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Current Drug Metabolism Jun 2008St. John's wort (Hypericum perforatum, SJW) is one of the most commonly used herbal antidepressants for the treatment of minor to moderate depression. Limited clinical... (Review)
Review
St. John's wort (Hypericum perforatum, SJW) is one of the most commonly used herbal antidepressants for the treatment of minor to moderate depression. Limited clinical trials suggest that hypericum and standard antidepressants have similar beneficial effects, but current evidence regarding the antidepression effects of SJW extracts is inconsistent. A major safety concern about SJW is its ability to alter the pharmacokinetics and/or clinical response of a variety of clinically important drugs. This review highlights and updates the knowledge regarding drug interactions with SJW by a systematic review of all the available evidence, including worldwide published literature and spontaneous case reports. A number of clinically significant interactions of SJW have been identified with conventional drugs. These interactions often result in a decrease in the concentration or effect of the combined drug, most probably due to the induction of cytochrome P450s (CYPs) and the key drug transporter P-glycoprotein (P-gp) by the major active constituents in SJW. SJW is a potent inducer of human CYP3A4 and P-gp in vitro and in vivo. In addition, pharmacodynamic interactions of SJW with some drugs (e.g. selective serotonin re-uptake inhibitors) have been identified, which are associated with an increased risk of adverse reactions. Since potential interactions of SJW with conventional drugs is a major safety concern, it is important to minimize and avoid these interactions by taking appropriate approaches. These include systematic research to identify SJW-drug interaction; close therapeutic drug monitoring when SJW is combined with conventional drugs with a narrow therapeutic window; proper dose and regimen adjustment; patient education and communication between the patient and physician; design of new preparations of SJW without inducing ability of CYP3A4 and P-gp while retaining its bioactivity; and appropriate regulation in herbal safety and efficacy. Further clinical and mechanistic studies are warranted to explore the interaction of SJW with other important drugs and clinical significance.
Topics: Animals; Antidepressive Agents; Databases, Factual; Drug Interactions; Drug Monitoring; Humans; Hypericum
PubMed: 18537576
DOI: 10.2174/138920008784746391 -
British Journal of Clinical Pharmacology Oct 2002The aim of this work is to identify the medicines which interact with the herbal remedy St John's wort (SJW), and the mechanisms responsible. (Review)
Review
AIMS
The aim of this work is to identify the medicines which interact with the herbal remedy St John's wort (SJW), and the mechanisms responsible.
METHODS
A systematic review of all the available evidence, including worldwide published literature and spontaneous case reports provided by healthcare professionals and regulatory authorities within Europe has been undertaken.
RESULTS
A number of clinically significant interactions have been identified with prescribed medicines including warfarin, phenprocoumon, cyclosporin, HIV protease inhibitors, theophylline, digoxin and oral contraceptives resulting in a decrease in concentration or effect of the medicines. These interactions are probably due to the induction of cytochrome P450 isoenzymes CYP3A4, CYP2C9, CYP1A2 and the transport protein P-glycoprotein by constituent(s) in SJW. The degree of induction is unpredictable due to factors such as the variable quality and quantity of constituent(s) in SJW preparations. In addition, possible pharmacodynamic interactions with selective serotonin re-uptake inhibitors and serotonin (5-HT(1d)) receptor-agonists such as triptans used to treat migraine were identified. These interactions are associated with an increased risk of adverse reactions.
CONCLUSIONS
In Sweden and the UK the potential risks to patients were judged to be significant and therefore information about the interactions was provided to health care professionals and patients. The product information of the licensed medicines involved has been amended to reflect these newly identified interactions and SJW preparations have been voluntarily labelled with appropriate warnings.
Topics: Contraceptives, Oral; Cyclosporine; Digoxin; Drug Interactions; HIV Protease Inhibitors; Herb-Drug Interactions; Humans; Hypericum; Plant Extracts; Selective Serotonin Reuptake Inhibitors; Theophylline; Warfarin
PubMed: 12392581
DOI: 10.1046/j.1365-2125.2002.01683.x -
Archives of Surgery (Chicago, Ill. :... Mar 2002St John's wort is one of the most popular herbal medicines, and health care professionals often are unaware that their patients take such supplements. St John's wort... (Review)
Review
HYPOTHESIS
St John's wort is one of the most popular herbal medicines, and health care professionals often are unaware that their patients take such supplements. St John's wort causes a decrease in cyclosporine levels, thus endangering the success of organ transplantations.
DESIGN
Systematic review.
METHODS
Five independent computerized literature searches were conducted to identify all reports of such interactions. Data were extracted and are summarized in narrative form.
RESULTS
Eleven case reports and 2 case series were located. In most instances, causality between St John's wort and the clinical or biochemical result is well established. The mechanism of interaction between St John's wort and cyclosporine has been recently elucidated and involves both P-glycoprotein and cytochrome P 450 3A4 expression. Collectively these data leave little doubt that St John's wort interacts with cyclosporine, causing a decrease of cyclosporine blood levels and leading in several cases to transplant rejection.
CONCLUSIONS
St John's wort can endanger the success of organ transplantations. Adequate information may be the best way to avoid future incidences.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Adult; Antidepressive Agents; Cyclosporine; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Drug Interactions; Female; Graft Rejection; Heart Transplantation; Humans; Hypericum; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mixed Function Oxygenases; Organ Transplantation; Pancreas Transplantation; Plant Extracts
PubMed: 11888457
DOI: 10.1001/archsurg.137.3.316