St. John's Wort May Reduce Efficacy of Chemotherapy Drug

SAN FRANCISCO--St. John's wort may reduce the efficacy of a drug used by chemotherapy patients, according to new research that was presented at the 93rd annual meeting of the American Association for Cancer Research (www.aacr.org). Researchers, led by Ron A.H.J. Mathijssen, M.D., of the Rotterdam Cancer Institute in the Netherlands, discovered that patients concurrently taking St. John's wort and irinotecan (a cancer chemotherapeutic drug) experienced about a 40-percent decrease in exposure to SN-38, a metabolite of irinotecan. This effect was observed up to three weeks after ending St. John's wort therapy.

"This is not necessarily new," said Mark Blumenthal, executive director of Austin, Texas-based American Botanical Council (ABC), which published a monograph of the herb on its Web site (www.herbalgram.org). "We might be able to add another class of drugs to the list of pharmaceuticals with which St. John's wort interacts."

Mathijssen's current study was based on previous findings that St. John's wort can stimulate cytochrome P450 (CYP3A4), an enzyme system involved in drug metabolism. Specifically, researchers went on the premise that hypericin and hyperforin--components of St. John's wort--seem to enhance CYP3A4 activity, and the fact that irinotecan is also partly metabolized by the enzyme system.

"Since 50 percent of all drugs are metabolized by CYP3A4, the combination effect we found with St. John's wort and irinotecan might occur with many other anticancer agents," Mathijssen said. "So, the problem is potentially more widespread than this single study shows."

Blumenthal added, "Forty percent to 50 percent of modern pharmaceutical drugs are believed to act on the P450 system. If that's the case, there are probably many drugs, or classes of drugs, that St. John's wort may be working on. That's why it's prudent for people to consult their physician or pharmacist if they're taking pharmaceutical medicine before taking St. John's wort."

Mathijssen and his colleagues treated three patients with a traditional regimen of irinotecan, followed three weeks later by a second course combining irinotecan and St. John's wort. Another group of patients received a combination of irinotecan and St. John's wort, and three weeks later received irinotecan alone. Tests indicated that the patients taking St. John's wort and irinotecan concurrently experienced reduced efficacy of the drug, and patients taking St. John's wort three weeks prior to drug therapy also experienced this reduction in efficacy.

"[P]eople have to realize that it's not good enough to stop using St. John's wort just prior to treatment with irinotecan," Mathijssen said. "We do not know at this time, however, how long patients should stop using St. John's wort before being treated with irinotecan as our study was not long enough to make such a determination."