St. John’s wort may interfere with cancer-fighting drug’s ability to prevent relapse in leukemia patients

Mar 26 2004

Researchers who studied healthy volunteers to determine whether the herbal preparation interacts with the prescription drug imatinib mesylate, known by the trade name Gleevec, found that taking the two together caused the amount of Gleevec in the blood to drop nearly 30 percent.

Because it targets only cancerous cells, Gleevec has been called a “magic bullet” drug that fights aggressive cancers such as chronic myelogenous leukemia, researchers say. Leukemia patients who go into remission must continue to take daily oral doses of the medicine to prevent a recurrence.

“A 30 percent decrease in the level of Gleevec is significant to cancer patients,” said Reginald F. Frye, associate director for the UF Center of Pharmacogenomics. “It is the same as lowering the dose - which is enough to allow for a relapse in the cancer growth.”

Frye began the study while he was still working at the University of Pittsburgh Schools of Pharmacy and Medicine, prior to arriving at UF’s College of Pharmacy in 2003.

“The emergence of studies such as this shows the need for health-care professionals to have current scientific information on the safety and efficacy of natural supplements,” said Veronika Butterweck, the DeSantis professor of natural products at the UF College of Pharmacy.

Patients should be aware that any product they take, whether herbal, nonprescription or prescription, has the potential to alter how their body handles other drugs they are taking, said study collaborator Dr. Merrill J. Egorin, co-director of the Molecular Therapeutics and Drug Discovery Program at the University of Pittsburgh Cancer Institute.

“The interactions of herbal preparations and even certain foods can be an important factor in how well a patient may absorb or metabolize certain drugs, and those differences can have important clinical consequences,” Egorin said.

Clinical trials performed on St. John’s wort in the United States show that while it doesn’t appear useful for major depression, it may help treat mild depression, Frye said.

The first indication that St. John’s wort interacts with other medications came after physicians noted drugs designed to prevent organ rejection weren’t as effective in transplant patients who were taking the herbal supplement, he added. A few years ago, the U.S. Food and Drug Administration issued a public health advisory after federal research showed St. John’s wort interferes with medicines used to treat patients with HIV. Those findings raised concerns that the herb also might interact with drugs taken by patients with heart disease, depression or seizures.

The National Nutritional Foods Association reported in 2000 that more than 242 million Americans used some form of dietary supplement, vitamins, minerals, herbal remedies or specialty products. Although St. John’s wort is available over the counter at most national drug stores, little is known about how it may interact with prescription medications. Herbal products aren’t evaluated or regulated by the FDA, and don’t normally go through the interaction studies required of marketed prescription drugs.

For the current UF study, researchers focused on 12 healthy, nonsmoking volunteers, six men and six women, who took one 400-milligram dose of imatinib mesylate. Researchers then took a series of blood samples over a 72-hour period to see how much of the drug had been metabolized. For two weeks after the blood tests, study participants took 300 milligrams of St. John’s wort three times each day. On the 15th day, they again were given one dose of imatinib mesylate, and the blood tests were repeated to measure drug levels.

Frye noted a marked decrease of imatinib mesylate in the subjects’ bloodstreams after they took the St. John’s wort regimen, indicating the herbal product caused the body to metabolize the medicine at a faster rate, weakening its effectiveness.

“Often, patients don’t think of herbal supplements as being a drug, and when their doctor asks what other medications they are taking, they may not report taking herbal products like St. John’s wort,” Frye said.

The National Center for Natural Products Research at the University of Mississippi School of Pharmacy conducts research on the chemical make-up of the St. John’s wort plant. Although only one type of the plant is used in dietary supplements, which rank among the top 10 herbal preparations in national sales, there are actually 370 known species, said Ikhlas Khan, the center’s assistant director.

“By examining the chemical profiles of all the species, we hope to better understand the efficacy of this plant,” Khan said. “A long-range goal at our center is to provide the science that may help industry and government to establish criteria for product quality and safety.”