Grapefruit's surprising effects prescription drugs

Published Dec. 21, 2012, 11:43 a.m. ET

Grapefruit can affect the response of 85 drugs, including cholesterol-lowering statin drugs, new anti-cancer agents, and some synthetic opiates and psychiatric drugs, as well as some birth control pills and estrogen treatments. (The list is at http://tinyurl.com/cu9yk3z )

For 43 of the 85 drugs, consumption with grapefruit can be life-threatening, said Canadian researcher David Bailey who compiled the list. Many are linked to an increase in heart rhythm, known as torsade de pointes, that can lead to death. It can occur even without underlying heart disease and has been seen in patients taking certain anti-cancer agents, erythromycin and other anti-infective drugs, some cardiovascular drugs like quinidine, the antipsychotics lurasidone and ziprasidone, gastrointestinal agents cisapride and domperidone, and solifenacin, used to treat overactive bladders.

Taken with grapefruit, other drugs like fentanyl, oxycodone and methadone can cause fatal respiratory depression. The interaction also can be caused by other citrus fruits, including Seville oranges, limes and pomelos; a published report suggests that pomegranate may raise the potency of some drugs.

Older people may be more vulnerable, because they are more likely to be both taking medications and drinking more grapefruit juice. The body's ability to cope with drugs also weakens with age, experts say.

Under normal circumstances, the drugs are metabolized in the gastrointestinal tract, and relatively little is absorbed, because an enzyme in the gut called CYP3A4 deactivates them. But grapefruit contains natural chemicals called furanocoumarins that inhibit the enzyme, and without it the gut absorbs much more of a drug and blood levels rise dramatically.

Someone taking simvastatin (Zocor) who also drinks a 200-milliliter, or 6.7-ounce, glass of grapefruit juice once a day for three days could see blood levels of the drug triple, raising the risk for rhabdomyolysis, a breakdown of muscle that can cause kidney damage.

stradiol and ethinyl estradiol, forms of estrogen used in oral contraceptives and hormone replacement, also interact with grapefruit juice. In one case in the journal Lancet, a 42-year-old woman taking the birth control pill Yaz developed a serious clot that threatened her leg several days after she started eating just one grapefruit a day, said Dr. Lucinda Grande, a physician in Lacey, Wash., and an author of the case report.

But Grande also noted that the patient had other risk factors and the circumstances were unusual. "The reason we published it as a case report was because it was so uncommon," she said. "We need to be careful not to exaggerate this."

Some drugs that have a narrow "therapeutic range" - where having a bit too much or too little can have serious consequences - require vigilance with regard to grapefruit, said Patrick McDonnell, clinical professor of pharmacy practice at Temple University. He said most patients suffering adverse reactions are consuming large amounts of grapefruit. "There's a difference between an occasional section of grapefruit and someone drinking 16 ounces of grapefruit juice a day," he said.

And, he cautioned, "Not all drugs in the same class respond the same way." While some statins are affected by grapefruit, for instance, others are not.

Here is some advice from experts for grapefruit lovers:

- If you take oral medication of any kind, check the list to see if it interacts with grapefruit. Make sure you understand the potential side effects of an interaction; if they are life-threatening or could cause permanent injury, avoid grapefruit altogether. Some drugs, such as clopidogrel, may be less effective when taken with grapefruit.

- If you take one of the listed drugs a regular basis, keep in mind that you may want to avoid grapefruit, as well as pomelo, lime and marmalade. Be on the lookout for symptoms that could be side effects of the drug. If you are on statins, this could be unusual muscle soreness.

- It is not enough to avoid taking your medicine at the same time as grapefruit. You must avoid consuming grapefruit the whole period that you are on the medication.

- In general, it is a good idea to avoid sudden dramatic changes in diet and extreme diets that rely on a narrow group of foods. If you can't live without grapefruit, ask your doctor if there's an alternative drug for you.

- New York Times