Buprenorphine and Fluconazole: 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
Fluconazole
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.
Here's what's going on. Fluconastan (Diflucan) is an antifungal that slows down a liver enzyme (called CYP3A4) that your body uses to break down buprenorphine. When that enzyme is blocked, more buprenorphine builds up in your body. That can make its opioid effects stronger and longer, so you might feel more drowsy, dizzy, or have slower breathing.
On top of that, both medicines can affect your heart's rhythm (the QT interval), and together that risk goes up. Because of these two things combined, this pairing is generally considered one to avoid. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor. Your care team can safely manage this.
Mechanism: Fluconazole is a CYP3A4 inhibitor; buprenorphine is a CYP3A4 substrate (not a prodrug), so inhibition increases buprenorphine exposure (AUC/Cmax) and prolongs opioid effects. Both agents independently prolong the QT interval, giving an additive proarrhythmic effect.
Direction: increased buprenorphine effect and toxicity risk.
Severity/evidence: Contraindicated; evidence probable; onset unspecified.
- Monitor for over-sedation, respiratory depression, and QT prolongation (consider ECG in at-risk patients).
- If toxicity occurs and fluconazole cannot be stopped, reduce buprenorphine dose or switch to a formulation allowing finer titration.
- On fluconazole discontinuation, watch for withdrawal and consider a buprenorphine dose increase.
What happens
An increased risk of QT interval prolongation, increased buprenorphine exposure and an increased risk of buprenorphine-related adverse events
Interaction Deep Dive
Giving fluconazole together with specific medications that both extend the QT interval and serve as CYP3A4 substrates, such as buprenorphine, is contraindicated23. Because fluconazole inhibits CYP3A4, taking it alongside buprenorphine can raise buprenorphine exposure and result in extended opioid effects. For patients being switched from a transmucosal buprenorphine regimen that included a CYP3A4 inhibitor, verify that the subQ buprenorphine delivers sufficient plasma buprenorphine levels through monitoring. When a patient already receiving subQ buprenorphine needs to start a CYP3A4 inhibitor, watch for indications of over-medication. Should signs and symptoms of buprenorphine toxicity or overdose appear while the accompanying drug can be neither lowered nor stopped, lower the buprenorphine dose instead. When the doses on hand cannot deliver the intended dose, stop the treatment and manage the patient using a buprenorphine formulation that allows finer dose adjustment. Upon stopping a CYP3A4 inhibitor in someone on buprenorphine therapy, weigh raising the buprenorphine dose until steady drug effects are reached, while monitoring for opioid withdrawal signs. If dosing cannot be modified once the CYP3A4 inhibitor is removed, move the patient back onto a buprenorphine formulation that enables more precise dose adjustments1.
Why it happens (mechanism)
Additive QT interval prolongation; inhibition of CYP3A-mediated metabolism of buprenorphine
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination is flagged as one to avoid, so the first step is letting your prescriber and pharmacist know you're on both.
- Your team may adjust and individualize your buprenorphine dose, or choose a formulation that allows more precise dosing.
- They may monitor you more closely for over-medication (excess drowsiness, slowed breathing) and, in some cases, check your heart rhythm.
- When fluconazole is stopped, watch for withdrawal signs; your buprenorphine dose may need adjusting again.
Get urgent help for very slow or shallow breathing, extreme sleepiness, fainting, or an 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 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 Fluconazole together?
Fluconazole raises buprenorphine levels and both can affect heart rhythm, so this pairing is generally avoided; do not change anything yourself, but tell your pharmacist or doctor so they can adjust dosing and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Fluconazole 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 Fluconazole interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination is flagged as one to avoid, so the first step is letting your prescriber and pharmacist know you're on both. Your team may adjust and individualize your buprenorphine dose, or choose a formulation that allows more precise dosing. They may monitor you more closely for over-medication (excess drowsines… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Buprenorphine or Fluconazole 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: DIFLUCAN(R) oral tablets, suspension, fluconazole oral tablets, suspension. Roerig (per FDA), New York, NY, 2024. DailyMed
- Product Information: DIFLUCAN(R) intravenous injection, fluconazole intravenous injection. Roerig (per FDA), New York, NY, 2024. DailyMed
Keep reading about Buprenorphine
Keep reading about Fluconazole
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