Butorphanol 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
Butorphanol
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.
Amitriptyline (Elavil) is a tricyclic antidepressant that raises serotonin levels and can make you sleepy. Butorphanol is an opioid pain reliever that also affects serotonin and can slow your breathing. Taking them together can add up in two ways: too much serotonin activity (a rare condition called serotonin syndrome, with symptoms like agitation, fast heartbeat, sweating, shakiness, or confusion) and extra drowsiness or slowed breathing.
This is mostly a theoretical concern, but it is worth taking seriously. The good news is your care team can manage it by using the lowest helpful dose and watching you closely, especially when you first start or change a dose. If you feel unusually drowsy or notice any of those symptoms, contact your doctor or pharmacist.
Interaction: Additive serotonergic activity plus additive CNS and respiratory depression when combining butorphanol (opioid, weak serotonergic) with amitriptyline (TCA that inhibits serotonin reuptake).
- Direction: Increased risk of serotonin syndrome and increased sedation/respiratory depression (PD interaction, not PK). Neither agent is a relevant prodrug here.
- Magnitude/onset: Unspecified; risk highest at initiation and dose escalation.
- Evidence: Theoretical.
- Management: Reserve concurrent use for when alternatives are inadequate. Use lowest effective dose and shortest duration. Consider lowering the dose of either agent. Monitor for sedation, respiratory depression, and serotonin syndrome (autonomic instability, neuromuscular excitability, mental status change).
What happens
Increased risk of serotonin syndrome; increased risk of respiratory and CNS depression
Interaction Deep Dive
Using butorphanol together with CNS depressants can lead to respiratory depression and sedation. When butorphanol is combined with serotonergic medications, such as SSRIs, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, triptans, 5-HT3 receptor antagonists, agents that interfere with serotonin metabolism, and other drugs acting on the serotonergic system, serotonin syndrome may develop. Should combined therapy with butorphanol and a serotonergic drug be required, monitor the patient particularly at the start of treatment and when adjusting the dose, and employ the lowest dose and the shortest treatment duration needed to meet therapeutic objectives12.
Why it happens (mechanism)
Additive serotonergic effects; additive CNS depression
How to manage this interaction
Both medications can be used together when needed, but your care team will take extra care.
- Keep taking both exactly as prescribed unless your doctor tells you otherwise.
- Your team may use the lowest effective dose of butorphanol and/or amitriptyline for the shortest time needed, and doses may be adjusted and individualized to you.
- Expect closer monitoring, especially when starting or changing a dose.
- Call your pharmacist or prescriber if you notice heavy drowsiness, slow or shallow breathing, or signs of serotonin syndrome (agitation, fast heartbeat, sweating, tremor, muscle twitching, fever, or confusion).
Ask your pharmacist whether a non-opioid pain option might suit you better.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Butorphanol and Amitriptyline together?
Combining amitriptyline and butorphanol can add up to increase drowsiness, slowed breathing, and the risk of serotonin syndrome, so this pairing is used cautiously at the lowest effective dose with close monitoring. Report unusual drowsiness, slow breathing, agitation, sweating, or muscle twitching to your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Butorphanol 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 Butorphanol and Amitriptyline interaction managed?
Both medications can be used together when needed, but your care team will take extra care. Keep taking both exactly as prescribed unless your doctor tells you otherwise. Your team may use the lowest effective dose of butorphanol and/or amitriptyline for the shortest time needed, and doses may be adjusted and individualized to you. Expect closer monitoring, especially when starting or changing a d… 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 Butorphanol 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: Butorphanol tartrate intramuscular injection, intravenous injection, butorphanol tartrate intramuscular injection, intravenous injection. Hospira Inc (per DailyMed), Lake Forest, IL, 2016.
- Product Information: Butorphanol tartrate nasal spray, butorphanol tartrate nasal spray. Mylan Pharmaceuticals Inc (per DailyMed), Morgantown, WV, 2016. DailyMed
Keep reading about Amitriptyline
Keep reading about Butorphanol
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