Lemborexant (Dayvigo)

Introduction

Lemborexant, marketed under the brand name Dayvigo, is a dual orexin receptor antagonist (DORA) approved for the treatment of insomnia. Its novel mechanism of action, targeting orexin receptors in the brain, makes it a safer alternative to traditional sedative-hypnotics, such as benzodiazepines and Z-drugs. Manufactured by Eisai Pharmaceuticals, Lemborexant is available in various countries, including India, where it is offered in 5 mg and 10 mg strengths.

Pharmacological Classification

Class: Dual Orexin Receptor Antagonist (DORA)
Mechanism of Action:
Blocks orexin-1 (OX1R) and orexin-2 (OX2R) receptors to inhibit wakefulness-promoting pathways.
Displays stronger affinity for OX2R, which is crucial for sleep maintenance.
Indications
FDA Approved: Insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults.
Off-Label Investigations: Irregular sleep-wake rhythm disorders, particularly in patients with Alzheimer’s disease (clinical trials underway).
Dosage and Administration
Starting Dose: 5 mg orally at bedtime.
Maximum Dose: 10 mg, based on tolerance and clinical response.
Important Instructions:
Take immediately before bedtime.
Ensure at least 7 hours remain before planned awakening.
Avoid taking with high-fat meals, as it may delay the drug’s onset.
Pharmacokinetics
Absorption: Time to peak plasma concentration: 1–3 hours.
Half-life:
5 mg: ~17 hours.
10 mg: ~19 hours.
Metabolism: Primarily via CYP3A enzymes.
Excretion: Elimination through feces and urine.
Brands Available in India
Dayvigo 5 mg Tablet:
Strength: 5 mg.
Price: ₹672 for a strip of 14 tablets.
Dayvigo 10 mg Tablet:
Strength: 10 mg.
Price: ₹904 for a strip of 14 tablets.
Side Effects
Common:
Somnolence.
Drowsiness or daytime sedation.
Sleep paralysis.
Hypnagogic (upon falling asleep) or hypnopompic (upon waking) hallucinations.
Rare/Serious:
Complex sleep behaviors (e.g., sleepwalking, sleep-eating).
Worsening depression or suicidal ideation.
Contraindications
Absolute:
Narcolepsy.
Relative:
Moderate hepatic impairment: Dose should not exceed 5 mg.
Severe hepatic impairment: Avoid use.
Special Populations:
Not recommended for children, pregnant women, or breastfeeding mothers due to limited data.
Drug Interactions
Avoid Co-administration With:
CYP3A Inhibitors: Strong inhibitors (e.g., itraconazole) increase the risk of adverse effects.
CYP3A Inducers: Strong inducers (e.g., rifampin) reduce efficacy.
Adjust Dose:
Use no more than 5 mg with weak CYP3A inhibitors.
Special Precautions
Activities Requiring Alertness: May cause drowsiness. Avoid driving or operating heavy machinery.
Alcohol: Increases the risk of sedation and serious side effects. Avoid concurrent use.
Psychiatric Conditions: Monitor for mood changes, particularly in patients with a history of depression.
Comparison with Alternatives
Compared to Zolpidem: Lemborexant has fewer side effects, lower dependency potential, and better efficacy for sleep maintenance.
Compared to Benzodiazepines: Minimal risk of tolerance or withdrawal symptoms; preferred in patients with a history of substance abuse.
Monitoring
Monitor for excessive sedation or impaired alertness.
Periodic review of the need for ongoing therapy.
Assess liver function in patients with hepatic impairment.
Storage
Store at room temperature (15°C–30°C) in a dry place, away from direct sunlight and moisture.
Keep out of reach of children.
Patient Education
Take only as prescribed to minimize the risk of side effects and dependency.
Do not increase the dose without consulting your doctor.
Inform your doctor about all medications and supplements you are taking.
Emergency Management
Overdose: Symptoms include excessive sedation, confusion, and respiratory depression.
Treatment: Symptomatic and supportive care; no specific antidote available.
References
FDA Approval Summary for Lemborexant.
Eisai Pharmaceuticals India Pvt Ltd – Product Information.
Clinical Trials on Orexin Receptor Antagonists.
Comparative Studies: Lemborexant vs. Zolpidem and Benzodiazepines.