Analysis of Effects of the Diuretics on Levels of Blood Potassium and Blood Sodium with Angiotensin Receptor Blockers and Thiazide Diuretics Combination Therapy: Data Mining of the Japanese Adverse Drug Event Report Database, JADER

Abstract

It is difficult to lower blood pressure to target levels recommended in the guidelines using antihypertensive monotherapy. Therefore combination therapy of several antihypertensive drugs is used at present for increased efficacy. Combination therapy may offset the adverse effects of drugs in some instances. However, the exact outcome of combination therapy is not clear. In this study, using the Japanese Adverse Drug Event Report database (JADER), we calculated the proportional reporting ratio (PRR), one of the safety signals of hypokalemia, hyperkalemia, hyponatremia and hypernatremia, to determine the effects of thiazide diuretic (TD) on blood potassium and blood sodium levels when used in combination therapy with an angiotensin receptor blocker (ARB).
The results suggested that the onset of hypokalemia by TD was not often offset by an increase in blood potassium levels induced by ARB. Although combination therapy with TD and ARB may decrease the risk of hypokalemia compared to use of ARB alone, it results in hyperkalemia. In addition, an increased risk of hyponatremia was suggested. While using a fixed-dose combination therapy, it is necessary to note that both drugs could increase the risk of the adverse events mentioned in this study.