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The FDA has asked health care professionals to caution patients about the risk of potentially significant interaction between St John's wort (Hypericum perforatum), an herbal product marketed as a dietary supplement, and other drugs, including indinavir, a protease inhibitor (PI) used for HIV infection.
The agency's warning is based on a study conducted by the National Institutes of Health with eight healthy, HIV-negative volunteers. Participants received 800 mg of indinavir administered on an empty stomach every 8 hours for 4 doses, with serial pharmacokinetic sampling before and after the fourth dose. For the next 14 days, volunteers took 300 mg of St John's wort (0.3% hypericin) three times daily with food. On the last day of St John's wort, volunteers again received took 800 mg of indinavir every four hours for a total of 4 doses, with pharmacokinetic sampling before and for 5 hours serially after the fourth dose.
In this study, St John's wort decreased the area under the curve (AUC) of indinavir plasma concentration by a mean (SD) of 57% (19%) and the extrapolated minimum plasma concentration (Cmin) 8 hours after dose by a mean (SD) of 81% (16%). (For full study results, see Lancet. 2000;355;547-548.)
Another report strongly suggests that the herb causes a drop in plasma levels of cyclosporine after heart transplantation (Lancet. 2000;355;548-549). St John's wort appears to be an inducer of the metabolic pathway cytochrome P450 and may significantly decrease blood concentrations of all PIs for HIV, including amprenavir, indinavir, nelfinavir, ritonavir, and saquinavir. The herbal product may have a similar effect on the nonnucleoside reverse transcriptase inhibitors (NNRTIs) delavirdine, efavirenz, and nevirapine, which are metabolized via the same pathway. Consequently, concomitant use of St John's wort and PIs or NNRTIs is not recommended, because it may result in suboptimal antiretroviral drug concentrations, leading to loss of virologic response and development of resistance or class cross-resistance.
Because many drugs that are used to treat heart disease (such as digoxin, diltiazem, nifedipine, digitoxin, or β-blockers), depression (such as imipramine, amoxapine, or amitriptyline), seizures (such as carbamazepine, phenytoin, or phenobarbital), certain cancers (such as cyclophosphamide, tamoxifen, taxol, or etoposide) or to prevent transplant rejection (such as cyclosporine, rapamycin, or tacrolimus) or pregnancy (ethinyl estradiol) are metabolized through this pathway, health care providers should alert patients about these potential drug interactions.
Serious adverse events associated with St John's wort–drug interaction should be reported to the FDA MEDWATCH by telephone at (800) FDA-1088, fax (800) FDA-0178, or Internet at http://www.fda.gov/medwatch.
Henney JE. Risk of Drug Interactions With St John's Wort. JAMA. 2000;283(13):1679. doi:10.1001/jama.283.13.1679
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