St. John's Wort Affects Other Drugs

May Reduce Effectiveness of Half of all Prescription and Over-the-Counter Drugs

From the WebMD Archives

Sept. 16, 2003 -- There is new evidence that taking the popular herbal supplement St. John's wort can reduce the effectiveness of as many as half of all prescription and over-the-counter drugs.

The findings provide a scientific explanation for largely anecdotal reports linking use of the unregulated supplement to drug failures among organ transplant patients, patients who are HIV positive, and even women taking oral contraceptives.

These reports and early clinical research prompted the U.S. Food and Drug Administration to issue an advisory to physicians early in 2000 urging them to caution their patients about the potential risks of taking St. John's wort along with other medications. Officials warned that use of the herbal remedy could reduce the effectiveness of a host of drugs, including many used to treat heart disease, depression, seizures, cancer, and to prevent organ rejection.

"Because herbal products are widely used in the United States and are available in various forms, such as combination products and teas, it is important that health-care professionals ask their patients about concomitant use of products that could contain St. John's wort," FDA officials Murray M. Lumpkin, MD, and Susan Alpert, PhD, MD, wrote.

Widely Used for Depression

It is not clear how many Americans take St. John's wort to treat depression, anxiety, and sleep disorders but it is one of the top-selling botanical products in the $4 billion a year herbal supplement market. While studies suggest that it can help people with mild to moderate depression, the supplement has been found to be of little value for treating major depression.

In the newly published study, funded by the National Center for Complementary and Alternative Medicine, researchers investigated the potential of St. John's wort to alter the activity of key enzymes that regulate the metabolism of other medications. The findings are reported in the Sept. 17 issue of TheJournal of the American Medical Association.

Twelve healthy adult volunteers, who were all under age 40, were given two drugs -- the cough suppressant dextromethorphan and the anti-anxiety drug Xanax. The drugs were chosen because very specific and different enzyme pathways drive their metabolism.

Researcher John S. Markowitz, PharmD, of the Medical University of South Carolina, says the drug metabolism pathway used by the two medications are involved in the metabolism of some 70% of prescription and over-the-counter drugs.

"Most drugs go through a number of different pathways, but there is usually one that predominates," he tells WebMD.


Use of St. John's wort was found to have little impact on the pathway used to metabolize the cough suppressant, but it had a dramatic effect on the enzyme -- known as CYP 3A4 -- driving the metabolism of Xanax, and some 50% of other medications, Markowitz says. Xanax was eliminated from plasma twice as fast when the study participants took the herbal supplement as when they did not. After 48 hours, none of the subjects had measurable levels of Xanax in their plasma after taking St. John's wort, but 11 of the 12 still had measurable levels of the drug at 48 hours when not taking the supplement.

"There are any number of drugs from just about every drug class that may be affected by the use of this supplement," Markowitz says. "But that doesn't mean that people shouldn't use St. John's wort."

It does mean that anyone taking the supplement should make sure their physicians and pharmacists know about it, Markowitz says. The researcher points to a recent survey indicating that most people don't tell their doctors about the herbal remedies and supplements they take.

"It is certainly not clear that this drug interaction is unique to St. John's wort," he says. "We aren't saying that you could generalize these results to ginkgo biloba or other herbals. They are just beginning to be studied, so we don't know as much about them."

Show Sources

SOURCES: Markowitz, J. The Journal of the American Medical Association, Sept. 17, 2003; vol 290: pp 1500-1504. John S. Markowitz, PharmD, Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, S.C. Murray Lumpkin, MD, Center or Drug Evaluation and Research, FDA. Susan Alpert, PhD, MD, Center for Food Safety and Applied Nutrition; FDA, 2000 Public Health Advisory on St. John's wort.
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