The short answer
Do not take St John's wort with linezolid unless the prescriber agrees. Linezolid is an MAO inhibitor whose label calls for monitoring for serotonin syndrome with serotonergic agents, and St John's wort acts on serotonin and has caused serotonin syndrome with serotonin reuptake inhibitors. No study or case report of this exact combination was found.
What this answer covers
St John's wort (Hypericum perforatum) extracts and teas containing hyperforin or hypericin, with linezolid by any route. Product strength varies between brands.
- Supplement or preparation
- St John's wort
- Medication ingredient
- linezolid
Why the label matters here
Linezolid reversibly inhibits monoamine oxidase, the enzyme that breaks down serotonin. Its label tells clinicians to monitor for serotonin syndrome when it is combined with serotonergic agents and to consider stopping one or both if signs appear. The label lists prescription drugs; it does not mention herbal products.
What St John's wort does
Hyperforin, a main active constituent, blocks serotonin reuptake. Serotonin syndrome and lethargy have been reported when the herb was combined with serotonin reuptake inhibitors, and federal consumer guidance warns of a potentially life-threatening serotonin increase with certain antidepressants.
No direct evidence for this exact pair
A search of Europe PMC for linezolid together with Hypericum or St John's wort returned no clinical study or case report of the combination. The precaution rests on the shared serotonin mechanism, not on a measured event rate.
What to do during a linezolid course
Tell the prescriber you use St John's wort before the first dose. Most linezolid courses are short, so pausing the herb is usually simpler than adding monitoring. Seek urgent care for agitation, confusion, fever, sweating, tremor, muscle twitching or a racing heartbeat.
Evidence and practical considerations
Side effects & toxicity
St John's wort is serotonergic and has caused serotonin syndrome with serotonin reuptake inhibitors; the linezolid label requires monitoring for serotonin syndrome with serotonergic agents, so co-use is a conditional precaution.
- Exact scope
- Hyperforin-containing St John's wort extracts and teas; strength varies by product. with Linezolid tablets, oral suspension and intravenous injection (ZYVOX and generics); the reversible, nonselective MAO inhibition is a property of the drug at all routes.
- Medication form and route
- oral medication; intravenous medication; oral supplement
What remains uncertain
- No exact-pair study or case report identified; the serotonin cases involved antidepressants; label wording covers serotonergic drugs generally.
Factors that may matter: Extract strength and hyperforin content; Other serotonergic medicines; Dose and duration of the herb; Age and comorbidity.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 22, 2026
Population: People prescribed linezolid
The label directs monitoring for serotonin syndrome when linezolid is taken with serotonergic agents and considering discontinuation if signs occur; linezolid is a reversible, nonselective MAO inhibitor with potential interaction with adrenergic and serotonergic agents.
How this applies: Exact linezolid (RxCUI 190376) at every marketed route; the label names tyramine, pseudoephedrine, phenylpropanolamine and serotonergic agents, not the supplements assessed here.
The label names prescription serotonergic drugs; it does not mention St John's wort or report a case with it.
Source 2: review of clinical observations
pubmed.ncbi.nlm.nih.gov · Source check Sep 22, 2026
Population: Patients in published case reports and trials of St John's wort co-medication.
Hyperforin inhibits reuptake of serotonin and other neurotransmitters; serotonin syndrome or lethargy was reported when St John's wort was given with serotonin reuptake inhibitors, alongside pharmacokinetic interactions with cyclosporin, contraceptives and antiretrovirals.
How this applies: Establishes that St John's wort is serotonergic in people and has produced serotonin syndrome with other serotonergic drugs; applied to linezolid by mechanism only.
Narrative review read as an abstract; the serotonin cases involved antidepressants, not linezolid.
Source 3: federal supplement safety guidance
nccih.nih.gov · Source check Sep 22, 2026
Population: General consumer population; no medication co-use data
Combining St John's wort with certain antidepressants can lead to a potentially life-threatening increase in serotonin; the herb also limits the effectiveness of many prescription medicines.
How this applies: Supports the serotonergic character and interaction record of St John's wort; not exact-pair evidence.
Consumer guidance about antidepressants; it does not address linezolid or MAO inhibitors specifically.
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 linezolid and Hypericum perforatum article from inspected current labeling and original sources, with uncertainty stated. |
Article revision: 107a4b6e2f7e9468
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.