyzine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Ibuprofen; Oxycodone: (Moderate) Concomitant use of oxycodone with lemborexant may cause excessive sedation and somnolence. Limit the use of oxycodone with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Idelalisib: (Major) Avoid coadministration of lemborexant and idelalisib as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong/moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Iloperidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Imatinib: (Major) Avoid coadministration of lemborexant and imatinib as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; imatinib mesylate is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Imipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and tricyclic antidepressants. Dosage adjustments of lemborexant and the tricyclic antidepressant may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Indinavir: (Major) Avoid coadministration of lemborexant and indinavir as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; indinavir is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Isavuconazonium: (Major) Avoid coadministration of lemborexant and isavuconazonium as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; isavuconazonium is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Isocarboxazid: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and monoamine oxidase inhibitors (MAOIs). Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Isoflurane: (Moderate) Although CNS depression is a desired effect of general anesthetics, monitor patients also receiving lemborexant closely for additive CNS depression that may prolong recovery after administration of a general anesthetic.
Isoniazid, INH: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with isoniazid, INH as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; isoniazid is a weak CYP3A4 inhibitor. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of lemborexant and rifampin as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with isoniazid, INH as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; isoniazid is a weak CYP3A4 inhibitor. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of lemborexant and rifampin as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with isoniazid, INH as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; isoniazid is a weak CYP3A4 inhibitor. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Istradefylline: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with istradefylline as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; istradefylline is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Itraconazole: (Major) Avoid coadministration of lemborexant and itraconazole as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; itraconazole is a strong CYP3A4 inhibitor. In a drug interaction study, itraconazole increased the lemborexant AUC by up to 4.5-fold.
Ivacaftor: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with ivacaftor as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; ivacaftor is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Ketamine: (Moderate) Although CNS depression is a desired effect of general anesthetics, monitor patients also receiving lemborexant closely for additive CNS depression that may prolong recovery after administration of a general anesthetic.
Ketoconazole: (Major) Avoid coadministration of lemborexant and ketoconazole as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; ketoconazole is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of lemborexant and clarithromycin as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Lapatinib: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with lapatinib as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; lapatinib is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Larotrectinib: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with larotrectinib as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; larotrectinib is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and lasmiditan. Dosage adjustments of lemborexant and lasmiditan may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Lefamulin: (Major) Avoid coadministration of lemborexant and lefamulin as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; lefamulin is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Lenacapavir: (Major) Avoid coadministration of lemborexant and lenacapavir as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; lenacapavir is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the lemborexant overall exposure by up to 4.5-fold.
Letermovir: (Major) Avoid coadministration of lemborexant and letermovir as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; letermovir is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Levocetirizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and cetirizine. Dosage adjustments of lemborexant and cetirizine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Levodopa: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and levodopa. Dosage adjustments of lemborexant and levodopa may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Levoketoconazole: (Major) Avoid coadministration of lemborexant and ketoconazole as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; ketoconazole is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Levorphanol: (Moderate) Concomitant use of levorphanol with lemborexant may cause excessive sedation and somnolence. Limit the use of levorphanol with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Lofexidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and lofexidine. Dosage adjustments of lemborexant and lofexidine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Lonafarnib: (Major) Avoid coadministration of lemborexant and lonafarnib as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; lonafarnib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lemborexant and ritonavir as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse CNS effects. Lemborexant is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Lorazepam: (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Lorlatinib: (Major) Avoid coadministration of lemborexant and lorlatinib as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; lorlatinib is a moderate CYP3A4 inducer.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of lemborexant and lumacaftor as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; lumacaftor is a strong CYP3A4 inducer. (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with ivacaftor as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; ivacaftor is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of lemborexant and lumacaftor as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; lumacaftor is a strong CYP3A4 inducer.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Lurasidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Maprotiline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and maprotiline. Dosage adjustments of lemborexant and maprotiline may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Maribavir: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with maribavir as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; maribavir is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Mavacamten: (Major) Avoid coadministration of lemborexant and mavacamten as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A substrate; mavacamten is a moderate CYP3A inducer.
Meclizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Melatonin: (Major) The use of lemborexant with other hypnotic drugs, such as melatonin, is not recommended. In a clinical trial, there was clear evidence for a transitory pharmacodynamic interaction between melatonin and another hypnotic agent 1 hour following co-dosing. Concomitant administration resulted in increased impairment of attention, memory and coordination compared to the hypnotic agent alone. Use of more than 1 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 should likely discontinue melatonin use.
Meperidine: (Moderate) Concomitant use of meperidine with lemborexant may cause excessive sedation and somnolence. Limit the use of meperidine with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Meprobamate: (Moderate) Use of lemborexant with other sedatives and hypnotics should generally be avoided due to duplication of treatments and due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed.
Metaxalone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and metaxalone. Dosage adjustments of lemborexant and metaxalone may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Methadone: (Moderate) Monitor for reduced efficacy of methadone and signs of opioid withdrawal if coadministration with lemborexant is necessary. Consider increasing the dose of methadone as needed. Also monitor for additive CNS effects. If lemborexant is discontinued, consider a dose reduction of methadone and frequently monitor for signs or respiratory depression and sedation. Methadone is a substrate of CYP3A4, CYP2B6, CYP2C19, CYP2C9, and CYP2D6; lemborexant is a weak CYP2B6 inducer. Concomitant use can decrease methadone exposure resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Methocarbamol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and methocarbamol. Dosage adjustments of lemborexant and methocarbamol may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Methohexital: (Major) Avoid coadministration of lemborexant and methohexital as concurrent use may decrease lemborexant exposure which may reduce efficacy. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Lemborexant is a CYP3A4 substrate; methohexital is a moderate CYP3A4 inducer.
Methyldopa: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and methyldopa. Dosage adjustments of lemborexant and methyldopa may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Metoclopramide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and metoclopramide. Dosage adjustments of lemborexant and metoclopramide may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Midazolam: (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Mifepristone: (Major) Avoid coadministration of lemborexant and mifepristone as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold. Due to the long half-life of mifepristone, a drug interaction is possible for a prolonged period after discontinuation of mifepristone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Mirtazapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and mirtazapine. Dosage adjustments of lemborexant and mirtazapine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Mitotane: (Major) Avoid coadministration of lemborexant and mitotane as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; mitotane is a strong CYP3A4 inducer.
Modafinil: (Major) Avoid coadministration of lemborexant and modafinil as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; modafinil is a moderate CYP3A4 inducer.
Monoamine oxidase inhibitors: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and monoamine oxidase inhibitors (MAOIs). Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Morphine: (Moderate) Concomitant use of morphine with lemborexant may cause excessive sedation and somnolence. Limit the use of morphine with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Morphine; Naltrexone: (Moderate) Concomitant use of morphine with lemborexant may cause excessive sedation and somnolence. Limit the use of morphine with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Nabilone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of nabilone and lemborexant. Concurrent use may result in additive CNS depression.
Nafcillin: (Major) Avoid coadministration of lemborexant and nafcillin as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; nafcillin is a moderate CYP3A4 inducer.
Nalbuphine: (Moderate) Concomitant use of opiate agonists-antagonists with lemborexant may cause excessive sedation and somnolence. Limit the use of the opiate agonists-antagonist with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Nefazodone: (Major) Avoid coadministration of lemborexant and nefazodone as concurrent use may increase lemborexant exposure and the risk of adverse effects. Additive CNS effects are also possible. Lemborexant is a CYP3A4 substrate; nefazodone is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Nelfinavir: (Major) Avoid coadministration of lemborexant and nelfinavir mesylate as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; nelfinavir mesylate is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Netupitant, Fosnetupitant; Palonosetron: (Major) Avoid coadministration of lemborexant and netupitant as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; netupitant is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Nicardipine: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with nicardipine hydrochloride as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; nicardipine has been shown to be a CYP3A4 inhibitor (weak). Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Nilotinib: (Major) Avoid coadministration of lemborexant and nilotinib as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; nilotinib is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Nirmatrelvir; Ritonavir: (Major) Avoid coadministration of lemborexant and ritonavir as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse CNS effects. Lemborexant is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Nirogacestat: (Major) Avoid coadministration of lemborexant and nirogacestat as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; nirogacestat is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the lemborexant overall exposure by up to 4.5-fold.
Nortriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and tricyclic antidepressants. Dosage adjustments of lemborexant and the tricyclic antidepressant may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Olanzapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Olanzapine; Fluoxetine: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with fluoxetine as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; fluoxetine is a weak CYP3A4 inhibitor and one metabolite, norfluoxetine, is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Olanzapine; Samidorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Oliceridine: (Moderate) Concomitant use of oliceridine with lemborexant may cause excessive sedation and somnolence. Limit the use of oliceridine with lemborexant 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.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid coadministration of lemborexant and rifabutin as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; rifabutin is a moderate CYP3A4 inducer.
Opiate Agonists-Antagonists: (Moderate) Concomitant use of opiate agonists-antagonists with lemborexant may cause excessive sedation and somnolence. Limit the use of the opiate agonists-antagonist with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Opicapone: (Moderate) Opicapone should be given cautiously with other agents that cause CNS depression, including lemborexant, due to the possibility of additive sedation. COMT inhibitors, such as opicapone, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Orphenadrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and orphenadrine. Dosage adjustments of lemborexant and orphenadrine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Osilodrostat: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with osilodrostat as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; osilodrostat is a weak CYP3A4 inhibitor. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Oxazepam: (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Oxycodone: (Moderate) Concomitant use of oxycodone with lemborexant may cause excessive sedation and somnolence. Limit the use of oxycodone with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Oxymorphone: (Moderate) Concomitant use of oxymorphone with lemborexant may cause excessive sedation and somnolence. Limit the use of oxymorphone with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Pacritinib: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with pacritinib as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; pacritinib is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Palbociclib: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with palbociclib as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; palbociclib is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Paliperidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Pazopanib: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with pazopanib as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; pazopanib is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Pentazocine; Naloxone: (Moderate) Concomitant use of opiate agonists-antagonists with lemborexant may cause excessive sedation and somnolence. Limit the use of the opiate agonists-antagonist with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Pentobarbital: (Major) Avoid coadministration of lemborexant and pentobarbital as concurrent use may decrease lemborexant exposure which may reduce efficacy. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Lemborexant is a CYP3A4 substrate; pentobarbital is a moderate CYP3A4 inducer.
Perampanel: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and perampanel. Dosage adjustments of lemborexant and perampanel may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Perphenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and phenothiazines. Dosage adjustments of lemborexant and the phenothiazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Perphenazine; Amitriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and phenothiazines. Dosage adjustments of lemborexant and the phenothiazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and tricyclic antidepressants. Dosage adjustments of lemborexant and the tricyclic antidepressant may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Pexidartinib: (Major) Avoid coadministration of lemborexant and pexidartinib as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; pexidartinib is a moderate CYP3A4 inducer.
Phenelzine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and monoamine oxidase inhibitors (MAOIs). Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Phenobarbital: (Major) Avoid coadministration of lemborexant and phenobarbital as concurrent use may decrease lemborexant exposure which may reduce efficacy. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Lemborexant is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of lemborexant and phenobarbital as concurrent use may decrease lemborexant exposure which may reduce efficacy. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Lemborexant is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atropine. Dosage adjustments of lemborexant and atropine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and scopolamine. Dosage adjustments of lemborexant and scopolamine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Phenothiazines: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and phenothiazines. Dosage adjustments of lemborexant and the phenothiazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Phenytoin: (Major) Avoid coadministration of lemborexant and phenytoin as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; phenytoin is a strong CYP3A4 inducer. Additive CNS effects, such as sedation or impairment, may also be possible.
Pirtobrutinib: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with pirtobrutinib as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; pirtobrutinib is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Posaconazole: (Major) Avoid coadministration of lemborexant and posaconazole as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Pramipexole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and pramipexole. Dosage adjustments of lemborexant and pramipexole may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and pregabalin. Dosage adjustments of lemborexant and pregabalin may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Primidone: (Major) Avoid coadministration of lemborexant and primidone as concurrent use may decrease lemborexant exposure which may reduce efficacy. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Lemborexant is a CYP3A4 substrate; primidone is a strong CYP3A4 inducer.
Prochlorperazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and phenothiazines. Dosage adjustments of lemborexant and the phenothiazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Promethazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and phenothiazines. Dosage adjustments of lemborexant and the phenothiazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Promethazine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and phenothiazines. Dosage adjustments of lemborexant and the phenothiazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Promethazine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and phenothiazines. Dosage adjustments of lemborexant and the phenothiazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Propofol: (Moderate) Although CNS depression is a desired effect of general anesthetics, monitor patients also receiving lemborexant closely for additive CNS depression that may prolong recovery after administration of a general anesthetic.
Protriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and tricyclic antidepressants. Dosage adjustments of lemborexant and the tricyclic antidepressant may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Pseudoephedrine; Triprolidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Quazepam: (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Quetiapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Quinine: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with quinine as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; quinine is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Ramelteon: (Major) The use of lemborexant with other hypnotic drugs, such as ramelteon, is not recommended. Additive sedative, CNS depressant effects, impairment, and effects on mood and behaviors, including sleep-related behaviors, may occur.
Ranitidine: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with ranitidine as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; ranitidine is a weak CYP3A4 inhibitor. Consider if an alternative to ranitidine would be appropriate for the patient. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Ranolazine: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with ranolazine as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; ranolazine is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Rasagiline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and rasagiline. Dosage adjustments of lemborexant and rasagiline may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Remifentanil: (Moderate) Concomitant use of remifentanil with lemborexant may cause excessive sedation and somnolence. Limit the use of remifentanil with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Remimazolam: (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Repotrectinib: (Major) Avoid coadministration of lemborexant and repotrectinib as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A substrate; repotrectinib is a moderate CYP3A inducer.
Ribociclib: (Major) Avoid coadministration of lemborexant and ribociclib as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Ribociclib; Letrozole: (Major) Avoid coadministration of lemborexant and ribociclib as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Rifabutin: (Major) Avoid coadministration of lemborexant and rifabutin as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; rifabutin is a moderate CYP3A4 inducer.
Rifampin: (Major) Avoid coadministration of lemborexant and rifampin as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer.
Rifapentine: (Major) Avoid coadministration of lemborexant and rifapentine as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer.
Risperidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Ritlecitinib: (Major) Avoid coadministration of lemborexant and ritlecitinib as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; ritlecitinib is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the lemborexant overall exposure by up to 4.5-fold.
Ritonavir: (Major) Avoid coadministration of lemborexant and ritonavir as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse CNS effects. Lemborexant is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Ropinirole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and ropinirole. Dosage adjustments of lemborexant and ropinirole may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Rotigotine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and rotigotine. Dosage adjustments of lemborexant and rotigotine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Rucaparib: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with rucaparib as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; rucaparib is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Safinamide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and safinamide. Dosage adjustments of lemborexant and safinamide may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Saquinavir: (Major) Avoid coadministration of lemborexant and saquinavir as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; saquinavir is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Scopolamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and scopolamine. Dosage adjustments of lemborexant and scopolamine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Secobarbital: (Major) Avoid coadministration of lemborexant and secobarbital as concurrent use may decrease lemborexant exposure which may reduce efficacy. Additive CNS effects, such as sedation and psychomotor impairment, are also possible. Lemborexant is a CYP3A4 substrate; secobarbital is a moderate CYP3A4 inducer.
Sedating H1-blockers: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Selegiline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and selegiline. Dosage adjustments of lemborexant and selegiline may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Selpercatinib: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with selpercatinib as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; selpercatinib is a weak CYP3A4 inhibitor. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Sevoflurane: (Moderate) Although CNS depression is a desired effect of general anesthetics, monitor patients also receiving lemborexant closely for additive CNS depression that may prolong recovery after administration of a general anesthetic.
Sodium Oxybate: (Contraindicated) Coadministration of sodium oxybate with other sedative hypnotic drugs, such as lemborexant, is contraindicated. The concurrent use of sodium oxybate and other CNS depressants may increase the risk of respiratory depression, hypotension, profound sedation, syncope, and death.
Sotorasib: (Major) Avoid coadministration of lemborexant and sotorasib as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; sotorasib is a moderate CYP3A4 inducer.
Spironolactone: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with spironolactone as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; spironolactone is a weak CYP3A4 inhibitor. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Spironolactone; Hydrochlorothiazide, HCTZ: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with spironolactone as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; spironolactone is a weak CYP3A4 inhibitor. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of lemborexant and St. John's Wort as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; St. John's Wort is a strong CYP3A4 inducer.
Stiripentol: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with stiripentol as concurrent use may increase lemborexant exposure and the risk of adverse effects. Additionally, monitor for excessive sedation and somnolence during coadministration as additive CNS effects are possible. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Lemborexant is a CYP3A4 substrate; stiripentol is a weak CYP3A4 inhibitor. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Streptogramins: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with streptogramins such as quinupristin as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; quinupristin inhibits CYP3A4. It is reasonable to expect that the concomitant administration may likely result in increased plasma concentrations of lemborexant. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Sufentanil: (Moderate) Concomitant use of sufentanil with lemborexant may cause excessive sedation and somnolence. Limit the use of sufentanil with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Suvorexant: (Major) Because of pharmacologic similarities as orexin receptor antagonists for insomnia, lemborexant and suvorexant should not be used together. The actions would be expected to be duplicative, and might result in additive side effects, such as somnolence, unusual behaviors or moods, next-day impairment, hallucinations, or adverse sleep-related behaviors.
Tapentadol: (Moderate) Concomitant use of tapentadol with lemborexant may cause excessive sedation and somnolence. Limit the use of tapentadol with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Tasimelteon: (Major) The use of lemborexant with other hypnotic drugs, such as tasimelteon, is not recommended. Additive sedative, CNS depressant effects, impairment, and effects on mood and behaviors, including sleep-related behaviors, may occur.
Temazepam: (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Tetrabenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and tetrabenazine. Dosage adjustments of lemborexant and tetrabenazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Tezacaftor; Ivacaftor: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with ivacaftor as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; ivacaftor is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Thalidomide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and thalidomide. Dosage adjustments of lemborexant and thalidomide may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Thioridazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and phenothiazines. Dosage adjustments of lemborexant and the phenothiazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Ticagrelor: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with ticagrelor as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; ticagrelor is a weak CYP3A4 inhibitor. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Tipranavir: (Major) Avoid coadministration of lemborexant and tipranavir as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; tipranavir is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Tizanidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and tizanidine. Dosage adjustments of lemborexant and tizanidine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Tolcapone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and tolcapone. Dosage adjustments of lemborexant and tolcapone may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Tramadol: (Moderate) Concomitant use of tramadol with lemborexant may cause excessive sedation and somnolence. Limit the use of tramadol with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Tramadol; Acetaminophen: (Moderate) Concomitant use of tramadol with lemborexant may cause excessive sedation and somnolence. Limit the use of tramadol with lemborexant 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. Educate patients about the risks and symptoms of excessive CNS depression.
Trandolapril; Verapamil: (Major) Avoid coadministration of lemborexant and verapamil as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; verapamil is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Tranylcypromine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and monoamine oxidase inhibitors (MAOIs). Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Trazodone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and trazodone. Dosage adjustments of lemborexant and trazodone may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. In general, the use of trazodone for sleep along with a hypnotic like lemborexant, should be avoided.
Triazolam: (Moderate) Monitor for excessive sedation and somnolence during use of lemborexant with benzodiazepines. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Use of more than 2 hypnotics should be avoided due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Tricyclic antidepressants: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and tricyclic antidepressants. Dosage adjustments of lemborexant and the tricyclic antidepressant may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Trifluoperazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and phenothiazines. Dosage adjustments of lemborexant and the phenothiazine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Trimipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and tricyclic antidepressants. Dosage adjustments of lemborexant and the tricyclic antidepressant may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Triprolidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Trofinetide: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with trofinetide as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; trofinetide is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Tucatinib: (Major) Avoid coadministration of lemborexant and tucatinib as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong/moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Valerian, Valeriana officinalis: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and valerian. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. Any substances that act on the CNS may theoretically interact with valerian, Valeriana officinalis. The valerian derivative, dihydrovaltrate, binds at barbiturate binding sites; valerenic acid has been shown to inhibit enzyme-induced breakdown of GABA in the brain; the non-volatile monoterpenes (valepotriates) have sedative activity. These interactions are probably pharmacodynamic in nature. Patients who are taking medications for insomnia, like lemborexant, should generally avoid concomitant administration of valerian.
Valproic Acid, Divalproex Sodium: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with valproic acid as concurrent use may increase lemborexant exposure and the risk of adverse effects. Additionally, monitor for excessive sedation and somnolence during coadministration as additive CNS effects are possible. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Lemborexant is a CYP3A4 substrate; valproic acid and related drugs (divalproex, valproate) are reported to be weak CYP3A4 inhibitors, but drug interactions due to this mechanism are not certain. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Verapamil: (Major) Avoid coadministration of lemborexant and verapamil as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; verapamil is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Viloxazine: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with viloxazine as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; viloxazine is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Vonoprazan: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with vonoprazan as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; vonoprazan is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Vonoprazan; Amoxicillin: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with vonoprazan as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; vonoprazan is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of lemborexant and clarithromycin as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold. (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with vonoprazan as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; vonoprazan is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Voriconazole: (Major) Avoid coadministration of lemborexant and voriconazole as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; voriconazole is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Voxelotor: (Major) Avoid coadministration of lemborexant and voxelotor as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; voxelotor is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased the lemborexant overall exposure by up to 4.5-fold.
Zafirlukast: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with zafirlukast as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; zafirlukast is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Zaleplon: (Moderate) Use of lemborexant with other sedatives and hypnotics should generally be avoided due to duplication of treatments and due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed.
Ziprasidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Zolpidem: (Moderate) Use of lemborexant with other sedatives and hypnotics should generally be avoided due to duplication of treatments and due to the additive CNS depressant and complex sleep-related behaviors that may occur. While anxiolytic medications may be used concurrently with lemborexant, a reduction in dose of one or both agents may be needed.
Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm.
The mechanism by which lemborexant exerts its therapeutic effect in treating insomnia is thought to occur through its competitive antagonism of orexin receptors. Lemborexant blocks the binding of wake-promoting neuropeptides orexin A and orexin B to the OX1R and OX2R receptors, which is thought to suppress the wake drive. A major metabolite of lemborexant, M10, binds with similar affinity as the parent drug to orexin receptors OX1R and OX2R. Lemborexant does not prolong the QTcF interval to any clinically relevant extent at a dose 5 times the maximum recommended dose.
Lemborexant is administered orally. Protein binding is approximately 94%. The volume of distribution is 1,970 liters. Lemborexant is primarily metabolized by CYP3A4, and to a lesser exetnt by CYP3A5. The major metabolite is M10. The half-lives of the 5 mg dose and 10 mg dose of lemborexant are 17 hours and 19 hours, respectively. Following oral administration, 57.4% of the dose was recovered in the feces and 29.1% in the urine, with less than 1% of the dose as unchanged lemborexant.
Affected Cytochrome P450 enzymes and drug transporters: CYP3A4, CYP3A5, CYP2B6
Lemborexant is primarily metabolized by CYP3A4, and to a lesser extent by CYP3A5. In vitro studies show that lemborexant and the major metabolite M10 have the potential to induce CYP3A and the weak potential to inhibit CYP3A and induce CYP2B6. Monitoring for adequate clinical response of 2B6 substrates (e.g., bupropion, methadone) is recommended during concurrent use of lemborexant. Lemborexant and M10 do not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2D6, CYP2A6, CYP2C19, CYP2E1, P-gp, BCRP, BSEP, OAT1, OAT3, OATP1B1, OATP1B3, OCT1, OCT2, MATE1, and MATE2-K. M10 is a P-gp substrate; however, the clinical significance has not been described. Lemborexant is a potential poor substrate of P-gp. Lemborexant and M10 are not substrates of BCRP, OATP1B1, or OATP1B3.
-Route-Specific Pharmacokinetics
Oral Route
The time to reach peak concentrations after an oral dose of lemborexant is about 1 to 3 hours. Following a high-fat and high-calorie meal (containing about 150, 250, and 500 to 600 calories from protein, carbohydrate, and fat, respectively), the maximum concentration (Cmax) is decreased by 23%, the AUC is increased by 18%, and tmax is delayed by 2 hour; therefore, patients should be advised that the effect of the drug may be delayed if taken with or soon after a meal.
-Special Populations
Hepatic Impairment
Lemborexant is not recommended in patients with severe hepatic impairment (Child-Pugh class C) because the drug has not been studied in this population. During premarketing evaluation, lemborexant exposure (AUC) and terminal half-life were increased in patients with moderate hepatic impairment (Child-Pugh class B); therefore, dosage adjustments are recommended in this population. In patients with mild hepatic impairment (Child-Pugh class A), the lemborexant AUC was increased, but the terminal half-life was not changed. No dosage adjustments are recommended in patients with mild hepatic impairment.
Renal Impairment
During premarketing evaluation, lemborexant AUC was increased in patients with severe renal impairment. However, no dosage adjustments are required in patients with mild, moderate, or severe renal impairment.
Pediatrics
The pharmacokinetics of lemborexant have not been formally studied in pediatric patients.
Geriatric
No clinically significant differences in kinetic parameters of lemborexant have been observed based on age.
Gender Differences
No clinically significant differences in kinetic parameters of lemborexant have been observed based on gender.
Ethnic Differences
No clinically significant differences in kinetic parameters of lemborexant have been observed based on race or ethnicity.
Obesity
No clinically significant differences in kinetic parameters of lemborexant have been observed based on body mass index.