Does St. John’s wort decrease OC efficacy?

A study which indicates that the widely used herbal product St. John’s wort (hypericum perforatum) can significantly compromise the effectiveness of an antiviral drug often prescribed to treat HIV infection might have wider implications for use of the herbal supplement with combined oral contraceptives (OCs).1

According to a public health advisory issued by the Food and Drug Administration (FDA) following the February 2000 publication of the study, St. John’s wort appears to be an inducer of the cytochrome P450 metabolic pathway.2

"As many prescription drugs used to treat conditions such as heart disease, depression, seizures, certain cancers or to prevent conditions such as transplant rejection or pregnancy [oral contraceptives] are metabolized via this pathway, health care providers should alert patients about these potential drug interactions to prevent loss of therapeutic effect of any drug metabolized via the cytochrome P450 pathway," states the closing paragraph of the advisory, which focuses on the HIV inhibitor indinavir and other antiretroviral agents.

Regulatory agencies react

The London-based British Committee on the Safety of Medicines has specifically advised British health care providers that St. John’s wort not be used with the following drugs: indinavir, warfarin, cyclosporin, oral contraceptives, digoxin, and theophylline.3 In Sweden, the Uppsala, Sweden-based Medical Products Agency has contacted companies marketing St John’s wort products and requested studies on the extent and implications of drug interactions. In the meantime, the agency has asked that packaging and patient information material include language stating that St. John’s wort products not be used concomitantly with any medicinal product.4

FDA guidance on oral contraceptive labeling is in process. However, the draft guidance does not include the possible impact of St. John’s wort on OCs under its drug interactions section.5 Will the final version include this information?

"The FDA is evaluating whether that information is appropriate for the oral contraceptive labeling and if we need a decision to include it," says agency spokeswoman Susan Cruzan. "We would then look at what would be the best way to do that."

Look at study findings

The study that prompted the FDA advisory was conducted by the Bethesda, MD-based National Institutes of Health (NIH) Clinical Center among eight healthy volunteers. Scientists first measured the amount of the drug indinavir in the body when it was taken alone, followed by a two-week round of St. John’s wort, and ending with participants taking the two medications concurrently. All the participants showed a marked drop in blood levels of indinavir after taking St. John’s wort, with the drop ranging from 49% to 99%.6

Based on the study’s results, it is expected that St. John’s wort may significantly decrease blood concentrations of all of the currently marketed HIV protease inhibitors (PIs) and possibly other drugs (to varying degrees) that are similarly metabolized, including the nonnucleoside reverse transcriptase inhibitors (NNRTIs), states the FDA advisory.

"Consequently, concomitant use of St. John’s wort with PIs or NNRTIs is not recommended because this may result in suboptimal antiretroviral drug concentrations, leading to loss of virologic response and development of resistance or class cross-resistance," the advisory notes.2

OC research needed

At this point, no definitive study has been done on St. John’s wort and oral contraceptives, observes Stephen Piscitelli, PharmD, coordinator of the NIH Clinical Pharmacokinetics Laboratory and lead author of the NIH study.

"From a mechanistic standpoint on how oral contraceptives are metabolized and what St. John’s does to the liver to speed up the metabo-lism, theoretically, there may need to be some caution used," states Piscitelli. "But I am not hearing of widespread pregnancy failures with St. John’s wort."

With drug metabolism, some patients will be markedly affected by St. John’s wort, while some might not show any effects, says Piscitelli. Since there will be people who may be at risk of OC failure, the most conservative approach would be to examine use of an alternative drug for St. John’s wort or consider another method of contraception, he suggests.

The bottom line is to solve the problem of disclosure, says Piscitelli. Patients often do not tell providers about use of herbal supplements, while in turn, providers may not specifically ask about nonprescription medications.

"We have a very big problem with disclosure on both sides of the desk, so to speak," he states.


1. Piscitelli SC, Burstein AH, Chaitt D, et al. Indinavir concentrations and St. John’s wort. Lancet 2000; 355:547-548.

2. Lumpkin MM, Alpert S. Risk of drug interactions with St. John’s wort and indinavir and other drugs. FDA Public Health Advisory. Rockville, MD; 2000.

3. Breckenridge A. Important Interactions Between St. John’s wort (Hypericum perforatum) and Prescribed Medicines. London: Committee on Safety of Medicines; 2000.

4. Yue QY, Bergquist C, Gerden B. Safety of St. John’s wort. Lancet 2000; 355:576-577.

5. Food and Drug Administration, Department of Health and Human Services. Draft guidance for industry on combined oral contraceptives — labeling for healthcare providers and patients. 65 Fed Reg 42387 (July 10, 2000).

6. National Institutes of Health. NIH Clinical Center Study Demonstrates Dangerous Interaction Between St. John’s wort and an HIV Protease Inhibitor. Bethesda, MD; 2000.