Buprenorphine and Telotristat Ethyl: 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
Telotristat Ethyl
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.
Let's talk about taking buprenorphine (like Belbuca, Sublocade, or Suboxone) together with telotristat ethyl (Xermelo). Telotristat can speed up how your body breaks down buprenorphine. That means there may be less buprenorphine in your system, so it may not work as well.
For someone on buprenorphine, that can mean the pain relief or the treatment for opioid use disorder wears thin, and you might even feel withdrawal symptoms (like feeling achy, restless, sweaty, or sick to your stomach). The good news is this is very manageable. Don't change anything on your own, but let your care team know you take both so they can adjust your dose and keep a close eye on how you feel.
Effect: Telotristat ethyl induces CYP3A4, which increases buprenorphine metabolism and reduces buprenorphine exposure (lower plasma concentrations), potentially causing loss of efficacy and opioid withdrawal.
- Direction: Reduced buprenorphine effect (enzyme induction; buprenorphine is active drug, not a prodrug requiring activation).
- Severity/Evidence: Major; substantiation probable. Onset unspecified.
- Management: If the inducer is needed, titrate buprenorphine upward to stable effect and monitor for withdrawal. On inducer discontinuation, consider dose reduction and monitor for respiratory depression. Prefer formulations allowing precise titration; for subQ depot products, monitor adequacy of levels.
What happens
Reduced buprenorphine exposure and reduced efficacy of buprenorphine
Interaction Deep Dive
Because plasma buprenorphine concentrations fall when a CYP3A4 inducer is taken alongside buprenorphine, symptoms of opioid withdrawal can develop. Should a patient on buprenorphine require a CYP3A4 inducer, one option is to raise the buprenorphine dose until stable drug effects are reached, while watching for withdrawal. Conversely, when a CYP3A4 inducer is being stopped in someone receiving buprenorphine, consider lowering the buprenorphine dose and observe for respiratory depression2. When dose adjustment is not feasible once the CYP3A4 inducer is gone, move the patient back to a buprenorphine formulation that allows finer dose titration. For patients switched from transmucosal buprenorphine given together with CYP3A4 inducers, verify that the plasma buprenorphine level achieved with subQ buprenorphine is sufficient. In those already receiving subQ buprenorphine who need a CYP3A4 inducer, monitor for withdrawal. If the buprenorphine dose proves inadequate while the concomitant drug is present, and that concomitant drug cannot be reduced or stopped, modify the buprenorphine dose. When the available doses do not allow the target dose to be reached, treat the patient with a buprenorphine formulation that permits more precise dose adjustments1.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of buprenorphine
How to manage this interaction
This interaction is manageable with a few steps your care team may take:
- Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise.
- Your buprenorphine dose may need to be adjusted and individualized while you are on telotristat, and your team may monitor you more closely for withdrawal symptoms.
- If telotristat is later stopped, your team may lower your buprenorphine dose and watch for over-sedation or slowed breathing.
- Tell your pharmacist or prescriber if you feel achy, restless, sweaty, nauseated, or notice your pain or symptoms returning.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The impact of concurrently administered CYP3A4 inducers on buprenorphine exposure in patients receiving subQ buprenorphine has not been investigated; nevertheless, interactions of this kind 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 Telotristat Ethyl together?
Telotristat ethyl can lower buprenorphine levels and trigger withdrawal or reduced effect, so your care team may adjust your buprenorphine dose and monitor you closely. Keep taking both as prescribed and report any withdrawal symptoms. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Telotristat Ethyl 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 Telotristat Ethyl interaction managed?
This interaction is manageable with a few steps your care team may take: Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise. Your buprenorphine dose may need to be adjusted and individualized while you are on telotristat, and your team may monitor you more closely for withdrawal symptoms. If telotristat is later stopped, your team may lower your buprenorp… 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 Telotristat Ethyl 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 (2)
- 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
Keep reading about Buprenorphine
Keep reading about Telotristat Ethyl
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