A Comprehensive Monograph on Levosimendan: Pharmacology, Clinical Evidence, and Therapeutic Placement

Section 1: Drug Profile and Introduction

1.1. Overview and Classification

Levosimendan is a small molecule drug that represents a distinct class of cardiotonic agents known as calcium sensitizers.[1] Due to its combined positive inotropic (contractility-enhancing) and vasodilatory properties, it is also functionally classified as an "inodilator".[3] It was developed to address the significant limitations of traditional inotropic agents, such as catecholamines (e.g., dobutamine) and phosphodiesterase-III (PDE-III) inhibitors (e.g., milrinone). These conventional agents exert their effects primarily by increasing intracellular calcium concentrations, a mechanism that, while increasing cardiac output, also elevates myocardial oxygen demand and carries a significant risk of tachyarrhythmias and increased mortality.[2] Levosimendan's novel mechanism of action is designed to enhance cardiac performance more efficiently, aiming to circumvent these critical liabilities.[7]

The primary approved indication for Levosimendan, marketed most commonly under the trade name Simdax, is the short-term treatment of acutely decompensated severe chronic heart failure (ADHF) in hospitalized patients for whom conventional therapy is insufficient and inotropic support is deemed necessary.[1] It is currently approved for this use in approximately 60 countries worldwide but remains investigational in the United States and Canada.[1]

1.2. Chemical Identity and Physicochemical Properties