Sertraline and Valdecoxib: 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 recordValdecoxib
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 sertraline (an antidepressant) together with valdecoxib (an anti-inflammatory pain reliever) can raise your chance of bleeding. Here is why: sertraline lowers the amount of serotonin stored in your platelets, the tiny cells that help your blood clot. Valdecoxib can irritate the stomach lining. Put together, they make bleeding a bit more likely, especially in the stomach and, rarely, more serious bleeds.
Watch for warning signs like black or tarry stools, throwing up something that looks like coffee grounds, easy bruising, or nosebleeds that won't stop. Please don't stop either medicine on your own. Talk with your pharmacist or doctor, they can manage this safely.
Effect: Additive risk of bleeding (GI and, rarely, intracranial hemorrhage) with concurrent SSRI + NSAID/COX-2 inhibitor.
Mechanism: Sertraline depletes platelet serotonin, impairing platelet aggregation; valdecoxib adds gastric mucosal/hemostatic insult. This is a pharmacodynamic (PD) interaction, not PK. Neither agent is metabolically activated in a way that changes direction here.
Evidence: Established. Severity: Major. Onset: Unspecified.
- Monitor for GI bleeding, epistaxis, ecchymosis, petechiae, hematoma.
- Higher risk in elderly and prior GI ulcer/bleed.
- Consider acetaminophen, an antidepressant with less serotonin reuptake inhibition, or add gastroprotection (eg, PPI).
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs are used together with antidepressants, SSRIs included, because of a heightened likelihood of intracranial hemorrhage1 and gastrointestinal (GI) bleeding 6. Reported bleeding episodes have encompassed epistaxis, ecchymosis, hematoma, petechiae, and hemorrhages that are life-threatening 5. In situations where an SSRI is administered alongside an NSAID, the patient should be watched carefully for indications of adverse events 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, favoring agents that produce less serotonin reuptake inhibition), or the use of antiulcer medications as prophylaxis 4.
Why it happens (mechanism)
Depletion of platelet serotonin by SSRI; additive effects on hemostasis
How to manage this interaction
This combination is manageable, but your care team will watch you more closely for bleeding.
- Keep taking both as prescribed unless your prescriber tells you otherwise.
- Your team may monitor you more closely, especially if you are older or have had stomach ulcers or bleeding.
- They may consider a different pain option (such as acetaminophen), a different antidepressant, or add a stomach-protecting medicine.
Call your pharmacist or doctor right away if you notice black or tarry stools, vomit that looks like coffee grounds, unusual bruising, or nosebleeds that won't stop. Avoid alcohol and other blood-thinning products unless cleared by your team.
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, was associated with a 60% higher risk of intracranial hemorrhage within 30 days of combined use compared with using an antidepressant by itself. No significant difference in the elevated risk was observed among the various antidepressant classes; however, 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 when NSAIDs or low-dose aspirin are used at the same time. Hospital admissions for upper GI bleeding were reviewed among 26,005 people using antidepressant medications and compared with the number of admissions among patients who were not prescribed 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. Concurrent use of SSRIs with NSAIDs or low-dose aspirin increased that risk still further 5.
c) Two metaanalyses examining cases 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 SSRI plus NSAID combination by 4.02 6 to 6.33 times 7.
d) Serotonin released from platelets plays a key role in preserving 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 Valdecoxib together?
Combining sertraline and valdecoxib raises bleeding risk (especially stomach bleeds), so watch for signs like black stools or easy bruising and let your care team monitor you; don't stop either drug on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Valdecoxib 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 Valdecoxib interaction managed?
This combination is manageable, but your care team will watch you more closely for bleeding. Keep taking both as prescribed unless your prescriber tells you otherwise. Your team may monitor you more closely, especially if you are older or have had stomach ulcers or bleeding. They may consider a different pain option (such as acetaminophen), a different antidepressant, or add a stomach-protecting m… 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 Valdecoxib 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 Valdecoxib
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist