Buprenorphine and Ketoconazole: 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
Ketoconazole
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.
Let's talk about taking buprenorphine (a pain or opioid-treatment medicine) together with ketoconazole (an antifungal). Ketoconazole slows down the liver enzyme that normally breaks down buprenorphine. That means buprenorphine can build up in your body and stick around longer, so you may feel stronger opioid effects like heavy drowsiness, slowed breathing, confusion, or feeling faint. Both drugs can also affect your heart's rhythm, and using them together adds to that risk.
Because of this, the combination is generally something doctors avoid. The good news is your care team can manage this safely. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor so they can guide you.
Effect: Ketoconazole (strong CYP3A4 inhibitor) reduces CYP3A4-mediated metabolism of buprenorphine (a CYP3A4 substrate), increasing buprenorphine exposure and prolonging opioid effects. Both agents prolong the QT interval, so the combination is additive for QT risk. This combination is rated contraindicated; evidence is probable, onset unspecified.
- Direction: increased buprenorphine AUC/effect (not a prodrug; inhibition raises active drug).
- Monitor: sedation, respiratory depression, over-medication; ECG/QTc, electrolytes.
- Manage: if toxicity occurs and the inhibitor cannot be stopped, reduce buprenorphine dose; use a formulation allowing precise titration. On discontinuing ketoconazole, watch for withdrawal and consider a dose increase.
What happens
Increased buprenorphine exposure, an increased risk of buprenorphine-related adverse events and an increased risk of QT interval prolongation
Interaction Deep Dive
Combining ketoconazole, a potent CYP3A4 inhibitor, with buprenorphine, a CYP3A4 substrate known to prolong the QT interval, is contraindicated2, because it can raise buprenorphine exposure and produce extended opioid effects. For patients being switched from transmucosal buprenorphine taken together with CYP3A4 inhibitors, verify through monitoring that the plasma buprenorphine concentration achieved with subQ buprenorphine is sufficient. When a patient already receiving subQ buprenorphine needs a CYP3A4 inhibitor, watch for indications of over-medication. Should buprenorphine toxicity or overdose signs and symptoms develop while the concurrent medication cannot be lowered or stopped, decrease the buprenorphine dose. If the doses on hand do not allow the target dose to be reached, stop treatment and manage the patient using a buprenorphine formulation that allows finer dose titration. Upon stopping a CYP3A4 inhibitor in a patient on buprenorphine therapy, consider raising the buprenorphine dose until stable drug effects are reached, and monitor for opioid withdrawal signs. When the dose cannot be modified once the CYP3A4 inhibitor is absent, move the patient back to a buprenorphine formulation permitting more precise dose adjustments 1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of buprenorphine; additive QT interval prolongation
How to manage this interaction
First, keep taking both medicines exactly as prescribed unless your care team tells you otherwise. This pairing is one clinicians usually try to avoid, so your prescriber may consider a different antifungal or a buprenorphine form that allows more precise dose changes.
- Your buprenorphine dose may need to be adjusted and individualized by your care team while you are on ketoconazole.
- They may monitor you more closely, including watching for over-sedation and possibly checking your heart rhythm (ECG).
- Tell your team right away about heavy drowsiness, slow or shallow breathing, confusion, fainting, or a racing/irregular heartbeat.
- When ketoconazole is stopped, watch for opioid withdrawal, since your dose may need raising again.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The impact of concurrently administered CYP3A4 inhibitors on buprenorphine exposure in individuals receiving subQ buprenorphine has not been investigated; nevertheless, these interactions have been demonstrated in studies employing transmucosal buprenorphine. Buprenorphine's effects may vary according to the route of administration 1.
Common questions
Can I take Buprenorphine and Ketoconazole together?
Combining ketoconazole with buprenorphine can raise buprenorphine levels and add to heart-rhythm risk, so it is generally avoided; do not change either medicine on your own, and contact your pharmacist or doctor to have this managed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Ketoconazole interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Buprenorphine and Ketoconazole interaction managed?
First, keep taking both medicines exactly as prescribed unless your care team tells you otherwise. This pairing is one clinicians usually try to avoid, so your prescriber may consider a different antifungal or a buprenorphine form that allows more precise dose changes. Your buprenorphine dose may need to be adjusted and individualized by your care team while you are on ketoconazole. They may monit… 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 Buprenorphine or Ketoconazole 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: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. DailyMed
- Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
Keep reading about Buprenorphine
Keep reading about Ketoconazole
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