Lemborexant and Esketamine Nasal Spray: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Lemborexant
Esketamine Nasal Spray
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increased risk of CNS depression and potential next-day somnolence, an increased lemborexant exposure, an increased risk of lemborexant-related adverse reactions, reduced esketamine exposure and reduced efficacy of esketamine
Interaction Deep Dive
Concomitant use of lemborexant with esketamine (weak CYP3A inhibitor and CYP2B6 substrate) increases lemborexant exposure, which may increase the risk of lemborexant-associated adverse reactions and may also reduce esketamine exposure, which may result in reduced efficacy of esketamine. If coadministered, the maximum recommended dose of lemborexant is no more than 5 mg once per night and monitor patients for adequate clinical response. In addition, lemborexant is a CNS depressant that can impair daytime wakefulness and may persist in some patients for up to several days after discontinuing therapy. Coadministration with esketamine (CNS depressant) increases the risk of CNS depression. Dosage adjustments of lemborexant and esketamine may be necessary when administered together because of potentially additive effects. Driving ability was impaired in some subjects taking lemborexant 10 mg. The risk of daytime impairment is increased if lemborexant is taken with less than a full night of sleep remaining or if a higher than recommended dose is taken. If lemborexant is taken in these circumstances, patients should be cautioned against driving and other activities requiring complete mental alertness. Advise patients about the potential for next-day somnolence because of additive effects. Because lemborexant can cause drowsiness, patients, particularly the elderly, are at a higher risk of falls1.
Why it happens (mechanism)
An increased risk of CNS depression; inhibition of CYP3A4-mediated metabolism of lemborexant; induction of CYP2B6-substrate metabolism of esketamine
Literature reports
3 reports — tap to read
a) A physiologically-based pharmacokinetic modeling study predicted that concomitant use of lemborexant and weak CYP3A inhibitors increased lemborexant exposure by less than 2-fold 1.
b) Driving ability was impaired in some subjects taking lemborexant 10 mg. The risk of daytime impairment is increased if lemborexant is taken with less than a full night of sleep remaining or if a higher than recommended dose is taken 1.
c) Physiologically-based pharmacokinetic modeling predicted that drug interactions between lemborexant and CYP2B6 substrates are clinically significant 1.
Common questions
Can I take Lemborexant and Esketamine Nasal Spray together?
An increased risk of CNS depression and potential next-day somnolence, an increased lemborexant exposure, an increased risk of lemborexant-related adverse reactions, reduced esketamine exposure and reduced efficacy of esketamine Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lemborexant and Esketamine Nasal Spray interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Lemborexant or Esketamine Nasal Spray need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Product Information: DAYVIGO(R) oral tablets, lemborexant oral tablets. Eisai Inc (per FDA), Nutley, NJ, 2025. DailyMed
Keep reading about Lemborexant
Keep reading about Esketamine Nasal Spray
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist