Imipramine and Buprenorphine: 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
Imipramine
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.
These two medicines can add up in a few ways. Buprenorphine (a pain or addiction medicine) and imipramine (an older antidepressant) can each affect the heart's rhythm, so together they may raise the chance of a rhythm change called QT prolongation. Both also touch the brain chemical serotonin, so combining them can slightly raise the risk of a reaction called serotonin syndrome (things like shakiness, fast heartbeat, sweating, or confusion). And because both can slow the gut, you could get severe constipation.
The good news is this concern is mostly theoretical, and your care team can manage it by watching you closely and adjusting doses. Never stop either medicine on your own. Just talk with your pharmacist or doctor.
Additive toxicity risk (theoretical). Combining buprenorphine and imipramine (a TCA) carries additive potential for:
- QT prolongation (both agents can prolong the QT interval; additive PD effect).
- Serotonin syndrome (additive serotonergic activity).
- Paralytic ileus (additive reduction in GI motility, compounded by TCA anticholinergic effects and opioid constipation).
Direction: additive/synergistic PD effects (neither is a relevant prodrug here). Evidence: theoretical. Onset: unspecified. Management: avoid if possible; if unavoidable, monitor ECG/QT, watch for serotonergic signs especially at initiation and dose titration, monitor bowel function, and discontinue if serotonin syndrome is suspected. Dosing should be individualized by the care team.
What happens
An increased risk of QT interval prolongation, an increased risk of serotonin syndrome and an increased risk of paralytic ileus
Interaction Deep Dive
Do not use buprenorphine together with medications that could prolong the QT interval34. Furthermore, combining buprenorphine with other agents acting on the serotonergic neurotransmitter system may heighten the likelihood of serotonin syndrome. When such combined use cannot be avoided, monitor the patient, particularly at the start of therapy and when adjusting the dose, and stop treatment if serotonin syndrome is suspected. Watch for indications of severe constipation, as this may lead to paralytic ileus 21.
Why it happens (mechanism)
Additive QT interval prolongation; additive serotonergic effects; additive effects on gastric motility
How to manage this interaction
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. This combination can sometimes be used with the right precautions.
- Your team may check your heart rhythm (ECG) and monitor you more closely, especially when starting or changing doses.
- Doses may need to be adjusted and individualized by your care team.
- Watch for serotonin syndrome: agitation, fast heartbeat, sweating, tremor, or confusion. Seek help right away if these occur.
- Report severe or ongoing constipation, since gut slowing can become serious.
Bring any new symptoms to your pharmacist or prescriber promptly.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Imipramine and Buprenorphine together?
Together, buprenorphine and imipramine may add up to raise the risk of heart-rhythm changes, serotonin syndrome, and severe constipation, so your care team should monitor you closely; keep taking both as prescribed and report any new symptoms. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Imipramine and Buprenorphine 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 Imipramine and Buprenorphine interaction managed?
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. This combination can sometimes be used with the right precautions. Your team may check your heart rhythm (ECG) and monitor you more closely, especially when starting or changing doses. Doses may need to be adjusted and individualized by your care team. Watch for serotonin syndrome: agitation, fast heartbeat, sweatin… 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 Imipramine or Buprenorphine 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 (4)
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. DailyMed
- Product Information: BUTRANS(R) transdermal system patch, buprenorphine transdermal system patch. Purdue Pharma L.P. (per FDA), Stamford, CT, 2016. DailyMed
- Product Information: BELBUCA(TM) buccal film, buprenorphine buccal film. Endo Pharmaceuticals Inc. (per FDA), Malvern, PA, 2016.
- Product Information: BUPRENEX(R) intravenous injection, intramuscular injection, buprenorphine HCl intravenous injection, intramuscular injection. Indivior Inc. (per DailyMed), Richmond, VA, 2016. DailyMed
Keep reading about Buprenorphine
Keep reading about Imipramine
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