Avoiding Dangerous Interactions With Grapefruit and Medications

Grapefruit juice, otherwise considered a healthy and nutritious drink, is well known to cause drug interactions, some of which can be serious. It does so by blocking enzymes that normally metabolize (break up) many over-the-counter and prescription drugs, causing them to remain in the blood for longer and at higher concentrations. This can lead to side effects and toxicity.

There are currently around 85 drugs that can interact with grapefruit. Some of these interactions are insignificant, while others can be serious and, on rare occasions, even life-threatening.

For example, drinking an 8-ounce cup of grapefruit juice with the statin drug Zocor (simvastatin) can triple the blood concentration after just three days, increasing the risk for kidney damage.

This article explains how grapefruit causes drug interaction and lists the drugs most commonly affected. It also offers tips on how to avoid grapefruit-drug interactions.

How Grapefruit Juice Affects Medications

Grapefruit is a potent CYP3A4 inhibitor. CYP3A4 (otherwise known as cytochrome P3A4) is an enzyme secreted by the small intestine that the body uses to metabolize many drugs.

By inhibiting (blocking) CYP3A4, certain drugs are not metabolized as they are meant to, causing them to accumulate in the bloodstream rather than being broken down and excreted in stool. This can lead to toxicity and an increased risk of side effects.

Some of the more serious consequences include:

• Nephrotoxicity: Also known as kidney toxicity, this can lead to kidney failure and damage. Grapefruit use with statins and tacrolimus can cause this.
• Rhabdomyolysis: This is the abnormal and potentially serious breakdown of muscle that can occur when grapefruit is used with certain statins.
• Myelotoxicity: This is the suppression of bone marrow which can lead to anemia and affect blood clotting. Colchicine is one drug that can cause this when taken with grapefruit.
• Thrombosis: This is the potentially serious formation of clots in blood vessels, including deep vein thrombosis (DVT). Grapefruit and ethinylestradiol are associated with this.
• Torsade de pointes: This is a potentially fatal heart rhythm disorder characterized by an abnormally accelerated heart rate. Amiodarone mixed with grapefruit can cause this.
• Complete heart block: This is a condition that causes the electrical signals of the heart to slow or stop entirely. Verapamil taken with grapefruit over several days can cause this.

In recent years, it's been found that grapefruit has the opposite effect on certain medications, causing their concentration in the blood to decrease rather than increase.

This is because grapefruit interferes with a protein called OATP1A2 (organic anion transporting polypeptide 1A2) that acts as a drug transporter, carrying certain medications into cells. When the blood concentration of a drug decreases, it can become far less effective. Other fruit juices can do the same.

Medications With Interactions

Most medications do not interact with grapefruit juice. However, grapefruit juice does interact with at least 85 drugs, including those used for the treatment of allergies, anxiety, birth control, cancer, depression, epilepsy, erectile dysfunction, heart disease, high blood pressure, high cholesterol, pain, and others.

Some of these interactions are insignificant and easily managed. Others for potentially severe and may require the complete avoidance of grapefruit or a change in medications.

Some of the more major grapefruit-drug interactions include:

How to Avoid Problems With Grapefruit

Grapefruit juice may only affect certain drugs in a drug class and not others. Check with your healthcare provider or pharmacist to find out if grapefruit can be taken with your specific drug.

There are other ways to safeguard against interactions:

• Read the patient information sheet that comes with your prescription drug. The FDA tests for drug interactions with grapefruit and will note this on the information sheet if there is an interaction.
• Read the drug facts label on over-the-counter (OTC) drugs and supplements, which will also note possible interactions.
• If you need to avoid grapefruit juice, check the labels of fruit juices or drinks to see whether they contain grapefruit juice.
• Pomelos, tangelos, and Seville oranges (often used to make orange marmalade) can also inhibit CYP3A4. Do not eat those fruits if your medicines interact with grapefruit juice.

Summary

Grapefruit juice can interact with many drugs. In most cases, it will increase the concentration of the drug, increasing the risk of side effects (some of which may be serious). Less commonly, the drug concentration can decrease, reducing the efficacy of the drug.

Not all interactions are severe, but it is nevertheless important to read the product label or patient information sheet to see if there is an interaction with grapefruit. You can also speak with your pharmacist and healthcare provider.