Trimethoprim and Amitriptyline: 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
Trimethoprim
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.
Both of these medicines can affect your heart's rhythm. Amitriptyline (Elavil), a tricyclic antidepressant, and trimethoprim (often part of a combo antibiotic) can each stretch out a part of the 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 doesn't happen to everyone, but it's serious enough that doctors generally avoid combining them. Please don't stop either drug on your own. Talk with your pharmacist or doctor, they can review your heart health and other medicines and decide the safest plan for you.
Interaction: Additive QTc prolongation with concurrent amitriptyline (TCA) and trimethoprim, increasing risk of torsades de pointes and cardiac arrest.
- Mechanism: Pharmacodynamic (additive), not a PK/enzyme interaction. Neither agent is a prodrug here.
- Direction/magnitude: Additive QTc effect; magnitude not quantified (no formal studies).
- Onset: Unspecified. Evidence: Probable. Severity: Major.
- Management: Combination not recommended. If unavoidable, obtain baseline/follow-up ECG, correct electrolytes (K+, Mg2+), review other QT-prolonging drugs, and consider an alternative antibiotic or antidepressant.
What happens
An increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest)
Interaction Deep Dive
At the doses recommended for therapy, both tricyclic antidepressants (TCAs) and cotrimoxazole have demonstrated the capacity to lengthen the QTc interval21. Although formal studies examining this drug interaction have not been carried out, giving tricyclic antidepressants together with other agents recognized as QTc-prolonging, cotrimoxazole among them, is advised against3.
Why it happens (mechanism)
Additive effects on QT prolongation
How to manage this interaction
Keep taking both exactly as prescribed until you speak with your care team, but do raise this combination with them soon, because coadministration is generally not recommended.
- Your team may choose an alternative antibiotic or antidepressant to avoid stacking the heart-rhythm effect.
- If both must be used, they may monitor you more closely, including an ECG and blood tests to check electrolytes like potassium and magnesium.
- Tell your pharmacist about any other medicines you take, since several can also affect QT.
- Seek urgent care for fainting, palpitations, or a racing/irregular heartbeat.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Trimethoprim and Amitriptyline together?
Combining amitriptyline and trimethoprim can add up to a higher risk of a dangerous heart rhythm, so this pairing is generally avoided; ask your doctor or pharmacist whether a safer alternative is right for you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Trimethoprim and Amitriptyline 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 Trimethoprim and Amitriptyline interaction managed?
Keep taking both exactly as prescribed until you speak with your care team, but do raise this combination with them soon, because coadministration is generally not recommended. Your team may choose an alternative antibiotic or antidepressant to avoid stacking the heart-rhythm effect. If both must be used, they may monitor you more closely, including an ECG and blood tests to check electrolytes lik… 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 Trimethoprim or Amitriptyline 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 Trimethoprim
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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