Sertraline and Feprazone: 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 recordFeprazone
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.
You're taking sertraline (an antidepressant) together with feprazone (an anti-inflammatory pain reliever, an NSAID). When these are used together, they can raise your risk of bleeding. Sertraline lowers the amount of a chemical called serotonin that your platelets use to help form clots, and the NSAID can irritate your stomach lining. Put together, that means a higher chance of bleeds like an upset, bleeding stomach, easy bruising, nosebleeds, or, more rarely, serious bleeding.
The good news is your care team can manage this. Watch for black or bloody stools, vomit that looks like coffee grounds, or unusual bruising, and let your doctor or pharmacist know. Don't stop either medicine on your own.
Effect: Additive bleeding risk (GI hemorrhage, intracranial hemorrhage, epistaxis, ecchymosis, petechiae) with concurrent sertraline (SSRI) and feprazone (NSAID).
Mechanism: SSRI-mediated depletion of platelet serotonin impairs platelet aggregation; NSAID adds antiplatelet and GI mucosal injury effects. This is a pharmacodynamic (additive), not pharmacokinetic, interaction. Neither is a prodrug issue here.
Evidence: Established. Severity: Major. Onset: Unspecified.
- Monitor for GI bleeding signs, especially in elderly and those with prior ulcers.
- Consider acetaminophen for pain, an antidepressant with less serotonin reuptake inhibition, or gastroprotection (eg, PPI).
What happens
An increased risk of bleeding
Interaction Deep Dive
Combining NSAIDs with antidepressants, SSRIs among them, warrants caution because of a heightened likelihood of intracranial hemorrhage1 and gastrointestinal (GI) bleeding 6. Reported bleeding manifestations have ranged from epistaxis, ecchymosis, hematoma, and petechiae to life-threatening hemorrhages 5. Patients receiving an SSRI together with an NSAID should be monitored closely for indications of adverse events such as GI bleeds, particularly the elderly and anyone with a prior history of GI ulcers. Options to consider include alternative approaches to pain control (for example, acetaminophen), reassessment of the selected antidepressant (that is, opting for agents exhibiting 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
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This is a manageable situation, and your care team has several options.
- Your team may monitor you more closely for bleeding, especially if you are older or have had stomach ulcers.
- They may consider a different pain option such as acetaminophen, review whether a different antidepressant fits you, or add a stomach-protecting medicine.
- Watch for warning signs: black or bloody stools, vomit like coffee grounds, unusual bruising, or nosebleeds.
Raise any of these signs with your pharmacist or prescriber promptly.
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, produced a 60% higher risk of intracranial hemorrhage within 30 days of the combined use than antidepressant use by itself. No significant difference in the increased risk was found among the antidepressant drug classes; however, male patients carried an increased risk relative to female patients 1.
b) SSRIs raise the risk 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 identified among 26,005 users of antidepressant medications and compared against the number of hospitalizations in patients who did not receive prescriptions for 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 using SSRIs. Combining SSRIs with NSAIDs or low-dose aspirin raised the risk even more 5.
c) Two metaanalyses examining occurrences of upper GI bleed attributable 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) Serotonin released by platelets plays an important role in maintaining hemostasis. Case-control and cohort studies have demonstrated that the combined use of SSRIs and NSAIDs has been linked with an increased risk of bleeding 8.
Common questions
Can I take Sertraline and Feprazone together?
Using sertraline with feprazone raises your bleeding risk, especially in the stomach. Keep taking both as prescribed, watch for signs of bleeding, and talk with your pharmacist or doctor about safer pain options or stomach protection. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Feprazone 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 Feprazone interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This is a manageable situation, and your care team has several options. Your team may monitor you more closely for bleeding, especially if you are older or have had stomach ulcers. They may consider a different pain option such as acetaminophen, review whether a different antidepressant fits you, or add a stomach-… 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 Feprazone 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 Feprazone
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