Sertraline and Niflumic 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 recordNiflumic 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 changes how your platelets, the tiny cells that help your blood clot, work. Niflumic acid is an anti-inflammatory painkiller (an NSAID), and NSAIDs can irritate the stomach and also thin the blood a little. Put together, they add up and make bleeding easier, especially in the stomach or gut.
Signs to watch for include easy bruising, nosebleeds, or black or bloody stools. This is a well-known combination, and your care team can manage it. Please keep taking both as prescribed and talk with your pharmacist or doctor about the best plan for you.
Effect: Additive increased bleeding risk (GI bleeding, intracranial hemorrhage, epistaxis, ecchymosis).
Mechanism: SSRIs such as sertraline deplete platelet serotonin, impairing platelet aggregation; NSAIDs (niflumic acid) add antiplatelet effect plus GI mucosal injury. Pharmacodynamic, not prodrug-related.
Evidence: Established. Onset: unspecified. Severity: major.
Management:
- Monitor for GI bleeding, especially in elderly or those with prior ulcers.
- Consider alternative analgesia (eg, acetaminophen).
- Consider an antidepressant with less serotonergic reuptake inhibition.
- Consider gastroprotection (eg, antiulcer prophylaxis).
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs and antidepressants, SSRIs among them, are taken together, since this combination raises the likelihood of intracranial hemorrhage1 as well as gastrointestinal (GI) bleeding 6. Reported bleeding episodes have ranged from epistaxis, ecchymosis, hematoma, and petechiae to hemorrhages that are life-threatening 5. In patients receiving an SSRI alongside an NSAID, watch carefully for indications of adverse events such as GI bleeds, particularly in the elderly and in individuals with prior GI ulcers. Options to consider include alternative approaches to pain control (for example, acetaminophen), reassessment of the selected antidepressant (that is, favoring agents with weaker serotonin reuptake inhibition), or the addition of prophylactic antiulcer medications 4.
Why it happens (mechanism)
Depletion of platelet serotonin by SSRI; additive effects on hemostasis
How to manage this interaction
The good news: your care team can manage this combination. Keep taking both medicines as prescribed unless your prescriber tells you otherwise.
Here is what a care team often does:
- Watches you more closely for bleeding, particularly if you are older or have had stomach ulcers.
- May suggest a different pain reliever, such as acetaminophen.
- May review your antidepressant choice.
- May add a stomach-protecting medicine to lower bleeding risk.
Call your pharmacist or doctor if you notice unusual bruising, nosebleeds, stomach pain, or black or bloody stools.
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 using an antidepressant by itself. No meaningful difference in this elevated risk was found among the different antidepressant drug classes; however, male patients carried a higher risk than 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 people using antidepressant medications and compared against the number of hospitalizations in patients who were not prescribed antidepressants. The number of upper GI bleeding events was 3.6 times higher than anticipated. Using an SSRI along 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. Combining SSRIs with NSAIDs or low-dose aspirin raised the risk still further 5.
c) Two metaanalyses examining cases of upper GI bleed 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 pairing of SSRIs with NSAIDs by 4.02 6 to 6.33 times 7.
d) The discharge of serotonin from platelets plays an important part in maintaining 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 Niflumic Acid together?
Combining sertraline with the NSAID niflumic acid adds up to a higher bleeding risk, especially in the stomach. Keep taking both as prescribed but watch for bleeding signs and ask your care team whether a safer painkiller or stomach protection makes sense for you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Niflumic 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 Niflumic Acid interaction managed?
The good news: your care team can manage this combination. Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Here is what a care team often does: Watches you more closely for bleeding, particularly if you are older or have had stomach ulcers. May suggest a different pain reliever, such as acetaminophen. May review your antidepressant choice. May add a stomach-pro… 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 Niflumic 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
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