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Systematic (IUPAC) name
Clinical data
Trade names Simdax
AHFS/Drugs.com International Drug Names
Legal status
  • ℞ (Prescription only)
Routes of
Pharmacokinetic data
Bioavailability 85% (oral)
Protein binding 97–98%
Metabolism Extensive hepatic
Biological half-life ~1 hour (levosimendan), 75–80 hours (metabolites)
Excretion urine (54%), feces (44%)
CAS Number 141505-33-1 YesY
ATC code C01CX08 (WHO)
PubChem CID: 3033825
DrugBank DB00922 YesY
ChemSpider 2298414 YesY
UNII C6T4514L4E YesY
KEGG D04720 YesY
ChEBI CHEBI:50567 YesY
Chemical data
Formula C14H12N6O
Molecular mass 280.28 g/mol
 NYesY (what is this?)  (verify)

Levosimendan (INN) /ˌlvsˈmɛndən/ is a calcium sensitiser used in the management of acutely decompensated congestive heart failure. It is marketed under the trade name Simdax (Orion Corporation).

Mechanism of action

Levosimendan is a calcium sensitizer — it increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium. 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. Moreover, by opening also the mitochondrial (ATP)-sensitive potassium channels in cardiomyocytes, the drug exerts a cardioprotective effect.[1]

Clinical use


Levosimendan is indicated for inotropic support in acutely-decompensated severe congestive heart failure.

Some of the Phase III studies in the extensive clinical program were the trials LIDO (200 patients), RUSSLAN (500), CASINO (250), REVIVE-I (100), REVIVE-II (600) and SURVIVE (1350). In total, the clinical data base includes more than 3500 patients in Phase IIb and III double-blind studies.[2]

In the SURVIVE study, despite a reduction in plasma B-type natriuretic peptide level in patients in the levosimendan group compared with patients in the dobutamine group, levosimendan did not significantly reduce all-cause mortality at 180 days.[3] However, the drug was proven to be superior to dobutamine for treating patients with a history of CHF or those on beta-blocker therapy when they are hospitalized with acute decompensations.[3]

In a meta-analysis of randomized controlled studies by Landoni et al. levosimendan is shown to reduce mortality and hospitalization.[4]

Licensing status

The Orion Corporation originally developed levosimendan and applied for a new drug application in 1998 in the U.S. However the Food and Drug Administration (FDA) requested further trials be conducted and Orion withdrew the application in November 1999. Initially, Orion obtained the approval to market the drug in Sweden in 2000.[5] Since then 60 countries worldwide have approved the drug but it remains non licensed in the USA, where it is currently under development for reduction in morbidity and mortality of cardiac surgery patients at risk of low cardiac output syndrome.[6]


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).[7]

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).


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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  5. Orion. "Simdax (levosimendan) Fact Sheet" (PDF). Orion. Retrieved 16 February 2013.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  6. OxygenBiotherapeutics. "Product Pipeline - Levosimendan development". OxygenBiotherapeutics. Retrieved 13 February 2013.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  7. Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006.