Buprenorphine and Dextromethorphan: 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
Dextromethorphan
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.
Both buprenorphine (a pain and addiction medicine) and dextromethorphan (the cough suppressant in many Delsym and cold products) can raise serotonin, a natural brain chemical. When two medicines nudge serotonin up at the same time, there is a small chance of too much, called serotonin syndrome.
Warning signs to know include shakiness, muscle twitching, sweating, a racing heart, fever, agitation, or confusion. This is considered a theoretical risk, meaning it is possible but not commonly reported. Many people take both without trouble. Your care team can manage this safely by watching how you feel, so just keep them in the loop and let them know if you feel unwell.
Effect: Additive serotonergic activity raising the theoretical risk of serotonin syndrome. Both agents have serotonergic properties (dextromethorphan inhibits serotonin reuptake; buprenorphine carries a class serotonergic caution).
Direction: Pharmacodynamic, additive; not a metabolic inhibition/induction issue.
- Severity: Major (labeling caution)
- Evidence: Theoretical
- Onset: Unspecified; highest risk at initiation and dose changes
Management: Use with caution. Monitor for autonomic instability, neuromuscular signs (clonus, hyperreflexia, rigidity), and mental status changes. Discontinue buprenorphine if serotonin syndrome is suspected. Note dextromethorphan is often short-course/OTC, so review true need.
What happens
An increased risk of serotonin syndrome
Interaction Deep Dive
Because serotonin syndrome may occur, use buprenorphine cautiously alongside other drugs that act on the serotonergic neurotransmitter system. Should combined use be necessary, watch for serotonin syndrome, especially when starting therapy and when doses are changed21. If serotonin syndrome is suspected, stop buprenorphine1.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Because both can affect serotonin, your care team simply watches you a bit more closely, especially when you first combine them or change a dose.
- Tell your pharmacist or doctor that you take buprenorphine before buying any cough or cold product, since many contain dextromethorphan.
- Watch for agitation, confusion, fast heartbeat, sweating, fever, tremor, or muscle twitching.
- Get urgent care if several of these appear together, and let your team know.
If serotonin syndrome is suspected, your prescriber may stop the buprenorphine. Do not stop it on your own.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Buprenorphine and Dextromethorphan together?
Taking buprenorphine with dextromethorphan slightly raises the theoretical risk of serotonin syndrome, so watch for symptoms like agitation, fever, fast heartbeat, or muscle twitching and check with your pharmacist before using cough or cold products. Your care team can manage this with monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Dextromethorphan 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 Dextromethorphan interaction managed?
Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Because both can affect serotonin, your care team simply watches you a bit more closely, especially when you first combine them or change a dose. Tell your pharmacist or doctor that you take buprenorphine before buying any cough or cold product, since many contain dextromethorphan. Watch for agitation, con… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Buprenorphine or Dextromethorphan 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 Buprenorphine
Keep reading about Dextromethorphan
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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