Buprenorphine and Posaconazole: 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
Posaconazole
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 are generally not used together. Posaconazole (Noxafil) is a strong antifungal that slows down the liver enzyme (CYP3A4) that normally breaks down buprenorphine. When that enzyme is blocked, buprenorphine can build up in your body, which can lead to stronger or longer-lasting opioid effects like heavy drowsiness, slowed breathing, or confusion.
On top of that, both drugs can affect your heart's rhythm (something called QT prolongation), and using them together raises that risk. The good news is your care team can manage this by choosing a safer combination or adjusting things carefully. Please don't change anything on your own. Talk with your pharmacist or doctor first.
Contraindicated combination. Two overlapping mechanisms:
- PK: Posaconazole is a potent CYP3A4 inhibitor; buprenorphine is a CYP3A4 substrate. Inhibition reduces buprenorphine clearance, increasing plasma exposure and prolonging opioid effects (respiratory depression, sedation).
- PD: Additive QT interval prolongation, as both agents can prolong QTc.
Evidence: probable. Onset: unspecified.
Management: Avoid coadministration where possible. If unavoidable, monitor for signs of buprenorphine toxicity/over-medication and consider ECG monitoring. Use a buprenorphine formulation allowing precise titration; reduce dose if toxicity occurs. On stopping posaconazole, anticipate a possible dose increase and monitor for withdrawal.
What happens
An increased risk of QT interval prolongation, increased buprenorphine exposure and an increased risk of buprenorphine-related adverse events
Interaction Deep Dive
It is contraindicated to combine buprenorphine with QT-prolonging agents that also inhibit CYP3A, such as posaconazole2. Because CYP3A4 inhibitors can raise buprenorphine plasma levels when the two are used together, opioid effects may be prolonged. For patients being switched from transmucosal buprenorphine taken alongside a CYP3A4 inhibitor, verify through monitoring that subQ buprenorphine delivers an adequate plasma buprenorphine concentration. When a patient already receiving subQ buprenorphine needs to start a CYP3A4 inhibitor, watch for indications of over-medication. Should buprenorphine toxicity or overdose signs and symptoms develop and the co-prescribed drug can neither be lowered nor stopped, decrease the buprenorphine dose. When the available doses cannot deliver the target dose, stop treatment and manage the patient using a buprenorphine formulation that allows finer dose titration. Upon stopping a CYP3A4 inhibitor in someone on buprenorphine therapy, weigh increasing the buprenorphine dose until stable drug effects are reached, while monitoring for opioid withdrawal signs. If dose adjustment is not feasible once the CYP3A4 inhibitor is gone, move the patient back to a buprenorphine formulation that supports more precise dose adjustments1.
Why it happens (mechanism)
Additive QT interval prolongation; inhibition of CYP3A-mediated metabolism of buprenorphine
How to manage this interaction
This pairing is labeled contraindicated, so the first step your care team usually takes is deciding whether one drug can be avoided or swapped for a safer option.
- Keep taking both exactly as prescribed until you speak with your prescriber or pharmacist. Do not stop or change doses on your own.
- If the combination must be used, your team may watch closely for over-medication (excess drowsiness, slowed breathing, confusion) and may check your heart rhythm.
- Your buprenorphine dose may need to be adjusted and individualized, and a formulation allowing precise dosing may be used.
- Tell your team right away if you feel unusually sedated, faint, or notice a racing or irregular heartbeat.
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 patients receiving subQ buprenorphine has not been investigated; nevertheless, these interactions have been documented in studies employing transmucosal buprenorphine. Buprenorphine's effects may vary according to the route of administration 1.
Common questions
Can I take Buprenorphine and Posaconazole together?
Combining buprenorphine with posaconazole is contraindicated because posaconazole can raise buprenorphine levels and both can affect heart rhythm; keep taking both as prescribed but contact your pharmacist or doctor promptly to sort out a safer plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Posaconazole 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 Posaconazole interaction managed?
This pairing is labeled contraindicated, so the first step your care team usually takes is deciding whether one drug can be avoided or swapped for a safer option. Keep taking both exactly as prescribed until you speak with your prescriber or pharmacist. Do not stop or change doses on your own. If the combination must be used, your team may watch closely for over-medication (excess drowsiness, slow… 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 Posaconazole 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: NOXAFIL(R) intravenous injection, oral delayed-release tablets, oral suspension, posaconazole intravenous injection, oral delayed-release tablets, oral suspension. Merck Sharp & Dohme Corp. (per FDA), Whitehouse Station, NJ, 2016. DailyMed
Keep reading about Buprenorphine
Keep reading about Posaconazole
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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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