orexin receptor antagonists
Controlled Substance Schedule: IV
Treatment of insomnia associated with difficulty in sleep onset and/or maintenance.
Antagonizes the effects of orexins A and B, naturally occurring neuropeptides that promote wakefulness, by binding to their receptors.
Absorption: 82% absorbed following oral administration; a high fat meal will delay absorption and sleep onset. ↑ absorption in obese females.
Distribution: Does not distribute into RBCs.
Protein Binding: >99%.
Metabolism and Excretion: Extensively metabolized by CYP3A (minor metabolism by CYP2C19; metabolites are not active). 66% excreted in feces, 23% in urine, mostly as metabolites.
Half-life: 12 hr (↑ in hepatic impairment).
TIME/ACTION PROFILE (sleep)
|PO||30 min (delayed by food)||unknown||7 hr†|
- Concurrent use of strong inhibitors of CYP3A;
- Severe hepatic impairment.
Use Cautiously in:
- History of substance abuse or drug dependence;
- Concurrent use of moderate inhibitors of CYP3A (dose ↓ recommended);
- Obese patients (↑ levels, especially in women, dose ↓ may be warranted);
- History of or concurrent psychiatric diagnoses;
- Underlying pulmonary disease;
- OB: Use during pregnancy only if potential benefit justifies potential fetal risk;
- Lactation: Use cautiously if breast feeding;
- Pedi: Safe and effective use in children has not been established.
Adverse Reactions/Side Effects
Adverse reactions, especially related to CNS depression are dose-related, especially at the 20 mg dose
CNS: drowsiness, cataplexy, daytime drowsiness, hallucinations (during sleep), worsening of depression/suicidal ideation, sleep driving, sleep paralysis
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Concurrent use of strong inhibitors of CYP3A including clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, and saquinavir risk of excessive sedation and should be avoided.
- Concurrent use of moderate inhibitors of CYP3A including aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, and verapamil may result in ↑ sedation (↓ dose recommended).
- 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; dose adjustments may be necessary).
- Concurrent use of CYP3A inducers including carbamazepine, phenytoin and rifampin may ↓ effectiveness.
- May alter digoxin levels (blood level monitoring recommended).
Grapefruit juice may result in ↑ blood levels and excess sedation (↓ dose recommended).
PO (Adults) 10 mg within 30 minutes of going to bed, if well tolerated but not optimally effective, dose may be increased next night, not to exceed 20 mg (dose may not be repeated on a single night and should be when at least 7 hr of sleep time is anticipated before planned awakening). Concurrent use of moderate inhibitors of CYP3A –5 mg initially, dose may be ↑ to 10 mg if lower dose is tolerated but not optimally effective. Lowest effective dose should be used.
Tablets: 5 mg, 10 mg, 15 mg, 20 mg
- Assess mental status, sleep patterns, and potential for abuse prior to administration. Prolonged use of >7–10 days may lead to physical and psychological dependence. Limit amount of drug available to the patient.
- Assess alertness at time of peak effect. Notify health care professional if desired sedation does not occur.
- Before administering, reduce external stimuli and provide comfort measures to increase effectiveness of medication.
- Protect patient from injury. Raise bed side rails. Assist with ambulation. Remove patient's cigarettes.
- Use lowest effective dose.
- PO Tablets should be swallowed whole with full glass of water. Take no more than once/night and within 30 min of going to bed. Take only if at least 7 hr remaining before awaking. For faster onset of sleep, do not administer with or immediately after a meal.
- Instruct patient to take suvorexant as directed. Advise patient not to take suvorexant unless able to stay in bed a full night (7 hr) before being active again. Do not take more than the amount prescribed because of the habit-forming potential. Not recommended for use longer than 7–10 days. Instruct patient to read Medication Guide for correct product before taking and with each Rx refill, changes may occur.
- Because of rapid onset, advise patient to go to bed immediately after taking suvorexant.
- May cause daytime drowsiness or dizziness. Advise patient to avoid driving or other activities requiring alertness until response to this medication is known.
- Caution patient that complex sleep-related behaviors (sleep-driving) may occur while asleep. Inform families and advise to notify health care professional if these behaviors occur.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to avoid concurrent use of Rx, OTC, and herbal products without consulting health care professional.
- Caution patient to avoid concurrent use of alcohol or other CNS depressants.
- Advise patient to notify health care professional if depression worsens or suicidal thoughts occur.
- Advise patient to notify health care professional immediately if signs of anaphylaxis (swelling of the tongue or throat, trouble breathing, and nausea and vomiting) occur.
- Advise female patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.
Relief of insomnia.
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