Sertraline and Etoricoxib: 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 recordEtoricoxib
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 lowers the amount of serotonin stored in your platelets, which are the tiny cells that help your blood clot. Etoricoxib is an anti-inflammatory pain reliever (an NSAID) that can irritate the stomach lining. Put together, they make bleeding more likely, especially in the stomach or gut.
Watch for things like black or bloody stools, vomit that looks like coffee grounds, easy bruising, or nosebleeds. Please don't stop either medicine on your own. Your doctor or pharmacist can help manage this safely, and there are good options if any changes are needed.
Effect: Additive bleeding risk (GI and intracranial hemorrhage). Severity major; evidence established.
Mechanism: Sertraline (SSRI) depletes platelet serotonin, impairing platelet aggregation; etoricoxib (COX-2-selective NSAID) adds a pharmacodynamic effect on hemostasis and mucosal integrity. This is a PD interaction, not a metabolic one, and neither agent is a prodrug in a way that alters direction.
- Monitor: signs of GI bleeding (melena, hematemesis), bruising, epistaxis; higher risk in elderly and prior PUD.
- Management: consider acetaminophen for pain, an antidepressant with less serotonergic reuptake inhibition, or gastroprotection (eg, PPI) if combination continues.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs are combined with antidepressants such as SSRIs, given the 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. In patients receiving an SSRI together with an NSAID, maintain close surveillance for adverse events including GI bleeds, particularly among elderly individuals and those with prior GI ulcers. Options to consider include alternative approaches to pain control (for example, acetaminophen), reassessing the selected antidepressant (that is, opting for agents that exert less serotonin reuptake inhibition), or providing prophylaxis with 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 as prescribed unless your care team tells you otherwise. This combination is manageable with the right precautions.
- 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 your antidepressant choice, or add a stomach-protecting medicine.
- Watch for black or tarry stools, coffee-ground vomit, unusual bruising, or nosebleeds, and report these promptly.
Ask your pharmacist or prescriber before starting, stopping, or changing either medicine, and mention any aspirin or other pain relievers you take.
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 combined use as compared with antidepressant use by itself. No meaningful difference was seen among the antidepressant drug classes regarding this elevated risk; nonetheless, the risk was greater in male patients than in female patients 1.
b) SSRIs raise the likelihood of upper gastrointestinal (GI) bleeding, and this effect is amplified by simultaneous use of NSAIDs or low-dose aspirin. Hospital admissions for upper GI bleeding were reviewed among 26,005 users of antidepressant drugs and compared with the number of admissions in patients who did not receive antidepressant prescriptions. The number of upper GI bleeding events was 3.6 times higher than anticipated. 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 using SSRIs. Using SSRIs together with NSAIDs or low-dose aspirin increased that risk even more 5.
c) Two metaanalyses examining occurrences of upper GI bleeding 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 release of serotonin from platelets plays an important role in preserving hemostasis. Case-control and cohort studies have demonstrated that the combined use of SSRIs and NSAIDs has been linked to a greater risk of bleeding 8.
Common questions
Can I take Sertraline and Etoricoxib together?
Combining sertraline with etoricoxib raises the risk of bleeding, especially in the stomach and gut. Keep taking both as prescribed, watch for bleeding signs, and talk with your pharmacist or doctor about monitoring or safer options. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Etoricoxib 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 Etoricoxib interaction managed?
Keep taking both as prescribed unless your care team tells you otherwise. This combination is manageable with the right precautions. 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 your antidepressant choice, or add a stomach-protecting medicine. Watch for black or… 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 Etoricoxib 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 Etoricoxib
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