Dayvigo (lemborexant) is a prescription medication used for the treatment of insomnia in adults. It belongs to a class of drugs called dual orexin receptor antagonists (DORAs).

Orexins are wake-promoting neuropeptides produced in the hypothalamus of the brain. They play a crucial role in regulating the sleep-wake cycle by promoting wakefulness.

Orexins act by binding to orexin receptors, known as OX1 and OX2, which are found throughout the central nervous system. By binding to these receptors, orexins stimulate brain activity and promote wakefulness. DORAs inhibit this action by selectively blocking both types of orexin receptors. This blockage decreases the wake-promoting signals, thereby facilitating the onset of sleep and helping to maintain sleep.

This mechanism of action is distinct from that of other classes of sleep medications, such as benzodiazepines and non-benzodiazepine hypnotics (e.g., zolpidem), which generally work by enhancing the activity of GABA, a neurotransmitter that promotes sleep. The specific targeting of the orexin system by DORAs offers a different therapeutic approach, potentially reducing some of the side effects associated with other sleep medications, such as dependency and next-day residual effects.

## Instructions

- Take lemborexant immediately before going to bed, when you have at least 7 hours available to sleep.
- Lemborexant typically begins to work shortly after it is taken, with its effects often noticeable within 30 minutes to 1 hour.
- Do not take the medication unless you are able to stay in bed for a full night (at least 7 hours).
- The recommended dose is 5 mg once per night.
- If needed, the dose can be increased to 10 mg based on clinical response and tolerability.
- Lemborexant can be taken with or without food, but it may take longer to work if you take it with or right after a meal.
- Do not take lemborexant with alcohol or other medications that can cause drowsiness.
- If you forget to take lemborexant before bed but still have at least 7 hours before you need to wake up, take it as soon as you remember.
- If there is less than 7 hours remaining, skip the missed dose and take your next dose as scheduled.
- Do not take two doses at the same time.
- Lemborexant may impair alertness and motor coordination. Do not drive or operate heavy machinery the day after taking lemborexant until you know how it affects you.
- If you experience any side effects, especially complex sleep behaviors like sleepwalking or worsening of depression, contact your healthcare provider immediately.
- Do not stop taking lemborexant abruptly without consulting your healthcare provider, as this may cause withdrawal symptoms.
- Lemborexant is intended for nightly use. Do not take it on an "as needed" basis.
- Some people may need it only for a short period, whereas others might need longer-term treatment.

## Common Side Effects

Common side effects of Dayvigo (lemborexant) include:

- **Headache**
- **Somnolence** (sleepiness)
- **Fatigue**
- **Dizziness**

## Drug Interactions

1. **CNS Depressants:** The use of Dayvigo with other central nervous system (CNS) depressants such as benzodiazepines, opioids, tricyclic antidepressants, antipsychotics, and other sleep aids can increase the risk of severe sedation, respiratory depression, and potentially dangerous side effects.
2. **Alcohol:** Combining alcohol with Dayvigo can enhance its sedative effects, increasing the risk of dizziness, severe sedation, and impaired cognitive and motor functions.
3. **CYP3A Inhibitors:** Drugs that inhibit the CYP3A enzyme can increase the blood levels of lemborexant, leading to potentially increased effects and side effects. These inhibitors include certain antifungal medications (e.g., ketoconazole), certain antibiotics (e.g., clarithromycin), and grapefruit juice.
4. **CYP3A Inducers:** Drugs that induce the CYP3A enzyme can decrease the blood levels of lemborexant, potentially reducing its effectiveness. These inducers include certain anticonvulsants (e.g., phenytoin, carbamazepine) and rifampin.

# Consensus

## [Lemborexant](https://consensus.app/results/?q=lemborexant&synthesize=on&copilot=on)

Lemborexant is a dual orexin receptor antagonist developed for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance. It has been approved for use in adults in several countries, including the USA and Japan, and is also being investigated for other sleep-related disorders.

**Key Insights**:

- Lemborexant has been approved for the treatment of adult patients with insomnia in the USA and Japan, demonstrating effectiveness in sleep onset and maintenance without evidence of rebound insomnia or withdrawal after discontinuation.
- Long-term use of lemborexant for up to twelve months shows sustained benefits for sleep parameters with most treatment-emergent adverse events being mild or moderate, including nasopharyngitis, somnolence, and headache.
- Compared to placebo, lemborexant has a favorable benefit-risk ratio, with robust number needed to treat (NNT) values and relatively high number needed to harm (NNH) values, indicating tolerability. Somnolence is the most common adverse event.
- Lemborexant demonstrates respiratory safety in individuals with mild obstructive sleep apnea (OSA), showing no significant differences in respiratory parameters compared to placebo.
- In a network meta-analysis, lemborexant showed greater efficacy in improving sleep onset and maintenance compared to suvorexant and other hypnotics, although it was associated with a higher risk of somnolence.
- Coadministration of lemborexant with alcohol can have additive negative effects on cognitive performance, but not on postural stability. Alcohol increases plasma lemborexant exposure, and patients are advised not to consume alcohol with lemborexant.
- Preclinical studies in animals suggest that lemborexant promotes REM and non-REM sleep without impairing motor coordination or increasing the sedative effects of ethanol, supporting its clinical evaluation for treating insomnia.
- Population pharmacokinetics analyses indicate that lemborexant can be administered without the need for dose adjustment due to small effect sizes of covariates and a low degree of association between adverse events and exposure.
- Lemborexant has a suitable pharmacokinetic, pharmacodynamic, and safety profile for treating insomnia, with no clinically relevant effects on next-morning residual sleepiness at doses up to 10 mg/day.
- A cost-effectiveness analysis in Japan suggests that lemborexant may be a better investment for treating insomnia compared to suvorexant, zolpidem immediate release, and untreated insomnia, considering the risk of falls, motor vehicle collisions, and workplace accidents.

**Conclusion**:

Lemborexant is an effective and generally well-tolerated treatment for adult patients with insomnia, offering sustained benefits for sleep onset and maintenance. It has a favorable benefit-risk profile with a low incidence of adverse events, most commonly somnolence. The medication is safe for use in patients with mild OSA and does not require dose adjustment for most patients. However, caution is advised when coadministering with alcohol due to potential additive negative effects on cognitive performance. Preclinical and clinical studies support its use for insomnia, and it may also offer cost-effectiveness benefits in the healthcare system.

## [Does discontinuation of lemborexant lead to withdrawal?](https://consensus.app/results/?q=Does%20discontinuation%20of%20lemborexant%20%20lead%20to%20withdrawal%3F&synthesize=on&copilot=on)


**Summary**: These studies suggest that discontinuation of lemborexant generally does not result in withdrawal symptoms or rebound insomnia, although there is a recognition that discontinuation of psychotropic medications can sometimes induce withdrawal syndromes.

Insomnia is a common sleep disorder, and lemborexant is a medication used to treat it. Discontinuation of such medications can raise concerns about potential withdrawal symptoms or rebound insomnia.

**Key Insights**:

- Less than 20% of subjects experienced significant worsening of insomnia symptoms after discontinuing lemborexant, with no evidence of withdrawal symptoms as assessed by the Tyrer Benzodiazepine Withdrawal Symptoms Questionnaire.
- Both the 5 mg and 10 mg doses of lemborexant maintained their effectiveness over 12 months, with no evidence of rebound insomnia or withdrawal symptoms following treatment discontinuation.
- Nonclinical studies in rats and rhesus monkeys indicated that lemborexant does not induce physical dependence, as there were no withdrawal signs following abrupt drug discontinuation.
- Clinical trials reported that lemborexant was not associated with rebound insomnia, withdrawal symptoms, or clinically meaningful impairment of next-day memory or driving performance.

**Conclusion**:

The research suggests that discontinuation of lemborexant after long-term treatment does not typically lead to withdrawal symptoms or rebound insomnia. The effectiveness of the medication appears to be maintained after cessation, and nonclinical studies support the low risk of physical dependence.