HIV patients who take herbals may be putting their drug therapy at risk

FDA advisory on St. John’s Wort may start trend

The Food and Drug Administration’s recent advisory on how St. John’s Wort reduces the effectiveness of certain HIV drugs is a reminder that herbal remedies are not always harmless ways to promote HIV patients’ health or placebos that can be ignored. It also means clinicians will have to be proactive in finding out what over-the-counter supplements their patients are taking and will need to determine if there’s a possibility those herbal remedies could have adverse interactions with antiretroviral medications, herbal experts say.

"Anyone taking herbals needs to know there is a risk, because herbals are bioactive compounds, just like any other agent you ingest," says Michael Cirigliano, MD, an assistant professor of medicine at the University of Pennsylvania Medical Center in Eddystone. Plus, herbal use has increased dramatically in recent years, Cirigliano notes.

Since the beginning of the HIV epidemic, dating back to the years when there were no or few treatments available, HIV patients have experimented with and sometimes relied on alternative medicine, including herbal remedies. In his book And the Band Played On, writer Randy Shilts described how vitamin and herbal companies exploited dying gay men in the early 1980s by promising that the products they sold would help the men maximize their immune systems. "The sewers of Manhattan and San Francisco flowed with the most vitamin-rich urine in the nation," Shilts wrote.1

Since those more desperate years, HIV patients have had access to better-proven treatments, but herbal remedies still hold some attraction for people who have a chronic and often fatal illness.

Until the recent FDA advisory, some HIV patients used St. John’s Wort because of reports that it not only alleviated depression but also had an antiretroviral effect on HIV, says Mary L. Hardy, MD, medical director of the Cedars-Sinai Integrative Medicine Medical Group in Los Angeles. Hardy specializes in herbal-drug interactions.

The St. John’s Wort study published in a February 2000 issue of The Lancet showed that the herb is an inducer of the cytochrome P450, which is the same pathway in which antiretroviral drugs such as indinavir are metabolized, Hardy says. (See related story, p. 53.)

St. John’s Wort significantly decreased blood concentrations of the protease inhibitor, putting patients at risk of developing drug-resistant HIV strains, she adds.

HIV patients frequently take St. John’s Wort in doses two to three times the regular dose because the herb has been shown in in vitro testing to be active against HIV, Hardy says. This makes the study immensely important.

"Often, HIV patients were taking St. John’s Wort as self-medicating for its antiretroviral effect, and before this study, that was a good choice to make," she adds.

The FDA issued an advisory in February that warns clinicians and HIV patients of the possible dangerous interaction between St. John’s Wort and the HIV protease inhibitor indinavir. The FDA also warned that St. John’s Wort might cause problems with other HIV drugs, both protease inhibitors and nonnucleoside reverse transcriptase inhibitors.

"So it’s imperative that physicians know what their patients are taking, because St. John’s Wort has been found to have lots of drug interactions," Cirigliano says.

Hardy recommends that no HIV patients take St. John’s Wort, because they are better served by conventional antiretroviral therapy and other antidepressants.

The FDA currently is collecting case studies of herbal interactions with medications and other adverse events reported by consumers or health care professionals. As part of the Special Nutritionals Adverse Event Monitoring System, established in 1993, health care professionals may report any cases they have of patients who have had an adverse reaction to a particular herbal remedy, whether or not it was in connection with another medication. To do so, they contact the FDA through its Web site at www.fda.gov/medwatch/how.htm or call (800) FDA-1088, or fax the information to (800) FDA-0178.

Lacking hard data about herb-drug interactions with antiretrovirals, clinicians should use common sense, pharmacy experts say.

When to avoid echinacea

For example, people with autoimmune disorders should avoid herbs such as echinacea, which is used to stimulate the immune system, say Teresa Klepser, PharmD, assistant professor and pharmacist at the University of Iowa College of Pharmacy in Iowa City, and Marjorie Robinson, PharmD, assistant professor for pharmacy at Nova Southeastern University in Ft. Lauderdale, FL.

Echinacea is not recommended because it could increase an HIV patient’s viral load at the same time that it is stimulating immune system cells, Robinson explains.

"Anybody who has an autoimmune or immune disorder should not use echinacea, including echinacea teas," Klepser says. "Usually tea preparations are weaker, and whether they have that much effect is questionable, but to be on the safe side, you don’t want their disease to be affected."

Because HIV patients sometimes have dual diagnoses, including diabetes, hypertension, and heart disease, there are other herbs they should avoid that might interact with medications used to treat these other conditions, Klepser notes.

For instance, when a patient is taking an anticoagulant, antiplatelet, or antihypertensive drug, patients should avoid the herbs ginkgo biloba, garlic, feverfew, and ginseng, she says.

Patients on diabetes medications should avoid herbs that lower blood sugar, such as ginseng, Klepser adds.

If an HIV patient is taking antidepressants or drugs for insomnia, then the patient should avoid herbs that may potentiate that effect, including kava kava and valerian.

The herbal remedy market was given a boost in 1994 when Congress passed the Dietary Supplement Health and Education Act of 1994 (DSHEA), which established a new category called dietary supplements. These are products that contain a vitamin, a mineral, an herb or botanical, an amino acid, or a dietary substance used to increase the total dietary intake. Extracts, concentrates, or combinations of these also are included under the definition of dietary supplement.

Essentially, DSHEA means the FDA cannot regulate herbal remedies to the extent that it regulates prescription and over-the-counter drugs, or even food items. For example, herbal supplements are permitted to make some claims about the product without offering proof in the form of clinical trials.

This underscores why clinicians should monitor patients’ use of herbal remedies, experts say.

"If you have a certain drug therapy and then you add another drug, there are certain parameters you want to monitor to ensure outcome and potential for drug interactions," says Donna Lee, RPh, president of Natural Alternatives Inc. and the director of nutritional new product concepts for Banner Pharmacaps, both of Greensboro, NC.

"View herbs as drugs and follow the same guidelines as if you were adding or taking away a medication," Lee adds. "I see no difference in herbs or drugs except regulatory issues and misinformation that’s sometimes made available."

Reference

1. Shilts R. And the Band Played On. New York: St. Martin’s Press; 1987, p. 182. n