Oxymorphone and Amitriptyline: 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
Amitriptyline
Oxymorphone
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.
Taking amitriptyline (Elavil) with oxymorphone can add up in two ways. Both can nudge your body's serotonin levels, and together they may raise the small risk of a reaction called serotonin syndrome, which can cause agitation, shakiness, sweating, a fast heartbeat, or confusion.
Also, amitriptyline can slow your gut and bladder, and opioids like oxymorphone do the same. Together they can cause severe constipation or trouble passing urine, and rarely the gut can nearly stop moving. This is mostly a theoretical concern, and your care team can manage it. Keep taking both as prescribed, and let your doctor or pharmacist know if you notice these symptoms.
Additive risk, theoretical evidence. Combining amitriptyline (a TCA with serotonergic and strong anticholinergic activity) with oxymorphone (an opioid with weak serotonergic potential) creates two additive concerns:
- Serotonin syndrome from additive serotonergic effects (PD interaction).
- Reduced GI/GU motility: additive anticholinergic plus opioid effects raise risk of urinary retention, severe constipation, and potentially paralytic ileus.
Onset: unspecified; highest during initiation and dose changes. Management: observe closely for serotonin syndrome (autonomic instability, neuromuscular signs, mental status change) and for GI/GU dysfunction. Discontinue oxymorphone if serotonin syndrome is suspected. Neither agent's effect here depends on prodrug activation.
What happens
Increased risk of paralytic ileus and an increased risk of serotonin syndrome
Interaction Deep Dive
When opioids like oxyMORphone are taken together with serotonergic agents, serotonin syndrome can develop. Combining oxyMORphone with anticholinergic medications can also heighten the likelihood of urinary retention and severe constipation, potentially progressing to paralytic ileus. Should combined therapy be necessary, monitor the patient closely, especially when starting treatment and when adjusting the dose, watching for serotonin syndrome as well as for indications of urinary retention or diminished gastric motility. If serotonin syndrome is suspected, stop oxyMORphone12.
Why it happens (mechanism)
Additive effects on gastric motility; additive serotonergic effects
How to manage this interaction
This combination can be used with care. Your care team will typically watch you more closely, especially when either medicine is started or a dose is changed.
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Watch for serotonin syndrome: agitation, tremor, sweating, fast heartbeat, fever, or confusion. Seek help promptly if these occur.
- Watch for severe constipation or trouble urinating, and report these to your team.
Your dose may be adjusted and individualized by your care team. Ask your pharmacist or doctor about a bowel routine and what warning signs to report.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Oxymorphone and Amitriptyline together?
Amitriptyline and oxymorphone together may add up to raise the risk of serotonin syndrome and of severe constipation or urinary retention, so keep taking both as prescribed but watch for those symptoms and tell your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Oxymorphone and Amitriptyline 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 Oxymorphone and Amitriptyline interaction managed?
This combination can be used with care. Your care team will typically watch you more closely, especially when either medicine is started or a dose is changed. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Watch for serotonin syndrome: agitation, tremor, sweating, fast heartbeat, fever, or confusion. Seek help promptly if these occur. Watch for severe constipati… 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 Oxymorphone or Amitriptyline 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: OPANA(R) oral tablets, oxymorphone HCl oral tablets. Endo Pharmaceuticals Inc (per FDA), Malvern, PA, 2019. DailyMed
- Product Information: OPANA(R) ER oral extended-release tablets, oxymorphone HCl oral extended-release tablets. Endo Pharmaceuticals Inc (per FDA), Malvern, PA, 2023. DailyMed
Keep reading about Amitriptyline
Keep reading about Oxymorphone
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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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