Can You Take Prozac (Fluoxetine) With Oxycodone?

In our latest question and answer, the pharmacist discusses whether or not you can take Prozac (fluoxetine) with oxycodone.

Jan 31, 2018

Frankie asked

Take Prozac 40mg a day. Is it OK to take oxycodone?


There is considered to be a moderate interaction between oxycodone and Prozac (fluoxetine). In fact, any medication that potentially causes an increase in the neurotransmitter serotonin has a theoretical interaction with oxycodone. There have been rare, but serious reports of serotonin syndrome in those taking oxycodone and serotonergic drugs (e.g. Prozac) at the same time.

Prozac - Oxycodone Interaction

Oxycodone is an opioid medication that is used for the treatment of moderate to severe pain. While the primary effects of oxycodone are due to its actions on opiate receptors, there have been studies that discuss its indirect effects on serotonin.

Prozac (fluoxetine) is a SSRI (selective serotonin reuptake inhibitor) medication and is used for a variety of indications such as major depressive disorder and panic disorders. It works by causing a net increase in the neurotransmitter serotonin in the brain.

The use of opioids, such as oxycodone, with other drugs that affect the neurotransmitter serotonin, have resulted in cases of serotonin syndrome. Serotonin syndrome is a serious reaction that is thought to occur from brain exposure to excess serotonin, or from hyperstimulation of serotonin receptors. While serious, cases of serotonin syndrome as a result of oxycodone and Prozac use appear to be relatively rare. 

There are multiple theories as to how oxycodone, a drug not typically associated with serotonin release, has resulted in reported cases of serotonin syndrome with other serotonergic drugs. One theory is that while opioids don't directly stimulate serotonin release, they may alter how our bodies respond and react to different concentrations of neurotransmitters (such as serotonin) and "trick" our bodies into releasing more of these neurotransmitters in situations where this normally wouldn't be the case.

As mentioned above, the chance of serotonin syndrome appears to be low and both Prozac and oxycodone have been used safely together. However, due to the seriousness of such reactions, it is prudent to carefully monitor individuals that are receiving both medications, especially when therapy is initiated and during dose adjustment.

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