Drug Interaction Report

Osimertinib 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

Amitriptyline

Elavil
+

Osimertinib

Tagrisso Tagrisso®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Jul 2, 2026
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 73 documented Osimertinib interactions, 71 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
At a glance + Theoretical Effects may be stronger
The Bottom Line
Taking amitriptyline and osimertinib together can add up to affect your heart rhythm, so your care team may avoid the combination or monitor you with periodic ECGs. Keep taking both as prescribed and report any dizziness, fainting, or palpitations.

Both amitriptyline (Elavil) and osimertinib (Tagrisso) can affect your heart's electrical rhythm in a similar way. Doctors call this "QT prolongation." When two medicines that both do this are taken together, the effect can add up and, in rare cases, lead to an abnormal heartbeat.

This concern is mostly theoretical, meaning it's based on how these drugs work rather than lots of real-world reports. Still, it's worth taking seriously. The good news is your care team can manage this easily, often by checking your heart with an ECG now and then. Please don't stop either medicine on your own. Just talk with your pharmacist or doctor.

Effect: Additive risk of QTc prolongation and, potentially, torsades de pointes.

Mechanism: Both agents independently prolong the QT interval (pharmacodynamic additive effect). Neither is a prodrug here; the concern is a PD interaction, not a metabolic one.

  • Direction: Increased combined QT-prolonging effect.
  • Onset: Unspecified.
  • Evidence: Theoretical.
  • Severity: Major.

Management: Avoid concomitant use where feasible. If co-administration is necessary, obtain periodic ECGs, monitor and correct electrolytes (K+, Mg2+), and review other QT-prolonging agents. Individualize based on baseline QTc and patient risk factors.

Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

Increased risk of QT interval prolongation

Interaction Deep Dive

Where feasible, refrain from using this together with medications recognized to extend the QTc interval and carry an established risk of torsades de pointes. Should coadministration be required, periodic ECG assessment is warranted1.

Why it happens (mechanism)

Additive QT interval prolongation

How to manage this interaction

Both drugs can lengthen the QT interval, so your care team will want to keep an eye on your heart rhythm if you take them together.

  • Keep taking both exactly as prescribed unless your doctor tells you otherwise.
  • Your team may check your heart with an ECG periodically and may review whether an alternative to one drug is possible.
  • They may also check blood minerals like potassium and magnesium, since these affect heart rhythm.
  • Tell your prescriber or pharmacist about any fainting, dizziness, or a fluttering or racing heartbeat, and mention all other medicines you take.

Management is individual — confirm any change with your pharmacist or prescriber.

Common questions

Can I take Osimertinib and Amitriptyline together?

Taking amitriptyline and osimertinib together can add up to affect your heart rhythm, so your care team may avoid the combination or monitor you with periodic ECGs. Keep taking both as prescribed and report any dizziness, fainting, or palpitations. Always confirm with your pharmacist or prescriber before making any change.

How serious is the Osimertinib 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 Osimertinib and Amitriptyline interaction managed?

Both drugs can lengthen the QT interval, so your care team will want to keep an eye on your heart rhythm if you take them together. Keep taking both exactly as prescribed unless your doctor tells you otherwise. Your team may check your heart with an ECG periodically and may review whether an alternative to one drug is possible. They may also check blood minerals like potassium and magnesium, since… 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 Osimertinib 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)

  1. Product Information: TAGRISSO(R) oral tablets, osimertinib oral tablets. AstraZeneca Pharmaceuticals LP (per manufacturer), Wilmington, DE, 2018. DailyMed
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Beyond drug–drug

These medications also interact with supplements

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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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.