- Levosimendan
drugbox
width=250
IUPAC_name = (-)-("R")-(4-(4-methyl-6-oxo-
1,4,5,6-tetrahydropyridazin-3-yl)phenyl)
carbonohydrazonoyl dicyanide
CAS_number = 141505-33-1
ATC_prefix=C01
ATC_suffix=CX08
PubChem=3033825
DrugBank=APRD01296
C=14 | H=12 | N=6 | O=1
molecular_weight = 280.28
bioavailability = 85% (oral)
metabolism =hepatic
elimination_half-life = 1 hour
excretion =renal
pregnancy_category = no data
legal_status = Prescription only. Not marketed in the U.S.
routes_of_administration = IVLevosimendan (INN) (pronEng|ˌliːvoʊsaɪˈmɛndən) is a
calcium sensitiser used in the management of acutely decompensatedcongestive heart failure . It is marketed under thetrade name Simdax (Abbott).Mode of action
Levosimendan is a calcium sensitiser – 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
myocyte s by binding to cardiac troponin C in a calcium-dependent manner. It also has a vasodilatory effect, by openingadenosine triphosphate (ATP)-sensitivepotassium channels in vascularsmooth muscle to cause smooth muscle relaxation. The combined inotropic and vasodilatory actions result in an increased force of contraction, decreased preload and decreasedafterload . Moreover, by opening also the mitochondrial (ATP)-sensitive potassium channels in cardiomyocytes, the drug exerts a cardioprotective effect.Clinical use
Indications
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 finally SURVIVE (1350),cite journal |last=Mebazaa |first=A |coauthors=Nieminen MS, Packer M, Cohen-Solal, Kleber FX, Pocock SJ, Thakkar R, Padley RJ, Poder P, Kivikko M for the SURVIVE investigators |year=2007 |title=Levosimendan vs dobutamine for patients with acute decompensated heart failure |journal=JAMA |volume=297 |issue=17 |pages=1883–91 |id= |url=http://jama.ama-assn.org/cgi/content/abstract/297/17/1883 |doi=10.1001/jama.297.17.1883 |pmid=17473298] a head-to-head trial between
levosimendan anddobutamine in acute decompensated heart failure. In total, the clinical data base includes more than 3500 patients in Phase IIb and III double-blind studies, which is the highest number ever in testing a drug for acute decompensated heart failure.fact|date=July 2008Despite an initial reduction in plasma B-type natriuretic peptide level in patients in the levosimendan group compared with patients in the dobutamine group in a head to head comparison study, levosimendan did not significantly reduce all-cause mortality at 180 days or affect any secondary clinical outcomes.
The drug has a marketing authorization in 48 countries.fact | date=July 2008
Contraindications
The use of levosimendan is contraindicated in patients with: moderate-to-severe renal impairment, severe
hepatic impairment, severeventricular filling or outflow obstruction, severehypotension andtachycardia , and/or history oftorsades de pointes . [Rossi S, editor.Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006.]Adverse effects
Common
adverse drug reaction s (≥1% of patients) associated with levosimendan therapy include: headache, hypotension,arrhythmia s (atrial fibrillation , extrasystoles, atrialtachycardia ,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.References
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