Dayvigo

— THERAPEUTIC CATEGORIES —
  • Sleep-wake disorders
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Dayvigo Generic Name & Formulations

    Legal Class

    CIV

    General Description

    Lemborexant 5mg, 10mg; tabs.

    Pharmacological Class

    Orexin receptor antagonist.

    How Supplied

    Tabs—30, 90

    How Supplied

    Dayvigo (lemborexant) tablets are supplied in 30- and 90-count bottles and are available as:  

    • 5 mg, pale yellow, round, biconvex, film-coated tablets, and debossed with "5" on one side and "LЄM" on the other side. 

    • 10 mg, orange, round, biconvex, film-coated tablets, and debossed with "10" on one side and "LЄM" on the other side. 

    Storage

    • Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP Controlled Room Temperature]. 

    Manufacturer

    Eisai Pharmaceuticals

    Generic Availability

    NO

    Mechanism of Action

    Lemborexant exerts its therapeutic effects in insomnia is presumed to be through antagonism of orexin receptors. The orexin neuropeptide signaling system is a central promoter of wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive.

    Dayvigo Indications

    Indications

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

    Dayvigo Dosage and Administration

    Adult

    Take immediately before bedtime, with (≥7hrs) remaining before the planned time of awakening. 5mg once per night; may increase to max 10mg once daily based on clinical response and tolerability. Concomitant weak CYP3A inhibitors or moderate hepatic impairment: max 5mg once daily. Effect may be delayed if taken with or soon after a meal.

    Children

    Not established.

    Nursing Considerations

    Dayvigo (lemborexant) tablets are supplied in 30- and 90-count bottles and are available as:  

    • 5 mg, pale yellow, round, biconvex, film-coated tablets, and debossed with "5" on one side and "LЄM" on the other side. 

    • 10 mg, orange, round, biconvex, film-coated tablets, and debossed with "10" on one side and "LЄM" on the other side. 

    Dayvigo Contraindications

    Contraindications

    Narcolepsy.

    Dayvigo Boxed Warnings

    Not Applicable

    Dayvigo Warnings/Precautions

    Warnings/Precautions

    CNS depression. Daytime impairment (including impaired driving w. 10mg dose). Monitor for somnolence. Discontinue immediately if any complex sleep behaviors develop. Compromised respiratory function (eg, moderate to severe COPD, mild to severe obstructive sleep apnea). Suicidal ideation or behavior. Depression. Monitor for worsening insomnia or new cognitive/behavioral abnormalities. Reevaluate if unresponsive after 7–10 days of treatment. Severe renal or mild hepatic impairment: possible increased risk of somnolence. Severe hepatic impairment: not recommended. Drug or alcohol abusers. Elderly. Pregnancy. Nursing mothers.

    Warnings/Precautions

    CNS Depressant Effects and Daytime Impairment

    • CNS depressant effects may persist in some patients for up to several days after discontinuing Dayvigo. Inform patients about the potential risk for next-day somnolence.

    • Increased risk for daytime impairment if Dayvigo is taken with less than a full night of sleep remaining or if a higher than recommended dose is taken. Caution patients against driving and other activities.

    • Increased risk for CNS depression when used with other CNS depressants (eg, benzodiazepines, opioids, tricyclics, alcohol.

    • Avoid consuming alcohol with Dayvigo.

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

    • Sleep paralysis may occur, which is an inability to move or speak for up to several minutes during sleep-wake transitions, and hypnagogic/hypnopompic hallucinations, including vivid and disturbing perceptions.

    Complex Sleep Behaviors 

    • Complex sleep behaviors, including sleep-walking, sleep-driving, and engaging in other activities while not fully awake (e.g., preparing and eating food, making phone calls, having sex) may occur.

    • Discontinue immediately if complex sleep behaviors occur.

    Patients with Compromised Respiratory Function 

    • The effect of Dayvigo has been evaluated in mild to severe Obstructive Sleep Apnea (OSA) and moderate to severe Chronic Obstructive Pulmonary Disease (COPD) in short-term clinical trials. Consider the effect of Dayvigo on respiratory function in patients with compromised respiratory function.

    Worsening of Depression/Suicidal Ideation

    • In primarily depressed patients treated with hypnotics, worsening of depression and suicidal thoughts and actions (including completed suicides) have been reported.

    • Monitor carefully for the emergence of any new behavioral sign or symptom of concern.

    Need to Evaluate for Comorbid Diagnoses 

    • Monitor for worsening insomnia or new cognitive/behavioral abnormalities. 

    • Reevaluate if unresponsive after 7–10 days of treatment. This may be the result of an unrecognized underlying psychiatric or medical disorder.

    Pregnancy Considerations

    Pregnancy Exposure Registry 

    • There is a pregnancy exposure registry that monitors pregnancy outcomes in women who are exposed to Dayvigo during pregnancy. Healthcare providers are encouraged to register patients in the Dayvigo pregnancy registry by calling 1-888-274-2378.  

    Risk Summary 

    • No available data in pregnant women to evaluate drug-associated risk.

    Nursing Mother Considerations

    Risk Summary 

    • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for Dayvigo and any potential adverse effects on the breastfed infant from Dayvigo or from the underlying maternal condition.

    Pediatric Considerations

    • Safety and efficacy of Dayvigo have not been established.

    Geriatric Considerations

    • In phase 3 studies, Dayvigo was found to have similar efficacy results for patients <65 years of age vs patients ≥65 years.

    • Increased risk for falls in patients, especially the elderly, due to somnolence and drowsiness. Use caution with doses greater than 5 mg in patients ≥65 years.

    Renal Impairment Considerations

    • No dose adjustment is required for mild, moderate, or severe renal impairment.

    • There may be an increased risk for somnolence among patients with severe renal impairment.

    Hepatic Impairment Considerations

    • Severe hepatic impairment: not studied.

    • Moderate hepatic impairment: dosage adjustment is recommended.

    • Mild hepatic impairment: may have increased risk for somnolence.

    Other Considerations for Specific Populations

    Patients with Compromised Respiratory Function

    • Obstructive Sleep Apnea (OSA): 

      • The effect of lemborexant on respiratory function in patients with OSA was evaluated in 2 randomized, placebo-controlled, 2-period crossover studies. In both trials, patients were assessed following 8 consecutive nights of treatment with lemborexant 10mg.

      • Among the 37 patients with mild OSA (apnea-hypopnea index <15 events/hour of sleep), the mean treatment difference (lemborexant-placebo) on day 8 for the apnea-hypopnea index was reported to be -0.06 (95% CI, -19.5, 1.83). 

      • Among the 33 patients with moderate to severe OSA (apnea-hypopnea index ≥15 events/hour of sleep), the mean treatment difference on day 8 for the apnea-hypopnea index was 0.80 (95% CI, -4.88-3.29).

    • Chronic Obstructive Pulmonary Disease (COPD):

      • Lemborexant 10mg dosed once daily was also evaluated in 30 patients with moderate to severe COPD. The mean treatment difference on day 8 for the mean peripheral capillary oxygen saturation during sleep was 0.47 (95% CI, 0.07-0.87). The treatment was not studied in patients with FEV1 < 30% of predicted.

    Dayvigo Pharmacokinetics

    Absorption

    The time to peak concentration (tmax) of lemborexant is ~1 to 3 hours. Lemborexant Cmax decreased by 23%, AUC0-inf increased by 18%, and tmax was delayed by 2 hours following administration of a high-fat and high-calorie meal (containing approximately 150, 250, and 500 to 600 calories from protein, carbohydrate, and fat, respectively).

    Distribution

    The volume of distribution of lemborexant is 1970 L. Plasma protein binding of lemborexant is ~88% in vitro and 94% in clinical samples. 

    Metabolism

    Primarily metabolized by CYP3A4, and to a lesser extent by CYP3A5. The major circulating metabolite is M10.

    Elimination

    Following administration of an oral dose, 57.4% of the dose was recovered in the feces and 29.1% in the urine (<1% as unchanged). The effective half-life for lemborexant 5 mg and 10 mg is 17 and 19 hours, respectively.

    Dayvigo Interactions

    Interactions

    Avoid alcohol. Potentiates CNS depression with other CNS depressants (eg, benzodiazepines, opioids, tricyclic antidepressants, alcohol); may need to adjust doses. Concomitant strong or moderate CYP3A inhibitors (eg, itraconazole, clarithromycin, fluconazole, verapamil); avoid. Concomitant weak CYP3A inhibitors (eg, chlorzoxazone, ranitidine); reduce dose (see Adults). Antagonized by strong or moderate CYP3A inducers (eg, rifampin, carbamazepine, St. John's wort, bosentan, efavirenz, etravirine, modafinil); avoid. Antagonizes CYP2B6 substrates (eg, bupropion, methadone); consider increasing dose of substrates.

    Dayvigo Adverse Reactions

    Adverse Reactions

    Somnolence/fatigue, headache, nightmare/abnormal dreams; complex sleep-related behaviors (eg, sleep-walking, sleep-driving), sleep paralysis, hypnagogic hallucinations, cataplexy-like symptoms.

    Dayvigo Clinical Trials

    Clinical Trials

    Controlled Clinical Studies 

    The approval of Dayvigo was based on data from two phase 3 studies (SUNRISE 1 [NCT02952820] and SUNRISE 2 [NCT02783729]) that enrolled approximately 2000 patients. 

    SUNRISE 1

    • This was a 6-month, randomized, double-blind, placebo-controlled, multi-center trial that included adult patients age 18 or older who met DSM-5 criteria for insomnia disorder. Patients were randomly assigned to receive either Dayvigo 10 mg, 5 mg, or placebo once nightly. 

    • The primary endpoint was the mean change from baseline to end of treatment at 6 months for log-transformed patient-reported (subjective) sleep onset latency (sSOL), defined as the estimated minutes from the time that the patient attempted to sleep until sleep onset. Pre-specified secondary efficacy endpoints for sleep maintenance were change from baseline to end of treatment at 6 months for patient-reported sleep efficiency (sSEF) and wake after sleep onset (sWASO).

    • Dayvigo 5 mg and 10 mg achieved statistically significant superiority on the primary efficacy measure, sSOL, compared to placebo. Dayvigo 5 mg and 10 mg also showed statistically significant superiority in sSEF and sWASO.

    SUNRISE 2

    • This study was a 1-month, randomized, double-blind, placebo- and active-controlled, multi-center, parallel-group clinical trial in adult female patients age 55 and older and male patients 65 years and older who met DSM-5 criteria for insomnia disorder. Patients were randomly assigned to receive Dayvigo 5 mg, 10 mg, placebo, or active comparator once nightly.

    • The primary efficacy endpoint was the mean change in log-transformed latency to persistent sleep (LPS) from baseline to end of treatment (Days 29/30), as measured by overnight polysomnography (PSG) monitoring. LPS was defined as the number of minutes from lights off to the first 10 consecutive minutes of non-wakefulness. The pre-specified secondary efficacy endpoints in Study 2 were the mean change from baseline to end of treatment (Days 29/30) in sleep efficiency (SEF) and wake after sleep onset (WASO) measured by PSG. 

    • Dayvigo 5 mg and 10 mg demonstrated statistically significant superiority on the primary efficacy measure, LPS, compared to placebo. Dayvigo 5 mg and 10 mg demonstrated statistically significant improvement in SEF and WASO compared to placebo. 

     

    Special Safety Studies

    Middle of the Night Safety

    • Patients should be cautioned about the potential for middle of the night postural instability, as well as attention and memory impairment.

    Effects on Next-day Postural Stability and Memory 

    • There were no meaningful differences between Dayvigo (5 mg or 10 mg) and placebo on next-day postural stability or memory compared to placebo. 

    Effects on Driving 

    • Although Dayvigo at doses of 5 mg and 10 mg did not cause statistically significant impairment in next-morning driving performance in adult or elderly subjects (compared with placebo), driving ability was impaired in some subjects taking 10 mg Dayvigo.

    • Patients using the 10 mg dose should be cautioned about the potential for next-morning driving impairment because there is individual variation in sensitivity to Dayvigo.  

    Rebound Insomnia 

    • Dayvigo was not associated with rebound insomnia following treatment discontinuation.

    Withdrawal Effects 

    •  There was no evidence of withdrawal effects following Dayvigo discontinuation at either dose.  

    Dayvigo Note

    Not Applicable

    Dayvigo Patient Counseling

    Patient Counseling

    Administration Instructions 

    • Take only when preparing for or getting into bed and only if they can stay in bed for a full night (at least 7 hours) before being active again.

    • The effect of Dayvigo may be delayed if taken with or soon after a meal.

    CNS Depressant Effects and Daytime Impairment

    • May impair daytime wakefulness even when used as prescribed. 

    • Caution against driving and other activities requiring complete mental alertness.

    • Increased drowsiness that may lead to an increased risk for falls.

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

    • May cause sleep paralysis.

    Complex Sleep Behaviors  

    • May cause complex sleep behaviors, including sleep-walking, sleep-driving, preparing and eating food, making phone calls, or having sex while not being fully awake.

    • Discontinue Dayvigo and notify their healthcare provider immediately if they develop any of these symptoms.

    Worsening of Depression/Suicidal Ideation

    • Report any worsening of depression or suicidal thoughts immediately. 

    Pregnancy

    • Monitors pregnancy outcomes in women exposed to Dayvigo during pregnancy.

    Tolerance, Abuse, and Dependence 

    • Advise patients to not increase the dose of Dayvigo on their own, and inform physician if you believe the drug “does not work”.

    Cost Savings Program

    Dayvigo Savings Card

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