Levosimendan

Levosimendan (INN) is a calcium sensitiser used in the management of severe congestive heart failure and is considered an agent of last resort. It is marketed under the trade name Simdax (Abbott).

Mode of action

Levosimendan is a calcium sensitiser – it increases the sensitivity of the heart to calcium, thus increasing cardiac contractility. Levosimendan exerts its positive inotropic effect by increasing calcium sensitivity of myocytes by binding to cardiac troponin C in a calcium-dependent manner. It also has a vasodilatory effect, by opening adenosine triphosphate (ATP)-sensitive potassium channels in vascular smooth muscle to cause smooth muscle relaxation. The combined inotropic and vasodilatory actions result in an increased force of contraction, decreased preload and decreased afterload.

Clinical use

Indications

Levosimendan is indicated for inotropic support in acutely-decompensated severe congestive heart failure. Owing to its cost, it is usually reserved for last-line therapy when other inotropes (eg. dobutamine) have failed.

Contraindications

The use of levosimendan is contraindicated in patients with: moderate-to-severe renal impairment, severe hepatic impairment, severe ventricular filling or outflow obstruction, severe hypotension and tachycardia, and/or history of torsades de pointes (Rossi, 2006).

Adverse effects

Common adverse drug reactions (≥1% of patients) associated with levosimendan therapy include: headache, hypotension, arrhythmias (atrial fibrillation, extrasystoles, atrial tachycardia, ventricular tachycardia), myocardial ischaemia, hypokalaemia and/or nausea (Rossi, 2006).

Formulations

Levosimendan is marketed as a 2.5 mg/mL concentrated solution for IV infusion. The concentrate is diluted with glucose 5% solution before infusion.

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