Previous research on the frequency of use of alternative medications has focused on the general public or on cardiac patients in general. In this study, we examined the use of nonprescription medications within a specific subpopulation, patients who were taking digoxin. Because both dietary supplements (herbal and nonherbal) and OTC medications are commonly used, they were considered collectively as nonprescription medications in this study. To further distinguish the use of herbal supplements, nonherbal supplements (e.g., vitamins and minerals) were grouped with OTC medications in subsequent analysis. Since digoxin has a narrow therapeutic window and is subject to various drug-drug and herb-drug interactions that might increase the risk of toxic effects, the use of nonprescription medications in this patient population is of particular concern. In fact, several recent articles have reviewed interactions involving herbal products and cardiovascular drugs, highlighting the importance of this issue.
Specifically, numerous herbal supplements have been proposed to interact with digoxin through various mechanisms. Herbs that contain cardiac glycosides, such as Adonis, foxglove (yellow and purple) (Digitalis grandifora and Digitalis purpurea), hawthorn, milkweed (Asclepias), lily of the valley (Convallaria majalis), and Kyushin, may have an additive effect when used in conjunction with digoxin.17-19,29,42 Herbal medications such as Siberian ginseng, Asian ginseng (Panax), and Dan Shen (Salvia miltiorrhiza) have been shown to cross- react with digoxin monitoring assays, producing falsely elevated digoxin levels.15,19,23,43 Pharmacokinetic interactions have been suggested for St John’s wort (via induction of P-glycoprotein) and guar gum (Cyamopsis tetrago- nolobus) (which reduces the absorption of digoxin). Long-term use of stimulant laxatives such as Cassia angustifolia, cascara sagrada (Rhamnuspurshiana), Aloe vera, licorice, and buckthorn (Rhamnus) may lead to hypokalemia, which could sensitize the heart tissue to digoxin and increase the risk of digoxin toxicity. Several controlled pharmacokinetic studies in healthy subjects found that hawthorn, goldenseal (Hydrastis canadensis), kava kava (Piper methysticum), milk thistle (Silybum marianum), and black cohosh (Cimicifuga racemosa) had no significant effects on the pharmacoki- netics of digoxin. However, most of these conclusions were based on case reports and studies with small sample sizes, which provided limited clinical evidence showing that concurrent use of digoxin and herbal supplements compromises treatment outcomes. The current study aimed to investigate the prevalence of nonprescription medication use by patients taking digoxin, with a focus on herbal supplements, and to determine whether use of herbal supplements was linked to digoxin-associated adverse events.
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Overall, the prevalence of herbal supplement use in this study population (21.5%) was comparable to that for other surveys of patients with cardiovascular disease. For example, Pharand and others reported that 17% of Canadian patients with cardiac disease used herbal products; Wood and others reported that 32% of patients with cardiovascular disease used herbal supplements, and Yeh and others reported that 18% did so. Saydah and Eberhardt recently explored the 2002 National Health Interview Survey (US) and reported that 19.5% of patients with cardiovascular disease had used “biologically based” alternative medicines (i.e., herbs, special diets, vitamins) in the past 12 months. However, given the perceived risk of toxic effects and drug interactions associated with digoxin, it is noteworthy that the prevalence of herbal supplement use in their sample of patients taking digoxin was similar to that previously reported for cardiac patients in general. Although the use of herbal supplements was common among participants in the study reported here, only 4 patients (2.3% of the total sample) reported using herbal supplements that are purported to interact with digoxin, a rate much lower than reported previously (6% and 22%). Initially, we speculated that the low frequency of use of potentially interacting herbal supplements might be due to patients being “herb-savvy” (i.e., well educated about potential interactions with digoxin). Interestingly, of the patients who did not use herbal supplements, 7.4% attributed the nonusage to physician and pharmacist counselling, and only 8.1% were aware of herb-digoxin interactions. These findings suggest that patient education and counselling about the use of herbal supplements are still wanting and improvement is warranted.
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