Sertraline and Bufexamac: 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 recordBufexamac
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 sertraline and bufexamac together can raise your risk of bleeding. Sertraline is an antidepressant (an SSRI). Besides lifting mood, it makes your platelets (the cells that help blood clot) a little less sticky. Bufexamac is an anti-inflammatory pain medicine (an NSAID), and NSAIDs can irritate the stomach lining and also thin the blood a bit. Put together, the two effects add up.
Warning signs to watch for include stomach pain, black or tarry stools, easy bruising, nosebleeds, or blood in vomit. Please don't stop either medicine on your own. Your pharmacist or doctor can manage this safely, so let them know you take both.
Effect: Additive bleeding risk (GI bleeding, intracranial hemorrhage) with concurrent SSRI plus NSAID.
Mechanism: Sertraline depletes platelet serotonin, impairing platelet aggregation; bufexamac (NSAID) adds antiplatelet and GI-mucosal effects. Pharmacodynamic, not a CYP/prodrug interaction. Neither drug's activation is affected.
Evidence/severity: Established, rated major; onset unspecified.
Management:
- Monitor for bleeding (epistaxis, ecchymosis, petechiae, hematoma, GI bleed) especially in elderly or those with prior GI ulcer.
- Consider acetaminophen for pain instead of an NSAID.
- Consider an antidepressant with less serotonin reuptake inhibition.
- Consider gastroprotection (e.g., antiulcer prophylaxis).
What happens
An increased risk of bleeding
Interaction Deep Dive
Combining NSAIDs with antidepressants, SSRIs among them, warrants caution because of a heightened risk of both intracranial hemorrhage1 and gastrointestinal (GI) bleeding6. Reported bleeding manifestations range from epistaxis, ecchymosis, hematoma, and petechiae to hemorrhages that are life-threatening5. Patients receiving an SSRI together with an NSAID should be watched carefully for indications of adverse events such as GI bleeds, particularly among the elderly and individuals with prior GI ulcers. Alternative approaches to pain control (for example, acetaminophen) may be considered, the selected antidepressant may be reassessed (that is, choosing agents that inhibit serotonin reuptake to a lesser degree), or antiulcer medications may be prescribed as prophylaxis4.
Why it happens (mechanism)
Depletion of platelet serotonin by SSRI; additive effects on hemostasis
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination is manageable, and your team has several options.
- Watch for bleeding: stomach pain, black or tarry stools, unusual bruising, nosebleeds, or blood in vomit or stool. Report these promptly.
- Your team may suggest a different pain reliever such as acetaminophen instead of the NSAID.
- They may review your antidepressant and consider one with less effect on bleeding.
- They may add a stomach-protecting medicine, especially if you are older or have had ulcers.
Raise any bleeding concerns with your pharmacist or prescriber right away.
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 among the antidepressant drug classes; nonetheless, the risk was higher in male patients than in female patients 1.
b) SSRIs raise the likelihood of upper gastrointestinal (GI) bleeding, and this effect is amplified when NSAIDs or low-dose aspirin are used at the same time. Hospitalizations for upper GI bleeding were examined among 26,005 individuals using antidepressant medications and compared with the number of hospitalizations in patients who were not prescribed antidepressants. The number of upper GI bleeding episodes was 3.6 times higher than anticipated. Using an SSRI together with NSAIDs or low-dose aspirin raised the risk to 12.2 and 5.2 times, respectively. The results of this study show an elevated risk of upper GI bleeding while SSRIs are being used. Concurrent use of SSRIs with NSAIDs or low-dose aspirin raised that risk still further 5.
c) Two metaanalyses of upper GI bleed events attributable to SSRIs, NSAIDs, and their combination determined 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 secretion of serotonin from platelets plays an important role in preserving hemostasis. Case-control and cohort studies have demonstrated that using SSRIs and NSAIDs together has been linked to a greater risk of bleeding 8.
Common questions
Can I take Sertraline and Bufexamac together?
Combining sertraline (an SSRI) with bufexamac (an NSAID) raises your bleeding risk, especially in the stomach. Keep taking both as prescribed, watch for signs of bleeding, and ask your pharmacist or doctor whether a safer pain option or added stomach protection makes sense. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Bufexamac 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 Bufexamac interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination is manageable, and your team has several options. Watch for bleeding: stomach pain, black or tarry stools, unusual bruising, nosebleeds, or blood in vomit or stool. Report these promptly. Your team may suggest a different pain reliever such as acetaminophen instead of the NSAID. They may review you… 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 Bufexamac 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 Bufexamac
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