Grapefruit, other juices decrease absorption of certain drugs, say researchers

RESEARCHERS explain how taking fruit juices with conventional medicines could lead to toxic overdose, and reduction in the absorption and efficacy of the drugs. These days it is the vogue. Most people drink fruit juices without reservation. Fruit juices are seen on the table at every meal and are used to swallow tablets and capsules. But new reasons are emerging why people should avoid taking grapefruit and other juices, including orange and apple, with certain drugs. Researchers have found that besides increasing the absorption of certain drugs-with the potential for turning normal doses into toxic overdoses-citrus fruit juices could substantially decrease the absorption of some drugs, potentially wiping out their beneficial effects. Previous studies have linked fruit juices to diabetes and heart problems. However, natural substances in citrus fruits- orange, grapefruit and tangerine- have been shown to help fight cancer, common cold, heart disease, obesity, iron deficiency, birth defects, and 'bad' cholesterol. In 2006, researchers from the University of North Carolina at Chapel Hill, United States identified and established the substance in grapefruit juice that causes potentially dangerous interactions with certain medications. It was originally assumed that the ingredients responsible for drug interactions were the flavonoids that give grapefruit juice its bitter taste, but the 2006 study showed that a group of chemicals called furanocoumarins are the likely culprit. The new study published in the Newsletter of the American Chemical Society provides a new reason to avoid drinking grapefruit juice and these other juices when taking certain drugs, including some that are prescribed for fighting life-threatening conditions such as heart disease, cancer, organ-transplant rejection, and infection. The researchers say the findings represent the first controlled human studies of this type of drug-lowering interaction. Leader of the team of researchers, Dr. David G. Bailey, a professor of clinical pharmacology with the University of Western Ontario in London, Ontario said: "Recently, we discovered that grapefruit and these other fruit juices substantially decrease the oral absorption of certain drugs undergoing intestinal uptake transport. "The concern is loss of benefit of medications essential for the treatment of serious medical conditions." Indeed, grapefruit is the most notable natural product that has been extensively studied for its potential interaction with conventional medicines. Grapefruit has been shown to interact with many cholesterol-lowering drugs, antihistamines (used as treatment for allergies), psychiatric medications, and others. In some cases, the results are fatal. The victims may suffer from severe, elevated side reactions, that is not normally observed when the drug is administered in prescribed doses. The most significant interaction of grapefruit juice occurred with antihistamines. Experts advise "Do not take grapefruit juice if you are taking terfenadine (seldane) or astemizole (Hismanal) due to the possibility of fata1 cardiac arrhythmias. Cardiac arrhythmias are conditions that make the heart pump less effectively, so that not enough blood reaches the brain and other vital organs. Other non-sedating antihistamines are available which do not appear to interact with grapefruit juice, (example, loratidine (Claritin) cetirizine (Reactine) or fexofenadine (Allegra)." The drugs affected by grapefruit juice usually have some difficulty entering the body after they are consumed because an intestinal enzyme, CYP3A, partially destroys them as they are absorbed. Grapefruit juice, but not other commonly consumed fruit juices, inhibits this enzyme, allowing more of these drugs to enter the body." On grapefruit possible interaction with some conventional medications,One thing is clear, that grapefruit is a natural product and it is healthy because it contains many health giving ingredients. At what point it begins to be harmful, I am not aware of that." Bailey and colleagues were the first to announce, almost 20 years ago, the unexpected finding that grapefruit juice can dramatically boost the body's levels of the high-blood-pressure drug felodipine, causing potentially dangerous effects from excessive drug concentrations in the blood. Since then, other researchers have identified nearly 50 medications that carry the risk of grapefruit-induced drug-overdose interactions. As a result of the so-called "Grapefruit Juice Effect," some prescription drugs now carry warning labels against taking grapefruit juice or fresh grapefruit during drug consumption. In the most recent research, Bailey's group had healthy volunteers take fexofenadine, an antihistamine used to fight allergies. The volunteers consumed the drug with either a single glass of grapefruit juice, water containing only naringin (substance in grapefruit juice that gives the juice its bitter taste), or water. When fexofenadine was taken with grapefruit juice, only half of the drug was absorbed compared to taking the drug with water alone, Bailey says. Loosing half of the amount of drugs taken into the body can be critical for the performance of certain drugs, he points out. They also showed that the active ingredient of grapefruit juice, naringin, appears to block a key drug uptake transporter, called OATP1A2, involved in shuttling drugs from the small intestine to the bloodstream. Blocking this transporter reduces drug absorption and neutralises their potential benefits, the researchers say. By contrast, drugs whose levels are boosted in the presence of grapefruit juice appear to block an important drug metabolising enzyme, called CYP3A4, that normally breaks down drugs. "This is just the tip of the iceberg," Bailey says. "I'm sure we'll find more and more drugs that are affected this way." To date, grapefruit, orange and apple juices have been shown to lower the absorption of etoposide, an anticancer agent; certain beta blockers (atenolol, celiprolol, talinolol) used to treat high blood pressure and prevent heart attacks; cyclosporine, a drug taken to prevent rejection of transplanted organs; and certain antibiotics (ciprofloxacin, levofloxacin, itraconazole). Bailey said additional drugs are likely to be added to the list, as physicians become more aware of this drug-lowering interaction. Orange and apple juices also appear to contain naringin-like substances that inhibit OATP1A2, Bailey says. The chemical in oranges appears to be hesperidin, but the chemical in apples has not yet been identified, the researchers notes. In Australia, it is routine practice to add auxiliary labelling to prescriptions for terfenadine warning of grapefruit-juice drug interactions. In the United States, the manufacturer of terfenadine has changed its prescribing information to indicate that grapefruit juice should not be taken with terfenadine. The most significant documented grapefruit juice drug interaction occurred with terfenadine (Seldane). A previously healthy 29-year old male used terfenadine twice daily for one year to treat allergic rhinitis. The patient drank grapefruit juice two to three times weekly. On the day of his death, he consumed two glasses of juice, took his terfenadine dose, and proceeded to mow the lawn. He became ill, collapsed and died. Post-mortem terfenadine metabolite plasma levels were reported as 35 ng/mL and 130, ng/mL respectively. (In normal cases, the plasma concentration is not detectable.) These levels are within range of previously noted arrhythmogenic levels of terfenadine. The individual had both cardiomegaly and hepatomega1y, but no evidence of impaired hepatic function. To study the effect of grapefruit juice on terfenadine 12 healthy subjects were given terfenadine 60 mg with either water or grapefruit juice, co-administered with terfenadine or delayed by two hours. The results showed that none of the 12 had quantifiable levels when the drug was given with water. Of subjects who took terfenadine co-administered with grapefruit juice, 100 percent had quantifiable terfenadine levels. Of subjects who delayed grapefruit juice ingestion by two hours, 33 per cent had quantifiable levels. In the group of subjects which co-administered grapefruit juice and terfenadine, a significant mean prolongation in the QT interval measured by electrocardiogram was demonstrated. I urged patients to consult with their doctor or pharmacist before taking any medications with grapefruit juice or other fruits and juices. Unless it is known to be a I advised "take most medications only with water."