FYI.
Frank J. Nice, DPA, CPHP

FDA PUBLIC HEALTH ADVISORY
February 10, 2000

Subject: RISK OF DRUG INTERACTIONS WITH ST JOHNS WORT AND INDINAVIR AND OTHER
DRUGS

Dear Health Care Professional:

The Food and Drug Administration would like to inform you about results from a
study conducted by The National Institutes of Health (NIH) that showed a
significant drug interaction between St John's wort (hypericum perforatum), an
herbal product sold as a dietary supplement, and indinavir, a protease inhibitor
used to treat HIV infection. In this study, concomitant administration of St.
Johns wort and indinavir substantially decreased indinavir plasma
concentrations, potentially due to induction of the cytochrome P450 metabolic
pathway. For additional information on this study please refer to the February
12, 2000 Lancet publication (Piscitelli, et al).

RECOMMENDATIONS:

Indinavir and other antiretroviral agents

At this time, pharmacokinetic data are available only for concomitant
administration of indinavir with St. Johns wort. However, based on these
results, it is expected that St Johns 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).
Consequently, concomitant use of St Johns 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.

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 patients about concomitant use of products that
could contain St. Johns wort (hypericum perforatum).

In addition, FDA is working closely with drug manufacturers to ensure that
product labeling of antiretrovirals is revised to highlight the potential for
drug interactions with St. Johns wort.

Other drugs

Based on this study and reports in the medical literature, St. Johns wort
appears to be an inducer of an important metabolic pathway, cytochrome P450. 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.

All health care professionals are encouraged to report any serious adverse event
associated with the concomitant use of prescription drugs and St. Johns wort
products to the FDAs MedWatch program at 1-800-FDA-1088 (fax 1-800-FDA-0178).

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