Mifepristone 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
Mifepristone
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 the timing of your heartbeat. Amitriptyline (Elavil), an older antidepressant, and mifepristone (Korlym) can each stretch out a part of the heart's electrical cycle called the QT interval. When taken together, that effect can add up, and in rare cases a very long QT can lead to a dangerous irregular heartbeat.
This concern is based mostly on how the drugs work rather than lots of real-world reports, but it is still taken seriously. The good news is your care team can manage this by using the lowest dose that works, choosing alternatives when possible, and keeping an eye on your heart. Please talk with your pharmacist or doctor before making any changes.
Effect: Additive QT/QTc prolongation, increasing torsades de pointes risk.
Mechanism: Both agents block the cardiac IKr (hERG) potassium current. Mifepristone and its metabolites cause dose-related QTc prolongation; amitriptyline (a TCA) independently prolongs QT. Effects are additive (pharmacodynamic, not a prodrug interaction).
- Severity: Major
- Evidence: Theoretical
- Onset: Unspecified
Management: Avoid coadministration where possible. If unavoidable, use the lowest effective mifepristone dose, correct electrolytes (K+, Mg2+), and monitor ECG/QTc. Wait at least 2 weeks after stopping mifepristone before starting a QT-prolonging drug.
What happens
An increased risk of QT interval prolongation
Interaction Deep Dive
Do not give miFEPRIStone together with additional agents that extend the QT interval, since this combination can heighten the likelihood of QT interval prolongation. Both miFEPRIStone and its metabolites inhibit IKr. The degree to which miFEPRIStone lengthens the QTc interval depends on the dose. There is minimal or no data available regarding high exposure, simultaneous administration alongside other QT prolonging medications, or potassium channel variants that produce a long QT interval. Using the smallest dose that remains effective helps limit this risk. Before starting any QT prolonging drugs, allow a minimum of 2 weeks to pass following discontinuation of miFEPRIStone1.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
Your care team has clear ways to keep you safe if both drugs are considered:
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Do not stop or change either one on your own.
- Your team may prefer to avoid using them together or use the lowest effective dose of mifepristone.
- They may check your heart rhythm (ECG) and blood minerals like potassium and magnesium.
- If mifepristone is stopped, at least 2 weeks should pass before starting a QT-prolonging medicine.
Tell your prescriber about any fainting, dizziness, or palpitations right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
6 reports — tap to read
a) Cases of ECG changes have been documented in the postmarketing setting with the use of chloroquine 2.
b) Flecainide and miFEPRIStone have each been linked to dose-dependent prolongation of the QT interval, and torsades de pointes has been reported during treatment with flecainide 3. Prochlorperazine is a phenothiazine tranquilizer, and certain agents within this class have been linked to distortions of the QT interval 4.
c) Ibutilide has been reported to cause QT prolongation and ventricular arrhythmias, including torsade de pointes 5. Tetrabenazine has been linked to prolongation of the QT interval 6.
d) Octreotide has been linked to prolongation of the QT interval 7.
e) Protriptyline has been linked to QT interval prolongation and arrhythmias 8.
f) Sorafenib is a CYP3A4 substrate and a competitive inhibitor of CYP3A4 that has been linked to rare instances of QT interval prolongation 9.
Common questions
Can I take Mifepristone and Amitriptyline together?
Amitriptyline and mifepristone can both prolong the QT interval, and combining them adds to that risk, so it is best avoided; if both are needed, your team will use the lowest dose and monitor your heart. Report any fainting or palpitations promptly. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Mifepristone 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 Mifepristone and Amitriptyline interaction managed?
Your care team has clear ways to keep you safe if both drugs are considered: Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Do not stop or change either one on your own. Your team may prefer to avoid using them together or use the lowest effective dose of mifepristone. They may check your heart rhythm (ECG) and blood minerals like potassium and magnesium. If m… 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 Mifepristone 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 (9)
- Product Information: KORLYM(R) oral tablets, mifepristone oral tablets. Corcept Therapeutics Incorporated (per Dailmed), Redwood City, CA, 2024. DailyMed
- Product Information: chloroquine phosphate oral tablets, chloroquine phosphate oral tablets. West-ward Pharmaceutical Corp, Eatontown, NJ, 2009. DailyMed
- Product Information: Flecainide acetate oral tablets, flecainide acetate oral tablets. Amneal Pharmaceuticals (DailyMed), Paterson, NJ, 2011. DailyMed
- Product Information: prochlorperazine edisylate intramuscular intravenous injection, prochlorperazine edisylate intramuscular intravenous injection. Bedford Laboratories (per Manufacturer), Bedford, OH, 2011.
- Product Information: ibutilide fumarate IV injection, ibutilide fumarate IV injection. Bioniche Pharma USA (per Manufacturer), Lake Forest, IL, 2009.
- Product Information: XENAZINE(R) oral tablets, tetrabenazine oral tablets. Lundbeck Inc. (per FDA), Deerfield, IL, 2011. DailyMed
- Product Information: Sandostatin LAR(R) Depot IM injectable suspension, octreotide acetate IM injectable suspension. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2011.
- Product Information: protriptyline hydrochloride oral tablets, protriptyline hydrochloride oral tablets. Boehringer Ingelheim Roxane Laboratories, Inc, Columbus, OH, 2009. DailyMed
- Product Information: NEXAVAR(R) oral tablets, sorafenib oral tablets. Bayer HealthCare Pharmaceuticals Inc (per manufacturer), Wayne, NJ, 2011. DailyMed
Keep reading about Amitriptyline
Keep reading about Mifepristone
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