Hyperforin content of St John's wort products and drug interactions.
Chrubasik-Hausman S, Vlachojannis J, McLachlan A. Understanding drug interactions with St John's wort (Hypericum perforatum L.): impact of hyperforin content. J Pharm Pharmacol 2018. Available online: doi:10/1111/jphp.12858
St John's wort (Hypericum perforatum) (SJW) is one of the most commonly used herbal medicines worldwide. Co-administration of SJW preparations is known to be associated with significant interactions with a range of medicines. SJW acts as an inducer of drug-metabolising enzymes and transporters, leading to reduced systemic exposure and risk of therapeutic failure; however, the extent of interactions are highly variable with interactions difficult to predict based on SJW dose alone.
Previous research has suggested that the interactions of SJW are likely to be related to the hyperforin content in products prepared from SJW. Furthermore, research suggests CYP3A4 induction by herbal medicines containing SJW is directly related to hyperforin dose ingested. The aim of the current study was to provide an update on the interactions of H. perforatum L. extracts and conventional medicines by considering clinical herb-drug interaction studies investigating SJW to explore the hypothesis that low-dose hyperforin products are associated with a lower risk of significant interaction.
The authors conducted a search in PUBMED from 30 July 2016 to 1 January 2010 using search terms "Hypericum" or "St John's wort". This was to identify recently published studies that could be added to previously published and analysed studies undertaken in prior work. Inclusion criteria were controlled clinical pharmacokinetic and/or pharmacodynamic studies in healthy participants or patients with an appropriate study design. Data on the SJW extract or product was collected to extract hyperforin content and the expected daily dose used in interaction studies.
In total, 59 pharmacokinetic interaction studies were identified, of which 12 had been published since 2010. Each study investigated interactions with SJW products reported to have a high hyperforin content. Studies were generally with small numbers (median 12 subjects) with SJW administration ranging from 10-56 days (median 14 days). The authors reported that significant pharmacokinetic interactions were more likely with drugs that were substrates for CYP3A4 and/or p-glycoprotein (ABCB1) and were less likely in studies that investigated SJW products with low-hyperforin content. Specifically, products that had a daily dose of <1 mg hyperforin were less likely to be associated with major interaction for drugs that were CYP3A4 or p-glycoprotein substrates.
Limitations of this study recognised by the authors include that relatively few studies have investigated SJW products with low-hyperforin content, thus not allowing for risk of interactions to be excluded with low dose hyperforin formulations. Additionally, the conclusions made are based on a calculated daily dose of hyperforin as per information on label content or as provided by suppliers rather than independent product analysis. The authors suggest consideration of mandating hyperforin content on labelling to facilitate effective and safe use of SJW products. With the widespread use of SJW products, understanding the basis of potential herb-drug interactions, and the influence of particular components is clinically important and relevant.
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|Publication:||Australian Journal of Herbal and Naturopathic Medicine|
|Date:||Jun 1, 2018|
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