Amitriptyline and Arsenic Trioxide Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Amitriptyline
Arsenic Trioxide Injection
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
Any drug known to have the potential to prolong the QT interval should not be used with arsenic trioxide. Possible pharmacodynamic interactions can occur between arsenic trioxide and potentially arrhythmogenic agents such as tricyclic antidepressants that prolong the QT interval4. Even though no formal drug interaction studies have been done, the coadministration of arsenic trioxide and other drugs known to prolong the QTc interval, including tricyclic antidepressants, is not recommended 56.
Why it happens (mechanism)
Additive effects on QT prolongation
Literature reports
2 reports — tap to read
a) An increased incidence in sudden death was observed in six out of 53 patients with cardiac disease receiving amitriptyline, compared to zero out of 53 in the control group using a hospital based information system. The authors recommended that amitriptyline not be used in patients with underlying cardiac disease except when depression was debilitating and no other drugs were helpful 12.
b) QT/QTc prolongation should be expected during treatment with arsenic trioxide and torsade de pointes as well as complete heart block has been reported. Over 460 ECG tracings from 40 patients with refractory or relapsed APL treated with arsenic trioxide were evaluated for QTc prolongation. Sixteen of 40 patients (40%) had at least one ECG tracing with a QTc interval greater than 500 msec. Prolongation of the QTc was observed between 1 and 5 weeks after arsenic trioxide infusion, and then returned towards baseline by the end of 8 weeks after arsenic trioxide infusion. In these ECG evaluations, women did not experience more pronounced QT prolongation than men, and there was no correlation with age 3.
Common questions
Can I take Amitriptyline and Arsenic Trioxide Injection 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 Injection 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 Injection 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 Injection
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