Sertraline and Mifepristone: 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
Mifepristone
Sertraline
No brand names on record
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.
Taking mifepristone (Korlym) and sertraline (an antidepressant) together needs some care. Both can affect your heart's electrical rhythm, stretching out something called the QT interval. When two medicines do this at the same time, the effect can add up and, in rare cases, lead to an irregular heartbeat.
On top of that, mifepristone can slow down how your body breaks sertraline down, so more sertraline may build up in your system than expected. The good news is that your care team can manage this. They may choose a different medicine, use the lowest helpful dose, or watch you more closely. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor first.
Effect: Additive QTc prolongation plus increased sertraline exposure.
- Mechanism: Mifepristone and its metabolites block IKr, causing dose-related QTc prolongation; sertraline also carries QT liability, so the effect is additive. Mifepristone is a strong CYP3A4 inhibitor, which can raise sertraline exposure (higher AUC/Cmax).
- Direction: Increased sertraline effect and increased arrhythmia risk (neither drug is a prodrug requiring activation).
- Evidence: Theoretical; severity rated major. Onset unspecified.
- Management: Prefer an alternative agent when feasible. If combined, use lowest dose/decreased frequency with ECG and electrolyte monitoring. Correct hypokalemia/hypomagnesemia. Allow at least 2 weeks after stopping mifepristone before initiating sertraline.
What happens
Increased sertraline exposure and an increased risk of QT interval prolongation
Interaction Deep Dive
Sertraline should not be combined with other agents known to lengthen the QT interval, since doing so can raise the likelihood of QT prolongation and/or ventricular arrhythmias1. MiFEPRIStone, along with its metabolites, inhibits IKr, and it extends the QTc interval in a dose related fashion. Data are limited or absent regarding high exposure levels, simultaneous administration with other QT prolonging medications, or potassium channel variants that produce a long QT interval. Because miFEPRIStone acts as a strong CYP3A4 inhibitor, exercise extreme caution when it is given together with drugs that undergo substantial first pass metabolism through CYP3A4, as this may likewise raise sertraline exposure. Employ the lowest possible dose and/or a reduced dosing frequency while conducting therapeutic monitoring. Where feasible, opt for alternative medications that lack these metabolic properties. Furthermore, allow a minimum of 2 weeks after discontinuing miFEPRIStone before starting sertraline2.
Why it happens (mechanism)
Additive QT interval prolongation
How to manage this interaction
This combination is one your care team will want to review, but it can be managed. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your team may prefer an alternative antidepressant that does not have these heart and metabolism effects.
- If both are needed, they may use the lowest effective dose or less frequent dosing, with closer monitoring (such as heart tracings and blood tests).
- Because mifepristone lingers, your team may wait at least 2 weeks after stopping it before starting sertraline.
- Report fainting, dizziness, palpitations, or an irregular heartbeat right away.
Raise any questions about timing or dosing with your pharmacist or doctor.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Sertraline and Mifepristone together?
Mifepristone and sertraline can both prolong the QT interval and mifepristone can raise sertraline levels, so this pairing should generally be avoided; your care team may pick an alternative or use the lowest dose with close monitoring. Never stop or change either drug on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Mifepristone 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 Sertraline and Mifepristone interaction managed?
This combination is one your care team will want to review, but it can be managed. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your team may prefer an alternative antidepressant that does not have these heart and metabolism effects. If both are needed, they may use the lowest effective dose or less frequent dosing, with closer monitoring (such as he… 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 Sertraline or Mifepristone 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 (2)
- Product Information: ZOLOFT oral tablets, oral solution, sertraline hydrochloride oral tablets, oral solution. Viatris Specialty LLC (per FDA), Morgantown, WV, 2023. DailyMed
- Product Information: KORLYM(R) oral tablets, mifepristone oral tablets. Corcept Therapeutics Incorporated (per Dailmed), Redwood City, CA, 2024. DailyMed
Keep reading about Mifepristone
Keep reading about Sertraline
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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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