Levosimendan
5205440
215593311
2008-05-28T21:42:20Z
DOI bot
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{{drugbox |
|width=250
|IUPAC_name = (-)-(''R'')-(4-(4-methyl-6-oxo-<br />1,4,5,6-tetrahydropyridazin-3-yl)phenyl)<br />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 = [[intravenous|IV]]
}}
'''Levosimendan''' ([[International Nonproprietary Name|INN]]) ({{pronEng|ˌliːvoʊsaɪˈmɛndən}}) is a [[calcium]] sensitiser used in the management of acutely decompensated [[congestive heart failure]]. It is marketed under the [[trade name]] '''Simdax''' ([[Abbott Laboratories|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 [[inotrope|inotropic]] effect by increasing calcium sensitivity of [[myocyte]]s by binding to cardiac [[troponin|troponin C]] in a calcium-dependent manner. It also has a [[vasodilation|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 (cardiology)|preload]] and decreased [[afterload]]. 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-[[decompensation|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)<ref>{{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}}</ref>
, a head-to-head trial between [[levosimendan]] and [[dobutamine]] 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.
The drug has a marketing authorization in 48 countries (Aug 9, 2007).
===Contraindications===
The use of levosimendan is contraindicated in patients with: moderate-to-severe [[chronic renal failure|renal impairment]], severe [[hepatic]] impairment, severe [[ventricular]] filling or outflow obstruction, severe [[hypotension]] and [[tachycardia]], and/or history of [[torsades de pointes]].<ref>Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006.</ref>
===Adverse effects===
Common [[adverse drug reaction]]s (≥1% of patients) associated with levosimendan therapy include: headache, hypotension, [[arrhythmia]]s ([[atrial fibrillation]], [[systole|extrasystoles]], [[atrium (anatomy)|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.
==References==
{{reflist}}
{{Cardiac stimulants excluding cardiac glycosides}}
[[Category:Inotropic agents]]
[[uk:Левосимендан]]