The short answer
Avoid St. John’s wort with lemborexant, as DAYVIGO labeling directs. It can increase CYP3A activity and lower drug exposure; taking the products a few hours apart is not an established solution.
What this answer covers
Hypericum perforatum products with varying hyperforin content and duration of use.
- Supplement or preparation
- Hypericum perforatum
- Medication ingredient
- lemborexant
The label names St. John’s wort
DAYVIGO labeling lists St. John’s wort among strong CYP3A inducers and directs avoidance of strong or moderate inducers. The concern is reduced lemborexant exposure and effectiveness.
Human studies support the pathway
A direct lemborexant study with rifampin showed a large exposure reduction. Human St. John’s wort studies with midazolam also demonstrate induction, but they did not test lemborexant and do not establish the herb’s exact effect size.
Product strength changes the evidence
A low-hyperforin preparation produced a much smaller midazolam effect than commonly studied preparations. This does not make an unidentified product acceptable with DAYVIGO or override its current labeling. Reduced metabolism-related exposure should not be described as proven loss of intestinal absorption.
Coordinate stopping or starting
Discuss any current St. John’s wort use with the prescriber. Do not raise lemborexant yourself to compensate for poorer sleep. Enzyme effects are not confined to the time a dose is swallowed, and no exact protective spacing interval is established.
Evidence and practical considerations
Absorption & effectiveness
Exact current DAYVIGO label names St John’s wort and directs avoiding strong/moderate CYP3A inducers. Supported as reduced exposure/possible effectiveness and avoidance, not proven reduced intestinal absorption or a protective hour interval; product-specific effect sizes unavailable.
- Exact scope
- Hypericum perforatum products with varying hyperforin content and duration of use. with Lemborexant2272403 IN, oral DAYVIGO tablets.
- Medication form and route
- oral medication; oral supplement
What remains uncertain
- No unmeasured pair incidence, blanket class transfer or arbitrary spacing interval.
Factors that may matter: Preparation; Dose; Other medicines; Organ function.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed lemborexant
Avoid strong/moderate CYP3A inhibitors and inducers; St John’s wort explicitly named. Other insomnia medicines not recommended. Additive CNS depression and complex sleep behaviors.
How this applies: Exact lemborexant RxCUI 2272403 IN, with stated salt/formulation/route bridge.
No measured seed-extract, CBD, kava or generic valerian combination risk.
Source 2: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Healthy adults in phase1 open-label studies.
Inhibitors increased exposure approximately3.7–4fold; rifampin reduced exposure over90%. No severe or serious adverse events reported.
How this applies: Other drugs, not supplements. Expected somnolence15minutes–9hours was not recorded as an adverse event unless more pronounced than expected. Lemborexant’s null effect on midazolam is the reverse interaction direction.
Other drugs, not supplements. Expected somnolence15minutes–9hours was not recorded as an adverse event unless more pronounced than expected. Lemborexant’s null effect on midazolam is the reverse interaction direction.
Source 3: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: 12 healthy adults.
Short-term dosing had no measured CYP effect; repeated use reduced oral midazolam AUC more than IV AUC.
How this applies: Original source interpreted for lemborexant only within the stated preparation and endpoint limits.
Not a direct lemborexant combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Source 4: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: 20 healthy men.
Small AUC decrease considered not clinically relevant by authors; no significant Cmax or half-life change.
How this applies: Original source interpreted for lemborexant only within the stated preparation and endpoint limits.
Not a direct lemborexant combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Research assessment: · Open full citations ↗
Timing & monitoring
Exact current DAYVIGO label names St John’s wort and directs avoiding strong/moderate CYP3A inducers. Supported as reduced exposure/possible effectiveness and avoidance, not proven reduced intestinal absorption or a protective hour interval; product-specific effect sizes unavailable.
- Exact scope
- Hypericum perforatum products with varying hyperforin content and duration of use. with Lemborexant2272403 IN, oral DAYVIGO tablets.
- Medication form and route
- oral medication; oral supplement
What remains uncertain
- No unmeasured pair incidence, blanket class transfer or arbitrary spacing interval.
Factors that may matter: Preparation; Dose; Other medicines; Organ function.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed lemborexant
Avoid strong/moderate CYP3A inhibitors and inducers; St John’s wort explicitly named. Other insomnia medicines not recommended. Additive CNS depression and complex sleep behaviors.
How this applies: Exact lemborexant RxCUI 2272403 IN, with stated salt/formulation/route bridge.
No measured seed-extract, CBD, kava or generic valerian combination risk.
Source 2: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Healthy adults in phase1 open-label studies.
Inhibitors increased exposure approximately3.7–4fold; rifampin reduced exposure over90%. No severe or serious adverse events reported.
How this applies: Other drugs, not supplements. Expected somnolence15minutes–9hours was not recorded as an adverse event unless more pronounced than expected. Lemborexant’s null effect on midazolam is the reverse interaction direction.
Other drugs, not supplements. Expected somnolence15minutes–9hours was not recorded as an adverse event unless more pronounced than expected. Lemborexant’s null effect on midazolam is the reverse interaction direction.
Source 3: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: 12 healthy adults.
Short-term dosing had no measured CYP effect; repeated use reduced oral midazolam AUC more than IV AUC.
How this applies: Original source interpreted for lemborexant only within the stated preparation and endpoint limits.
Not a direct lemborexant combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Source 4: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: 20 healthy men.
Small AUC decrease considered not clinically relevant by authors; no significant Cmax or half-life change.
How this applies: Original source interpreted for lemborexant only within the stated preparation and endpoint limits.
Not a direct lemborexant combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Research summary published | |
| Article prepared | |
| Prepared exact lemborexant article with formulation-specific evidence and uncertainty. |
Article revision: 0a17642aaea4b59f
This guide brings together the evidence records used by our interaction checker. Each finding retains its own preparation limits, research date, and source summaries.
Full citations require verification. Reading this answer and the source summaries does not.
Taking other supplements or medications?
Use the checker to explore your other combinations. Ask a pharmacist to review the exact products, amounts and medical conditions in your complete list.
Open the interaction checkerInformation, not medical advice. Do not change prescribed treatment based on this guide.