Amoxicillin and Sulfasalazine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Sulfasalazine
Amoxicillin
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increased risk of drug reaction with eosinophilia and systemic symptoms
Interaction Deep Dive
Concomitant use of amoxicillin and sulfasalazine has resulted in drug reaction with eosinophilia and systemic symptoms (DRESS) in a 16-year-old adolescent with ulcerative colitis. Sulfasalazine has been associated with DRESS syndrome. Altered sulfasalazine metabolism by amoxicillin resulting in excess toxic metabolites is reported to have caused DRESS in this patient1.
Why it happens (mechanism)
Altered sulfasalazine metabolism resulting in excess toxic metabolites
Literature reports
1 report — tap to read
a) A 16-year-old adolescent with ulcerative colitis experienced drug reaction with eosinophilia and systemic symptoms (DRESS) 1 week following coadministration of sulfasalazine and amoxicillin. He presented with fever and abdominal pain 3 weeks following a change in therapy from mesalamine to sulfasalazine. He did not have a rash, eosinophilia, or any signs of internal organ involvement. He was treated with amoxicillin for presumptive streptococcal pharyngitis. One week later he returned with daily fevers, a new diffuse erythematous rash on his upper extremities and trunk spreading caudally, extending bilaterally to his feet. He also had predominantly cervical, and submandibular lymphadenopathy. Laboratory findings included elevated absolute eosinophil count, hyponatremia, and mildly elevated liver enzymes. Sulfasalazine was discontinued and treatment with IV corticosteroids later changed to oral steroids, water restriction, and high-potency topical steroids resulted in a gradual resolution 1.
Common questions
Can I take Amoxicillin and Sulfasalazine together?
An increased risk of drug reaction with eosinophilia and systemic symptoms Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amoxicillin and Sulfasalazine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Amoxicillin or Sulfasalazine need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Sussman S, Devlin V, & Dimitriades VR: A teenager with sulfasalazine-associated DRESS syndrome after the introduction of amoxicillin. Clin Pediatr (Phila) 2017; 56(3):290-291. PubMed
Keep reading about Sulfasalazine
Keep reading about Amoxicillin
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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