A somewhat odd and alarming warning is listed on the prescription bottle of numerous medications: "Do not take this medication with grapefruit juice". This warning is in fact listed for the most prescribed medication class in the world, the statin medications for high cholesterol. How could grapefruit juice possibly interact with a medication? Is the interaction actually dangerous? Can I still eat just one grapefruit?
These are common questions pharmacists and other health professionals get, yet the exact answers to these questions are usually muddled with a sort of dubiousness by those responding. Information regarding the interaction was sparse at best when it was first discovered and information in scientific literature always seems to change.
One year it was okay to eat just one grapefruit or have one glass of juice and the next year that turned into a resounding no. One year it is okay to have grapefruit as long as it is separated by a few hours, and again, the next year that turned out to be false. This article will discuss the real and current evidence behind this mysterious interaction and offer advice for patients and healthcare professionals alike.
What is the actual interaction between grapefruit and certain drugs that we are
worried about? The interaction can occur by several different mechanisms which we will
discuss, but in the end, there can be a significant increase or decrease in the concentrations of the medications you are taking. This could either significantly increase the risk of serious side effects or cause the medication you are taking to not be as effective. The interaction between grapefruit and medications is highly unpredictable, and the side effects such as an increased risk of stomach bleeding with certain blood thinners could be life threatening.
There are two supposed mechanisms of how grapefruit affects the way we absorb drugs in our body. The first is by what is called CYP 3A4 inhibition. CYP 3A4 is a metabolizing enzyme in the body that helps break down and digest many substances, including medications. It is found in both the liver and the GI tract. When this enzyme is inhibited, the drugs that are supposed to be broken down aren't, and thus their concentrations increase. It's important to note that grapefruit inactivates the CYP 3A4 that is found in our gut and not in our liver. Therefore, only drugs that are taken by mouth are affected. Drugs that are introduced into our bodies via injection bypass the gut and are not affected.The second is by OATP (organic anion-transporting polypeptides) inhibition. OATP transports certain medications into our cells, enhancing their absorption. Inhibition of OATPs would therefore decrease the amount of medications absorbed into our body.
There are some myths regarding the drug interaction with grapefruit that need to be known to both health providers and patients.
Myth One: It's OK to consume grapefruit with medications that interact with it if I just have a small amount.
Recent research has shown that as little as 200 ml (less than one cup) of grapefruit juice can cause a significant interaction and inactivate the CYP 3A4 enzyme.
Myth Two: Separating grapefruit and my medications by a few hours with avoid any interactions.
This was a common recommendation by health care providers when not much was known about the interaction, only that it existed. It is now known that grapefruit inactivates the CYP 3A4 enzyme in the gut for a significant length of time. In fact, many studies have shown that it takes one full day to recover 50% of the enzyme activity and it can be 3 days until the enzyme activity is completely recovered. It is clear that medications that are taken daily cannot avoid the grapefruit interaction.
Myth Three: All medications that are metabolized by the CYP 3A4 enzyme are affected.
Only medications that are taken by mouth are affected since it is the CYP 3A4 enzyme in the gut that is inhibited, not the enzyme in the liver. Also, some drugs that are metabolized by CYP 3A4 and are taken by mouth aren't affected. Alprazolam is an exmaple of this since it's significant metabolsim only occurs in the liver.
There are over 80 reported and published interactions between medications and grapefruit. While we would love to list every major drug interaction, there list would be too extensive. Here is a list of some of the major drugs that interact with grapefruit:
- Amiodarone (antiarrhythmic) - 50% increase in concentration reported in studies. Increases the possibility of severe cardiac side effects.
- Nifedipine - 60% increase in concentration reported in studies. Increases the possibility of cardiac side effects and hypotension.
- Colchicine - 50% increase in concentration reported in studies. Increases the risk of GI side effects,
- Statin medications (simvastatin/atorvastation/lovastatin) over 40% increase in concentrations reported in studies. Increases the risk of rhabdomyolysis (the breakdown of muscle fibers)
- Brilinta - Over a two-fold increase in concentrations reported in studies. Increases the risk of stomach bleeds.
It is very important to talk to your doctor or pharmacist if you are concerned about the possibility of your medication interacting grapefruit.