Loss of potassium due to cascara (Rhamnus purshiani cortex) abuse could theoretically increase the effects of digoxin and other similar heart medications, with potentially fatal consequences. However, no cases of such an interaction have yet been reported.

Digitalis (Digitalis purpurea) refers to a group of plants commonly called foxglove that contain chemicals with actions and toxicities similar to digoxin. Digitalis was used as an herbal medicine to treat some heart conditions before the drug digoxin was available. Some doctors continue to use digitalis in the United States, and it is used as an herbal medicine in other countries as well. Due to the additive risk of toxicity, digitalis and digoxin should never be used together.

People taking digoxin require regular monitoring of serum digoxin levels. In one report, addition of a product identified as Siberian ginseng to stable, therapeutic digoxin treatment was associated with dangerously high serum digoxin levels. The patient never experienced symptoms of digoxin toxicity. Laboratory analysis found the product was free of digoxin-like compounds but the contents were not further identified. This report may reflect an interaction of eleuthero with the laboratory test to cause a falsely elevated reading, rather than actually increasing digoxin levels.

Potassium deficiency increases the risk of digoxin toxicity. Excessive use of licorice plant or licorice plant products may cause the body to lose potassium. Artificial licorice flavoring does not cause potassium loss. People taking digoxin should read product labels carefully for licorice plant ingredients.

As pleurisy root and other plants in the Aesclepius genus contain cardiac glycosides, it is best to avoid use of pleurisy root with heart medications such as digoxin.

Sarsaparilla may increase the absorption of digitalis and bismuth, increasing the chance of toxicity.

One preliminary trial has suggested that St. John’s  wort(Hypericum perforatum) may reduce blood levels of digoxin. In this study, healthy volunteers took digoxin for five days, after which they added 900 mg per day of St. John’s wort while continuing the daily digoxin. A normal blood level of digoxin was reached after five days of taking the drug, but this level dropped significantly when St. John’s wort was added. This may have occurred because certain chemicals found in St. John’s wort activate liver enzymes that are involved in the elimination of some drugs. Until more is known, people taking digoxin should avoid St. John’s wort.