Evaluation of Documented Drug Interactions and Contraindications Associated With Herbs and Dietary Supplements

A Systematic Literature Review

H.-H. Tsai; H.-W. Lin; A. Simon Pickard; H.-Y. Tsai; G. B. Mahady


Int J Clin Pract. 2012;66(11):1056-1078. 

In This Article

Abstract and Introduction


Background and Aims: The use of herbs and dietary supplements (HDS) alone or concomitantly with medications can potentially increase the risk of adverse events experienced by the patients. This review aims to evaluate the documented HDS-drug interactions and contraindications.
Methods: A structured literature review was conducted on PubMed, EMBASE, Cochrane Library, tertiary literature and Internet.
Results: While 85 primary literatures, six books and two web sites were reviewed for a total of 1,491 unique pairs of HDS-drug interactions, 213 HDS entities and 509 medications were involved. HDS products containing St. John's Wort, magnesium, calcium, iron, ginkgo had the greatest number of documented interactions with medications. Warfarin, insulin, aspirin, digoxin, and ticlopidine had the greatest number of reported interactions with HDS. Medications affecting the central nervous system or cardiovascular system had more documented interactions with HDS. Of the 882 HDS-drug interactions being described its mechanism and severity, 42.3% were due to altered pharmacokinetics and 240 were described as major interactions. Of the 152 identified HDS contraindications, the most frequent involved gastrointestinal (16.4%), neurological (14.5%), and renal/genitourinary diseases (12.5%). Flaxseed, echinacea, and yohimbe had the largest number of documented contraindications.
Conclusions: Although HDS-drug interactions and contraindications primarily concerned a relatively small subset of commonly used medications and HDS entities, this review provides the summary to identify patients, HDS products, and medications that are more susceptible to HDS-drug interactions and contraindications. The findings would facilitate the health-care professionals to communicate these documented interactions and contraindications to their patients and/or caregivers thereby preventing serious adverse events and improving desired therapeutic outcomes.


The marketing and consumer use of herbs and dietary supplements (HDS) has risen dramatically in the USA over the past two decades.[1,2] It is estimated that > 50% of patients with chronic diseases or cancers ever use HDS,[3] and nearly one-fifth of patients take HDS products concomitantly with prescription medications.[4,5] Despite their widespread use, the potential risks associated with combining HDS with other medications are poorly understood by these consumers. Although many HDS users believe that HDS are safe,[6] HDS products have been reported to be associated with mild-to-severe adverse effects such as heart problems, chest pain, abdominal pain and headache.[2,7,8] Because a majority of patients often fail to disclose that they have taken HDS products to their healthcare providers, e.g. one study estimated only 30% disclosure,[9] patient-provider communication concerning the risks and benefits of HDS is critically important.

A major challenge for healthcare providers in counselling patients about HDS is that the available clinical evidence may be ambiguous and sometimes conflicting for HDS adverse events and drug interactions.[10,11] Also, there are often practice-based barriers to identifying the evidence on HDS–drug interactions,[12] including lack of familiarity or access to HDS-related textbooks and databases.[13,14] In general, fewer and less rigorous studies are available for HDS than that of prescription drugs, particularly with respect to randomised controlled clinical trials.[15] Many available references for HDS list numerous 'potential HDS–drug interactions' with little clinical significance or risk. Many reference books are replete with errors that serve only to confuse healthcare practitioners or consumers. The aim of this review was to provide healthcare professionals with a resource that concisely summarises the scientific evidence for HDS–drug interactions and contraindications from 2000 to 2010.