Buprenorphine and Larotrectinib: 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
Larotrectinib
No brand names on record
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 (a pain or opioid-dependence medicine) together with larotrectinib (a cancer medicine). Larotrectinib can slow down the liver enzyme that normally breaks buprenorphine down. When that happens, more buprenorphine can build up in your body than usual.
That extra buildup can make the opioid effects stronger and last longer. The main thing to watch for is too much sedation or slowed breathing. The good news is your care team knows how to handle this. They can tailor your buprenorphine dose and keep a closer eye on you. Please don't change anything on your own. Just talk with your pharmacist or doctor so they can plan it out safely.
Effect: Larotrectinib (a CYP3A4 inhibitor) is expected to reduce CYP3A4-mediated metabolism of buprenorphine, increasing buprenorphine plasma concentrations and exposure, with risk of prolonged opioid effects including respiratory depression.
- Direction: Increased buprenorphine effect (neither agent is dose-activated in a way that reverses this).
- Severity/Evidence: Major; probable substantiation. Onset unspecified.
- Management: If starting larotrectinib, consider reducing buprenorphine dose until stable, monitor closely for sedation and respiratory depression. On larotrectinib discontinuation, anticipate reduced buprenorphine levels and monitor for withdrawal, adjusting dose upward as needed. Use formulations permitting precise titration if needed.
What happens
Increased buprenorphine exposure and an increased risk of buprenorphine-related adverse events
Interaction Deep Dive
Combining buprenorphine with a CYP3A4 inhibitor can raise buprenorphine plasma levels, potentially leading to extended opioid effects such as respiratory depression. When a patient on buprenorphine must also receive a CYP3A4 inhibitor, it may be appropriate to lower the buprenorphine dose until stable drug effects are reached, along with frequent monitoring for sedation and respiratory depression. Conversely, if a CYP3A4 inhibitor is stopped in a patient being treated with buprenorphine, an increase in the buprenorphine dose may be warranted until stable drug effects are achieved, with observation for indications of opioid withdrawal2. Should dose adjustment prove impossible once the CYP3A4 inhibitor is no longer present, the patient should be switched back to a buprenorphine formulation allowing finer dose titration. For patients transitioned from transmucosal buprenorphine given alongside CYP3A4 inhibitors, confirm through monitoring that the plasma buprenorphine level delivered by subQ buprenorphine is sufficient. When a patient already receiving subQ buprenorphine needs a CYP3A4 inhibitor, watch for indications of over-medication. If buprenorphine toxicity or overdose signs and symptoms develop and the co-administered drug cannot be reduced or stopped, lower the buprenorphine dose. When the available doses are insufficient to reach the intended dose, stop the current treatment and manage the patient with a buprenorphine formulation that allows more precise dose adjustments 1.
Why it happens (mechanism)
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. Here is what a team typically does:
- Dose tailoring: Your buprenorphine dose may need to be adjusted and individualized by your care team while you are on larotrectinib.
- Closer monitoring: Expect to be watched more closely for excess sedation and slowed breathing.
- When larotrectinib stops: Your team may raise the buprenorphine dose again and watch for withdrawal symptoms.
Contact your pharmacist or prescriber right away if you feel unusually drowsy, confused, or notice slow or shallow breathing.
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 inhibitors on buprenorphine exposure in patients receiving subQ buprenorphine has not been evaluated; nevertheless, such interactions have been demonstrated in studies utilizing transmucosal buprenorphine. Buprenorphine's effects may vary according to the route of administration 1.
Common questions
Can I take Buprenorphine and Larotrectinib together?
Larotrectinib can raise buprenorphine levels and increase the risk of sedation and slowed breathing, so your care team may adjust your buprenorphine dose and monitor you more closely. Talk with your pharmacist or doctor before making any changes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Larotrectinib 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 Larotrectinib interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Here is what a team typically does: Dose tailoring: Your buprenorphine dose may need to be adjusted and individualized by your care team while you are on larotrectinib. Closer monitoring: Expect to be watched more closely for excess sedation and slowed breathing. When larotrectinib stops: Your team may rais… 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 Larotrectinib 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 Larotrectinib
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