Potential Drug-Drug Interactions

There is a potential for drug-drug interactions between St John's wort and certain prescribed medicines

caduceus resizedAs the popularity of St. John’s wort has increased, there has been an increasing number of case reports of drug-herb interactions (Ernst, 1999; Johne et al., 1999; Nebel et al., 1999; Ruschitzka et al., 2000; Yue et al., 2000; de Maat et al., 2001). 

Recent reports indicate that St. John’s wort extracts may potentiate certain sub-enzymes of the cytochrome P450 enzyme system, decreasing the serum concentration of a number of concomitant drugs, including warfarin, digoxin, theophylline, cyclosporin and oral contraceptives (Biffignandi et al., 2000), as well as the HIV protease inhibitor indinavir (Piscitelli et al., 2000) and nevirapine, a non-nucleoside reverse transcriptase inhibitor (de Maat et al., 2001).  

In vitro experiments have shown that P-glycoprotein expression was strongly induced by SJW (400% increase) and more so by hypericin (700% increase) in a dose-dependent fashion (Greenblatt et al., 2001; and Perloff et al., 2001).  

In vitro experiments have also shown that hyperforin is a potent ligand (Ki = 27 nM) for the pregnane X receptor, an orphan nuclear receptor that regulates expression of the cytochrome P450 (CYP) 3A4 monooxygenase (Kliewer et. al, 2000).  

Chronic administration of St. John’s wort extracts was shown to increase expression of P-glycoprotein in healthy volunteers and enhance cellular efflux of rhodamine (Hennessy et al., 2000).  

It recently has been hypothesized that Hypericum extract may interfere with anesthetic drugs (Koupparis, 2000). However, this hypothesis is based on the assumption that hypericin exhibits clinically significant MAOI activity, an effect which is not supported by the current scientific literature.

It is clear that St. John’s wort extracts alter the pharmacokinetics of a wide variety of therapeutic agents such that significant adverse clinical consequences can occur.  The exact contributions of St. John’s wort constituents such as hyperforin, hypericin, I3 and II8-biapigenin, a potent competitive inhibitor of CYP1A2, CYP2C9 and CYP3A4, to cytochrome P450 induction/inhibition are unclear.   

Thus, there are issues of efficacy (bioactive antidepressant ingredients), safety (drug-drug interactions) and stability that are very relevant to the standardization of this popular herb.


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