Health Canada Warning - St. John's Wort
Hypericum perforatum
Health Canada has advised physicians, pharmacists, complementary medicine practitioners, and other health care professionals of the potential for clinically significant drug interactions between St. John's Wort (
Hypericum perforatum) and other medications. The herbal is available without a prescription at supermarkets, pharmacies, and health food stores as capsules, tablets, liquids, ointments and teas. St. John's Wort products with DIN status are labelled for use as remedies for a range of disorders including nervousness, tension, insomnia, nervous headache and neuralgic pain. Various reports also attribute antidepressant properties to this herb.
St. John's Wort appears to decrease the blood levels of some concomitantly administered drugs, which may be related to the induction of drug-metabolizing enzymes of the cytochrome P450 metabolic pathway and/or the P-glycoprotein transporter. Substances which induce drug metabolism decrease the plasma concentration of co-administered drugs that are substrates for these enzymes. Induction can be expected to reduce the therapeutic effects of medicines that are de-activated by these enzymes and to enhance the pharmacodynamic activity of prodrugs that are activated as a result of metabolism.
St. John's Wort also effects neurotransmitter availability in the brain. It has been reported to increase levels of serotonin and other neurotransmitters. Concomitant administration with certain prescription antidepressants which also elevate levels of these neurotransmitters has been reported to a cause a pattern of adverse events known as "serotonin syndrome".
Clinical trials have shown that St. John's Wort interacts with indinavir (Crixivan®), an HIV-1 protease inhibitor used to treat HIV infection, resulting in a substantial decrease of indinavir plasma concentrations. It may also interact with other antiretroviral agents, including non-nucleoside reverse transcriptase inhibitors (NNRTIs). It also interacts with digoxin, decreasing levels of the cardiac glycoside.
Other drug interactions with St. John's Wort are suspected on the basis of published case reports:
- Organ transplant patients taking the immunosuppressant, cyclosporine, with St. John's Wort have been reported to experience acute graft rejection in association with decreased blood levels of cyclosporine.
- Use of St. John's Wort with the anticoagulant, warfarin, has been associated with a reduced anticoagulant effect and a need to increase warfarin levels.
- Interactions between St. John's Wort and the asthma therapy, theophylline, are suspected.
- Breakthrough bleeding in some women receiving St. John's Wort with oral contraceptives suggests the possibility of unwanted pregnancies when taking this combination.
- St. John's Wort has also been reported to inhibit the neuronal reuptake of serotonin and certain other neurotransmitters in the brain. When St. John's Wort is administered with prescription antidepressant drugs which also elevate the availability of serotonin in the brain, patients may experience a pattern of side effects described as "serotonin syndrome", including nausea, vomiting, restlessness, dizziness, tremor and headache. Case reports have been published describing the occurrence of "serotonin syndrome" when St. John's Wort is used with certain prescription antidepressant drugs such as selective serotonin reuptake inhibitors and nefazodone.
- Diminished plasma concentrations of the anti-epileptic drugs phenytoin, carbamazepine and phenobarbital, may be anticipated on the basis of theoretical considerations.
Potential drug interactions with St. John's Wort are not limited to the drugs mentioned above. As research of this issue continues, it is likely that the list of confirmed and suspected interactions will expand to include many other drugs that are metabolized by enzymes in the liver.
General Recommendations
Given the widespread availability of herbal products in foods and over-the-counter medications, it is important that healthcare professionals actively question their patients about the use of St. John's Wort preparations before issuing drug prescriptions or while monitoring the effectiveness of a prescription treatment. In many cases, it may be advisable for the patient to discontinue products containing this herbal ingredient prior to initiating treatment with a conventional medication (such as those listed above).
In the case of patients who have been stabilized on a higher than usual dose of a prescription drug in the presence of St. John's Wort, attention should be directed to the possibility of undesirable increases in the blood levels of the interacting drug when St. John's Wort is discontinued.
For drugs with a narrow therapeutic range (warfarin, digoxin, and cyclosporine), monitoring and dosing adjustment may be necessary to avoid an increased risk of toxicity.
Persons receiving serotonergic antidepressants or migraine therapies (triptan class) should avoid St. John's Wort products due to the possibility of an increased risk of serotonin syndrome during concomitant administration.
The capacity of St. John's Wort products to cause drug interactions may vary between preparations and batches, owing to differences in the content of the active ingredients. In the absence of controlled testing of the available preparations, it is not possible to comment on the comparative potency of individual products in this regard.
No information is available to determine the long-term consequences of increased liver enzyme production in individuals receiving St. John's Wort. The possibility that the drug may affect the enzymatic breakdown of exogenous chemicals entering the body through dietary or environmental exposure should be considered.
Cases of adverse events or therapeutic failure associated with the concomitant use of prescription drugs and St. John's Wort products should be reported to the
Adverse Reaction and Medication Error Assessment Division of the Bureau of Licensed Product Assessment at 613-957-0337 or by fax at 613-957-0335.
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