Clarithromycin 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
Clarithromycin
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. Clarithromycin (Biaxin) is an antibiotic that slows down a liver enzyme called CYP3A4, the same enzyme that breaks down your buprenorphine. When the antibiotic slows that cleanup, buprenorphine can build up in your body. That can mean stronger opioid effects like heavy sleepiness and slowed breathing.
On top of that, both drugs can affect your heart's rhythm (something called QT prolongation), so using them together can add to that risk. Please don't stop either medicine on your own. This is very manageable. Your care team may adjust your buprenorphine dose and watch you a little more closely while you take both. Just let them know you're on both.
Mechanism: Clarithromycin is a potent CYP3A4 inhibitor; buprenorphine is a CYP3A4 substrate (not a prodrug). Inhibition reduces buprenorphine metabolism, increasing plasma exposure and prolonging opioid effects. Both agents also independently prolong the QT interval, giving an additive PD effect.
Direction: increased buprenorphine effect/toxicity plus additive QT risk. Evidence: probable. Severity: major.
- Monitor for sedation and respiratory depression frequently.
- Obtain ECG/monitor QT, especially with other QT risk factors or electrolyte abnormalities.
- Consider reducing buprenorphine dose until stable effects achieved.
- On clarithromycin discontinuation, anticipate reduced exposure; consider dose increase and monitor for withdrawal.
- Use formulations permitting precise titration when 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 plasma buprenorphine concentrations rise when buprenorphine is taken alongside a CYP3A4 inhibitor, opioid effects such as respiratory depression may be prolonged. The combined use of agents that influence cardiac conduction also raises the likelihood of QT prolongation. When these drugs are given together, watch the patient carefully for QT interval prolongation. It may be appropriate to lower the buprenorphine dose until drug effects stabilize, while checking frequently for sedation and respiratory depression. If a CYP3A4 inhibitor is stopped in someone on buprenorphine, consider raising the buprenorphine dose until stable effects are reached and observe for indications of opioid withdrawal2. When the dose cannot be adjusted once the CYP3A4 inhibitor is no longer present, move the patient back to a buprenorphine formulation that allows finer dose titration. For patients switched from transmucosal buprenorphine that was combined with CYP3A4 inhibitors, verify that the plasma buprenorphine level delivered by subQ buprenorphine is sufficient. For those already receiving subQ buprenorphine who need a CYP3A4 inhibitor, monitor for indications of over-medication. Should signs and symptoms of buprenorphine toxicity or overdose develop while the concomitant drug cannot be lowered or stopped, reduce the buprenorphine dose. If the available doses do not allow the target dose to be reached, stop treatment and manage the patient using a buprenorphine formulation that permits more precise dose adjustments1.
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 prescriber tells you otherwise. This combination can be managed with the right adjustments and monitoring.
- Your team may lower your buprenorphine dose while you're on clarithromycin, and adjust it back up when the antibiotic is finished. The dose may need to be individualized by your care team.
- They may check your heart rhythm (ECG) and watch more closely for heavy drowsiness or slowed breathing.
- Call your prescriber or pharmacist right away if you notice unusual sleepiness, confusion, very slow or shallow breathing, dizziness, or a fluttering heartbeat.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a healthy volunteer study (N=12), giving oral buprenorphine together with voriconazole produced a significant rise in the mean AUC(0 to 18 hours) of buprenorphine of 4.3-fold (from 0.43 to 2.1 nanograms (ng) x hr/mL), increased Cmax by 3.9-fold (from 0.057 to 0.22 ng/mL), prolonged half-life (from 9.1 to 14.5 hours), and raised 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, then 200 mg twice daily on days 2 to 5, followed by a 4-week washout 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 concurrently administered CYP3A4 inhibitors on buprenorphine exposure in patients 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 Clarithromycin and Buprenorphine together?
Clarithromycin can raise buprenorphine levels and add to heart-rhythm (QT) risk, so watch for extra drowsiness or slowed breathing. Don't change anything yourself; your care team can manage this by adjusting the dose and monitoring you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Clarithromycin 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 Clarithromycin and Buprenorphine interaction managed?
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. This combination can be managed with the right adjustments and monitoring. Your team may lower your buprenorphine dose while you're on clarithromycin, and adjust it back up when the antibiotic is finished. The dose may need to be individualized by your care team. They may check your heart rhythm (ECG) and watch more… 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 Clarithromycin 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 Clarithromycin
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist