Felodipine Sandoz Mechanism of Action

Pharmacotherapeutic group: Calcium channel blockers, selective calcium channel blockers with mainly vascular effects, dihydropyridine derivatives.
Pharmacology: Pharmacodynamics: Felodipine is a vascular selective calcium antagonist, which lowers arterial blood pressure by decreasing systemic vascular resistance. Due to the high degree of selectivity for smooth muscle in the arterioles, felodipine in therapeutic doses has no direct effect on cardiac contractility or conduction. Because there is no effect on venous smooth muscle or adrenergic vasomotor control, felodipine is not associated with orthostatic hypotension.
Felodipine Sandoz is effective in all grades of hypertension. It can be used as monotherapy or in combination, e.g. with beta-receptor blockers or diuretics.
Felodipine Sandoz has antianginal and antiischemic effects due to improved myocardial oxygen supply/demand balance. Coronary vascular resistance is decreased and coronary blood flow as well as myocardial oxygen supply are increased by Felodipine Sandoz due to dilatation of both epicardial arteries and arterioles. Felodipine Sandoz effectively counteracts coronary vasospasm. The reduction in systemic blood pressure caused by Felodipine Sandoz leads to decreased left ventricular afterload.
Felodipine Sandoz improves exercise tolerance and reduces anginal attacks in patients with stable effort induced angina pectoris. Both symptomatic and silent myocardial ischemia are reduced by felodipine in patients with vasospastic angina.
Felodipine Sandoz can be used as monotherapy or in combination with β-receptor blockers in patients with stable angina pectoris.
Felodipine possesses a mild natriuretic/diuretic effect and fluid retention does not occur.
Felodipine Sandoz is generally well tolerated, also in patients with concomitant diseases such as congestive heart failure, asthma, diabetes, gout, hyperlipidemia, and Raynaud's diseases.
Paediatric population: There is limited clinical trial experience of the use of felodipine in hypertensive paediatric patients. In a randomised, double-blind, 3-week, parallel group study in children aged 6-16 years with primary hypertension, the antihypertensive effects of once daily felodipine 2.5 mg (n=33), 5 mg (n=33) and 10 mg (n=31) were compared with placebo (n=35). The study failed to demonstrate the efficacy of felodipine in lowering blood pressure in children aged 6-16 years.
The long-term effects of felodipine on growth, puberty and general development have not been studied. The long-term efficacy of antihypertensive therapy as therapy in childhood to reduce cardiovascular morbidity and mortality in adulthood has also not been established.
Pharmacokinetics: Absorption: Felodipine is administered as extended-release tablets, from which it is completely absorbed in the gastrointestinal tract. The systemic availability of felodipine is approximately 15% and is independent of dose in the therapeutic dose range. The extended-release tablets produce a prolonged absorption phase of felodipine. This results in even felodipine plasma concentrations within the therapeutic range for 24 hours. Maximum blood plasma levels (t_max) are achieved with the prolonged-release form after 3 to 5 hours. The rate but not the extent of absorption of felodipine is increased when taken simultaneously with food with a high fat content.
Distribution: The plasma protein binding of felodipine is approximately 99%. It is bound predominantly to the albumin fraction. Volume of distribution at steady state is 10 l/kg.
Biotransformation: Felodipine is extensively metabolised in the liver by cytochrome P450 3A4 (CYP3A4) and all identified metabolites are inactive. Felodipine is a high clearance medicinal product with an average blood clearance of 1200 ml/min. There is no significant accumulation during long-term treatment.
Elderly patients and patients with reduced liver function have on average higher plasma concentrations of felodipine than younger patients. The pharmacokinetics of felodipine is not changed in patients with renal impairment, including those treated with haemodialysis.
Elimination: The half-life of felodipine in the elimination phase is approximately 25 hours and steady state is reached after 5 days. There is no risk of accumulation during long-term treatment. About 70% of a given dose is excreted as metabolites in the urine; the remaining fraction is excreted in the faeces. Less than 0.5% of a dose is recovered unchanged in urine.
Linearity/non-linearity: Plasma concentrations are directly proportional to dose within the therapeutic dose range 2.5 - 10 mg.