Sertraline and Fepradinol: 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 recordFepradinol
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 changing how your body uses serotonin, and serotonin also helps your blood platelets clump together to stop bleeding. Fepradinol is an anti-inflammatory pain reliever (an NSAID), and NSAIDs can irritate the stomach lining and make bleeding more likely too. Put together, they can add up.
This can show as easy bruising, nosebleeds, or, more seriously, stomach or intestinal bleeding. The good news is your care team can manage this. Please don't stop either medicine on your own talk with your pharmacist or doctor, who can adjust your plan and watch you more closely.
Effect: Additive bleeding risk (GI hemorrhage, intracranial hemorrhage, epistaxis, ecchymosis, petechiae).
Mechanism: Sertraline (SSRI) depletes platelet serotonin, impairing platelet aggregation; fepradinol (NSAID) adds GI mucosal injury and antiplatelet effects. Additive PD interaction, not a CYP/prodrug issue.
- Direction: Increased bleeding risk.
- Severity/evidence: Major, established.
- Onset: Unspecified.
Management: Monitor for bleeding, especially GI, in the elderly and those with prior ulcers. Consider acetaminophen for pain, an antidepressant with less serotonin reuptake inhibition, or gastroprotective prophylaxis (e.g., a PPI).
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs and antidepressants, SSRIs among them, are taken together, because this combination raises the likelihood of intracranial hemorrhage1 and gastrointestinal (GI) bleeding6. Reported bleeding manifestations have ranged from epistaxis, ecchymosis, hematoma, and petechiae to hemorrhages that are life-threatening5. If an SSRI and an NSAID are used at the same time, monitor the patient carefully for indications of adverse effects such as GI bleeds, particularly in the elderly and in individuals with a prior history of GI ulcers. Options to weigh include alternative approaches to pain control (for example, acetaminophen), reassessment of the selected antidepressant (that is, choosing agents with weaker serotonin reuptake inhibition), or the prescription of prophylactic antiulcer medications4.
Why it happens (mechanism)
Depletion of platelet serotonin by SSRI; additive effects on hemostasis
How to manage this interaction
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. This combination is manageable when your team is aware of it.
Here's what care teams often do and what you can do:
- Watch you more closely for bleeding, especially if you are older or have had stomach ulcers.
- Consider a different pain option such as acetaminophen where appropriate.
- Review your antidepressant choice, or add a stomach-protecting medicine to lower bleeding risk.
Call your pharmacist or doctor promptly if you notice black or bloody stools, vomit that looks like coffee grounds, unusual bruising, nosebleeds, or a severe headache.
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 to using an antidepressant on its own. No meaningful difference in this elevated risk was seen across the antidepressant drug classes; nevertheless, the risk was higher for male patients than for 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. Hospital admissions for upper GI bleeding were reviewed among 26,005 people taking antidepressant medications and compared against the number of admissions among patients who did not have prescriptions for antidepressants. The number of upper GI bleeding events 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 a heightened risk of upper GI bleeding while taking SSRIs. Using SSRIs together with NSAIDs or low-dose aspirin increased that risk still further 5.
c) Two metaanalyses examining upper GI bleed events linked 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 sustaining 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 Fepradinol together?
Using sertraline with the NSAID fepradinol adds up to a higher bleeding risk, especially in the stomach. Don't stop either drug on your own, but ask your pharmacist or doctor about safer pain options or stomach protection, and watch for signs of bleeding. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Fepradinol 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 Fepradinol interaction managed?
Keep taking both exactly as prescribed unless your prescriber tells you otherwise. This combination is manageable when your team is aware of it. Here's what care teams often do and what you can do: Watch you more closely for bleeding, especially if you are older or have had stomach ulcers. Consider a different pain option such as acetaminophen where appropriate. Review your antidepressant choice,… 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 Fepradinol 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 Fepradinol
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