St. John's wort, an herbal dietary supplement, is popularly used to reduce depression and anxiety. However, the herb has been thought to induce the CYP3A4, which could have an effect on plasma concentrations of protease inhibitors and other drugs. A recent article in The Lancet (355:9203, February 12, 2000) reports that in an open-label study with eight healthy volunteers St. John's wort significantly reduced concentrations of indinavir (Crixivan). After taking St. John's wort, the AUC of indinavir decreased by a mean of 57%, which could lead to treatment failure and the development of drug resistance. The authors conclude that since other protease inhibitors and non-nucleosides (NNRTIs) are also metabolized by CYP3A4, patients should "avoid St. John's wort with those agents in the absence of definitive data."

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