Suvorest

• Approved Indications:
• Treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults.
• Off-label Uses:
• Occasionally used off-label for circadian rhythm sleep disorders.
• May be considered for sleep disturbances associated with psychiatric conditions under specialist supervision.
• Suvorexant is indicated for chronic insomnia when behavioral and non-pharmacological treatments have proven insufficient.

• Adults:
• Initial dose: 10 mg orally once daily, taken within 30 minutes before bedtime, with at least 7 hours remaining before planned awakening.
• Dose may be increased to 20 mg if needed and tolerated.
• Elderly:
• Initiate at 5 mg once daily; maximum recommended dose is 15 mg due to increased sensitivity.
• Hepatic Impairment:
• For mild to moderate impairment, start with 5 mg; use is not recommended in severe hepatic impairment.
• Renal Impairment:
• No dose adjustment necessary for mild to moderate renal impairment.
• Pediatrics:
• Safety and efficacy have not been established; use is not recommended.
• Administration Instructions:
• Swallow tablets whole with or without food.
• Take within 30 minutes before bedtime.
• Duration of Therapy:
• Should be used for the shortest duration necessary. Long-term use should be regularly reassessed by the physician.

Suvorexant is a selective dual orexin receptor antagonist. It blocks the binding of orexin A and orexin B neuropeptides to their receptors OX1R and OX2R in the brain. Orexins play a crucial role in promoting wakefulness by activating arousal pathways. By antagonizing these receptors, Suvorexant decreases wake drive, thereby facilitating both sleep onset and maintenance, improving overall sleep quality without significantly disrupting sleep architecture.

• Absorption: Rapidly absorbed with peak plasma concentrations approximately 2 hours after oral administration.
• Bioavailability: Approximately 82%; food delays peak concentration but does not affect total absorption.
• Distribution: Highly protein-bound (>99%); volume of distribution is approximately 105 liters.
• Metabolism: Extensively metabolized in the liver primarily via CYP3A4 and to a lesser extent by CYP2C19 enzymes.
• Active Metabolites: No active metabolites of clinical significance.
• Elimination: Primarily excreted as metabolites via feces (about 66%) and urine (about 23%).
• Half-life: Approximately 12 hours.

• Pregnancy: Classified as FDA Pregnancy Category C. Animal studies have shown adverse effects at high doses; there are no adequate, well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.
• Lactation: It is unknown whether Suvorexant is excreted in human milk. Caution is advised, and use during breastfeeding should be considered only if the benefits outweigh potential risks to the infant.
• Data: Limited clinical data on use during pregnancy and lactation.

• Primary Class: Hypnotic agent.
• Subclass: Dual Orexin Receptor Antagonist (DORA).

• Known hypersensitivity to Suvorexant or any excipients.
• Diagnosis of narcolepsy (due to orexin deficiency).
• Severe hepatic impairment.
• Concomitant use with strong CYP3A inhibitors without dose adjustment.

• CNS Depression: May impair next-day alertness and motor coordination; caution patients about activities requiring full alertness such as driving or operating machinery.
• Complex Sleep Behaviors: Reports of sleepwalking, sleep-driving, and other complex behaviors during sleep have been observed; discontinue if these occur.
• Respiratory Impairment: Use cautiously in patients with compromised respiratory function or obstructive sleep apnea.
• Psychiatric Effects: Monitor for worsening depression or suicidal ideation.
• Dependence and Abuse Potential: Schedule IV controlled substance; assess patients for signs of misuse, abuse, or dependence.
• Elderly Patients: Increased sensitivity to sedative effects; dose adjustments recommended.
• Alcohol: Concurrent use may increase CNS depressant effects and should be avoided.

• Common (≥5%):
• Somnolence, headache, fatigue, dizziness.
• Less Common:
• Abnormal dreams, dry mouth, upper respiratory tract infection.
• Serious but Rare:
• Complex sleep behaviors (sleepwalking, sleep-driving).
• Hypersensitivity reactions such as rash or angioedema.
• Suicidal ideation or behavior.
• Side effects typically manifest early in treatment and are dose-related.

• CYP3A4 Inhibitors: Co-administration increases Suvorexant plasma concentrations; dose adjustment necessary.
• CYP3A4 Inducers: Can decrease Suvorexant levels and reduce efficacy.
• Other CNS Depressants: Additive sedative effects when combined with benzodiazepines, opioids, alcohol, or other hypnotics.
• Food: High-fat meals delay absorption but do not significantly affect overall exposure.
• Avoid concomitant use with strong CYP3A inhibitors unless dose is adjusted accordingly.

• Suvorexant is increasingly recognized as an alternative non-benzodiazepine hypnotic with a novel mechanism and a comparatively lower risk of dependence.
• FDA labeling updates include warnings regarding complex sleep behaviors and next-day impairment of alertness.
• Guidelines recommend cautious use in elderly patients and those with respiratory disorders.
• No recent changes in approved indications or dosage recommendations have been made.

• Store at controlled room temperature: 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep the medication in its original container until use.
• Do not freeze.
• Keep out of reach of children.