Phenylbutazone and Sertraline: 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 recordPhenylbutazone
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.
Let me explain how these two work together. Sertraline is an antidepressant (an SSRI). Besides lifting mood, it lowers the amount of serotonin your platelets use to help form clots, so your blood clots a little less easily. Phenylbutazone is an anti-inflammatory pain drug (an NSAID) that can irritate the stomach lining and also thins your ability to clot. Taken together, these effects add up and can raise your chance of bleeding, such as nosebleeds, easy bruising, or, more seriously, stomach or brain bleeds.
This is a real and known interaction, but it is manageable. Please do not stop either medicine on your own. Talk with your pharmacist or doctor so they can watch you closely and help protect your stomach.
Effect: Additive bleeding risk (GI and intracranial hemorrhage).
Mechanism: Sertraline (SSRI) depletes platelet serotonin, impairing platelet aggregation; phenylbutazone (NSAID) inhibits platelet function and causes GI mucosal injury. Pharmacodynamic, additive on hemostasis. Neither is a prodrug in this context.
Evidence: Established. Severity: Major. Onset unspecified.
Management:
- Monitor for epistaxis, ecchymosis, petechiae, hematoma, and GI bleeding, especially in elderly patients or those with prior ulcers.
- Consider alternative analgesia (eg, acetaminophen) or an antidepressant with less serotonin reuptake inhibition.
- Consider gastroprotection (eg, antiulcer prophylaxis) if concurrent use continues.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs are combined with antidepressants, SSRIs included, because of a heightened likelihood of intracranial hemorrhage1 as well as gastrointestinal (GI) bleeding 6. Reported bleeding manifestations have encompassed epistaxis, ecchymosis, hematoma, petechiae, and hemorrhages that are life-threatening 5. During simultaneous administration of an SSRI and an NSAID, keep a close watch on the patient for indications of adverse events such as GI bleeds, particularly in the elderly and in individuals with prior GI ulcers. Options to consider include alternative approaches to pain control (for example, acetaminophen), reassessing the selected antidepressant (that is, favoring agents that produce less 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
If you have been prescribed both, keep taking them as directed unless your care team tells you otherwise. Here is what a care team typically does:
- Watches you more closely for bleeding, especially if you are older or have had stomach ulcers.
- May suggest a different pain option, such as acetaminophen, when appropriate.
- May review whether a different antidepressant with less effect on clotting fits you.
- May add a stomach-protecting medicine to lower bleeding risk.
Call your pharmacist or doctor right away if you notice black or bloody stools, vomit that looks like coffee grounds, unusual bruising, frequent nosebleeds, 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 using an antidepressant by itself. No meaningful difference was seen among the antidepressant drug classes with respect to the elevated risk; nevertheless, an increased risk was associated with male patients relative to 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 examined among 26,005 users of antidepressant medications and compared against the number of hospitalizations in patients who did not receive antidepressant prescriptions. 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 increased risk of upper GI bleeding while using SSRIs. Combining SSRIs with NSAIDs or low-dose aspirin increased the risk still further 5.
c) Two metaanalyses of upper GI bleed events attributed 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) The release of serotonin from platelets plays an important role in maintaining hemostasis. Case-control and cohort studies have demonstrated that combined use of SSRIs and NSAIDs has been linked to an increased risk of bleeding 8.
Common questions
Can I take Phenylbutazone and Sertraline together?
Combining sertraline and phenylbutazone adds up to a higher bleeding risk, so watch closely for signs of bleeding and ask your care team about safer pain options or stomach protection. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Phenylbutazone and Sertraline 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 Phenylbutazone and Sertraline interaction managed?
If you have been prescribed both, keep taking them as directed unless your care team tells you otherwise. Here is what a care team typically does: Watches you more closely for bleeding, especially if you are older or have had stomach ulcers. May suggest a different pain option, such as acetaminophen, when appropriate. May review whether a different antidepressant with less effect on clotting fits… 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 Phenylbutazone or Sertraline 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 Phenylbutazone
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