Cardiovascular Safety of Tamsulosin Modified Release in the Fasted and Fed State in Elderly Healthy Subjects

Abstract

Objectives: The effect of food on the cardiovascular safety of tamsulosin modified release (MR) capsules 0.4 mg in elderly subjects was assessed both after single and multiple dosing. Methods: Thirty-six elderly (age ≥ 60 years) male volunteers were recruited and after a single-blind, placebo run-in period of 1 day were randomised to active treatment ( n = 24) or placebo ( n = 12). In each group the effect of food on vital signs and orthostatic stress testing was assessed in a crossover design after a single dose (Days 1 and 8 with a 7 day wash-out) and after 14 days of multiple dosing under fasting and fed conditions. Results: Changes in vital signs and orthostatic stress responses were more pronounced in the fasted than in the fed state. A total of 86 positive orthostatic stress tests were observed of which only three were symptomatic. Forty-six of these 86 tests were considered positive because of an effect on at least two criteria. The incidence of positive tests was higher in the fasted state and was increased by tamsulosin MR compared with placebo. Conclusions: Vital signs and orthostatic stress testing are more influenced by tamsulosin 0.4 mg MR capsules in the fasted than in the fed state. As tamsulosin MR is intended to be taken after breakfast or the first meal of the day, lack of compliance with this instruction may increase the incidence of cardiovascular adverse events in elderly males.