Sertraline and Oxyphenbutazone: 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
Sertraline
No brand names on recordOxyphenbutazone
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. Sertraline (an antidepressant) lowers the amount of serotonin your blood platelets use to form clots. Oxyphenbutazone is an anti-inflammatory pain drug (an NSAID) that can irritate the stomach lining and also affect clotting. Put together, they make bleeding, especially in the stomach or gut, more likely.
Watch for warning signs like black or bloody stools, vomit that looks like coffee grounds, easy bruising, nosebleeds, or unusual tiredness. This is very manageable. Your care team can adjust your plan, watch you more closely, or suggest a safer pain option. Don't stop either medicine on your own, just talk with your pharmacist or doctor.
Effect: Additive bleeding risk (GI bleeding, intracranial hemorrhage) with concurrent SSRI and NSAID use.
Mechanism: Sertraline depletes platelet serotonin, impairing platelet aggregation; oxyphenbutazone adds antiplatelet effects plus direct GI mucosal injury. Additive, pharmacodynamic (neither is a prodrug here).
- Severity/Evidence: Major; established. Onset unspecified.
- Higher-risk patients: elderly, prior GI ulcer/bleed, other antithrombotics.
- Management: Monitor for epistaxis, ecchymosis, melena, hematemesis. Consider acetaminophen instead of the NSAID, consider an antidepressant with less serotonergic reuptake inhibition, or add GI prophylaxis (e.g., PPI/antiulcer agent).
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs are combined with antidepressants such as SSRIs, given the heightened potential for both intracranial hemorrhage1 and gastrointestinal (GI) bleeding 6. Reported bleeding manifestations range from epistaxis, ecchymosis, hematoma, and petechiae to hemorrhages that are life-threatening 5. If an SSRI is administered together with an NSAID, keep the patient under close observation for indications of adverse events such as GI bleeds, particularly among elderly individuals and those with prior GI ulcers. Alternative approaches to pain control (for example, acetaminophen) may be considered, the selected antidepressant may be reassessed (that is, favoring agents that inhibit serotonin reuptake to a lesser degree), or prophylactic antiulcer medication may be prescribed 4.
Why it happens (mechanism)
Depletion of platelet serotonin by SSRI; additive effects on hemostasis
How to manage this interaction
Keep taking both as prescribed unless your prescriber tells you otherwise. This combination is manageable with a few sensible steps that your care team can tailor to you.
- Your team may monitor you more closely for bleeding, especially if you are older or have had stomach ulcers or bleeds.
- They may suggest a different pain option such as acetaminophen, review the antidepressant choice, or add a stomach-protecting (antiulcer) medicine.
Call your pharmacist or doctor right away if you notice black or bloody stools, coffee-ground vomit, unusual bruising, or nosebleeds that won't stop.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) Taking NSAIDs together with antidepressants, such as tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, led to a 60% higher risk of intracranial hemorrhage within 30 days of combined use when compared with antidepressant use by itself. No meaningful difference in the elevated risk was seen between the antidepressant drug classes; nevertheless, male patients had a greater risk than female patients 1.
b) SSRIs raise the likelihood of upper gastrointestinal (GI) bleeding, and this effect is intensified by simultaneous use of NSAIDs or low-dose aspirin. Hospitalizations for upper GI bleeding were reviewed among 26,005 users of antidepressant drugs and compared against the number of hospitalizations in patients who did not receive antidepressant prescriptions. The number of upper GI bleeding events was 3.6 times higher than anticipated. Concurrent use of an SSRI with NSAIDs or low-dose aspirin raised the risk to 12.2 and 5.2 times, respectively. The results of this study show a heightened risk of upper GI bleeding while using SSRIs. Combining SSRIs with NSAIDs or low-dose aspirin elevated the risk still more 5.
c) Two metaanalyses examining occurrences of upper GI bleed related to SSRIs, NSAIDs, and their combination found that SSRIs raised the risk by 1.73 6 to 2.36 times 7, NSAIDs by 2.55 times 6, and the combination of SSRIs and NSAIDs by 4.02 6 to 6.33 times 7.
d) The release of serotonin from platelets plays an important role in preserving hemostasis. Case-control and cohort studies have demonstrated that using SSRIs together with NSAIDs has been linked to a greater risk of bleeding 8.
Common questions
Can I take Sertraline and Oxyphenbutazone together?
Combining sertraline with the NSAID oxyphenbutazone raises your risk of bleeding, especially in the stomach and gut, so keep taking both as prescribed but watch for bleeding signs and ask your care team whether a safer pain option or a stomach-protecting medicine is right for you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Oxyphenbutazone 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 Sertraline and Oxyphenbutazone interaction managed?
Keep taking both as prescribed unless your prescriber tells you otherwise. This combination is manageable with a few sensible steps that your care team can tailor to you. Your team may monitor you more closely for bleeding, especially if you are older or have had stomach ulcers or bleeds. They may suggest a different pain option such as acetaminophen, review the antidepressant choice, or add a sto… 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 Sertraline or Oxyphenbutazone 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 (8)
- 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
- Product Information: VIMOVO(TM) delayed release oral tablets, naproxen and esomeprazole magnesium delayed release oral tablets. AstraZeneca LPW, Wilmington, DE, 2010. DailyMed
- Product Information: SPRIX(TM) nasal spray, ketorolac tromethamine nasal spray. Roxro Pharma, Inc, Menlo Park, CA, 2009. DailyMed
- Mort JR, Aparasu RR, & Baer RK: Interaction between selective serotonin reuptake inhibitors and nonsteroidal antiinflammatory drugs: review of the literature. Pharmacotherapy 2006; 26(9):1307-1313. PubMed
- Dalton S, Johansen C, Mellemkjoer L, et al: Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding. Arch Intern Med 2003; 163:59-64. DOI
- Oka Y, Okamoto K, Kawashita N, et al: Meta-analysis of the risk of upper gastrointestinal hemorrhage with combination therapy of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs. Biol Pharm Bull 2014; 37(6):947-953. PubMed
- Loke YK, Trivedi AN, & Singh S: Meta-analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 2008; 27(1):31-40. PubMed
- Product Information: CELEXA(R) oral tablets, citalopram oral tablets. Allergan USA Inc (per FDA), Madison, NJ, 2023. DailyMed
Keep reading about Sertraline
Keep reading about Oxyphenbutazone
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