Levosimendan

ADMINISTRATION ROUTES:

IV

ALTERNATIVE NAMES:

Simdax

ICU INDICATIONS:

1. Patients undergoing cardiac surgery who have impaired systolic function & evidence of acute decompensated heart failure despite maximal medical therapy

Note:Administration in ICU is only possible after discussion with an ICU Specialist

PRESENTATION AND ADMINISTRATION:

IV:

5 mL vial containing 12.5 mg (2.5 mg/mL)

Store refrigerated. Administer by infusion only. Compatible with the following IV fluids: 5% dextrose

Levosimendan can be safely co-administered with frusemide (10 mg/mL), digoxin (0.25 mg/mL) or glyceryl trinitrate (0.1 mg/mL)

Levosimendan is prepared by diluting one 5 mL vial of 2.5 mg/mL solution in 500 mL of 5% dextrose to make a 0.025 mg/mL solution

DOSAGE:

Do NOT administer a loading dose as this increases the risk of adverse events. The following infusion rates apply only to the 0.025 mg/mL preparation of levosimendan prepared as directed above.

1. Begin the infusion at a rate of 0.05 mcg/kg/min (see DOSAGE TABLE below)
2. If this is tolerated for one hour, increase the infusion rate to 0.1 mcg/kg/min
3. If this is tolerated for the subsequent hour, increase the infusion rate to 0.2 mcg/ kg/min. This is the maximum dose. The infusion should be ceased after 24 hours

DOSAGE TABLE

The table below lists the infusion rates in mLs/hr for each step by patient's weight:

The blood pressure should be checked both 15 minutes & 1 hour after either commencing the infusion or adjusting the infusion rate, if not already continuously monitored.

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

No dose adjustment is required for mild to moderate renal failure but the resultant increase in active metabolite concentration may cause a more pronounced and prolonged haemodynamic effect. Levosimendan is contraindicated in severe renal impairment (defined below). It is not removed by haemodialysis.

DOSAGE IN PAEDIATRICS:

Levosimendan should not be administered to children or adolescents under 18 years old

CLINICAL PHARMACOLOGY:

Levosimendan is a calcium sensitiser which increases cardiac contractility by enhancing the sensitivity of the heart to calcium. Haemodynamic effects persists for at least 24 hours and may be seen up to 9 days after discontinuation of a 24-hour infusion due to the presence of active metabolites that reach maximum plasma concentrations about 48 hours after the infusion has stopped

CONTRAINDICATIONS:

1. Hypersensitivity to levosimendan
2. Severe hepatic impairment
3. Severe renal impairment (creatinine clearance <30 mL/min)
4. Severe hypovolaemia (this potentiates the hypotensive effects)

WARNINGS:

Cardiovascular adverse effects

Hypotension, QT prolongation and arrhythmias (ectopy, atrial fibrillation and ventricular tachycardia) may be frequently seen. If hypotension or arrhythmias occur, the infusion should be stopped pending medical review; the infusion may be subsequently restarted at a lower dose.

Patients receiving a levosimendan infusion should undergo continuous ECG monitoring with blood pressure monitored as described in DOSAGE above.

Electrolytes

Levosimendan may cause a decrease in serum potassium concentration. Hypokalaemia should be corrected prior to administration.

PRECAUTIONS:

General:

Co-administration with other drugs that prolong the QT interval should be undertaken with caution. Continuous ECG monitoring is required for these patients as well as for those already showing arrhythmias prior to Levosimendan administration.

Laboratory Tests:

No tests are required in addition to routine ICU blood tests; vigilance for & correction of hypokalaemia is recommended.

Drug/Laboratory Test Interactions:

None known

Pregnancy:

Levosimendan has been given to only a limited number of pregnant women and women of childbearing age without an increase in the frequency of malformation on the human fetus having been observed. Animal studies have shown evidence of an increased occurrence of fetal damage of uncertain significance in humans.

Nursing Mothers:

Levosimendan is excreted into maternal milk in animal studies. No human data is available.

Paediatric Use:

Levosimendan should not be administered to children or adolescents under 18 years of age.

IMPORTANT DRUG INTERACTIONS IN ICU:

See PRECAUTIONS

ADVERSE REACTIONS:

Nervous System:

Headaches, dizziness, insomnia

Cardiovascular System:

Arrhythmias (VT, AF, ventricular extrasystoles, tachycardia), hypotension

Digestive System:

Diarrhoea, vomiting, constipation, nausea