Sertraline and Flufenamic Acid: 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 recordFlufenamic Acid
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 is an antidepressant (an SSRI). It works partly by affecting serotonin, and serotonin also helps your blood platelets stick together to form clots. So sertraline can make you bleed a little more easily. Flufenamic acid is an NSAID (a pain and inflammation reliever), and NSAIDs can irritate the stomach lining and also thin the blood a bit.
Put them together and those effects add up. This can show up as nosebleeds, easy bruising, or stomach bleeding. The good news is your care team can manage this by watching you more closely and, if needed, adjusting your pain plan. Please talk with your pharmacist or doctor before making any changes.
Effect: Additive increase in bleeding risk (GI bleed, intracranial hemorrhage, epistaxis, ecchymosis, petechiae).
Mechanism: Sertraline (SSRI) depletes platelet serotonin, impairing platelet aggregation; flufenamic acid (NSAID) inhibits platelet function and causes GI mucosal injury. Effects are additive on hemostasis. Neither is a relevant prodrug here; the interaction is pharmacodynamic, not PK-based.
Onset: Unspecified. Evidence: Established. Severity: Major.
Management:
- Monitor for bleeding, particularly GI; higher risk in elderly and those with prior ulcers.
- Consider acetaminophen for analgesia, or an antidepressant with less serotonin reuptake inhibition.
- Consider gastroprotection (eg, PPI/antiulcer prophylaxis) if coadministration continues.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs are taken alongside antidepressants, SSRIs among them, because the combination raises the likelihood of intracranial hemorrhage1 and gastrointestinal (GI) bleeding 6. Reported bleeding manifestations have ranged from epistaxis, ecchymosis, hematoma, and petechiae to hemorrhages that are life-threatening 5. In cases where an SSRI and an NSAID are administered together, watch the patient carefully for indications of adverse effects such as GI bleeds, particularly in elderly individuals and those with prior GI ulcers. Options to weigh include alternative approaches to pain control (for example, acetaminophen), reassessing the selected antidepressant (that is, considering agents that produce less serotonin reuptake inhibition), or providing prophylactic antiulcer medication 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 when your care team knows about it.
Here is what teams typically do:
- Watch more closely for bleeding, especially stomach or gut bleeding, and more so in older adults or anyone with a history of ulcers.
- Consider a different pain reliever such as acetaminophen instead of the NSAID.
- Review whether an antidepressant with less effect on serotonin might fit better.
- Sometimes add a stomach-protecting medicine to lower the risk.
Call your pharmacist or doctor right away if you see black or bloody stools, vomit that looks like coffee grounds, unusual bruising, or nosebleeds that will not 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, including tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, produced a 60% higher risk of intracranial hemorrhage within 30 days of combined use compared with using an antidepressant on its own. No meaningful difference in the elevated risk was seen among the various antidepressant drug classes; however, the risk was higher for male patients than for female patients 1.
b) SSRIs raise the risk 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 users of antidepressant medications and compared against the number of hospitalizations in patients who did not receive antidepressant prescriptions. The number of upper GI bleeding episodes was 3.6 times greater than expected. 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 taking SSRIs. Combined use of SSRIs with NSAIDs or low-dose aspirin raised the risk still further 5.
c) Two meta-analyses of upper GI bleed events related to SSRIs, NSAIDs, and their combination reported that SSRIs raised the risk by 1.73 6 to 2.36 times 7, NSAIDs by 2.55 times 6, and the SSRI plus NSAID combination by 4.02 6 to 6.33 times 7.
d) The release of serotonin from platelets plays an important role in maintaining hemostasis. Case-control and cohort studies have demonstrated that using SSRIs and NSAIDs together is linked to a greater risk of bleeding 8.
Common questions
Can I take Sertraline and Flufenamic Acid together?
Combining sertraline with the NSAID flufenamic acid adds up to a higher bleeding risk, especially in the stomach and gut. Keep taking both as prescribed, watch for signs of bleeding, and ask your pharmacist or doctor whether acetaminophen, a stomach-protecting drug, or a different antidepressant would be safer for you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Flufenamic Acid 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 Flufenamic Acid interaction managed?
Keep taking both as prescribed unless your prescriber tells you otherwise. This combination is manageable when your care team knows about it. Here is what teams typically do: Watch more closely for bleeding, especially stomach or gut bleeding, and more so in older adults or anyone with a history of ulcers. Consider a different pain reliever such as acetaminophen instead of the NSAID. Review whethe… 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 Flufenamic Acid 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 Flufenamic Acid
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