Introduction
Levosimendan is a calcium sensitizer and inodilator used to manage acute decompensated heart failure. It improves myocardial contractility without increasing intracellular calcium, which reduces the risk of arrhythmias. Additionally, it has vasodilatory properties that help to reduce preload and afterload, improving cardiac output.
Pharmacokinetics
Levosimendan is administered intravenously. It has a half-life of 1 hour, but its active metabolite (OR-1896) extends the drug’s effects for up to a week. The drug is metabolized by the liver and primarily excreted via urine and feces.
Mechanism of Action
Levosimendan increases the sensitivity of troponin C to calcium, enhancing myocardial contractility without raising intracellular calcium levels. It also opens ATP-sensitive potassium channels in vascular smooth muscle, causing vasodilation.
Pharmacodynamics
Levosimendan improves cardiac output and reduces systemic vascular resistance, without significantly increasing myocardial oxygen consumption. Its inotropic effects last beyond the infusion due to the active metabolite.
Adverse Effects
Hypotension: Due to vasodilation, Levosimendan can cause significant hypotension.
Arrhythmias: Tachycardia and other arrhythmias may occur, although the risk is lower than with other inotropes.
Headache: Vasodilation can cause headaches.
Hypokalemia: Levosimendan may cause a drop in potassium levels.
Drug Interactions
Beta-blockers: The positive inotropic effects of Levosimendan may be reduced by beta-blockers.
Other vasodilators: Concurrent use with vasodilators may cause excessive hypotension.
Dosages
Adults (Heart Failure): The recommended dose is a loading dose of 6-12 mcg/kg over 10 minutes, followed by a continuous infusion of 0.1 mcg/kg/min. If well tolerated, the infusion rate can be increased to 0.2 mcg/kg/min.