Health - St. John's Wort and Drug Interactions

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Those using St John's Wort might want to know about poetential drug interactions, as with warfarin and prescription anti-depressants:

HerbalGram. 2003;60:22-23 American Botanical Council

by Mariann Garner-Wizard

http://www.herbalgram.org/younglivin...iew.asp?a=2588

SJW contains at least nine groups of compounds that may contribute to its reported effects. The effects of many constituents are unknown. SJW significantly affects the central nervous system, which may explain its usefulness in mild-to-moderate depression. Hyperforin is now considered the most likely constituent responsible for SJW's interaction potential.
SJW products are commonly standardized to hypericin, although there are several SJW products standardized to hyperforin, a totally different type of compound. Due to the variability of hypericin content in different parts of the plant at different times and under different conditions, a standard hypericin content may not indicate consistent levels of other constituents; thus, different SJW preparations may have different levels of efficacy and/or adverse reaction profiles.
The most common adverse reactions to SJW are gastrointestinal upsets, allergic reactions, dizziness or confusion, tiredness, and dry mouth -- all of which are considered mild, moderate, or transient. While potentially serious, photosensitivity reactions, with increased sensitivity reported at higher doses, have mostly been observed in cattle which have eaten SJW plants and, in rare cases, extremely light-skinned humans. Overall, SJW has produced few reported adverse reactions. Of 1,757 patients who took SJW in clinical trials, only 3 (0.8%) dropped out due to adverse reactions, compared with 7 (3%) who took conventional antidepressants in the same trials. Adverse reactions were reported in only 19.8% of patients using SJW, compared with 52.8% of those taking conventional antidepressants. Adverse reactions were more likely to be reported in clinical trials comparing SJW with conventional antidepressants than in placebo-controlled trials; this may reflect patient preconceptions.
Despite these relatively minor adverse reactions, SJW has been shown to have a number of potentially serious interactions with prescription drugs. The authors write that these interactions fall into two general categories: (1) those indicating the induction of certain drug-metabolizing enzymes in the cytochrome P450 system of digestive/hepatic enzymes and transport proteins, and (2) those potentiating serotonin concentrations. However, HerbalGram peer reviewers have stated that the authors are misinformed and incorrect on the second proposed mechanism; there is not adequate evidence to support the idea that SJW potentiates serotonin function, and in fact may be another example of a kinetic interaction.
The P450 enzyme system consists of a series of isozymes, some of which have been linked with the metabolism of specific drugs. Induction (i.e., increased activity) of isozymes has the effect of reducing the blood serum levels of various drugs, thereby reducing their activity and, in a few cases, rendering the drugs ineffective. While one study suggests that hypericin may induce activity of isozyme CYP1A2, several other studies show no effect of hypericin on this isozyme. Some evidence suggests that hyperforin may induce isozyme CYP3A4. The long-term effects of SJW constituents on various enzymes have not been studied. This may be particularly important as the use of SJW for mild-to-moderate depression usually involves long-term use. Interaction between SJW and the blood-thinning drug warfarin (phenoprocumon), identified from case reports, may be caused by induction of CYP2C9, however, direct studies found no effect on this enzyme. Interaction with the immunosuppressant drug cyclosporin, identified from case reports involving transplant patients, may be due to induction of both CYP3A4 and the transport protein P-glycoprotein. All oral contraceptives (OCs) are metabolized by cytochrome P450 enzymes. Several reports have been made of breakthrough bleeding or unplanned pregnancy in women taking both OCs and SJW. Induction of isozymes 2C9 and 3A4 by SJW are all implicated. The authors point out that, while most SJW-drug interactions involve medications which require regular blood level monitoring, OCs do not, and this interaction is likely to affect many people. There is no indication that the SJW-OC interactions occur with specific products, such as low dose or progesterone-only OCs.
Interaction between SJW and theophylline, an alkaloid found in tea (Camellia sinensis (L.) Kuntze, Theaceae) formerly used in asthma patients identified from only one case, suggests the possible induction of CYP1A2. Clinical pharmacology studies indicate that this is not the case, however. Interaction with digoxin, the widely-used cardiac glycoside derived from foxglove leaves (Digitalis purpurea L., Scrophulariaceae, and D. lanata Ehrh.) identified in a pharmacokinetic study, is believed to be due to induction of P-glycoprotein after multiple-dose treatment with SJW extract. No case reports of this interaction were found. Interaction with HIV protease inhibitors was also identified in a pharmacokinetic study; one case report from the UK was found. Many other medicines are metabolized by either CYP1A2, 2C9, or 3A4, and the authors think it likely that more SJW-drug interactions will be identified. HerbalGram peer reviewers emphasize that the only direct evidence for CYP1A2 and 2C9 isozymes show no effect of SJW.
In interactions involving SJW and selective serotonin re-uptake inhibitors (SSRIs), symptoms suggest central serotonin excess, thought to be due to similar effects of SJW and conventional antidepressants. The authors did not mention, however, that pharmacokinetic interactions (increased antidepressant blood level) resulting from initial (first 2 or 3 days) inhibition of CYP3A4 by SJW could also explain these effects since there is no direct evidence that SJW enhances serotonin function. (SJW frequently causes an initial, acute, inhibition of the isozyme for up to 2 or 3 days, followed after 7-10 days with induction, according to HerbalGram reviewers.) The authors suggest that people taking any of these medications should not concurrently use SJW. In most clinical trials of SJW products, people using conventional antidepressants have been excluded.
Some clinical trials have not excluded participants taking medication for hypertension, circulatory disorders, bronchial asthma, or menopausal symptoms. In these trials, there have been no reported interactions between SJW and these drugs.
The paper includes four tables. Table 1 lists the main constituents of SJW, Table 2 summarizes possible pharmacokinetic and pharmacodynamic interactions, Table 3 provides a breakdown of unintended pregnancies attributable to the presumed interaction of SJW on OCs (where the OCs levels were diminished apparently to the point of inactivity), and Table 4 summarizes specific drug reactions, implications for patient health, and suggested management of patients already taking any of these drugs and SJW. HIV non-nucleoside reverse transcriptase inhibitors and anticonvulsants are included in Table 4, as their pharmacology suggests that they may also interact with SJW, with potentially serious results. However, the authors fail to mention that the only clinical trial with SJW and the anticonvulsant, carbamazepine, found no interaction. Among suggestions for patient management, which include monitoring blood levels and dose adjustments for some medications, the recommendation to "stop SJW" is made in every instance.

[Jatelka]

There's also anarticle in the archive here...

http://www.drugs-forum.com/forum/loc...d=821&catid=69

on this topic