Usage
- Lemborexant is prescribed for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults.
- Pharmacological Classification: Hypnotic; Orexin Receptor Antagonist.
- Mechanism of Action: Lemborexant acts by blocking the binding of orexin neuropeptides (orexin A and orexin B) to their receptors (OX1R and OX2R), thereby inhibiting the wake-promoting effects of the orexin system.
Alternate Names
- International Nonproprietary Name (INN): Lemborexant
- Brand Name: Dayvigo
How It Works
- Pharmacodynamics: Lemborexant reduces sleep latency (the time it takes to fall asleep) and improves sleep maintenance (the ability to stay asleep). It achieves this by suppressing neuronal activity in the wake-promoting orexin system.
- Pharmacokinetics:
- Absorption: Lemborexant is readily absorbed after oral administration, with a time to peak concentration (Tmax) of approximately 1 to 3 hours. Food may delay absorption.
- Metabolism: Primarily metabolized by the liver, mainly by CYP3A enzymes (CYP3A4 and CYP3A5).
- Elimination: Excreted primarily in feces, with a smaller portion eliminated in urine. The elimination half-life is approximately 17 hours.
- Mode of Action: Lemborexant competitively binds to both orexin receptors, OX1R and OX2R, exhibiting higher affinity for OX2R. By blocking orexin signaling, it dampens the activity of the orexin system, which plays a crucial role in promoting wakefulness.
- Receptor Binding: Dual orexin receptor antagonist (OX1R and OX2R).
- Elimination Pathways: Hepatic metabolism (primarily CYP3A), followed by fecal and urinary excretion.
Dosage
Standard Dosage
Adults:
- Initial dose: 5 mg orally once daily, immediately before bedtime, with at least 7 hours remaining before the planned time of awakening.
- Dosage may be increased to 10 mg once daily based on clinical response and tolerability.
- Maximum dose: 10 mg once daily.
Children:
- Safety and efficacy have not been established in pediatric patients. Use is not recommended.
Special Cases:
- Elderly Patients (≥65 years): Start with 5 mg. Caution should be exercised when increasing to 10 mg due to increased risk of somnolence and falls.
- Patients with Renal Impairment: No dose adjustment is necessary. However, those with severe renal impairment may have increased exposure and should be monitored for somnolence.
- Patients with Hepatic Dysfunction:
- Mild hepatic impairment: No dose adjustment needed, but monitor for somnolence.
- Moderate hepatic impairment: Maximum dose is 5 mg once daily.
- Severe hepatic impairment: Lemborexant is not recommended.
- Patients with Comorbid Conditions: Use with caution in patients with sleep apnea, COPD, or depression. Consider lower doses for patients taking concomitant CYP3A inhibitors.
Clinical Use Cases
- Lemborexant is specifically indicated for insomnia. It is not currently recommended or routinely used for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Such uses would be off-label and require careful consideration of risks and benefits.
Dosage Adjustments
- CYP3A Inhibitors:
- Strong or moderate inhibitors: Avoid concomitant use.
- Weak inhibitors: Maximum dose of lemborexant is 5 mg.
- CYP3A Inducers:
- Strong or moderate inducers: Avoid concomitant use.
Side Effects
Common Side Effects:
- Somnolence/drowsiness
- Fatigue
- Headache
- Vivid/unusual dreams or nightmares
Rare but Serious Side Effects:
- Sleep paralysis
- Complex sleep behaviors (sleepwalking, sleep-driving, preparing/eating food while not fully awake)
- Suicidal ideation/worsening of depression
- Hallucinations
- Cataplexy-like symptoms
- Angioedema
Long-Term Effects:
- Potential for dependence, although this risk appears lower compared to some other hypnotics.
Adverse Drug Reactions (ADR):
Contraindications
- Narcolepsy
- Hypersensitivity to lemborexant
Drug Interactions
- CYP3A Inhibitors: Concomitant use can significantly increase lemborexant plasma concentrations.
- CYP3A Inducers: Concomitant use can significantly decrease lemborexant plasma concentrations, potentially reducing efficacy.
- CNS Depressants (e.g., alcohol, opioids, benzodiazepines, antihistamines): Additive CNS depression may occur.
- Other Medications: Consult a drug interaction checker for a comprehensive list.
- Food: Food can delay the absorption of lemborexant.
- Alcohol: Avoid concurrent use due to additive CNS depressant effects.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Limited data are available. Animal studies suggest potential risks at high doses. Use only if the potential benefit outweighs the potential risk to the fetus.
- Breastfeeding: Lemborexant is present in breast milk at low levels. Monitor infants for excessive sedation. Consider the developmental and health benefits of breastfeeding alongside the mother’s clinical need for the medication.
Drug Profile Summary
- Mechanism of Action: Dual orexin receptor antagonist (OX1R and OX2R), inhibiting wake promotion.
- Side Effects: Somnolence, fatigue, headache, unusual dreams, sleep paralysis (rare), complex sleep behaviors (rare).
- Contraindications: Narcolepsy, hypersensitivity.
- Drug Interactions: CYP3A inhibitors/inducers, CNS depressants.
- Pregnancy & Breastfeeding: Limited data, use with caution.
- Dosage: Adults: 5-10 mg orally once daily at bedtime; elderly: start with 5 mg.
- Monitoring Parameters: Observe for excessive daytime sleepiness, complex sleep behaviors, and mood changes.
Popular Combinations
- Lemborexant is typically used as monotherapy for insomnia. Combinations with other sleep medications are generally not recommended due to increased risk of adverse effects.
Precautions
- General Precautions: Assess for history of depression, substance abuse, and comorbid medical conditions.
- Specific Populations: See Dosage section for considerations related to pregnant women, breastfeeding mothers, children, and elderly patients.
- Lifestyle Considerations: Advise patients to avoid alcohol and to exercise caution when driving or operating machinery the day after taking lemborexant due to potential next-day impairment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Lemborexant?
A: Adults: 5 mg orally once daily at bedtime, with the option to increase to 10 mg based on clinical response and tolerability. Elderly patients should be started on 5 mg.
Q2: How does Lemborexant work?
A: It blocks orexin receptors, which regulate the sleep-wake cycle, promoting sleep.
Q3: What are the common side effects?
A: Drowsiness, fatigue, headache, and unusual dreams.
Q4: Can Lemborexant be used with alcohol?
A: No, alcohol should be avoided as it can potentiate the CNS depressant effects of lemborexant.
Q5: Is Lemborexant safe for patients with liver disease?
A: Dose adjustment is needed for moderate hepatic impairment (max 5mg). It is not recommended in severe hepatic impairment.
Q6: Can Lemborexant be used during pregnancy?
A: Limited data exist. Use only if the potential benefit outweighs the potential risk to the fetus.
Q7: What if a patient experiences sleep paralysis while taking Lemborexant?
A: Discontinue the medication and contact a physician immediately.
Q8: How does Lemborexant compare to other sleep medications?
A: It has a different mechanism of action than benzodiazepines and “Z-drugs”. It may have a lower risk of dependence.
Q9: Are there any drug interactions I should be aware of?
A: Yes, significant interactions can occur with CYP3A inhibitors and inducers. Consult a drug interaction checker for a comprehensive list.
Q10: Can Lemborexant be used long-term?
A: It can be used for extended periods under the supervision of a physician. Monitor for potential dependence.
