Buprenorphine and Levoketoconazole: 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
Levoketoconazole
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.
These two medicines can be a risky pair. Buprenorphine (a pain or opioid-dependence medicine) and levoketoconazole (Recorlev, used for Cushing's syndrome) can each affect your heart's rhythm. Together they can add up and cause a heart rhythm change called QT prolongation, which in rare cases can be dangerous.
On top of that, levoketoconazole slows down the liver enzyme (CYP3A4) that clears buprenorphine, so buprenorphine can build up and cause stronger effects like drowsiness or slowed breathing. Because of this, the two are usually not used together. The good news: your care team can spot this and manage it, often by choosing a different medicine and by monitoring your heart with an ECG. Please talk with your pharmacist or doctor before combining them.
Contraindicated combination. Two concerns:
- Additive QT prolongation: both agents can prolong the QT interval, raising torsades de pointes risk. Levoketoconazole labeling contraindicates use with known QT-prolonging drugs.
- PK interaction: levoketoconazole is a potent CYP3A4 inhibitor; buprenorphine is a CYP3A4 substrate. Inhibition reduces buprenorphine clearance, increasing exposure (AUC/Cmax) and opioid-related adverse effects (sedation, respiratory depression).
Evidence is theoretical; onset unspecified. Management: avoid coadministration. If unavoidable, frequent ECG monitoring, electrolyte correction, and close observation for opioid toxicity with individualized dose adjustment by the care team.
What happens
An increased risk of QT interval prolongation and torsades pointes, an increased CYP3A4 substrate exposure and an increased risk of CYP3A4 substrate-related adverse reactions
Interaction Deep Dive
Patients receiving medications recognized to prolong the QT interval should not be given levoketoconazole, as this combination is contraindicated. ECG monitoring should be performed frequently. When levoketoconazole is administered together with CYP3A4 substrates, exposure to those CYP3A4 substrates may rise, potentially leading to more adverse reactions associated with the CYP3A4 substrate1.
Why it happens (mechanism)
Additive QT interval prolongation; inhibition of CYP3A4-substrate metabolism by levoketoconazole
How to manage this interaction
Because this pair is flagged as contraindicated, the usual approach is to avoid using them together.
- Your care team may choose a different medicine for either the pain/opioid-dependence need or the Cushing's treatment.
- If both are truly needed, expect frequent ECG checks to watch your heart rhythm and closer monitoring for opioid side effects like drowsiness or slowed breathing. Your buprenorphine dose may need to be adjusted and individualized by your care team.
What to do: Keep taking both exactly as prescribed and do not stop on your own. Contact your pharmacist or prescriber promptly so they can review this combination.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Buprenorphine and Levoketoconazole together?
Buprenorphine and levoketoconazole are contraindicated together because they can both prolong the QT interval and levoketoconazole can raise buprenorphine levels; talk to your prescriber or pharmacist before combining them. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Levoketoconazole 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 Levoketoconazole interaction managed?
Because this pair is flagged as contraindicated, the usual approach is to avoid using them together. Your care team may choose a different medicine for either the pain/opioid-dependence need or the Cushing's treatment. If both are truly needed, expect frequent ECG checks to watch your heart rhythm and closer monitoring for opioid side effects like drowsiness or slowed breathing. Your buprenorphine… 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.
Questions for your pharmacist
- Does my dose of Buprenorphine or Levoketoconazole 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)
- Product Information: RECORLEV(R) oral tablets, levoketoconazole oral tablets. Xeris Pharmaceuticals Inc (per FDA), Chicago, IL, 2023. DailyMed
Keep reading about Buprenorphine
Keep reading about Levoketoconazole
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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