Adagrasib 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
Adagrasib
Amitriptyline
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. Adagrasib (Krazati) is a cancer medicine, and amitriptyline (Elavil) is often used for mood or nerve pain. Each one can stretch out a part of your heartbeat called the QT interval. When taken together, that effect can add up, which in rare cases can lead to a dangerous irregular heartbeat.
This is a caution based on how these drugs work, not on lots of real-world reports. The good news is that your care team can manage this. They may check an ECG (heart tracing) and your blood minerals like potassium and magnesium, and adjust things as needed. Keep taking both as prescribed and talk with your doctor or pharmacist about the best plan for you.
Effect: Additive QTc prolongation, increasing risk of torsade de pointes and other serious ventricular arrhythmias.
Mechanism: Both agents independently prolong the QTc interval; combined use produces additive repolarization delay. Neither is a prodrug relevant to this pharmacodynamic interaction.
Evidence: Theoretical; severity major; onset unspecified.
- Avoid concomitant use where possible.
- If unavoidable, obtain baseline ECG and electrolytes (K+, Mg2+), and monitor during therapy, especially with CHF, bradyarrhythmias, or electrolyte disturbance.
- Withhold adagrasib if QTc >500 msec or change from baseline >60 msec; resume at next lower dose once QTc
What happens
An increased risk of QT interval prolongation, torsade de pointes, polymorphic ventricular tachycardia, other serious arrhythmias
Interaction Deep Dive
Do not administer adagrasib together with other agents recognized as having the potential to lengthen the QTc interval, since adagrasib itself produces QTc interval prolongation. Combining adagrasib with additional products that prolong the QTc interval may lead to a larger increase in the QTc interval, along with adverse reactions linked to QTc interval prolongation, such as torsade de pointes, other serious arrhythmias, and sudden death. Perform electrocardiogram and electrolyte monitoring before initiating adagrasib, throughout concomitant use, and as clinically warranted in patients with congestive heart failure, bradyarrhythmias, or electrolyte abnormalities, as well as in those unable to avoid concurrent medications known to prolong the QT interval. Hold adagrasib when the QTc interval exceeds 500 msec or the change from baseline exceeds 60 msec, continuing to withhold until the QTc interval falls below 481 msec or returns to baseline. Restart adagrasib at the next lower dose level. Discontinue adagrasib permanently in the event of torsade de pointes, polymorphic ventricular tachycardia, or any signs or symptoms of a serious or life-threatening arrhythmia1.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
The main strategy is to avoid using these two together when possible. If your care team decides you need both, they can manage this safely with monitoring.
- Expect an ECG and blood tests for potassium and magnesium before starting and during treatment.
- Your team may adjust or pause the adagrasib dose based on your ECG results, and can restart it at a lower dose if needed.
- Extra caution applies if you have heart failure, a slow heartbeat, or low electrolytes.
Keep taking both exactly as prescribed and do not stop on your own. Tell your doctor or pharmacist right away if you feel fainting, dizziness, palpitations, or a fluttering heartbeat.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Adagrasib and Amitriptyline together?
Combining adagrasib and amitriptyline can add up their effects on heart rhythm (QT prolongation), so your care team will usually avoid the pair or watch you closely with ECGs and electrolyte checks. Keep taking both as prescribed and report any fainting or palpitations. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Adagrasib 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 Adagrasib and Amitriptyline interaction managed?
The main strategy is to avoid using these two together when possible. If your care team decides you need both, they can manage this safely with monitoring. Expect an ECG and blood tests for potassium and magnesium before starting and during treatment. Your team may adjust or pause the adagrasib dose based on your ECG results, and can restart it at a lower dose if needed. Extra caution applies if y… 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 Adagrasib 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 (1)
- Product Information: KRAZATI(TM) oral tablets, adagrasib oral tablets. Mirati Therapeutics Inc (per FDA), San Diego, CA, 2024. DailyMed
Keep reading about Adagrasib
Keep reading about Amitriptyline
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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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