John's wort -- drug interaction
St. John's wort (Hypericum
perforatum) has been widely shown to be effective as an
antidepressant. Studies of extracts standardized for hypericin (one
of the herb's constituents) have found it to be about twice as effective
as a placebo, and in some cases, more effective than a standard
antidepressant. February 2000, British journal Lancet carried reports
that research-grade (HBC Protocols) St. John's wort could potentially
interfere with the effectiveness of certain life preserving medications (like
the AIDS remedy Indinavir) or the immunosuppressive drug (cyclosporin)
which is used to protect patients from organ rejection after heart
transplantation as well as the anticoagulant (warfarin) Based
on this study and other reports in the medical literature, the FDA issued
a Public Health Advisory stating:
St. John's 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.
The most widely documented St. John’s wort–drug interaction has been with cyclosporine (Neoral®, Sandimmune®), a drug taken by transplant patients to fend off the immune system’s tendency to reject a transplanted organ. As blood levels of the drug decrease, the risk of organ rejection rises. The tendency for blood levels of the drug to decrease when people start taking St. John’s wort has been cited in several case reports in the medical literature, including a report totaling 45 transplant patients.
Other reports in the medical literature of St. John’s wort–drug interactions include the protease inhibitor indinavir (Crivaxin®), used to treat persons with HIV infection, as well as digoxin (Lanoxin®), warfarin (Coumadin®), theophylline (e.g., Slo-Bid®, Theo-Dur®), and birth control pills.
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While there is no consensus as to why these interactions occur, evidence appears
to suggest that St. John’s wort interacts with enzymes in the liver responsible for metabolizing drugs. Known as the cytochrome P450 system, these enzymes are the body’s way of ensuring normal clearance of drugs once they’ve done their job. St. John’s
wort appears to induce some of these enzymes to act a bit more quickly than
normal, leading to a drop in therapeutic blood levels of some medications.
In addition to the medications previously listed, persons should discuss
the use of St. John’s wort with their doctor or pharmacist if they are taking anti-anxiety drugs such as alprazolam (Xanax®), sleep medications, heart medications such as nifedipine (Procardia®, Adalat®), cortisone (internally), nonsedating antihistamines, estrogens, carbamazepine (Tegretol®), and ketoconazole (Nizoral®; internally). While there is no data to prove that St. John’s wort has interacted with these medications, each is metabolized by the part of the cytochrome P450 system with which St. John’s wort has previously been reported to interact. Thus, the potential exists for a St. John’s
wort supplement to decrease blood levels of these drugs.
As is the case with drug-drug interactions, knowledge of potential herb-drug
interactions is important for persons choosing to use herbal supplements.
Armed with this knowledge, consumers should be able to make a more informed
choice about whether to use St. John’s wort.
- Linde K and others. St. John's wort for depression -- an overview and
meta-analysis of randomised clinical trials. British Medical Journal
- De Smet PAGM, Nolen WA. St. John's wort as an antidepressant: Longer term
studies are needed before it can be recommended in major depression British
Medical Journal 313:241-242, 1996.
- Gaster B, Holroyd J. St. John's wort in depression Archives of Internal
Medicine 160:152-156, 2000.
- Piscitelli SC and others. Indinavir
concentrations and St John's wort. Lancet 355:547, 2000.
- Ruschitzka F and others. Acute heart transplant rejection due to Saint
John's wort Lancet 355:548, 2000.
- Jobst KA and others. Safety of St John's wort. Lancet 355:576, 2000.
- Lumpkin MM, Alpert S. Risk of drug interactions with St. John's wort and
indinavir and other drugs FDA Health Advisory, Feb 10, 2000.
- St. John's wort study launched. Complementary and Alternative Medicine at
the NIH 4(4):5, October 1997.
- Good Housekeeping Institute. New Good Housekeeping Institute study finds
drastic discrepancy in potencies of popular herbal supplement. News release,
Consumer Safety Symposium on Dietary Supplements and Herbs, New York City,
March 3, 1998.
- Monmaney T. Labels' potency claims often inaccurate, analysis finds. Spot
check of products finds widely varying levels of key ingredient. But some
firms object to testing method and defend their brands' quality. Los Angeles
Times, Aug 31, 1998.
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