Felodipine ER formulation in the treatment of mild hypertension: efficacy and tolerability vs placebo.

Abstract

1 Felodipine is a new calcium-antagonist dihydropyridine derivative with a high degree of selectivity for smooth muscle of arteriolar resistance vessels, as opposed to cardiac cells. 2 In this double-blind, cross-over study the antihypertensive efficacy and tolerability of the new extended release (ER) formulation of felodipine 10 mg, once daily, in patients with mild essential hypertension was evaluated. After a 4-week single-blind placebo period 28 patients (15 males; mean age 48 ± 12 years) were randomized to receive felodipine 10 mg ER once daily or placebo for 4 weeks and the alternative treatment for a further 4 weeks. Supine blood pressure and heart rate were measured in the out-patients department every 2 weeks, 22-24 h after the last drug administration. 3 Felodipine 10 mg ER induced a significant reduction in blood pressure in comparison with placebo (from 149 ± 16/97 ± 6 to 140 ± 12/89 ± 6 mm Hg). Heart rate remained unchanged. Seven patients dropped-out; five during felodipine ER administration and two during placebo.4 A once daily dose of felodipine ER significantly reduces blood pressure in mild hypertensive patients 22-24 h after administration. It is well tolerated and the adverse events are related to its pharmacodynamic effects.

The antihypertensive efficacy and tolerability of a low dose combination of ramipril and felodipine ER in mild to moderate essential hypertension

“…Felodipine is an effective antihypertensive treatment which has been evaluated as monotherapy [15], as a second line agent [16,17] and as a third line agent in refractory hypertension [18]. Ramipril is comparable with enalapril [19] in terms of antihypertensive efficacy.…”

“…The withdrawal rate can be up to 42% when higher doses of felodipine are used as monotherapy [28]. Bossini and colleagues [15] reported the incidence of adverse events in 28 mild hypertensives who attempted to take 10 mg felodipine ER for 4 weeks: five patients had to be withdrawn. The incidence of adverse events with ramipril monotherapy has been estimated as 6.7% for a range of doses [29].…”

Development of Physiologically Based Biopharmaceutical Model (PBBM) for Felodipine Prolonged-Release Tablet as useful tool for prediction of formulation.

“…Felodipine is used in the treatment of hypertension and available 5 mg immediate release tablets (administered twice daily) and 10 mg prolonged release tablets (administered once daily). Felodipine prolonged release 10 mg tablets are designed to improve the patient acceptability and the similar safety and therapeutic efficacy 16 , when compared immediate release tablets. Generic felodipine prolonged release tablet consists of a fast hydrating polymer, which facilitates rapid formation of gel.…”