Buprenorphine and Amitriptylinoxide: 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
Amitriptylinoxide
No brand names on recordBuprenorphine
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.
You've been prescribed amitriptylinoxide (a tricyclic antidepressant) along with buprenorphine (a pain and opioid-treatment medicine). Both of these can raise levels of a brain chemical called serotonin. When two serotonin-boosting medicines are used together, there's a small chance of a reaction called serotonin syndrome.
Signs to watch for include feeling agitated or restless, shivering, sweating, a racing heart, muscle twitching or stiffness, fever, or confusion. This is mostly a theoretical concern, so please don't panic. Keep taking both as prescribed, and let your doctor or pharmacist know if any of these symptoms show up, especially in the first days or after a dose change.
Interaction: Additive serotonergic effects between amitriptylinoxide (a TCA with serotonin reuptake inhibition) and buprenorphine, increasing theoretical risk of serotonin syndrome.
- Mechanism: Pharmacodynamic (additive serotonergic activity), not a PK/enzyme interaction.
- Direction: Additive CNS serotonergic effect; neither agent is a prodrug requiring activation.
- Severity/Evidence: Major severity, theoretical substantiation; onset unspecified.
- Management: Use with caution. Monitor for hyperthermia, autonomic instability, neuromuscular findings (clonus, hyperreflexia, rigidity), and mental status changes, especially at initiation and dose titration. Discontinue buprenorphine if serotonin syndrome is suspected.
What happens
An increased risk of serotonin syndrome
Interaction Deep Dive
Because of the risk of serotonin syndrome, buprenorphine should be combined cautiously with other drugs that act on the serotonergic neurotransmitter system. When such combined therapy is necessary, watch for signs of serotonin syndrome, especially at the start of treatment and whenever doses are changed21. Should serotonin syndrome be suspected, buprenorphine should be stopped1.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
Your care team can manage this safely. Here's what typically happens and what you can do:
- Keep taking both medications as prescribed unless your doctor tells you otherwise.
- Your team may monitor you more closely, especially when either medication is started or the dose is changed.
- Watch for symptoms such as agitation, sweating, shivering, fast heartbeat, muscle twitching or stiffness, fever, or confusion.
- Contact your pharmacist or prescriber if these occur. If symptoms are severe, seek urgent care.
Let your team know every medication and supplement you take so they can tailor your plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Buprenorphine and Amitriptylinoxide together?
Using amitriptylinoxide with buprenorphine can add up to raise serotonin and, in rare cases, cause serotonin syndrome. Keep taking both as prescribed, watch for symptoms like agitation, sweating, or muscle twitching, and tell your care team promptly, especially when starting or changing doses. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Amitriptylinoxide 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 Amitriptylinoxide interaction managed?
Your care team can manage this safely. Here's what typically happens and what you can do: Keep taking both medications as prescribed unless your doctor tells you otherwise. Your team may monitor you more closely, especially when either medication is started or the dose is changed. Watch for symptoms such as agitation, sweating, shivering, fast heartbeat, muscle twitching or stiffness, fever, or co… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Buprenorphine or Amitriptylinoxide 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: PROBUPHINE(R) subdermal implant, buprenorphine subdermal implant. Braeburn Pharmaceuticals Inc (per FDA), Princeton, NJ, 2016.
Keep reading about Amitriptylinoxide
Keep reading about Buprenorphine
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.
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