Maria asked
I have been taking Prozac (fluoxetine) for about twenty years. I have been taking Plavix (clopodogril) for about fifteen years. Whenever I have any thing surgical done, I am told to stop taking clopodogril for a few days before. Are these two drugs safe to take together? I also take monocord, amlopodine, statin and lanzoprozil.
Answer
There is an interaction between Prozac (fluoxetine) and Plavix (clopidogrel), with most sources classifying it as a major interaction that should be avoided. Studies have shown that the combination of the two drugs can significantly decrease the effect of Plavix on platelet aggregation, potentially making it less effective.
How The Interaction Betwwen Prozac & Prozac Works
As a drug compound, Plavix itself is inactive and has no effect on blood platelets. Plavix is required to go through metabolic activation in the body in order to produce the active compound. After taking Plavix by mouth, it is metabolized by the cytochrome (CYP) P450 isoenzymes in the liver and an active metabolite is created. This active metabolite exerts the antiplatelet effect. Drugs that require metabolic activation are sometimes referred to as 'prodrugs' (i.e. a medication that is metabolized into a pharmacologically active drug).
There are multiple cytochrome P450 isoenzymes that metabolize Plavix but the major one is known as 'CYP2C19'. Prozac is a known inhibitor of this enzyme. Inhibition of CYP2C19 results in less Plavix being converted to the active metabolite, thus reducing its effectiveness.
There have been a variety of studies that have investigated just how much Prozac can affect the antiplatelet effect of Plavix.
One large study of Plavix and CYP2C19 inhibiting selective serotonin reuptake inhibitors (such as Prozac) showed that patients receiving the enzyme inhibiting drugs had an increased risk of ischemic events (restriction of blood supply to tissues). This risk was found to be more pronounced in patients 65 years and older.
Another study showed in patients that received the combination of Plavix and Prozac, the maximum concentration of the active Plavix metabolite was 25.3% lower when compared to patients who took Plavix alone.
Due to what we know about the potential interaction between Plavix and Prozac, the combination should be avoided in most situations.
On November 17, 2009 The FDA released a drug safety statement regarding the use of Plavix with known CYP2C19 inhibitors (e.g. Prozac, omeprazole etc...). They recommended the combination of Plavix and CYP2C19 inhibitors be avoided.
Having said all this, there is still some controversy as to whether cardiovascular outcomes are significantly affected due to this interaction. There could also be cases where Prozac and Plavix are simply to best therapy option for certain individuals. If you have concerns about your drug therapy, please speak with your doctor.
