The short answer
Melatonin may add to butorphanol-related drowsiness and impairment. The exact combination has not been shown to produce a particular adverse-event rate, but the sedating effects warrant review before co-use.
What this answer covers
Oral melatonin; dose, timing and release formulation vary.
- Supplement or preparation
- Melatonin
- Medication ingredient
- butorphanol
The medicine itself affects alertness
An intravenous butorphanol study found dose-related sedation and impaired performance. Combining it with midazolam increased these effects, but that prescription sedative is not evidence for the size of a supplement interaction.
What the supplement evidence adds
A daytime melatonin study found impaired performance without butorphanol. Dose, formulation and time of use influence alertness; this experiment does not establish an exact combination risk.
The exact product and route matter
Butorphanol nasal spray and injected butorphanol have different dosing and exposure. There is no established safe supplement dose or short timing gap for this pair.
Respond to sedation promptly
Discuss the product with the prescriber before use and avoid driving while impaired. Slow or difficult breathing or unusual difficulty waking needs emergency help. Do not adjust butorphanol yourself.
Evidence and practical considerations
Side effects & toxicity
Conditional additive-sedation precaution supported by exact human butorphanol labeling and supplement effects/guidance; midazolam trial is indirect for this supplement, with no transferable incidence.
- Exact scope
- Oral melatonin; dose, timing and release formulation vary. with Butorphanol1841 IN; human nasal tartrate or IV/IM tartrate, with route-specific label distinctions.
- Medication form and route
- intranasal medication; intravenous medication; intramuscular 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 butorphanol
Mixed opioid agonist-antagonist with sedation and respiratory-depression warnings; general serotonergic-drug and CYP3A4 interaction precautions.
How this applies: Exact butorphanol RxCUI 1841 IN, with stated salt/formulation/route bridge.
Nasal formulation-specific pharmacokinetic warnings; not an oral drug or veterinary preparation.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed butorphanol
Warns about CNS-depressant combinations and serotonin syndrome with serotonergic drugs.
How this applies: Exact butorphanol RxCUI 1841 IN, with stated salt/formulation/route bridge.
No exact supplement-pair event rate; nasal CYP3A wording is not assumed identical for injection.
Source 3: federal supplement safety guidance
nccih.nih.gov · Source check Sep 10, 2026
Population: Users of the specified supplement.
Daytime drowsiness can occur; people with epilepsy need medical supervision when using melatonin.
How this applies: Original source interpreted for butorphanol only within the stated preparation and endpoint limits.
Not a direct butorphanol 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: 16 healthy young adults.
Reaction, response and tracking performance worsened after daytime melatonin.
How this applies: Original source interpreted for butorphanol only within the stated preparation and endpoint limits.
Not a direct butorphanol combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Source 5: original human study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: 126 healthy preoperative patients.
Dose-related sedation and psychomotor impairment; high-dose combination produced greater-than-additive sedation and respiratory slowing. No significant euphoria or dysphoria.
How this applies: Published abstract is truncated at 250 words; no supplement tested and rates cannot transfer to nasal dosing or botanical combinations.
Published abstract is truncated at 250 words; no supplement tested and rates cannot transfer to nasal dosing or botanical combinations.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Article prepared | |
| Prepared exact butorphanol article with formulation-specific evidence and uncertainty. | |
| Research summary published |
Article revision: f921a60d8236cb75
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.