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This best practice guideline has been designed for critical care units, however, it can be applied to other areas within your health service who use vasoactive infusions, such as anaesthetics, cardiology and emergency departments.

Mechanism of action/pharmacology

Levosimendan is an inodilator, which increases myocardial contractility by enhancing cardiac sensitivity to calcium. Despite the improvement in ventricular function, levosimendan does not increase myocardial oxygen uptake significantly.1 Intracellular calcium is unaffected, thus limiting arrhythmic potential. The positive inotropic effect is independent of β receptors and cAMP (cyclic adenosine monophosphate).

Levosimendan also opens ATP-sensitive vascular potassium channels, causing vasodilation in veins, arteries and coronary arteries. This results in afterload reduction.1

Onset of action: Rapidly distributed. Peak plasma concentration of active metabolite (OR-1986) in 48–78 hours.1

Duration of action: Haemodynamic effects sustained for approximately one week after cessation of parent drug.2

Half life: 1 hour (parent drug); 80 hours (active metabolite OR-1986).2

Indications

Severe decompensated heart failure unresponsive to other therapies.

Cardiogenic shock post cardiac surgery in patients with left ventricular ejection fraction less than 40%.

Evidence of mortality benefit for these indications is lacking.3,4

Precautions

  • Hypersensitivity to levosimendan or any of the excipients5
  • Hypotension due to uncorrected hypovolaemia5
  • Significant mechanical obstruction affecting ventricular filling, outflow or both5
  • Hypertrophic obstructive cardiomyopathy5
  • Atrial fibrillation with rapid ventricular response, ventricular tachycardia, history of Torsades de Pointes, long QTc or concomitantly on medications that prolong the QTc interval5
  • Ongoing coronary ischaemia5
  • Heart failure due to diastolic dysfunction – unlikely to benefit
  • Severe hepatic impairment may result in more pronounced and prolonged effects6
  • Severe renal impairment may result in more pronounced and prolonged effects.7

Medication presentation

12.5 mg/5mL vial

Stock not registered in Australia – will require completion of a Special Access Scheme Category A form.

Medication storage

Refrigerate (2–8°C). Do not freeze.  During storage, concentrate in vial is clear/yellow to orange. May turn more orange during storage, which does not indicate a loss of potency (may still be used until labelled expiry date).5,8

Infusion solution is stable for 24 hours at 25°C.8

Preparation

Dilute 12.5 mg (5 mL) in 250 mL glucose 5%.

 

Infusion pump

Prescribe

12.5 mg in 250 mL

Make up infusion in

250 mL bag of glucose 5%*

Volume to be removed from IV bag

5 mL

Drug dose to be added

12.5 mg (5 mL)

Final volume

250 mL

Final concentration

50 microg/mL

1mL/hr =

0.83 microg/min

Administration - this guideline is intended for central access only

Administer continuous intravenous infusion through a central access line.

Infusions should be administered via an infusion pump, preferably with medication error reduction software enabled.

Avoid administration in lines where other drugs or fluids may be bolused or flushed.

Dosing

In common practice the loading dose is omitted as it is associated with hypotension.9

Usual dose range: 0.05 to 0.2 microg/kg/min. Dose based on actual body weight up to a maximum of
120 kg.5

Commence infusion at 0.05 microg/kg/min. If the initial rate is tolerated, consider increasing the maintenance rate to 0.1 microg/kg/min after 60 minutes. If the patient remains haemodynamically stable, further increase the dose to 0.2 microg/kg/min for the remainder of the infusion.

If the patient is haemodynamically unstable, postpone the dose increase for several hours or consider returning to previously stable dose. When adjusting the dose rate, take into account the long half-life of the active metabolite.

The infusion is usually ceased at 24 hours without weaning the infusion rate. Experience with use of infusions beyond 24 hours, and with repeat doses, is limited.1,4

Infusion rate guide: Continuous infusion rate (mL/hr) (using 50 microg/mL solution).

Patient’s weight (kg)

Infusion rate (mL/hr)
0.05 microg/kg/min

Infusion rate (mL/hr)
0.1 microg/kg/min

Infusion rate (mL/hr)
0.2 microg/kg/min

40

2

5

10

50

3

6

12

60

4

7

14

70

4

8

17

80

5

10

19

90

5

11

22

100

6

12

24

110

7

13

26

120

7

14

29

Monitoring

  • Continuous blood pressure and cardiac monitoring for the duration of the infusion
  • Continue monitoring ECG, blood pressure, heart rate and electrolytes for 7–10 days after infusion completion. Extended periods of monitoring may be needed in patients with renal or hepatic impairment.4

Side effects

  • Hypotension1
  • Headache1
  • Hypokalaemia4
  • Arrhythmias including tachycardia, atrial fibrillation and ventricular tachycardia.4

Compatibilities

Consult the following references, which are available online through the Clinicians Health Channel:

  • Australian injectable drugs handbook
  • Trissel’s™ in IV compatibility (Micromedex) – from the site homepage, select the ‘IV Compatibility’ tab.

Important drug interactions

Isosorbide mononitrate – significant potentiation of orthostatic hypotension.4

References

  1. Antila S, Sundberg S, Lehtonen LA. Clinical pharmacology of levosimendan. Clinical Pharmacokinetics. 2007; 46(7):535–552
  2. Pathak A, Lebrin M, Vaccaro A, et al. Pharmacology of levosimendan: inotropic, vasodilatory and cardioprotective effects. Journal of Clinical Pharmacy and Therapeutics. 2013; 38(5):341–349.
  3. Landoni G, Lomivorotov VV, Alvaro G, et al. Levosimendan for hemodynamic support after cardiac surgery. New England Journal of Medicine. 25 May 2017
  4. Mebazaa A, Nieminen MS, Packer M, et al. Survive Investigators. Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA. 2007; 297(17):1883–1891
  5. Orion Pharma. Simdax Product Information (updated 2012) [online] (accessed 12 October 2017). Available from: www.simdax.com
  6. Puttonen J, Kantele S, Ruck A, et al. Pharmacokinetics of intravenous levosimendan and its metabolites in subjects with hepatic impairment. The Journal of Clinical Pharmacology. 2008; 48(4):445–454
  7. Puttonen J, Kantete S, Kivikko M, et al. Effect of severe renal failure and haemodialysis on the pharmacokinetics of levosimendan and its metabolites. Clinical Pharmacokinetics. 2007; 46(3):235–246
  8. Australian injectable drugs dandbook (AIDH) [online] (accessed 11 October 2017)
  9. Aidonidis G, Kanonidis I, Koutsimanis V, et al. Efficiency and safety of prolonged levosimendan infusion in patients with acute heart failure. Cardiology Research and Practice. 2011 31 Mar:342302.

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Centre of Clinical Excellence - Acute
Safer Care Victoria

Acknowledgements

We would like to thank the pharmacists involved in writing the guidelines: Melissa Ankravs, Melanie Kowalski, Rachel Fyfe, Robyn Ingram, Annalie Jones, Susan Trevillian, and Lucy Sharrock.

Page last updated: 11 Nov 2020

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