Grapefruit Food Drug Interactions

People frequently ask me about the interaction between grapefruit and their medications. There are many medications that are effected by grapefruit or grapefruit juice. Recently, I ran across a nice list of those  from our local hospital and a Mayo Clinics Proceedings Journal article(2000;75:933-42). With all due respect to them I have plagiarized their list and reformatted it for your use. The Generic names of medications are listed in the table on the left alphabetically with the Brand names on the right side. This list is likely not exhaustive, but it is a good start for many commonly used drugs. Below the table you can find some commentary on this potentially common issue.  Please be aware, this list may not be all inclusive as of this writing. It is utterly dependent on the literature easily available to me and may have glaring deficiencies. 

Physiology of Drug Breakdown

There is a large group of proteins called cytochrome proteins. They make up a family of proteins called the cytochrome P-450 system. This family of proteins is responsible for breaking down many drugs we take. These proteins are found in the lining of the small intestine and in the liver mostly. These proteins are generally designated by a symbol that looks like this: CYP2A, CYP3A, CYP3A4, etc. The CYP simply stands for the cytochrome P system. The next number and letter designate a particular cytochrome protein out of the many we all have in our bodies. The most common cytochrome protein in our small intestine is the CYP3A. Some cytochrome proteins actually pump drugs and toxins back into the small intestine in order to keep them out of the body.

Medications such as itraconazole, ketoconazole, cyclosporine, diltiazem, and erythromycin can cause both the small intestine and liver cytochrome proteins to work poorly. When these proteins work poorly the result is that you absorb more of the drug than might have been expected. You can more easily have toxic reactions to medicines in this case; a reaction to either the medicine you took or another medicine that might normally have been handled by this same protein.

Grapefruit juice has been shown to be a cause for these cytochrome proteins to malfunction also. One 8 ounce glass of grapefruit juice can cause the cytochrome proteins in the intestinal wall to not work. You will then get more of certain drugs absorbed into your system. Several glasses of grapefruit juice or drinking concentrated grapefruit juice can cause both the small intestine and the liver cytochrome proteins to not work correctly. This can result in a marked change in how drugs are handled by your body.

This problem was first noted during a research study with a blood pressure drug called felodipine (Plendil). One glass of grapefruit juice will double the amount of felodipine in your body. This is a big difference. It can result in an enhanced effect in terms of lowering your blood pressure. The problem could be that your blood pressure might get to low because more of the medicine is around in your system. Nisoldipine (Sular) has been shown to be effected by grapefruit juice, with one glass causing a 50% increase in the amount of the drug in your system. You can see how this could be problematic. Nifedipine (Procardia) and Amlodipine (Norvasc) have shown about 20-30% increases with a single glass of grapefruit juice, but have shown less problems in terms of lowering blood pressure on accident.

Cyclosporine is also increased by grapefruit juice. This effect can be used to a person's advantage. Sometimes, as in this case, you can get away using less cyclosporine which can result in a substantial cost savings. I would not alter your dose without discussing it with your doctor thoroughly first.

Drugs such as tacrolimus used in transplant patients can be greatly increased when given with a drug like ketoconazole that inhibits the function of a cytochrome protein. An antimalarial drug, artemether, is doubled in your system by grapefruit juice. Cilostazol (Pletal) and Sildenafil (Viagra) may be effected by grapefruit juice, but has not been tested, however other drugs such as erythromycin or and diltiazem can raise it significantly such that the Pletal manufacturer advises against taking grapefruit juice while using this drug. Sildenafil might work better with grapefruit juice, but side-effects might be worse, also. A protease inhibitor, saquinavir, can be raised in your body by grapefruit juice. Diazepam (Valium), midazolam (Versed) and triazolam are all increased by grapefruit juice. Most other benzodiazepines have not been tested, but are felt not to be a problem because they are highly absorbed already without grapefruit juice. Buspirone (Buspar) is raised by high doses of grapefruit juice, but lower dose effects are uncertain, therefore it is recommended to avoid grapefruit juice on general principles. Sertraline (Zoloft) is increased by 50% by a single glass of juice. The significance is unclear for sertraline, and could be helpful in terms of the effects, but could also increase side effects. Carbamazepine (Tegretol, Carbatrol) is increased by 40% with a single glass of grapefruit juice, and may result in higher than anticipated drug levels. Clomipramine appears to be effected by grapefruit juice significantly. Several drugs might be effected by grapefruit juice but testing has not been performed, including: methadone and zaleplon. Hormones such as estrogen and progesterone may be increased by grapefruit juice.

Conclusion

You should take care with your medicines and the potential effects of grapefruit juice, grapefruit slices, or any other form (i.e. dried, etc). All forms of grapefruit and its parts are able to cause the effect apparently. The exact compound that causes the problem is not quite clear yet. So, be warned and discuss this with us if we forget.

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