orexin receptor antagonists
Controlled Substance Schedule: IV
Insomnia associated with difficulty in sleep onset and/or sleep maintenance.
Antagonizes the effects of orexins A and B, naturally occurring neuropeptides that promote wakefulness, by binding to their receptors.
Absorption: High-fat, high-calorie meal delays absorption and sleep onset.
Distribution: Extensively distributed to extravascular tissues.
Protein Binding: 94%.
Metabolism and Excretion: Extensively metabolized by liver via CYP3A into active metabolite (M10). 57% excreted in feces, 29% in urine, mostly as metabolites.
Half-life: 17–19 hr.
TIME/ACTION PROFILE (sleep)
|PO||15–20 min||unknown||7 hr†|
- Concurrent use of strong or moderate CYP3A inhibitors;
- Concurrent use of strong or moderate CYP3A inducers;
- Severe hepatic impairment.
Use Cautiously in:
- History of substance abuse or addiction;
- Severe renal impairment
- Mild or moderate hepatic impairment
- Concurrent use of weak CYP3A inhibitors;
- History of or concurrent psychiatric diagnoses;
- Pulmonary disease or obstructive sleep apnea;
- OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
- Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
- Pedi: Safety and effectiveness not established in children;
- Geri: Older adults at ↑ risk for falls.
Adverse Reactions/Side Effects
Neuro: SUICIDAL BEHAVIOR/IDEATION, cataplexy, depression, drowsiness, hallucinations (during sleep), headache, sleep driving, sleep paralysis, sleep walking
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Strong CYP3A inhibitors, including clarithromycin or itraconazole as well as moderate CYP3A inhibitors, including fluconazole or verapamil may ↑ levels and risk of excessive sedation; avoid concurrent use.
- Weak CYP3A inhibitors, including chlorzoxazone, may ↑ levels and risk of adverse reactions; do not exceed dose of 5 mg/day.
- Strong CYP3A inducers, including carbamazepine or rifampin as well as moderate CYP3A inducers, including bosentan, efavirenz, etravirine, or modafanil may ↓ levels and risk of effectiveness; avoid concurrent use.
- May ↓ levels and effectiveness of CYP2B6 substrates, including bupropion or methadone ; dosage adjustments may be needed.
- Risk of CNS depression, next-day impairment, "sleep-driving" and other complex behaviors while not fully awake ↑ with other CNS depressants including alcohol, some antihistamines, opioids, other sedative/hypnotics (including benzodiazepines ), and tricyclic antidepressants ; dosage adjustments may be needed.
St. John's wort may ↓ levels and risk of effectiveness; avoid concurrent use.
Grapefruit juicemay ↑ levels and risk of excessive sedation; avoid concurrent use.
PO (Adults): 5 mg immediately before going to bed; if well tolerated but not optimally effective, dose may be ↑ to 10 mg (max dose = 10 mg/night); do not repeat dose on a single night. Concurrent use of weak CYP3A inhibitor– Do not exceed dose of 5 mg/night.
PO (Adults): Moderate hepatic impairment– Do not exceed dose of 5 mg/night.
Tablets: 5 mg, 10 mg
- Assess sleep patterns prior to and during administration. Continued insomnia after 7–10 days of therapy may indicate primary psychiatric or mental illness.
Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
- Before administering, reduce external stimuli and provide comfort measures to increase effectiveness of medication.
- PO Onset is rapid. Administer immediately before going to bed or after patient has gone to bed and has experienced difficulty falling asleep, only on nights when patient is able to get 7 or more hours of sleep before being active again.
- Time to sleep onset may be delayed if taken with or soon after a meal.
- Instruct patient to take lemborexant immediately before going to bed, as directed; do not increase dose. May result in short-term memory impairment, hallucinations, impaired coordination, and dizziness. Do not take lemborexant if consumed alcohol that evening. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
- Advise patient to avoid grapefruit juice during therapy.
- May cause daytime and next-day drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
- Caution patient the balance during nighttime waking may be impaired with increased risk of falls. Nighttime attention and memory may also be impaired.
- Inform patient and family of potential for signs and symptoms of sleep paralysis (inability to move or speak for up to several min during sleep-wake transitions, and hallucinations, including vivid and disturbing perceptions) and mild cataplexy (leg weakness lasting from seconds to a few min, occurring at night or during the day.
Caution patient and family that lemborexant may cause complex sleep behaviors (sleep walking, sleep-driving, making and eating food, talking on the phone, having sex) while unaware. Patient may not remember anything done during the night; increased risk with alcohol or other CNS depressants. Discontinue lemborexant immediately and notify health care professional if complex sleep behaviors occur.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products, especially St. John's Wort.
- Caution patient to avoid concurrent use of alcohol or other CNS depressants.
Encourage patient and family to be alert for emergence of worsening of depression and suicidal ideation. If these symptoms occur, notify health care professional immediately.
- Rep: Advise patient to notify health care professional if pregnancy is planned or suspected, or if breastfeeding. Inform pregnant patient of pregnancy exposure registry that monitors pregnancy outcomes in women who are exposed to lemborexant during pregnancy. Register patient by calling 1-888-274-2378.
Decreased sleep latency and improved sleep maintenance.