Itraconazole 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
Itraconazole
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. Itraconazole (Sporanox) is an antifungal that slows down a liver enzyme called CYP3A4, which is the same enzyme that helps break down your buprenorphine. When that clean-up slows down, more buprenorphine can build up in your body. That can make its effects, including sleepiness and slowed breathing, stronger and last longer.
On top of that, both medicines can affect your heart's rhythm (something called QT prolongation), so using them together can add to that risk.
The good news: this is manageable. Your care team can adjust your buprenorphine dose and watch you more closely. Keep taking both as prescribed and talk with your pharmacist or doctor about the best plan.
Mechanism: Itraconazole is a potent CYP3A4 inhibitor; buprenorphine is CYP3A4-metabolized. Inhibition reduces buprenorphine clearance, increasing plasma exposure and prolonging opioid effects (sedation, respiratory depression). Additive QT prolongation is also expected since both agents can affect cardiac conduction.
Direction: increased buprenorphine effect. Evidence: probable. Severity: major. Onset: unspecified.
- Monitor ECG/QT, especially with other QT-prolonging drugs or electrolyte abnormalities.
- Consider reducing buprenorphine dose until stable; monitor for sedation/respiratory depression.
- On itraconazole discontinuation, consider dose increase and watch for withdrawal.
- For subQ/long-acting formulations, ensure adequate but not excessive exposure; transition to titratable forms if precise adjustment is needed.
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 a CYP3A4 inhibitor raises buprenorphine plasma concentrations, using it together with buprenorphine may lead to extended opioid effects, such as respiratory depression. There is also a heightened risk of QT prolongation when drugs influencing cardiac conduction are given together. Should these agents be used concurrently, watch the patient closely for any lengthening of the QT interval. It may be advisable to lower the buprenorphine dose until drug effects stabilize, while checking frequently for sedation and respiratory depression. If a CYP3A4 inhibitor is stopped in a patient on buprenorphine, consider raising the buprenorphine dose until stable effects are reached and observe 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 moved from transmucosal buprenorphine taken with CYP3A4 inhibitors, confirm that the plasma buprenorphine concentration achieved with subQ buprenorphine is sufficient. For those already receiving subQ buprenorphine who need a CYP3A4 inhibitor, monitor for indications of over-medication. If buprenorphine toxicity or overdose signs and symptoms develop but the accompanying drug cannot be lowered or stopped, decrease the buprenorphine dose. When the available doses do not allow the target dose to be reached, halt treatment and manage the patient with a buprenorphine formulation that permits 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 as prescribed unless your care team tells you otherwise. This combination can be managed with the right monitoring and dosing.
- Your team may lower your buprenorphine dose while you are on itraconazole, then adjust again when the antifungal is stopped.
- They may monitor you more closely for excess sedation, slowed breathing, and heart rhythm (an ECG may be done).
- With long-acting or injectable buprenorphine, your team may switch to a form that allows more precise dose adjustments if needed.
Tell your care team right away if you feel unusually drowsy, confused, dizzy, faint, or notice slow or shallow breathing.
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), an increase in Cmax by 3.9-fold (from 0.057 to 0.22 ng/mL), a longer half-life (from 9.1 to 14.5 hours), and greater 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 reducing 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, and 200 mg twice daily on days 2 to 5, followed by 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 coadministered CYP3A4 inhibitors on buprenorphine exposure in subjects receiving subQ buprenorphine has not been investigated; nevertheless, such interactions have been demonstrated in studies with transmucosal buprenorphine. The effects of buprenorphine may vary according to the route of administration 1.
Common questions
Can I take Itraconazole and Buprenorphine together?
Itraconazole can raise buprenorphine levels and add to heart-rhythm (QT) risk, so effects like sedation and slowed breathing may be stronger. Keep taking both as prescribed, but ask your care team about dose adjustments and closer monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Itraconazole 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 Itraconazole and Buprenorphine interaction managed?
Keep taking both as prescribed unless your care team tells you otherwise. This combination can be managed with the right monitoring and dosing. Your team may lower your buprenorphine dose while you are on itraconazole, then adjust again when the antifungal is stopped. They may monitor you more closely for excess sedation, slowed breathing, and heart rhythm (an ECG may be done). With long-acting or… 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 Itraconazole 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 Itraconazole
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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:
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