Buprenorphine and Ranolazine: 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
Ranolazine
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 buprenorphine (a pain or opioid-dependence medicine) together with ranolazine (a heart medicine for chest pain) can cause two things. First, ranolazine slows down a liver enzyme that clears buprenorphine, so more buprenorphine can build up in your body. That means stronger opioid effects, like extra sleepiness or slowed breathing. Second, both medicines can affect your heart's rhythm, and together they may raise the chance of a change called QT prolongation.
Please don't stop either medicine on your own. This is manageable. Your care team can adjust your buprenorphine dose and watch you more closely to keep you safe.
Effect: Ranolazine inhibits CYP3A4, reducing buprenorphine metabolism and increasing its exposure, raising the risk of opioid adverse events (sedation, respiratory depression). Both agents also cause additive QT prolongation.
- Direction: Increased buprenorphine effect (neither is a prodrug in this pathway).
- Onset: Unspecified; Evidence: probable; Severity: major.
- Management: Monitor ECG/QT and for sedation and respiratory depression. Consider reducing buprenorphine dose until stable effects achieved. On stopping ranolazine, consider increasing buprenorphine and watch for withdrawal. For subQ depot formulations, use products allowing precise titration if 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
Using buprenorphine together with a CYP3A4 inhibitor can raise buprenorphine plasma concentrations, which may lead to extended opioid effects such as respiratory depression. The concurrent use of agents that influence cardiac conduction also heightens the likelihood of QT prolongation. When these drugs are given together, watch the patient carefully for any lengthening of the QT interval. It may be appropriate to lower the buprenorphine dose until consistent drug effects are reached, while frequently checking for sedation and respiratory depression. If a CYP3A4 inhibitor is stopped in someone on buprenorphine therapy, an increase in the buprenorphine dose may be warranted until stable drug effects are obtained, with monitoring for indications of opioid withdrawal2. Should the dose be unable to be modified once the CYP3A4 inhibitor is removed, switch the patient back to a buprenorphine formulation that allows finer dose titration. For patients transitioned from transmucosal buprenorphine used alongside CYP3A4 inhibitors, confirm that the plasma buprenorphine concentration delivered by subQ buprenorphine is sufficient. In those already receiving subQ buprenorphine who need a CYP3A4 inhibitor, observe for indications of over-medication. If features of buprenorphine toxicity or overdose develop and the co-administered drug cannot be lowered or stopped, reduce the buprenorphine dose. When the available doses do not allow the target dose to be reached, discontinue treatment and manage the patient with a buprenorphine formulation that enables 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 medicines exactly as prescribed unless your care team tells you otherwise. This combination can be managed with the right adjustments and monitoring.
- Your team may reduce your buprenorphine dose and individualize it until your effects are stable.
- They may monitor you more closely for excess sleepiness, slowed breathing, and check your heart rhythm (an ECG for QT).
- If ranolazine is later stopped, your buprenorphine dose may need to be raised, so watch for withdrawal symptoms.
Tell your pharmacist or prescriber right away if you notice unusual drowsiness, confusion, very slow or shallow breathing, fainting, or palpitations.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In an investigation involving healthy volunteers (N=12), giving oral buprenorphine together with voriconazole produced a significant rise in the mean buprenorphine AUC(0 to 18 hours) of 4.3-fold (from 0.43 to 2.1 nanograms (ng) x hr/mL), in Cmax of 3.9-fold (from 0.057 to 0.22 ng/mL), in half-life (from 9.1 to 14.5 hours), and in 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 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, and 200 mg twice daily on days 2 to 5, followed by a 4-week washout period before switching over to the alternate regimen. On the fifth day, every subject was given a single oral dose of buprenorphine 0.2 mg or 3.6 mg during the placebo phase 3.
b) How coadministered CYP3A4 inhibitors influence buprenorphine exposure in subjects receiving subQ buprenorphine has not been examined; nonetheless, such interactions have been demonstrated in studies employing transmucosal buprenorphine. Buprenorphine effects may vary according to the route of administration 1.
Common questions
Can I take Buprenorphine and Ranolazine together?
Combining buprenorphine and ranolazine can increase buprenorphine levels (more sedation and slowed breathing) and add to QT prolongation, so your care team may lower the buprenorphine dose and monitor you closely. Don't change either medicine on your own; call your pharmacist or doctor with any concerns. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Ranolazine 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 Ranolazine interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. This combination can be managed with the right adjustments and monitoring. Your team may reduce your buprenorphine dose and individualize it until your effects are stable. They may monitor you more closely for excess sleepiness, slowed breathing, and check your heart rhythm (an ECG for QT). If ranolazine is… 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 Buprenorphine or Ranolazine 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 Ranolazine
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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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