Serious adverse events during clinical trial for pharmacokinetic interaction between telmisartan and chlorthalidone in healthy Korean subjects: A case report

ABSTRACT

Telmisartan is an angiotensin II receptor antagonist and chlorthalidone is a thiazide-like diuretics. In this study, we report serious adverse events (SAEs) during clinical trial for pharmacokinetic interaction between telmisartan and chlorthalidone in healthy Korean subjects. Two separate, randomized, multiple-dose, two-period, one-sequence studies were conducted at Kyungpook National University Hospital. In part A, 43 volunteers received telmisartan for 7 days, and then chlorthalidone for 14 days (days 8-21). Telmisartan was co-administered during day 15-21 to evaluate the effects of chlorthalidone on the pharmacokinetics of telmisartan at steady state. A healthy 36-year-old male in part A was referred to the emergency room due to severe nausea and vomiting developed about 3 h after administration of chlorthalidone on day 9. Hypokalemia and QT prolongation were observed during his initial laboratory examination and electrocardiogram (ECG) monitoring in the emergency unit. Nausea and vomiting improved after conservative management with hospitalization for 9 days. We consider that the episodes of excessive nausea and vomiting resulted in hypokalemic state which was potentiated by chlorthalidone. And the hypokalemic state caused the lengthening of the QT interval on ECG.