Risk Factors for Pseudoaldosteronism with Yokukansan Use: Analysis Using the Japanese Adverse Drug Report (JADER) Database.

Yokukansan is a Kampo formula that is commonly used by the elderly because it is expected to improve peripheral symptoms of dementia and delirium. However, side effects from its use are frequently reported in the elderly. In particular, pseudoaldosteronism caused by the licorice contained in yokukansan leads to hypertension, hypokalemia, and muscle weakness, which may result in death. This study aimed to identify the risk factors of pseudoaldosteronism with yokukansan use. Using cases reported in the Japanese Adverse Drug Report (JADER) database, the reporting odds ratio (ROR) was calculated and compared to assess the risk of pseudoaldosteronism for each licorice-containing Kampo formula. We also analyzed the risk factors for pseudoaldosteronism in patients taking yokukansan. Yokukansan (ROR 2.4, 95% confidence interval (CI) 1.9-2.8; p < 0.001) had a higher risk of pseudoaldosteronism than that of other licorice-containing Kampo formulas. Furthermore, the results of a logistic regression analysis in patients taking yokukansan showed that the licorice dose (OR 1.5, 95% CI 1.2-2.0; p < 0.01), older age (<70 years, OR 5.9, 95% CI 1.8-20; p < 0.01), dementia (OR 2.8, 95% CI 1.6-4.9; p < 0.001), low body weight (<50 kg, OR 2.2, 95% CI 1.1-3.5; p = 0.034) were risk factors for pseudoaldosteronism, Although not significant, treatment with loop diuretics (OR 1.8, 95% CI 0.98-3.5; p = 0.059) tended to increase the risk of pseudoaldosteronism. In summary, patients must understand the risk factors when considering taking yokukansan and reduce the licorice dose they consume.

Risk factors for pseudoaldosteronism with rhabdomyolysis caused by consumption of drugs containing licorice and differences between incidence of these conditions in Japan and other countries: case report and literature review.

BACKGROUND: The pathogenesis of licorice-induced pseudoaldosteronism is thought to involve the inhibition of 11ß-hydroxysteroid dehydrogenase type 2 by glycyrrhetinic acid. Some risk factors have been reported, but differences between Japan and other countries have not been reported. CASE PRESENTATION: A 79-year-old woman was hospitalized because of pseudoaldosteronism with rhabdomyolysis caused by ingestion of herbal medicines containing licorice. She had been prescribed shakuyakukanzobushito (decocted, 3 g of licorice) and keishikajutsubuto (decocted, 2 g of licorice) for the treatment of lower back pain and had been taking antihypertensive agents for the treatment of essential hypertension. After taking the herbal medicines for 2 weeks, the patient developed weakness of the extremities and pain in both thighs. On admission, she had hypertension, oliguria, an elevated serum creatine kinase level, hypokalemia, alkalemia associated with metabolic alkalosis, low plasma renin activity, and low plasma aldosterone levels. Intravenous and oral potassium supplementation and the administration of spironolactone resulted in the normalization of her condition within approximately 2 weeks. DISCUSSION: An analysis of case reports of pseudoaldosteronism with rhabdomyolysis revealed that in Japan, most cases occurred in elderly women with essential hypertension and were caused by drugs such as herbal medicines. In contrast, in other countries, many cases involved younger men, and the dominant causes were foods containing licorice. The use of herbal medicines is increasing all over the world, and when a patient with risk factors is prescribed an herbal medicine containing licorice, careful follow-up is required.