Piketoprofen 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
Piketoprofen
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) together with piketoprofen (an anti-inflammatory pain medicine) can raise your risk of bleeding. Both medicines can affect how well your blood forms clots, so using them together may make bleeding a little more likely. In rare cases this can include bleeding in the brain, especially in the first month of using them together.
This does not mean you cannot use them, but it is worth a conversation with your care team. Watch for warning signs like unusual bruising, blood in your stool or urine, nosebleeds that won't stop, or a bad headache. Please let your pharmacist or doctor know you take both so they can keep an eye on you.
Effect: Increased bleeding risk, including reports of intracranial hemorrhage, particularly within 30 days of starting concurrent therapy.
Mechanism: Not fully established. NSAIDs (piketoprofen) inhibit platelet aggregation and can irritate GI mucosa; TCAs (amitriptyline) may contribute additive antiplatelet/bleeding effects. This is a pharmacodynamic, additive interaction, not a metabolic one.
Evidence: Established. Severity: Major. Onset: Unspecified.
- Monitor for signs/symptoms of bleeding (GI, mucocutaneous, neurologic).
- Consider GI protection or an alternative analgesic in high-risk patients.
- Reassess in patients with prior bleeding, anticoagulant use, or elderly status.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution if NSAIDs are given together with tricyclic antidepressants, since combined use may raise the likelihood of bleeding, such as intracranial hemorrhage occurring within 30 days of concurrent administration1. During concomitant therapy with NSAIDs and tricyclic antidepressants, watch the patient for indications of heightened bleeding.
Why it happens (mechanism)
Unknown
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination is manageable with awareness and monitoring.
- Tell your pharmacist and doctor you take both amitriptyline and piketoprofen.
- Your team may monitor you more closely for bleeding, especially in the first month.
- They may suggest an alternative pain reliever or add stomach protection if you are at higher risk.
- Watch for and report: unusual bruising, black or bloody stools, vomiting blood, prolonged nosebleeds, or a sudden severe headache.
Any dosing decisions should be individualized by your care team.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Taking NSAIDs together with antidepressants, such as tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, led to a higher risk of intracranial hemorrhage within 30 days of combined use when compared with using an antidepressant by itself. No meaningful difference in this elevated risk was found across the different antidepressant drug classes; nevertheless, male patients had an increased risk relative to female patients 1.
Common questions
Can I take Piketoprofen and Amitriptyline together?
Combining amitriptyline and piketoprofen can increase bleeding risk, so keep taking them as prescribed but tell your care team and watch for signs of bleeding like unusual bruising, bloody stools, or a severe headache. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Piketoprofen 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 Piketoprofen and Amitriptyline interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination is manageable with awareness and monitoring. Tell your pharmacist and doctor you take both amitriptyline and piketoprofen. Your team may monitor you more closely for bleeding, especially in the first month. They may suggest an alternative pain reliever or add stomach protection if you are at higher… 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 Piketoprofen 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 (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 Piketoprofen
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