Two interactions between St John's wort and other medication have been reported. In the first, Dr Stephen Piscitelli (department of pharmacy, National Institutes of Health, US) and colleagues describe a study in which St John's wort was observed to lower plasma concentrations of the protease inhibitor indinavir.
Eight healthy volunteers participated in the study. All received indinavir for two days and blood samples were taken to measure the drug's pharmacokinetics. Next, the trial participants took a two-week course of St John's wort (300mg three times a day, as a preparation containing 0.3 per cent hypericin). The indinavir dosing and measurements were then repeated. The researchers found "a large reduction in indinavir concentrations by concomitant St John's wort". They report that the area under the curve of indinavir was decreased by 57 per cent after St John's wort therapy. The mean maxium plasma concentration fell from 12.3g/ml to 8.9g/ml. The authors conclude: "St John's wort should be avoided in patients receiving indinavir as their sole protease inhibitor." They add that because other protease inhibitors and non-nucleoside reverse transcriptase inhibitors are metabolised by the same mechanism as indinavir, it would also be "reasonable" to avoid concomitant St John's wort with these drugs (Lancet 2000;355:547).
In a second letter (ibid, p548), two cases of heart transplant rejection as a result of St John's wort therapy are reported. Dr Frank Ruschitzka (cardiology division, University hospital, Zurich, Switzerland) and colleagues say that, in both cases, plasma concentrations of cyclosporin had fallen below therapeutic levels after three weeks of St John's wort therapy, resulting in acute organ rejection. After the herbal product was stopped, cyclosporin levels returned to therapeutic values.
The authors comment that one of the constituents of St John's wort extract, naphtodiantrons, induces the CYP3A isoenzyme of the cytochrome P-450 complex. The risk of St John's wort therapy should be considered when an important co-medication is metabolised by this mechanism, they conclude.
Dr Ruschitzka comments in a Lancet press release: "The common misconception that herbs always equate with no risk must be effectively disproved. Hence, authorities should reconsider whether herbal medicines (as conventional drugs) need regulation and should be tested for safety, tolerability and efficacy for the benefit of our patients."
A spokeswoman for the Department of Health told The Journal on February 15 that an ongoing assessment of the safety of St John's wort was being conducted by the Medicines Control Agency. It would particularly look at the safety of combining St John's wort therapy with other medication.