Buprenorphine and Erythromycin: 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
Erythromycin
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. Erythromycin, an antibiotic, slows down the liver enzyme (called CYP3A4) that clears buprenorphine out of your body. When that happens, buprenorphine can build up higher than usual. That can lead to stronger opioid effects like heavy drowsiness or slowed, shallow breathing.
On top of that, both medicines can affect your heart's rhythm (something called QT prolongation), and using them together can add to that risk.
Please don't stop or change either medicine on your own. Your care team can absolutely manage this, often by adjusting your buprenorphine dose and watching you a little more closely. Let your pharmacist or doctor know you're taking both.
Mechanism: Erythromycin is a CYP3A4 inhibitor and reduces buprenorphine metabolism, increasing buprenorphine plasma exposure. Both agents also independently prolong the QT interval (additive PD effect). Buprenorphine is not a prodrug, so inhibition increases its effect.
Direction/effect: Increased buprenorphine exposure, risk of sedation and respiratory depression, plus additive QT prolongation.
- Severity: Major; evidence probable; onset unspecified.
- Monitor: ECG/QT, sedation, respiratory status; watch electrolytes.
- Manage: Consider reducing buprenorphine dose until stable; on discontinuation of erythromycin, consider dose increase and monitor for withdrawal. For subQ formulations, monitor for over-medication or transition to a formulation allowing precise titration.
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 can raise plasma buprenorphine levels, using it alongside buprenorphine may lead to extended opioid effects, respiratory depression among them. There is also a heightened risk of QT prolongation when medications that influence cardiac conduction are given together. Should these agents be used concurrently, watch the patient carefully for any lengthening of the QT interval. It may be advisable to lower the buprenorphine dose until drug effects stabilize, while frequently checking for sedation and respiratory depression. If a CYP3A4 inhibitor is stopped in a patient on buprenorphine, an increase in the buprenorphine dose may be warranted until stable effects are reached, along with monitoring for indications of opioid withdrawal2. When dose adjustment is not feasible after the CYP3A4 inhibitor is withdrawn, switch the patient back to a buprenorphine formulation that allows finer dose titration. For patients transitioned from transmucosal buprenorphine taken with CYP3A4 inhibitors, confirm that the plasma buprenorphine level delivered by subQ buprenorphine is sufficient. In those already receiving subQ buprenorphine who need a CYP3A4 inhibitor, remain alert for indications of over-medication. If features of buprenorphine toxicity or overdose develop and the co-administered drug cannot be lowered or stopped, decrease the buprenorphine dose. When the available doses cannot deliver the target dose, halt treatment and manage the patient with a buprenorphine formulation permitting 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 exactly as prescribed unless your care team tells you otherwise. Here is how a team usually handles this combination:
- They may reduce your buprenorphine dose while you are on erythromycin, and adjust it back once the antibiotic is stopped.
- They may monitor you more closely for sedation and slowed breathing, and may check your heart rhythm (an ECG).
- If you use a long-acting or injectable buprenorphine, they may switch you to a form that allows more precise dose changes.
Call for urgent help if you notice severe drowsiness, very slow or shallow breathing, fainting, or a pounding/irregular heartbeat. Otherwise, raise this combination with your pharmacist or prescriber.
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, with AUC(0 to 18 hours) increased by nearly 4-fold and Cmax by 3.3-fold, while lowering renal clearance (from 7.2 to 2.9 L/hr). Participants reported mild dizziness and nausea in both phases. Subjects were given either placebo or voriconazole 400 mg twice daily on day 1, then 200 mg twice daily on days 2 to 5, after which a 4-week washout occurred before crossover 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 concurrent CYP3A4 inhibitors on buprenorphine exposure in patients receiving subQ buprenorphine has not been investigated; nevertheless, such 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 Erythromycin together?
Erythromycin can raise buprenorphine levels and add to heart-rhythm (QT) risk, so watch for excess sedation or slowed breathing; your care team can manage this by adjusting your buprenorphine dose and monitoring you more closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Erythromycin 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 Buprenorphine and Erythromycin interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. Here is how a team usually handles this combination: They may reduce your buprenorphine dose while you are on erythromycin, and adjust it back once the antibiotic is stopped. They may monitor you more closely for sedation and slowed breathing, and may check your heart rhythm (an ECG). If you use a long-acting or inje… 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 Erythromycin 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 Erythromycin
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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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