DRUG INTERACTIONS WITH GRAPEFRUIT JUICE

     One of the critical considerations with any drug is how that drug is eliminated from the body.  Beginning with the lower forms of life including fish and even plants, nature equipped life forms with systems to eliminate various naturally occurring materials.  As an example, a certain form of mold called penicillium naturally made a drug which we call penicillin.  This drug was discovered in 1938 and was one of our first antibiotics.  But just as nature provided the mold with a chemical to kill bacteria, the bacteria developed a tool of their own that degraded penicillin.  Today most strains of bacteria that we encounter in our hospitals are resistant to penicillin.  This is because those bacteria which could be killed by penicillin died and those that were equipped with the penicillin-degrading system survived and continued to grow through the present time.

     The example given above is one describing naturally-occurring products.  But through eons of genetic mutations, human beings are now known to have at least 57 different drug-eliminating proteins.  These proteins can each be thought of as an individual machine that eliminates natural products within the body and also just incidentally eliminates one or more of the various drugs supplied by our pharmacies.

     It turns out that each of these 57 different drug-eliminating proteins can be induced so that the body makes more of a given protein or be inhibited so that the body makes less of it and thus a given drug-eliminating protein can be sped up or slowed down.  In addition just as there are blue eyes, brown eyes, and green eyes, any one of these given 57 proteins can have mutations of their own that results in some forms working a little faster or a little slower.

     The reason to present this information is to point out the mind-boggling variations in drug elimination that occur from one individual to the next.  I am always amazed that any one drug can have a predictable dose from one person to the next.

     The story of grapefruit juice begins in the mid 1980’s when a large pharmaceutical company was preparing to release a drug called Plendil (felodipine).  They suspected that alcohol might have some effect on the drug concentration when a person took a felodipine pill.  They wanted to test this so they gave a 10 mg dose of felodipine to a large group of people and gave half of them several ounces of alcohol to see its effect on the felodipine blood concentrations.  In fact, there wasn’t any effect of the alcohol.

     But in order to hide the taste of the alcohol in the tests being done, the drug company added two ounces of double strength grapefruit juice to those receiving the alcohol.  It turned out that the felodipine drug concentrations were much higher in those individuals who drank the grapefruit juice.  Subsequent research demonstrated that grapefruit juice inhibited one of the 57 proteins that our body uses to eliminate drugs.  Incidentally it just so happened that it inhibited the drug-eliminating protein responsible for metabolizing about half of the drugs that we take.  For those interested in looking up the specific drug-eliminating protein, it is called cytochrome-P450 isoenzyme CYP3A4.

     So from a practical standpoint what does this mean?  Suppose a person is using the drug, Plendil (felodipine) and some days drinks grapefruit juice for breakfast and other days not.  I have had several people come to the clinic stating that their medicine seems to work some days and other days their blood pressures are too low and they have dizzy spells.  When one inquires about grapefruit juice, they indicate that some days they drink it and when that is investigated further it frequently turns out that the days they drink grapefruit juice their Plendil has a much bigger effect in lowering their blood pressure.  Of course if they are willing to drink the same amount of grapefruit juice every day they might save some money on their Plendil.

     The second example occurs in some patients who have seizure disorders using a drug called Tegretol (carbamazepine).  When a person drinks grapefruit juice intermittently with this drug, the drug level can go too high causing the person to have side effects of dizziness and an unsteady walk.

     For those who are trying to avoid the high cost of drugs grapefruit is probably cheaper.  Grapefruit juice will increase the activity of cholesterol-lowering drugs Mevacor (lovastatin), Zocor (simvastatin), and possibly Lipitor (atorvastatin).  The biggest effect of grapefruit juice may occur in individuals who have a kidney transplant or transplant of another organ.  The drugs cyclosporin, sirolimus, and tacrolimus are all drugs used to prevent a person from having a rejection of their transplant.  Grapefruit juice markedly slows the elimination of these drugs from the body and toxicities can occur.

     As a last example, there is a condition called sick sinus syndrome in which the clock that runs the heart begins to run too slowly.  The result is that the persons normal pulse of 60-70 can slow down into the 30’s and 40’s .  This is just like running your engine too slowly.  People feel like they are very fatigued and often have fainting spells.  If a person is using a drug called diltiazem (Cardizem, Tiazac) or verapamil (Calan, Verelan), the blood concentrations of these drugs can be increased if a person drinks grapefruit juice.  Both of these drugs tend to slow the heart rate.  If a person has a sick sinus syndrome and their heart rates is in the 50’s, the use of grapefruit juice can unmask the problem and slow their pulses into the 30’s and 40’s causing fainting spells.  Thus the use of grapefruit juice in a person taking diltiazem or verapamil is to be avoided.

     The list of drugs with which grapefruit juice interferes is quite long and the above examples are just a few of the more clinically common problems that can arise.  The healthcare providers at your local clinic have a comprehensive list of drug interactions with grapefruit juice.  Fortunately, orange juice and tangerines and other common citrus fruits do not have the same effect as grapefruit juice.

     As a last comment, January is frequently a time when individuals initiate weight loss programs and substituting a grapefruit or grapefruit juice for other more delectable holiday foods is a common practice.  One needs to be careful about drug interactions with the various medications described above.  Unfortunately, the effects are not uniform and they vary from using white grapefruit or pink grapefruit or grapefruit grown in different parts of the country.