Indications for: DAYVIGO
Treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.
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.
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.
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.
Dayvigo was not associated with rebound insomnia following treatment discontinuation.
There was no evidence of withdrawal effects following Dayvigo discontinuation at either dose.
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.
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.
Orexin receptor antagonist.
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.
Somnolence/fatigue, headache, nightmare/abnormal dreams; complex sleep-related behaviors (eg, sleep-walking, sleep-driving), sleep paralysis, hypnagogic hallucinations, cataplexy-like symptoms.
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.
Generic Drug Availability: