Amitriptyline and Erythromycin: 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
Erythromycin
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 amitriptyline (Elavil) and erythromycin can affect your heart's electrical rhythm in a similar way. They can each stretch out a part of the heartbeat called the QT interval. When you take them together, that effect can add up, which in rare cases could lead to an irregular heartbeat.
I want to be clear that this concern is theoretical, meaning it's based on how each drug works rather than lots of real-world reports. The good news is your care team can manage this easily by keeping an eye on your heart and adjusting things if needed. Please don't stop either medicine on your own. Just talk with your pharmacist or doctor.
Effect: Additive QT interval prolongation with concurrent use of amitriptyline (TCA) and erythromycin (macrolide). Both independently prolong the QT interval, so combined use raises theoretical risk of QTc prolongation and torsades de pointes.
- Mechanism: Additive/pharmacodynamic effect on cardiac repolarization (both are known QT-prolonging agents). Note erythromycin also inhibits CYP3A4, which may increase amitriptyline exposure.
- Evidence: Theoretical. Severity: Major. Onset: Unspecified.
- Management: Assess baseline QTc and electrolytes (K+, Mg2+); consider ECG monitoring, especially with other risk factors. Dose may need individualization; consider alternatives where feasible.
What happens
Increased risk of QT interval prolongation
Interaction Deep Dive
When erythromycin is given together with additional agents that prolong the QT interval, the effects on QT interval prolongation may be additive123.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
Your care team is aware that combining these two medicines can add to their effect on heart rhythm, and they can manage it well.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise.
- Your team may monitor you more closely, such as checking your heart rhythm (ECG) or blood levels of minerals like potassium and magnesium.
- Doses may need to be adjusted and individualized by your care team, or they may choose an alternative antibiotic.
- Tell your doctor right away if you feel fainting, dizziness, palpitations, or a fluttering heartbeat.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a retrospective study involving 49 patients, erythromycin produced a significant lengthening of the QTc interval relative to baseline. Erythromycin was given at 500 milligrams or 1 gram four times daily, and patients received a mean of 15 doses. All patients (n equal to 9) who were given 60 mg/kg/day or more experienced QT interval increases of 15% or more. Across the entire group, the mean QTc interval rose from 432 milliseconds (msec) at baseline to 483 msec (p less than 0.01). Among patients who had delayed repolarization at baseline (n equal to 9), the QTc interval went from 473 msec to 525 msec (p less than 0.01). Among patients with heart disease (n equal to 30), every one showed a rise in QTc interval (mean of 15%), versus an 8% rise in those without heart disease (p less than 0.05). Severe QTc interval prolongation occurred in 5 patients (10%). Torsades de pointes attributed to erythromycin developed in one patient. Among 16 patients taking cotrimoxazole at the same time, 8 developed QT prolongation of 15% or more 4.
b) Erythromycin has been linked to lengthening of the QT interval and to uncommon instances of arrhythmia. During postmarketing surveillance, torsades de pointes cases have been reported spontaneously in patients taking erythromycin. Deaths have been reported 123.
Common questions
Can I take Amitriptyline and Erythromycin together?
Taking amitriptyline and erythromycin together can add to their effect on heart rhythm (QT prolongation), so keep taking both as prescribed and ask your care team whether monitoring or an alternative is right for you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Erythromycin 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 Erythromycin interaction managed?
Your care team is aware that combining these two medicines can add to their effect on heart rhythm, and they can manage it well. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Your team may monitor you more closely, such as checking your heart rhythm (ECG) or blood levels of minerals like potassium and magnesium. Doses may need to be adjusted and individualize… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
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 Erythromycin 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 (4)
- Product Information: Erythromycin Lactobionate IV injection lyophilized powder for solution, erythromycin lactobionate IV injection lyophilized powder for solution. Nexus Pharmaceuticals (per DailyMed), Lincolnshire, IL, 2024.
- Product Information: Erythromycin oral delayed-release capsules, erythromycin oral delayed-release capsules. Dr. Reddy's Laboratories Inc. (per DailyMed), Princeton, NJ, 2025. DailyMed
- Product Information: ERYTHROMYCIN ETHYLSUCCINATE oral suspension granule, erythromycin ethylsuccinate oral suspension granule. ANI Pharmaceuticals, Inc (per DailyMed), Baudette, MN, 2025. DailyMed
- Oberg KC & Bauman JL: QT interval prolongation and torsades de pointes due to erythromycin lactobionate. Pharmacotherapy 1995; 15(6):687-692. DOI
Keep reading about Amitriptyline
Keep reading about Erythromycin
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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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