Drug & supplement interaction

St. John's Wort + Sulfamethoxazole, Trimethoprim

Sulfamethoxazole, Trimethoprim brand names: Bactrim, Bactrim DS, Cotrim DS, Septra, Septra DS, and others.

Moderate Interaction
Medically reviewed by · Updated October 2026
The bottom line Moderate

Sulfamethoxazole, Trimethoprim falls into 2 drug categories that St. John's Wort can interact with; the most serious is rated moderate. Theoretically, St. John's wort might increase the likelihood for photosensitivity reactions when used in combination with photosensitizing drugs.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

St. John's Wort and Sulfamethoxazole, Trimethoprim

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

St. John's Wort interacts with whole categories of medication. Sulfamethoxazole, Trimethoprim falls into 2 of those categories, so it can interact with St. John's Wort in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

PHOTOSENSITIZING DRUGS

1 of 2

Why this applies to Sulfamethoxazole, Trimethoprim

Sulfamethoxazole, Trimethoprim falls under PHOTOSENSITIZING DRUGS — the group St. John's Wort interacts with.

Theoretically, St. John's wort might increase the likelihood for photosensitivity reactions when used in combination with photosensitizing drugs.
St. John's wort might increase photosensitivity reactions due to its hypericin content. However, some clinical research shows that very high doses of St. John's wort are needed to produce phototoxicity in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing to know if you're pairing St. John's wort with Bactrim (sulfamethoxazole and trimethoprim). Both can make your skin more sensitive to sunlight. Bactrim is already a known culprit for sun sensitivity, and St. John's wort can add to that because of a compound it contains called hypericin. Together, the worry is an easier sunburn, redness, or a rash on skin that gets sun exposure.

I want to keep this in perspective, though. This concern is mostly theoretical, and research suggests it usually takes very high doses of St. John's wort to actually trigger a sun reaction in people. Still, while you're on this combo, it's smart to use sunscreen, cover up, and limit strong sun. And since St. John's wort interacts with many medicines, run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Miller LG. Herbal Medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158:2200-11.
  2. Peirce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York, NY: William Morrow and Co., 1999.
  3. Schempp CM, Muller K, Winghofer B, et al. Single-dose and steady-state administration of Hypericum perfotatum extract (St. John's wort) does not influence skin sensitivity to UV radiation, visible light, and solar-stimulated radiation. Arch Dermatol 2001;
  4. Bernd A, Ramirez-Bosca A, Kippenberger S, and et al. Phototoxic effects of Hypericum extract in cultures of human keratinocytes compared with those of psoralen. Photochem Photobiol 1999;2(69):218-221.
  5. Pochet S, Lechon AS, Lescrainier C, et al. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12(1):14178. PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 2

Sulfamethoxazole, Trimethoprim also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

St. John's wort may increase the metabolism and reduce the levels of CYP2C9 substrates.
There is contradictory research about the effect of St. John's wort on CYP2C9. Some in vitro research shows that St. John's wort induces CYP2C9, but to a lesser extent than CYP3A4. St. John's wort also induces metabolism of the S-warfarin isomer, which is a CYP2C9 substrate. Other research shows that St. John's wort 300 mg three times daily for 21 days does not significantly affect the pharmacokinetics of a single 400 mg dose of ibuprofen, which is also a CYP2C9 substrate. Until more is known, use St. John's wort cautiously in patients who are taking CYP2C9 substrates.
Severity Moderate Likelihood Possible Evidence B

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for Bactrim (sulfamethoxazole/trimethoprim). St. John's wort can speed up certain liver enzymes, including one called CYP2C9 that helps process the sulfamethoxazole part. In theory, that could lower the antibiotic's level a bit and make it work less effectively, which matters when you're trying to clear an infection.

That said, the evidence here is mixed and on the weak side. St. John's wort affects CYP2C9 much less than other enzymes, and one study showed it didn't meaningfully change a similar CYP2C9 drug. So this is more of a be cautious note than a red alert. Since you usually take Bactrim for a short, specific course, I'd just run the combination by your pharmacist or doctor before mixing the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Henderson L, Yue QY, Bergquist C, et al. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002;54:349-56..
  2. Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
  3. Komoroski BJ, Zhang S, Cai H, et al. Induction and inhibition of cytochromes P450 by the St. John's wort constituent hyperforin in human hepatocyte cultures. Drug Metab Dispos 2004;32:512-8. PubMed
  4. Jiang X, Williams KM, Liauw WS, et al. Effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2004;57:592-9. PubMed
  5. Bell EC, Ravis WR, Lloyd KB, Stokes TJ. Effects of St. John's wort supplementation on ibuprofen pharmacokinetics. Ann Pharmacother 2007;41:229-34. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

St. John's Wort Also Interacts With Other Medications

St. John's Wort has 756 major, 386 moderate known drug interactions in our database — the Sulfamethoxazole, Trimethoprim one above is among them. If you take anything else, check it against the full list below.

Major 756 Moderate 386 No known interaction 1,688 (incl. Sulfamethoxazole, Trimethoprim)
Taking anything else?

Check Another of Your Medications Against St. John's Wort

Covers the 2,830 medications we’ve checked against St. John's Wort. Pick one to open its full report.

From our Q&A

Questions About St. John's Wort or Sulfamethoxazole, Trimethoprim

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers St. John's Wort or Sulfamethoxazole, Trimethoprim, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Sulfamethoxazole, Trimethoprim

This page covers St. John's Wort only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Sulfamethoxazole, Trimethoprim page lists 174 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), Arsenic (major), Beer (major) and Cesium (major).

By severity: 11 major · 139 moderate · 24 minor.

From our pharmacist’s overview on the Sulfamethoxazole, Trimethoprim page

“The supplement I check first with sulfamethoxazole and trimethoprim (Bactrim, Septra) is PABA, because it feeds bacteria the exact compound this antibiotic works by blocking and can cancel the treatment outright. It is one of 11 major-rated entries among 174 supplements and herbs on file here, a count that calls for genuine care.”

Reviewed by 2 · Jul 18, 2026

Open the Sulfamethoxazole, Trimethoprim interaction page

One more smart check

Taking St. John's Wort as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,159 real supplement products containing St. John's Wort, each one broken down to its full ingredient list — and combination products often carry several ingredients besides St. John's Wort. Your product may carry other ingredients that interact with Sulfamethoxazole, Trimethoprim too, on top of St. John's Wort — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where St. John's Wort and Sulfamethoxazole, Trimethoprim Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement St. John's Wort
Top 10%

#144 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Sulfamethoxazole, Trimethoprim
Top 5%

#138 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About St. John's Wort

What is St. John's Wort?

St. John's Wort
  • Mild to moderate depression
  • Anxiety and stress
  • Sleep problems
  • Menopausal symptoms
  • Wound healing (topical)

St. John's wort is a well-studied herb most often used for mild to moderate depression, and some research suggests it may help with this. However, it has many serious interactions with prescription medicines and is not safe for everyone, so always talk to your pharmacist or doctor before taking it.

Read the full St. John's Wort monograph & all interactions
Keep checking

Other Drugs & St. John's Wort

Browse every other medication we’ve checked against St. John's Wort — both the ones with a known interaction and the ones without. Select any drug for the full detail.

756Major
386Moderate
0Minor
1,687No known interaction
756 Major 386 Moderate 1,687 No interaction
Major

756 interactions

Showing 60 of 756 major interactions — see all 756 on the St. John's Wort page.

Moderate

386 interactions

Showing 60 of 386 moderate interactions — see all 386 on the St. John's Wort page.

No interaction 1,687 drugs checked — show the list

We also checked St. John's Wort against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,687 medications checked with no known interaction — see the full St. John's Wort list.

See the full St. John's Wort interactions page
See every supplement checked against Sulfamethoxazole, Trimethoprim, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
St. John's Wort monograph › Uses, safety, and every drug interaction in one place Sulfamethoxazole, Trimethoprim supplement interactions › Every supplement checked against Sulfamethoxazole, Trimethoprim, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking St. John's Wort and Sulfamethoxazole, Trimethoprim Together: Common Questions

Can you take St. John's Wort with Sulfamethoxazole, Trimethoprim?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for St. John's Wort and Sulfamethoxazole, Trimethoprim?
Sulfamethoxazole, Trimethoprim belongs to more than one drug category, and St. John's Wort interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the St. John's Wort and Sulfamethoxazole, Trimethoprim interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.