Sertraline and Clonixin: 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 recordClonixin
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 with clonixin can raise your risk of bleeding. Sertraline is an antidepressant (an SSRI). It lowers the amount of serotonin your platelets use to help form clots. Clonixin is an anti-inflammatory pain medicine (an NSAID) that can irritate the stomach lining and also affect clotting. Put together, they make bleeding easier, especially in the stomach or gut.
Watch for things like black or tarry stools, vomit that looks like coffee grounds, easy bruising, nosebleeds, or unusual tiredness. The good news is your care team can manage this by watching you closely, choosing a gentler pain option, or adding stomach protection. Please talk with your pharmacist or doctor before changing anything.
Interaction: Additive bleeding risk when the SSRI sertraline is combined with the NSAID clonixin.
- Mechanism: Sertraline depletes platelet serotonin, impairing platelet aggregation; NSAIDs add antiplatelet effects plus GI mucosal injury. Neither is a prodrug here; effect is pharmacodynamic, not PK-based.
- Direction/magnitude: Increased risk of GI bleeding and intracranial hemorrhage; qualitative additive effect.
- Evidence: Established. Onset unspecified.
- Management: Monitor for GI bleeds, epistaxis, ecchymosis, especially in elderly or those with prior ulcers. Consider acetaminophen, an antidepressant with less serotonergic activity, 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 risk of both intracranial hemorrhage1 and gastrointestinal (GI) bleeding 6. Reported bleeding events range from epistaxis, ecchymosis, hematoma, and petechiae to hemorrhages that are life-threatening 5. In cases where an SSRI is administered alongside an NSAID, monitor the patient carefully for indications of adverse effects such as GI bleeds, particularly among the elderly and individuals with a prior history of GI ulcers. Options to consider include alternative approaches to pain control (for example, acetaminophen), reassessing the selected antidepressant (that is, favoring agents with reduced serotonin reuptake inhibition), 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 prescriber tells you otherwise. This combination is manageable when your team keeps an eye on things.
- Your care team may monitor you more closely for signs of bleeding, especially if you are older or have had stomach ulcers.
- They may consider a different pain reliever such as acetaminophen, review your antidepressant choice, or add a stomach-protecting medicine.
- Report any black or tarry stools, coffee-ground vomit, unusual bruising, nosebleeds, or severe headache right away.
- Ask your pharmacist before adding any other NSAID (like ibuprofen or naproxen).
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 compared with using an antidepressant on its own. No significant difference in the increased risk was observed between the antidepressant drug classes; however, an increased risk was seen in male patients compared with female patients 1.
b) SSRIs raise the risk of upper gastrointestinal (GI) bleeding, and this effect is amplified by concurrent use of NSAIDs or low-dose aspirin. Hospitalizations for upper GI bleeding were reviewed among 26,005 users of antidepressant medications and compared with the number of hospitalizations in patients who were not prescribed antidepressants. The number of upper GI bleeding episodes was 3.6 times greater than expected. 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 an elevated risk of upper GI bleeding while using SSRIs. Combined use of SSRIs with NSAIDs or low-dose aspirin increased the risk even more 5.
c) Two metaanalyses examining upper GI bleed events 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 concurrent use of SSRIs and NSAIDs has been linked to an increased risk of bleeding 8.
Common questions
Can I take Sertraline and Clonixin together?
Combining sertraline with clonixin raises the risk of bleeding, especially in the stomach and gut. Keep taking both as prescribed, watch for bleeding signs, and ask 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 Clonixin 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 Clonixin interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This combination is manageable when your team keeps an eye on things. Your care team may monitor you more closely for signs of bleeding, especially if you are older or have had stomach ulcers. They may consider a different pain reliever such as acetaminophen, review your antidepressant choice, or add a stomach-pro… 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 Clonixin 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 Clonixin
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