Drug & supplement interaction

Grapefruit + Sulfamethoxazole, Trimethoprim

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

Major Interaction
Medically reviewed by · Updated September 2026
The bottom line Major

Sulfamethoxazole, Trimethoprim falls into 2 drug categories that Grapefruit can interact with; the most serious is rated major. Grapefruit or grapefruit juice, especially if consumed in large amounts, can cause additive QT interval prolongation when taken with QT interval-prolonging drugs, potentially increasing the risk of ventricular arrhythmias.

Read the full interaction report
SeverityMajor
LikelihoodProbable
Interactions2
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Grapefruit and Sulfamethoxazole, Trimethoprim

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

Why Are There 2 Interactions?

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

Major

QT INTERVAL-PROLONGING DRUGS

1 of 2

Why this applies to Sulfamethoxazole, Trimethoprim

Sulfamethoxazole, Trimethoprim falls under QT INTERVAL-PROLONGING DRUGS — the group Grapefruit interacts with.

Grapefruit or grapefruit juice, especially if consumed in large amounts, can cause additive QT interval prolongation when taken with QT interval-prolonging drugs, potentially increasing the risk of ventricular arrhythmias.
Clinical research in healthy volunteers shows that drinking 6 liters of grapefruit juice over 6 hours prolonged the QTc by a peak amount of 14 milliseconds (ms). This prolongation was similar to the QT prolongation caused by the drug moxifloxacin. In individuals with long QT syndrome, a smaller dose of grapefruit juice, 1.5 liters, resulted in a greater peak QTc prolongation of about 30 ms. The effect of smaller quantities of grapefruit juice on the QT interval is unclear.
Severity Major Likelihood Probable Evidence B

Interaction 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..

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

Here's something most folks don't realize about Bactrim (sulfamethoxazole/trimethoprim): on its own, it can slightly stretch out the heart's electrical recovery time, what doctors call the QT interval. Grapefruit can do a little of the same thing. When you stack the two, the effect can add up, and in rare cases that raises the risk of a dangerous irregular heartbeat.

Now let me put this in perspective. The research showed real QT changes only with huge amounts of grapefruit juice (we're talking liters in a single day), so a normal glass with breakfast is unlikely to be the problem. The bigger concern is for people who already have heart rhythm issues, low potassium or magnesium, or who take other QT-affecting medicines. If that's you, or you drink grapefruit juice heavily, please check with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Chorin E, Hochstadt A, Granot Y, et al. Grapefruit juice prolongs the QT interval of healthy volunteers and patients with long QT syndrome. Heart Rhythm. 2019. pii: S1547-5271(19)30368-6. PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 2

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

Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP2C9.
In vitro research suggests that grapefruit juice might inhibit CYP2C9 enzymes. So far, this interaction has not been reported 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 short version on grapefruit and Bactrim (sulfamethoxazole and trimethoprim): the sulfamethoxazole part is partly cleared by a liver enzyme called CYP2C9. In lab (test-tube) studies, grapefruit can slow that enzyme down a bit. In theory, that could let sulfamethoxazole build up slightly and nudge up the chance of side effects like nausea, rash, or sun sensitivity.

I want to be honest about the strength here, though. This is only seen in test-tube work and has never actually been reported in real people taking this combo, so I wouldn't lose sleep over an occasional grapefruit. Still, if you eat grapefruit regularly or drink the juice daily, mention it to your pharmacist or doctor so they can give you a personal thumbs-up.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 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

Grapefruit Also Interacts With Other Medications

Grapefruit has 775 major, 151 moderate, 63 minor 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 775 Moderate 151 Minor 63 No known interaction 1,841 (incl. Sulfamethoxazole, Trimethoprim)
Taking anything else?

Check Another of Your Medications Against Grapefruit

Covers the 2,830 medications we’ve checked against Grapefruit. Pick one to open its full report.

From our Q&A

Questions About Grapefruit 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 Grapefruit 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 Grapefruit 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 Grapefruit as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,144 real supplement products containing Grapefruit, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Grapefruit. Your product may carry other ingredients that interact with Sulfamethoxazole, Trimethoprim too, on top of Grapefruit — 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 Grapefruit 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 Grapefruit
Top 10%

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

29 days ago today
Medication Sulfamethoxazole, Trimethoprim
Steady interest

#1,546 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 Grapefruit

What is Grapefruit?

Grapefruit
  • Source of vitamin C
  • Digestive complaints
  • Antimicrobial (seed extract)
  • Weight management
  • Skin and cosmetic uses

Grapefruit is a nutritious citrus fruit rich in vitamin C and other nutrients, and it is generally safe to eat. However, grapefruit is famous for serious interactions with many prescription medicines, so anyone taking medication should check with a pharmacist or doctor before consuming it regularly.

Read the full Grapefruit monograph & all interactions
Keep checking

Other Drugs & Grapefruit

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

775Major
151Moderate
63Minor
1,840No known interaction
775 Major 151 Moderate 63 Minor 1,840 No interaction
Major

775 interactions

Showing 60 of 775 major interactions — see all 775 on the Grapefruit page.

Moderate

151 interactions

Showing 60 of 151 moderate interactions — see all 151 on the Grapefruit page.

Minor

63 interactions

Showing 60 of 63 minor interactions — see all 63 on the Grapefruit page.

No interaction 1,840 drugs checked — show the list

We also checked Grapefruit against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,840 medications checked with no known interaction — see the full Grapefruit list.

See the full Grapefruit 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
Grapefruit 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 Grapefruit and Sulfamethoxazole, Trimethoprim Together: Common Questions

Can you take Grapefruit with Sulfamethoxazole, Trimethoprim?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Grapefruit and Sulfamethoxazole, Trimethoprim?
Sulfamethoxazole, Trimethoprim belongs to more than one drug category, and Grapefruit 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 Grapefruit and Sulfamethoxazole, Trimethoprim interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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.