Sertraline and Propyphenazone: 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 recordPropyphenazone
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 SSRI antidepressant. Besides lifting mood, it lowers the amount of serotonin in your platelets, which are the tiny cells that help your blood clot. Propyphenazone is an anti-inflammatory pain reliever (in the NSAID family) that can irritate the stomach lining and also make bleeding easier. Put together, they add up.
Watch for things like nosebleeds, easy bruising, or black or bloody stools. This does not mean you cannot use them, but it is worth a quick chat. Please talk with your pharmacist or doctor, they can adjust things or add stomach protection to keep you safe.
Effect: Additive bleeding risk (GI and intracranial hemorrhage) with concurrent SSRI (sertraline) and NSAID (propyphenazone).
Mechanism: Sertraline inhibits serotonin reuptake into platelets, depleting platelet serotonin and impairing serotonin-mediated aggregation; the NSAID adds antiplatelet and gastric mucosal effects. Pharmacodynamic, not CYP-mediated. Neither agent's effect here depends on prodrug activation.
Evidence: Established. Onset: unspecified. Severity: major.
Management:
- Monitor for epistaxis, ecchymosis, petechiae, and GI bleeding, especially in elderly patients or those with prior ulcer/GI bleed.
- Consider acetaminophen for analgesia, or an antidepressant with less serotonergic activity.
- Consider gastroprotection (eg, PPI) if concurrent use continues.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs and antidepressants, such as SSRIs, are taken together, because the combination raises the likelihood of intracranial hemorrhage1 as well as gastrointestinal (GI) bleeding 6. Reported bleeding events range from epistaxis, ecchymosis, hematoma, and petechiae to life-threatening hemorrhages 5. In patients receiving an SSRI alongside an NSAID, watch 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, opting for agents with weaker serotonin reuptake inhibition), or providing prophylactic antiulcer medication 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 a little extra care.
Your pharmacist or prescriber may:
- Suggest a different pain option such as acetaminophen when appropriate.
- Review whether another antidepressant fits your needs.
- Add a stomach-protecting medicine to lower ulcer and bleeding risk.
- Monitor you more closely, especially if you are older or have had ulcers or GI bleeds.
Call your care team promptly if you notice nosebleeds, unusual bruising, black or bloody stools, vomit that looks like coffee grounds, or a severe headache.
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 when compared with antidepressant use by itself. No meaningful difference was seen between the various antidepressant drug classes with respect to the elevated risk; 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. Hospitalizations for upper GI bleeding were reviewed among 26,005 people using antidepressant medications and compared against the number of hospitalizations among patients who did not have prescriptions for 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 SSRIs are being used. Combining SSRIs with NSAIDs or low-dose aspirin raised the risk even more 5.
c) Two meta-analyses examining occurrences of upper GI bleeding attributable to SSRIs, NSAIDs, and their combination reported 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 maintaining hemostasis. Case-control and cohort studies have demonstrated that using SSRIs and NSAIDs in combination has been linked to a greater risk of bleeding 8.
Common questions
Can I take Sertraline and Propyphenazone together?
Combining sertraline with the NSAID propyphenazone raises the risk of stomach and other bleeding, so keep taking both as prescribed but ask your pharmacist or doctor about safer pain options, stomach protection, or closer monitoring, and report any signs of bleeding right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Propyphenazone 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 Propyphenazone interaction managed?
Keep taking both as prescribed unless your care team tells you otherwise. This combination is manageable with a little extra care. Your pharmacist or prescriber may: Suggest a different pain option such as acetaminophen when appropriate. Review whether another antidepressant fits your needs. Add a stomach-protecting medicine to lower ulcer and bleeding risk. Monitor you more closely, especially if… 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 Propyphenazone 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 Propyphenazone
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