Sertraline and Oxaprozin: 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 recordOxaprozin
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 with oxaprozin can raise your risk of bleeding. Sertraline is an antidepressant (an SSRI), and one thing it does is make your platelets (the cells that help your blood clot) a little less sticky. Oxaprozin is an anti-inflammatory pain reliever (an NSAID) that can irritate your stomach lining and also affects clotting. Put them together and the effects add up.
The most common concern is stomach bleeding, but bruising, nosebleeds, and rarer serious bleeds are possible. This matters more if you're older or have had ulcers. Don't stop either medicine on your own. Talk with your pharmacist or doctor, who can manage this safely.
Effect: Additive bleeding risk (GI and intracranial hemorrhage) with concurrent SSRI plus NSAID.
Mechanism: Sertraline depletes platelet serotonin, impairing serotonin-mediated platelet aggregation; oxaprozin adds antiplatelet effect plus direct GI mucosal injury. Additive PD interaction, not PK; neither drug's metabolism drives this.
- Direction: Increased bleeding risk (both agents contribute).
- Evidence: Established; severity major.
- Monitoring: Watch for epistaxis, ecchymosis, melena, hematemesis; heightened vigilance in elderly and prior GI ulcer/bleed.
Management: Consider acetaminophen for pain, a less serotonergic antidepressant, or gastroprotection (PPI/misoprostol) if the combination continues.
What happens
An increased risk of bleeding
Interaction Deep Dive
Combining NSAIDs with antidepressants, SSRIs among them, warrants caution because it raises the likelihood of intracranial hemorrhage1 as well as gastrointestinal (GI) bleeding 6. Reported bleeding events have ranged from epistaxis, ecchymosis, hematoma, and petechiae to life-threatening hemorrhages 5. In patients receiving an SSRI together with an NSAID, watch carefully for indications of adverse effects such as GI bleeds, with particular attention to elderly individuals and those who have previously had GI ulcers. Options to consider include alternative approaches to pain control (for example, acetaminophen), reassessment of the selected antidepressant (that is, choosing agents that inhibit serotonin reuptake to a lesser degree), 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 care team tells you otherwise. This combination is manageable with a few sensible steps.
- Your team may monitor you more closely for bleeding, especially if you are older or have had stomach ulcers.
- They may suggest a different pain option (such as acetaminophen), review your antidepressant choice, or add a stomach-protecting medicine.
- Watch for warning signs: black or bloody stools, vomit that looks like coffee grounds, easy bruising, frequent nosebleeds, or unusual headache.
Report any of these to your pharmacist or doctor right away so they can adjust your plan.
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 antidepressant use by itself. No meaningful difference was observed among the different antidepressant drug classes with respect to this elevated risk; nevertheless, an increased risk was seen in male patients relative to female patients 1.
b) SSRIs raise the risk of upper gastrointestinal (GI) bleeding, and this effect is amplified by simultaneous use of NSAIDs or low-dose aspirin. Hospitalizations for upper GI bleeding were examined among 26,005 users of antidepressant medications and compared with the number of hospitalizations in patients who did not receive antidepressant prescriptions. The number of upper GI bleeding events was 3.6 times higher than expected. Concurrent use of an SSRI with NSAIDs or low-dose aspirin raised the risk to 12.2 and 5.2 times, respectively. These results show an elevated risk of upper GI bleeding while taking SSRIs. Combined use of SSRIs with NSAIDs or low-dose aspirin increased the 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 maintaining hemostasis. Case-control and cohort studies have demonstrated that the combined use of SSRIs and NSAIDs has been linked to an increased risk of bleeding 8.
Common questions
Can I take Sertraline and Oxaprozin together?
Using sertraline with oxaprozin adds up to a higher bleeding risk, mainly in the stomach. Keep taking both as prescribed, watch for bleeding signs, and ask your pharmacist or doctor whether a safer pain option or a stomach-protecting medicine makes sense for you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Oxaprozin 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 Oxaprozin interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination is manageable with a few sensible steps. Your team may monitor you more closely for bleeding, especially if you are older or have had stomach ulcers. They may suggest a different pain option (such as acetaminophen), review your antidepressant choice, or add a stomach-protecting medicine. Watch for… 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 Oxaprozin 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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Keep reading about Oxaprozin
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