Amitriptyline and Loxoprofen: 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
Loxoprofen
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 these two together can raise your risk of bleeding. Amitriptyline (Elavil) is a tricyclic antidepressant, and loxoprofen is an anti-inflammatory painkiller (an NSAID). Each one can affect how your body forms clots, and when they are combined, the chance of bleeding goes up. In rare cases this can include serious bleeding, even in the brain, especially in the first weeks of using both.
Please don't stop either medicine on your own. Both are helping you for a reason. Just let your pharmacist or doctor know you take both, and watch for things like unusual bruising, nosebleeds, black or bloody stools, or a bad headache. Your care team can manage this safely.
Effect: Increased bleeding risk with concurrent NSAID (loxoprofen) and TCA (amitriptyline), including reports of intracranial hemorrhage within 30 days of combined use.
- Direction: Additive bleeding risk; both agents can impair hemostasis (NSAID inhibits platelet COX/prostaglandins; TCAs affect serotonin-mediated platelet aggregation). Neither is a prodrug here.
- Mechanism: Unknown/unconfirmed, likely pharmacodynamic and additive.
- Evidence: Established. Onset: unspecified.
- Management: Use with caution; monitor for signs of bleeding (bruising, GI bleeding, epistaxis, neurologic changes). Consider gastroprotection and reassess NSAID necessity/duration.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution if NSAIDs are given together with tricyclic antidepressants, since this combination may raise the risk of bleeding, such as intracranial hemorrhage occurring within 30 days of using both agents together1. If a patient receives both an NSAID and a tricyclic antidepressant at the same time, watch for indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
The good news: your care team can manage this by watching you a bit more closely.
- Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Tell your pharmacist and doctor that you take both, so they can decide if the NSAID is still needed and for how long.
- Watch for warning signs: easy bruising, nosebleeds, bleeding gums, black or bloody stools, vomiting blood, or a sudden severe headache.
- Get urgent care for any severe or unusual bleeding or a bad headache.
Your doses may be adjusted and individualized by your care team, and they may monitor you more closely for bleeding.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The combined use of NSAIDs with antidepressants, encompassing tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, led to a heightened risk of intracranial hemorrhage within 30 days of concurrent administration when compared with the use of antidepressants alone. No significant difference in this elevated risk was observed among the various antidepressant drug classes; nevertheless, an increased risk was seen in male patients relative to female patients 1.
Common questions
Can I take Amitriptyline and Loxoprofen together?
Combining amitriptyline with the NSAID loxoprofen can add up to a higher bleeding risk, so keep taking both as prescribed but watch for bruising or bleeding and tell your pharmacist or doctor. Seek urgent help for severe bleeding or a bad headache. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Loxoprofen 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 Amitriptyline and Loxoprofen interaction managed?
The good news: your care team can manage this by watching you a bit more closely. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Tell your pharmacist and doctor that you take both, so they can decide if the NSAID is still needed and for how long. Watch for warning signs: easy bruising, nosebleeds, bleeding gums, black or bloody stools, vomiting blood,… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Amitriptyline or Loxoprofen 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 (1)
- Shin JY, Park MJ, Lee SH, et al: Risk of intracranial haemorrhage in antidepressant users with concurrent use of non-steroidal anti-inflammatory drugs: nationwide propensity score matched study. BMJ 2015; 351:h3517. PubMed
Keep reading about Amitriptyline
Keep reading about Loxoprofen
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