Amitriptyline and Arsenic Trioxide: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Amitriptyline
Arsenic Trioxide
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 cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest)
Interaction Deep Dive
Arsenic trioxide should be avoided in combination with any medication recognized as capable of prolonging the QT interval. Pharmacodynamic interactions are possible between arsenic trioxide and agents with arrhythmogenic potential, such as tricyclic antidepressants, which prolong the QT interval4. Although formal studies of drug interactions have not been conducted, giving arsenic trioxide together with other agents known to prolong the QTc interval, tricyclic antidepressants among them, is not advised56.
Why it happens (mechanism)
Additive effects on QT prolongation
Literature reports
2 reports — tap to read
a) Using a hospital based information system, a higher rate of sudden death was noted in six of 53 patients with cardiac disease who were given amitriptyline, versus zero of 53 in the control group. The authors advised against the use of amitriptyline in patients with underlying cardiac disease, unless the depression was debilitating and no other medications provided benefit 12.
b) QT/QTc prolongation is anticipated with arsenic trioxide therapy, and torsade de pointes along with complete heart block have been reported. More than 460 ECG tracings from 40 patients with refractory or relapsed APL treated with arsenic trioxide were assessed for QTc prolongation. Sixteen of the 40 patients (40%) showed at least one ECG tracing with a QTc interval exceeding 500 msec. QTc prolongation occurred between 1 and 5 weeks following arsenic trioxide infusion, then moved back toward baseline by the end of 8 weeks after the arsenic trioxide infusion. In these ECG assessments, women did not have more marked QT prolongation than men, and no correlation with age was found 3.
Common questions
Can I take Amitriptyline and Arsenic Trioxide together?
An increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Arsenic Trioxide 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 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 Arsenic Trioxide 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 (6)
- Moir DC, Crooks J, Cornwell WB, et al: Cardiotoxicity of amitriptyline. Lancet 1972; 2:561-564. PubMed
- Coull DC, Crooks J, Dingwall-Fordyce I, et al: Amitriptyline and cardiac disease. Lancet 1970; 1:590-591. DOI
- Product Information: Trisenox(R), arsenic trioxide. Cell Therapeutics, Inc. Seattle, WA, 2000. DailyMed
- Product Information: Trisenox(R), arsenic trioxide. Cell Therapeutics, Inc. Seattle, WA, 2000. DailyMed
- Product Information: Elavil(R), amitriptyline. Merck & Co, Inc, West Point, PA, 1999. DailyMed
- 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
Keep reading about Amitriptyline
Keep reading about Arsenic Trioxide
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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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