The short answer
SAMe raises a possible serotonin-related concern with metaxalone. Review the combination before use; there is no established exact-pair event rate or safe dosing interval.
What this answer covers
Oral S-adenosylmethionine preparations.
- Supplement or preparation
- S-Adenosylmethionine
- Medication ingredient
- metaxalone
The current label supports a precaution
Metaxalone labeling reports serotonin syndrome with recommended-dose metaxalone plus serotonergic drugs, and with excessive metaxalone alone. Supplement guidance also cautions about medicines affecting serotonin.
Published overdose cases have a different scope
An original report describes severe toxicity with high metaxalone concentrations and SSRI co-use. It did not test this supplement, and its overdose findings cannot be used as the risk at an ordinary prescribed dose.
A warning is not a universal prohibition
The label calls for reassessment when serotonergic co-use is warranted. It does not supply a safe supplement amount or imply that every serotonin-related product is formally contraindicated. Individual medicines and organ function matter.
Review the product and recognize symptoms
Ask the prescriber or pharmacist before combining them. A few hours of dose separation is not proven protection. Agitation with fever, tremor, rigidity, unusual sweating or confusion warrants urgent medical assessment.
Evidence and practical considerations
Side effects & toxicity
Conditional serotonergic precaution from current exact metaxalone label and supplement guidance; human overdose cases are indirect and cannot define exact-pair routine-dose incidence.
- Exact scope
- Oral S-adenosylmethionine preparations. with Metaxalone59078 IN; oral640mg/800mg formulation boundaries and non-opioid muscle-relaxant scope.
- 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 metaxalone
CNS depression and serotonin-syndrome precautions with serotonergic drugs; contraindicated with severe renal/hepatic impairment.
How this applies: Exact metaxalone RxCUI 59078 IN, with stated salt/formulation/route bridge.
640mg and 800 mg products are not mutually substitutable mg-for-mg; no supplement-specific incidence.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed metaxalone
Drowsiness/CNS-depressant and serotonin-syndrome warnings; food can affect exposure.
How this applies: Exact metaxalone RxCUI 59078 IN, with stated salt/formulation/route bridge.
Separate formulation instructions; not a pain opioid or evidence that every supplement is contraindicated.
Source 3: federal supplement safety guidance
nccih.nih.gov · Source check Sep 10, 2026
Population: Users of the named oral supplement
Possible interaction with products that increase serotonin.
How this applies: Original source interpreted for metaxalone only within the stated preparation and endpoint limits.
Not a direct metaxalone combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Source 4: original case report
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Two adults.
Severe serotonin-toxicity features with markedly elevated metaxalone concentrations.
How this applies: Overdose cases, not routine-dose 5-HTP or SAMe; do not infer incidence or dose thresholds.
Overdose cases, not routine-dose 5-HTP or SAMe; do not infer incidence or dose thresholds.
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 metaxalone article with formulation-specific evidence and uncertainty. | |
| Research summary published |
Article revision: 059f19baf419ce7f
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.