Amitriptyline and Ivosidenib: 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
Ivosidenib
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 your medicines can affect the timing of your heartbeat. Amitriptyline (an older antidepressant) and ivosidenib (a cancer medicine) can each stretch out a part of the heart's electrical cycle called the QT interval. When they are taken together, that effect can add up, which in rare cases could lead to a dangerous irregular heartbeat.
This concern is based mostly on how these drugs are known to work rather than lots of real-world reports, but it is still worth taking seriously. Please don't stop either medicine on your own. Talk with your doctor or pharmacist, who can decide whether an alternative is a better fit or keep a closer eye on your heart with EKGs and blood tests.
Effect: Additive QTc prolongation with increased risk of torsades de pointes.
Mechanism: Both agents independently prolong the QT interval; ivosidenib is a documented QTc-prolonging drug, and amitriptyline (a TCA) has intrinsic QT-prolonging effects. This is pharmacodynamic (additive), not a metabolic interaction. Neither drug's therapeutic direction is reversed.
Evidence: Theoretical; severity rated major. Onset unspecified.
- Avoid coadministration where possible; consider alternative therapy.
- If combined, obtain baseline and periodic ECGs and monitor/correct electrolytes (K+, Mg2+).
- Assess additional QT risk factors (bradycardia, other QT drugs, hepatic impairment).
What happens
An increased risk of QT interval prolongation
Interaction Deep Dive
QTc interval prolongation has been linked to ivosidenib. Coadministration with other medicinal products recognized to prolong the QTc interval should be avoided, or such products should be swapped for alternative therapies. When avoidance is not possible, patients should be monitored for the heightened risk of QTc interval prolongation1.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
Your care team knows how to manage this safely.
- Keep taking both medicines as prescribed unless your doctor tells you otherwise.
- Because both drugs can prolong the QT interval, your team may prefer to avoid the combination or choose an alternative when possible.
- If you do need both, expect closer monitoring, such as periodic EKGs and blood tests to check electrolytes.
- Tell your pharmacist or prescriber about any fainting, dizziness, palpitations, or a fluttering heartbeat, and mention every other medicine you take.
The dose and monitoring plan can be individualized to keep you safe.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Amitriptyline and Ivosidenib together?
Combining amitriptyline and ivosidenib can add up to a higher risk of QT prolongation and abnormal heart rhythms, so your care team may avoid this pairing or monitor your heart closely with EKGs. Don't stop either drug on your own; ask your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Ivosidenib 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 Ivosidenib interaction managed?
Your care team knows how to manage this safely. Keep taking both medicines as prescribed unless your doctor tells you otherwise. Because both drugs can prolong the QT interval, your team may prefer to avoid the combination or choose an alternative when possible. If you do need both, expect closer monitoring, such as periodic EKGs and blood tests to check electrolytes. Tell your pharmacist or presc… 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 Ivosidenib 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 (1)
- Product Information: TIBSOVO(R) oral tablets, ivosidenib oral tablets. Agios Pharmaceuticals Inc (per FDA), Cambridge, MA, 2018. DailyMed
Keep reading about Amitriptyline
Keep reading about Ivosidenib
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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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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