Atazanavir 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
Atazanavir
Buprenorphine
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.
Taking these two together needs some care. Atazanavir (Reyataz) is an HIV medicine that slows down the liver enzyme that breaks down buprenorphine. When that happens, buprenorphine can build up in your body. That means stronger, longer-lasting opioid effects, like more drowsiness or slowed breathing.
On top of that, both drugs can affect your heart's rhythm (something called QT prolongation), and using them together can add to that risk. The good news is your care team can manage this. They may adjust your buprenorphine dose and watch you more closely. Please don't change anything on your own, just talk with your doctor or pharmacist.
Mechanism: Atazanavir inhibits CYP3A4-mediated metabolism of buprenorphine, increasing buprenorphine exposure. Both agents contribute to additive QT prolongation. Buprenorphine may also reduce atazanavir exposure.
- Direction: Increased buprenorphine effect (sedation, respiratory depression); reduced atazanavir exposure.
- Evidence/onset: Probable; onset unspecified.
- Management: If coadministered, consider reducing buprenorphine dose until stable, and monitor QTc, sedation, and respiratory status frequently. On atazanavir discontinuation, consider a buprenorphine dose increase and monitor for withdrawal. For subQ buprenorphine, monitor for over-medication; a sublingual product allowing precise titration may be preferred. Atazanavir without ritonavir is not recommended.
What happens
An increased risk of QT interval prolongation, increased buprenorphine exposure, an increased risk of buprenorphine-related adverse events and reduced atazanavir exposure
Interaction Deep Dive
Taking buprenorphine together with atazanavir can raise buprenorphine exposure and potentially cause opioid effects to last longer. The combination may also produce additive prolongation of the QT interval. When these agents are used together, consider lowering the buprenorphine dose until stable drug effects are reached, and frequently watch the patient for QT interval prolongation, sedation, and respiratory depression. If atazanavir is stopped in a patient who is on buprenorphine, consider raising the buprenorphine dose until stable drug effects are attained, while monitoring for indications of opioid withdrawal2. Should dose adjustment not be feasible once atazanavir is absent, switch the patient back to a buprenorphine formulation that allows more precise titration. For patients switched from transmucosal buprenorphine given alongside atazanavir, monitor to confirm that the plasma buprenorphine concentration achieved by subQ buprenorphine is sufficient. In patients already receiving subQ buprenorphine who need atazanavir, whether or not combined with ritonavir, watch for signs and symptoms of over-medication. If buprenorphine toxicity develops but atazanavir cannot be lowered or stopped, decrease the buprenorphine dose. It may become necessary to stop subQ buprenorphine and instead treat the patient with a sublingual buprenorphine product that allows rapid dose changes 1. In addition, the combination can decrease atazanavir exposure. Buprenorphine without ritonavir is not recommended 4.
Why it happens (mechanism)
Additive QT interval prolongation; inhibition of CYP3A4-mediated metabolism of buprenorphine; unknown
How to manage this interaction
The key message: keep taking both as prescribed unless your care team tells you otherwise. This interaction is manageable with dosing and monitoring.
- Your buprenorphine dose may need to be adjusted and individualized by your care team while you are on atazanavir.
- Your team may monitor you more closely for sedation, slowed breathing, and heart rhythm (QT).
- If atazanavir is later stopped, your buprenorphine dose may need to go back up, with watching for withdrawal signs.
- Tell your prescriber or pharmacist about any unusual sleepiness, confusion, slow or shallow breathing, dizziness, or fainting.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 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, increasing it 4.3-fold (from 0.43 to 2.1 nanograms (ng) x hr/mL), raised the Cmax 3.9-fold (from 0.057 to 0.22 ng/mL), extended the half-life (from 9.1 to 14.5 hours), and increased urinary clearance (from 0.31 to 0.73 L/hr). Voriconazole also produced a significant increase in exposure to the active metabolite norbuprenorphine, with the AUC (0 to 18 hours) rising almost 4-fold and the Cmax rising 3.3-fold, while renal clearance fell (from 7.2 to 2.9 L/hr). Participants reported mild dizziness and nausea during 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 period before crossing over 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 patients receiving subQ buprenorphine has not been investigated; nevertheless, such interactions have been demonstrated in studies employing transmucosal buprenorphine. The effects of buprenorphine may vary according to the route of administration 1.
c) Signs of opioid excess have been reported in postmarketing accounts of patients taking buprenorphine and atazanavir together, both with and without ritonavir 1.
Common questions
Can I take Atazanavir and Buprenorphine together?
Combining atazanavir and buprenorphine can raise buprenorphine levels and add to heart-rhythm risk, so your care team may lower the buprenorphine dose and monitor you closely. Keep taking both as prescribed and report any excess sedation or slowed breathing. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Atazanavir 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 Atazanavir and Buprenorphine interaction managed?
The key message: keep taking both as prescribed unless your care team tells you otherwise. This interaction is manageable with dosing and monitoring. Your buprenorphine dose may need to be adjusted and individualized by your care team while you are on atazanavir. Your team may monitor you more closely for sedation, slowed breathing, and heart rhythm (QT). If atazanavir is later stopped, your bupre… 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 Atazanavir 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 (4)
- 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
- Product Information: REYATAZ(R) oral capsules, oral powder, atazanavir oral capsules, oral powder. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2023. DailyMed
Keep reading about Atazanavir
Keep reading about Buprenorphine
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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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