St. John's Wort, Rx Drug Use Warning Adopted By CHPA

Consumer Healthcare Products Association member companies soon will be incorporating a prescription drug use warning on their St. John's wort supplements.

Under a voluntary labeling program announced by the trade association May 2, the warning, "If you are taking a prescription drug, ask a health professional," will appear on St. John's wort supplements as early as the next label printing and no later than April 2, 2001.

Although the statement applies to all CHPA members marketing St. John's wort products, companies may use alternative statements as long as the wording is "reasonably substantially equivalent."

The program allows companies to combine the St. John's wort caution with other voluntary label statements, such as the pregnancy/nursing warning announced by CHPA in March (¹ (Also see "Supplements Pregnancy Warning Statement Petition Pending From CHPA" - Pink Sheet, 27 Mar, 2000.)). Such a combination could read, "If you are taking a prescription medicine, or if you are pregnant or nursing a baby, ask a doctor."

The association is preparing a citizen petition asking FDA adopt as a regulation the St. John's wort labeling program. CHPA's filing of a similar petition for pregnancy/nursing warning language is imminent.

Although most of its members already use appropriate label statements on St. John's wort products, CHPA says it is instituting an across-the-board program to help reduce the likelihood of interactions between the herbal ingredient and prescription drugs.

Concerns over St. John's wort/Rx drug interactions were spurred by reports published Feb. 12 in The Lancet. In the issue, National Institutes of Health researchers reported blood plasma levels of the HIV protease inhibitor indinavir dropped significantly in subjects also taking St. John's wort.

Concomitant use of the botanical with other similarly metabolized HIV drugs, such as nonnucleoside reverse transcriptase (NNRT) inhibitors, also should be avoided, NIH researchers warned.

In the same issue of The Lancet, Swiss physicians reported acute rejection in two heart transplant patients due to a metabolic interaction between St. John's wort and the immunosuppressive Rx ciclosporin. Reports of St. John's wort interaction with other Rx drugs, such as oral contraceptives and warfarin, also were cited.

Upon publication of the reports, FDA and NIH warned HIV patients taking protease inhibitors to avoid using St. John's wort supplements. The agencies noted many Rx drugs, including treatments for heart disease, depression, seizure, cancer, organ transplant rejection and birth control, are metabolized along the same pathway as protease and NNRT inhibitors, creating the potential for interactions with the herbal.

FDA said it is working with drug makers to ensure labeling for antiretrovirals is revised to highlight the potential interaction.

The U.K. Committee on the Safety of Medicines' Feb. 29 warning against taking St. John's wort with 17 Rx drugs was cited by Public Citizen in a March 2 letter to FDA. Public Citizen wants FDA to require that Rx labels bear warnings about potential interactions with the herbal (² (Also see "St. John's wort complications" - Pink Sheet, 6 Mar, 2000.)).

Future studies of St. John's wort should include more detailed reporting of adverse effects, the American College of Physicians-American Society of Internal Medicine urges in new guidelines for pharmacologic treatment of acute major depression and dysthymia.

The recommendations, published in the May 2 Annals of Internal Medicine, suggest St. John's wort therapy "may be considered" for short-term treatment of mild, acute depression, "but patients should be cautioned that this treatment is not approved by [FDA] and that preparations may vary substantially from those tested in randomized trials."

The guidelines are based on an analysis of 14 trials comparing St. John's wort with placebo or older antidepressant drugs, such as tricyclics. Data indicate the botanical was more effective than placebo in treating mild to moderate depression, producing benefits similar to those of older antidepressant agents.

However, data comparing the effectiveness of St. John's wort with newer agents, such as selective serotonin reuptake inhibitors (SSRIs), are sparse. The guidelines call for more detailed study in this area, as well as examination of standardized dosing and the effects of long-term St. John's wort therapy.

A Duke University study examining the effects of St. John's wort, Pfizer's SSRI drug Zoloft (sertraline) and placebo in treating depression is currently recruiting patients. The National Institute of Mental Health and the National Center for Complementary & Alternative Medicine are the sponsors.