A Comprehensive Monograph on Nifedipine: Pharmacology, Clinical Applications, and Safety Profile

Executive Summary

Nifedipine is a first-generation dihydropyridine calcium channel blocker that has been a significant component of the cardiovascular therapeutic landscape for over four decades. Identified by DrugBank ID DB01115 and CAS Number 21829-25-4, this small molecule exerts its primary pharmacological effect by inhibiting the influx of calcium ions through voltage-gated L-type calcium channels in vascular smooth muscle. This action results in potent peripheral and coronary arterial vasodilation, forming the basis of its principal indications for the management of hypertension and angina pectoris. A critical aspect defining Nifedipine's clinical profile is the profound difference between its immediate-release (IR) and extended-release (ER) formulations. The rapid pharmacokinetics of IR Nifedipine can lead to abrupt hypotension and a clinically significant reflex tachycardia, a profile that has restricted its use due to safety concerns. In contrast, advanced ER formulations, particularly the Gastrointestinal Therapeutic System (GITS), provide smooth, 24-hour plasma concentrations, mitigating these adverse hemodynamic effects and establishing a superior safety and tolerability profile. This distinction has rendered ER Nifedipine a reliable agent for chronic cardiovascular conditions. Beyond its approved uses, Nifedipine has a prominent off-label role as a first-line tocolytic agent for managing preterm labor. The drug's disposition is almost entirely dependent on metabolism by the cytochrome P450 3A4 (CYP3A4) enzyme system, making it highly susceptible to a wide range of drug-drug and food-drug interactions, most notably with grapefruit juice. This comprehensive monograph will explore the chemical properties, pharmacodynamics, pharmacokinetics, clinical efficacy, and safety considerations of Nifedipine, underscoring its status as a durable, eff