Clinical Briefs-With Comments from John La Puma, MD, FACP
St. John’s Wort: Drug Interactions and Safety
June 2000; Volume 3; 71-72
Sources: Piscitelli SC, et al. Indinavir concentrations and St. John’s wort. Lancet 2000;355:547-548.
Ruschitzka F, et al. Acute heart transplant rejections due to Saint John’s wort. Lancet 2000;355:548-549.
Jobst KA et al. Safety of St. John’s wort. Lancet 2000;355:575.
De Smet PA, Touw DJ. Safety of St. John’s wort. Lancet 2000;355:575-576.
Wheatley D. Safety of St. John’s wort. Lancet 2000;355:576.
Yue QY, et al. Safety of St John’s wort. Lancet 2000;355:576-577.
"St john’s wort reduced the area under the curve of the HIV-1 protease inhibitor indinavir by a mean of 57% (SD 19) and decreased the extrapolated 8-hour indinavir trough by 81% (16) in healthy volunteers. A reduction in indinavir exposure of this magnitude could lead to the development of drug resistance and treatment failure."
COMMENT
The lead piece, from the NIH, reports an open-label study with eight healthy HIV-negative volunteers that showed a 16-19% drop in the plasma level of indinavir, a protease inhibitor.
The second piece, from Zurich, showed a reduction in cyclosporine levels after heart transplantation in two patients, with episodes of acute rejection in both patients, without recurrence after discontinuation of the St. John’s wort.
Yue Qun-Ying documents seven case reports in Sweden that show reduced anticoagulant effect of warfarin. The investigators report that the Medical Products Agency (an FDA equivalent) has "contacted the companies ... requested studies on the extent and implications of the drug-drug interactions ... and add(ing) on the packaging and patient information leaflet that St. John’s wort products should not be used concomitantly with any medicinal product."
Taken together, these research letters and correspondence add up to an FDA advisory letter about interactions between St. John’s wort and several other drugs. All share, and St. John’s wort appears to induce, the microsomal P450 complex, increasing metabolism of all drugs that pass through it. St. John’s wort probably induces a broad range of drug-metabolizing enzymes. As the reports noted above confirm, it probably reduces the levels and effectiveness of drugs that use these pathways as well.
Drugs that share the cytochrome P450 metabolic pathway include protease inhibitors and reverse transcriptase inhibitors, and even more widely used medications such as digoxin, diltiazem, nifedipine, beta-blockers, imipramine, amoxapine, amitriptyline, phenytoin, phenobarbital, carbamazepine, cyclo-phosphamide, tamoxifen, taxol, etoposide, cyclosporine, rapamycin, tacro-limus, and ethinyl estradiol.
Recommendation
Play it safe. Patients taking St. John’s wort should be warned that the herbal supplement interacts with other drugs in ways that are not well-studied or known. Use another antidepressant in patients taking the medications listed, other antidepressants, and photosensitizing drugs.
June 2000; Volume 3; 71-72
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