Mifepristone and Buprenorphine: 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
Buprenorphine
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.
You've been prescribed buprenorphine (a pain or opioid-dependence medicine) and mifepristone. Here's what matters. Mifepristone slows down a liver enzyme that normally breaks down buprenorphine, so more buprenorphine can build up in your body. That can make its effects stronger, including too much sedation and slowed breathing. On top of that, both drugs can affect your heart's rhythm (the "QT interval"), and together that risk goes up.
The good news is your care team can manage this. They may adjust your buprenorphine dose, watch your heart with an EKG, and check on you more closely. Please don't change or stop either medicine on your own, but do call your pharmacist or doctor if you feel very drowsy, foggy, or short of breath.
Effect: Mifepristone inhibits CYP3A4, reducing buprenorphine metabolism and increasing buprenorphine exposure, with prolonged opioid effects (sedation, respiratory depression). Both agents prolong the QT interval, giving additive cardiac conduction risk.
- Direction: Increased buprenorphine effect (CYP3A4 inhibition); neither is a prodrug requiring activation here.
- Severity/evidence: Major; probable substantiation. Onset unspecified.
- Management: Monitor ECG/QT and electrolytes. Consider reducing buprenorphine dose until stable effects achieved; monitor frequently for sedation and respiratory depression. On mifepristone discontinuation, anticipate reduced buprenorphine levels and possible withdrawal, adjusting dose upward as needed. For subQ/depot formulations, favor products allowing precise titration.
What happens
An increased risk of QT interval prolongation, increased buprenorphine exposure and an increased risk of buprenorphine-related adverse events
Interaction Deep Dive
Because plasma buprenorphine concentrations rise when buprenorphine is taken together with a CYP3A4 inhibitor, opioid effects may be extended, including respiratory depression. There is also a heightened risk of QT prolongation when drugs that alter cardiac conduction are given at the same time. Watch the patient carefully for QT interval prolongation if these agents are used together. Lowering the buprenorphine dose until steady drug effects are reached is worth considering, along with frequent monitoring for sedation and respiratory depression. If a CYP3A4 inhibitor is stopped in a patient on buprenorphine, consider raising the buprenorphine dose until stable drug effects occur and watch for indications of opioid withdrawal2. When the dose cannot be modified after the CYP3A4 inhibitor is removed, switch the patient back to a buprenorphine formulation that allows finer dose titration. For patients switched from transmucosal buprenorphine that had been given with CYP3A4 inhibitors, confirm that the plasma buprenorphine level delivered by subQ buprenorphine is sufficient. For patients already receiving subQ buprenorphine who need a CYP3A4 inhibitor, watch for indications of over-medication. Should signs and symptoms of buprenorphine toxicity or overdose emerge while the concomitant drug cannot be lowered or stopped, decrease the buprenorphine dose. If the available doses do not allow the target dose to be reached, stop therapy and manage the patient with a buprenorphine formulation that supports more precise dose adjustments 1.
Why it happens (mechanism)
Additive QT interval prolongation; inhibition of CYP3A4-mediated metabolism of buprenorphine
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. Because these two together can raise buprenorphine levels and affect heart rhythm, your team will manage this actively.
- They may check your heart rhythm with an EKG and monitor you more closely for sedation and slowed breathing.
- Your buprenorphine dose may be adjusted and individualized until your response is stable.
- When mifepristone is stopped, your team may adjust buprenorphine again and watch for withdrawal signs.
Call your pharmacist or prescriber promptly if you feel unusually drowsy, confused, short of breath, or notice a racing or irregular heartbeat, dizziness, or fainting.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a study of healthy volunteers (N=12), giving oral buprenorphine together with voriconazole produced a significant rise in the mean AUC(0 to 18 hours) of buprenorphine by 4.3-fold (from 0.43 to 2.1 nanograms (ng) x hr/mL), a 3.9-fold increase in Cmax (from 0.057 to 0.22 ng/mL), a longer half-life (from 9.1 to 14.5 hours), and higher urinary clearance (from 0.31 to 0.73 L/hr). Voriconazole likewise significantly raised exposure to the active metabolite norbuprenorphine by nearly 4-fold for AUC(0 to 18 hours) and by 3.3-fold for Cmax, while lowering renal clearance (from 7.2 to 2.9 L/hr). Participants had mild dizziness and nausea in both phases. Subjects were given either placebo or voriconazole 400 mg twice daily on day 1, followed by 200 mg twice daily on days 2 to 5, and then a 4-week washout period before switching to the alternate regimen. On the fifth day, every subject received a single dose of buprenorphine 0.2 mg orally, or 3.6 mg during the placebo phase 3.
b) The impact of concurrently administered CYP3A4 inhibitors on buprenorphine exposure in patients receiving subQ buprenorphine has not been investigated; nevertheless, such interactions have been documented in studies employing transmucosal buprenorphine. Buprenorphine's effects may depend on the route by which it is administered 1.
Common questions
Can I take Mifepristone and Buprenorphine together?
Mifepristone can raise buprenorphine levels and add to QT-prolongation risk, so your care team may adjust the buprenorphine dose and monitor your heart and breathing more closely. Do not change either medicine on your own; report heavy drowsiness, slow breathing, or palpitations right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Mifepristone and Buprenorphine 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 Buprenorphine interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. Because these two together can raise buprenorphine levels and affect heart rhythm, your team will manage this actively. They may check your heart rhythm with an EKG and monitor you more closely for sedation and slowed breathing. Your buprenorphine dose may be adjusted and individualized until your response is stabl… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Mifepristone or Buprenorphine 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 (3)
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. DailyMed
- Product Information: ZUBSOLV(R) sublingual tablets, buprenorphine naloxone sublingual tablets. Orexo US Inc (per FDA), Morristown, NJ, 2023. DailyMed
- Fihlman M, Hemmila T, Hagelberg NM, et al: Voriconazole greatly increases the exposure to oral buprenorphine. Eur J Clin Pharmacol 2018; 74(12):1615-1622. PubMed
Keep reading about Buprenorphine
Keep reading about Mifepristone
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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