Can You Take Prozac And Ibuprofen Together?

In our latest question and answer, the pharmacist discusses whether or not there is a drug interaction between Prozac (fluoxetine) and ibuprofen.


I was prescribed Prozac and hydroxyzine. I want to take ibuprofen or a muscle relaxer but I'm not sure that it's safe. I take my medicine in the evening.

Asked by Mikki On Sep 23, 2022

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Sep 23, 2022
Last updated Sep 23, 2022

Key points

  • Taking ibuprofen with Prozac will increase your risk of bleeding.
  • Ibuprofen and Prozac can be used with caution in certain situations, but there are safer alternatives like taking acetaminophen (Tylenol) or using pain-relieving creams/gels/sprays.
  • Using non-drug options like cold/heat packs, stretching, physical therapy, etc. may help your pain as well and could be good alternatives.


There is a potential drug interaction between ibuprofen and Prozac (fluoxetine). Taking both together can increase the risk of bleeding, especially stomach bleeds.

Selective serotonin re-uptake inhibitors (SSRIs), like Prozac, have been reported to increase the risk of gastrointestinal bleeding (i.e. stomach bleeds), particularly when taken with non-steroidal anti-inflammatory drugs (NSAIDs), like ibuprofen.

Why This Interaction Happens

SSRIs are thought to increase bleed risk via inhibition of serotonin uptake into platelets, thus impairing their ability to properly aggregate.

NSAIDs inhibit enzymes (cyclooxygenase, or COX) involved in the protection of gastric mucosa as well as platelet aggregation, thus increasing the risk of bleeding. As both SSRIs and NSAIDs are independently associated with an increased bleed risk, this interaction is likely to be the result of an additive pharmacodynamic effect (though some have proposed a pharmacokinetic mechanism3).

What Do The Studies Say

There have been a variety of studies that have shown associations between the combined use of SSRI and NSAID medications and the risk of gastrointestinal bleeding. In fact, data indicates the risk of GI bleeding can be increased two to fifteenfold depending on the individual and certain risk factors.

What To Do

In most cases, it is recommended to use alternative analgesics (such as Tylenol) rather than using an NSAID (such as ibuprofen) when taking Prozac. If ibuprofen use cannot be avoided, the addition of an acid-reducing agent, such as a PPI (proton pump inhibitor) like Prevacid, may reduce the risk of bleeds. 

In addition, the risk of bleeding is typically more of a concern if you are at high risk of bleeding (elderly, taking other blood thinners like warfarin, etc.) or when ibuprofen is taken regularly (every 4-6 hours) for multiple days.

Before taking ibuprofen with Prozac, be sure to speak with your doctor to better understand your pain treatment options.

Background Information on Prozac (Fluoxetine)

Prozac is in a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs) and is most commonly used to treat major depressive disorder. SSRIs work by increasing the amount of serotonin available in the brain.

Serotonin is a natural chemical made by the body that is important for regulating mood, but it also helps platelets in the blood bind together when there is tissue damage, like from a cut, and stop bleeding.  SSRIs cause serotonin levels to decrease in platelets and this causes platelets to not bind together as well and increases the risk of bleeding.

Background Information on Ibuprofen

Ibuprofen is in a class of pain relievers called non-steroidal anti-inflammatory drugs (NSAIDs).  All NSAIDs work by stopping the creation of prostaglandins which are chemicals made by the body and central in inflammatory processes. Prostaglandins are also needed for blood platelets to bind together and stop bleeding. 

Additional Information

There is no interaction between ibuprofen and the other medication you are taking, hydroxyzine. Adding on a muscle relaxant as you mentioned could potentially increase the sedation effects from hydroxyzine, however.

Final Words

Thanks so much for reaching out to us! Let us know if we can help further.


  • Combined use of SSRIs and NSAIDs increases the risk of gastrointestinal adverse effects, PubMed
  • Ibuprofen Monograph, PubChem
  • Fluoxetine Monograph, PubChem

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