Amitriptyline and Sulfamethoxazole: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Amitriptyline
Sulfamethoxazole
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.
Amitriptyline (Elavil) and sulfamethoxazole can each affect the heart's rhythm in the same way. They both can stretch out a part of your heartbeat called the QT interval. When you take them together, that effect can add up and, in rare cases, lead to a dangerous irregular heartbeat.
This does not mean something bad will happen to you, but it is worth taking seriously. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor. Your care team can check your heart rhythm, review your other medicines, and decide the safest plan for you.
Effect: Additive QTc prolongation, with increased risk of torsades de pointes and cardiac arrest.
Mechanism: Both agents independently prolong the QTc interval at therapeutic doses (pharmacodynamic, additive). Neither drug is a prodrug; this is a PD interaction, not a metabolic one.
- Direction: Combined effect greater than either alone.
- Evidence: Probable; no formal interaction studies, but QTc effects documented for each.
- Onset: Unspecified.
Management: Concurrent use is generally not recommended. If unavoidable, correct electrolytes (K+, Mg2+), obtain baseline and follow-up ECGs, minimize other QT-prolonging agents, and consider alternative therapy.
What happens
An increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest)
Interaction Deep Dive
At recommended therapeutic doses, both tricyclic antidepressants (TCAs) and cotrimoxazole have demonstrated the ability to lengthen the QTc interval21. Although no formal studies of this drug interaction have been conducted, giving tricyclic antidepressants together with other agents known to prolong the QTc interval, cotrimoxazole among them, is not advised3.
Why it happens (mechanism)
Additive effects on QT prolongation
How to manage this interaction
The safest approach here is usually to avoid using these two together, so your care team may choose a different antibiotic or a different antidepressant when possible.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise.
- If both are needed, your team may monitor you more closely, including checking your heart rhythm (ECG) and blood electrolyte levels.
- Tell your prescriber about any other medicines that affect heart rhythm.
- Get medical help right away if you feel fainting, dizziness, or a fast or irregular heartbeat.
Raise this combination with your pharmacist or prescriber so they can tailor the safest plan for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Amitriptyline and Sulfamethoxazole together?
Taking amitriptyline with sulfamethoxazole can add up to a higher risk of a dangerous heart rhythm problem, so this combination is generally avoided. Contact your pharmacist or doctor, and keep taking both until they advise you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Sulfamethoxazole interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Amitriptyline and Sulfamethoxazole interaction managed?
The safest approach here is usually to avoid using these two together, so your care team may choose a different antibiotic or a different antidepressant when possible. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. If both are needed, your team may monitor you more closely, including checking your heart rhythm (ECG) and blood electrolyte levels. Tell your pres… Management is individual — always follow your own care team's guidance.
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 Amitriptyline or Sulfamethoxazole 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 (3)
- Marshall JB & Forker AD: Cardiovascular effects of tricyclic antidepressant drugs: therapeutic usage, overdose, and management of complications. Am Heart J 1982; 103:401-414. PubMed
- Lopez JA, Harold JG, Rosenthal MC, et al: QT prolongation and torsades de pointes after administration of trimethoprim-sulfamethoxazole. Am J Cardiol 1987; 59:376-377. PubMed
- Product Information: Elavil(R), amitriptyline. Merck & Co, Inc, West Point, PA, 1999. DailyMed
Keep reading about Amitriptyline
Keep reading about Sulfamethoxazole
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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