Effects of Long Term Administration of Shakuyaku-kanzo-To and Shosaiko-To on Serum Potassium Levels

Typical adverse effects of Shakuyaku-kanzo-To (SKT), an herbal medicine containing licorice, is a licorice-induced pseudoaldosteronism with hypokalemia and hypertension. The risk factors for this side effect are still unclear. To identify the risk factors, we surveyed 37 cases of licorice-induced pseudoaldosteronism in the literature and serum potassium levels in our patients receiving SKT and Shosaiko-To (SST), which contain 6 g and 1.5 g of licorice in the daily dose, respectively. In the case report survey, pseudoaldosteronism developed a median 35 (range 2-231) days after the administration of SKT, which is shorter than after SST (450, range 150-2190 days) and other licorice products including glycyrrhizin (210, range 14-730 days). A significant correlation was observed between the glycyrrhizin contents in the licorice preparations and the dosing periods for developing pseudoaldosteronism (r=-0.700, p<0.01). A negative correlation was also observed between serum potassium level and dosing period for SKT, but not for SST. The difference in age (65.3+/-11.6 vs. 57.2+/-17.3 y) and dosing period (57.3+/-66.3 vs. 19.0+/-24.3 days) between the patients with and without hypokalemia after the administration of SKT was statistically significant (p<0.05). The occurrence rate of hypokalemia including pseudoaldosteronism was around 80% with SKT administration for more than 30 days for patients exceeding 60 years old. It was suggested that patient age (>60 y) and dosing period of SKT (>30 days) might be risk factors for developing pseudoaldosteronism or hypokalemia as well as coadministration of drugs inducing hypokalemia.