Sertraline and Loxoprofen: 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 recordLoxoprofen
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've been prescribed sertraline (an antidepressant) along with loxoprofen (an anti-inflammatory pain reliever, like ibuprofen). Taking these two together can raise your risk of bleeding. Here's why: sertraline lowers the amount of serotonin stored in your platelets, which are the cells that help your blood clot. Loxoprofen also makes it harder for platelets to do their job. Put together, they can lead to easier bruising, nosebleeds, or bleeding in the stomach.
This is a well-known combination, so don't panic. Keep taking both exactly as prescribed and talk with your pharmacist or doctor. Watch for black or tarry stools, vomit that looks like coffee grounds, or unusual bruising, and report those right away.
Effect: Additive bleeding risk (GI and, less commonly, intracranial hemorrhage) with concurrent SSRI plus NSAID.
Mechanism: Sertraline depletes platelet serotonin, impairing serotonin-mediated platelet aggregation; loxoprofen inhibits COX-mediated thromboxane-driven aggregation and damages GI mucosa. These are additive pharmacodynamic effects on hemostasis (not a CYP-based interaction; neither agent is relevant here as a prodrug in this context).
Evidence: Established. Severity: Major. Onset: Unspecified.
- Monitor for epistaxis, ecchymosis, hematoma, petechiae, and GI bleeding, especially in elderly patients or those with prior peptic ulcer disease.
- Consider acetaminophen for pain, an antidepressant with less serotonin reuptake inhibition, or gastroprotective prophylaxis (eg, PPI).
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs and antidepressants, SSRIs among them, are used together, given the heightened likelihood of intracranial hemorrhage1 and gastrointestinal (GI) bleeding 6. Reported bleeding events encompass epistaxis, ecchymosis, hematoma, petechiae, and hemorrhages that are life-threatening 5. In cases where an SSRI is combined with an NSAID, monitor the patient carefully for indications of adverse effects such as GI bleeds, particularly in older individuals and those who have previously had GI ulcers. Options to weigh include alternative approaches to pain management (for example, acetaminophen), reassessing the selected antidepressant (that is, considering agents that inhibit serotonin reuptake to a lesser degree), or providing prophylaxis using 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 the right precautions.
Your care team may:
- Watch you more closely for bleeding, especially if you're older or have had stomach ulcers.
- Suggest a different pain option such as acetaminophen.
- Review your antidepressant choice.
- Add a stomach-protecting medicine (such as an acid reducer) to lower GI bleeding risk.
Call your pharmacist or doctor promptly if you notice black or tarry stools, blood in vomit or stool, frequent nosebleeds, or unusual bruising.
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 with antidepressant use by itself. No significant difference was observed among the antidepressant drug classes with respect to 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 heightened when NSAIDs or low-dose aspirin are used at the same time. Hospitalizations for upper GI bleeding were identified among 26,005 people using antidepressant medications and compared with the number of hospitalizations among patients who were not prescribed antidepressants. The number of upper GI bleeding episodes was 3.6 times greater 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 SSRIs are being used. Concurrent use of SSRIs with NSAIDs or low-dose aspirin raised the risk still further 5.
c) Two metaanalyses examining 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 SSRI and NSAID combination by 4.02 6 to 6.33 times 7.
d) Serotonin released by platelets plays an important part in preserving hemostasis. Case-control and cohort studies have demonstrated that using SSRIs and NSAIDs together has been linked to a heightened risk of bleeding 8.
Common questions
Can I take Sertraline and Loxoprofen together?
Combining sertraline and loxoprofen raises your bleeding risk, especially in the stomach. Keep taking both as prescribed, watch for signs of bleeding, and ask your pharmacist or doctor whether safer pain options or a stomach-protecting medicine make sense for you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Loxoprofen 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 Loxoprofen interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination is manageable with the right precautions. Your care team may: Watch you more closely for bleeding, especially if you're older or have had stomach ulcers. Suggest a different pain option such as acetaminophen. Review your antidepressant choice. Add a stomach-protecting medicine (such as an acid redu… 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 Loxoprofen 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 Loxoprofen
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