Simendan

Levosimendan is indicated for the short-term treatment of acute heart failure (AHF) in situations where conventional therapy is not sufficient, and in cases where inotropic support is considered appropriate.

Consistent with current medical practice, levosimendan should be used with caution when used with other intravenous vasoactive medicinal products due to a potentially increased risk of hypotension. No pharmacokinetic interactions have been observed in a population analysis of patients receiving digoxin and levosimendan infusion. levosimendan infusion can be used in patients receiving beta-blocking agents without loss of efficacy. Co-administration of isosorbide mononitrate and levosimendan in healthy volunteers resulted in significant potentiation of the orthostatic hypotensive response.

In placebo-controlled clinical trials for AHF (REVIVE programme), 53% of patients experienced adverse reactions, the most frequent of which were ventricular tachycardia, hypotension, and headache. In a dobutamine-controlled clinical trial for AHF (SURVIVE), 18% of patients experienced adverse reactions, the most frequent of which were ventricular tachycardia, atrial fibrillation, hypotension, ventricular extrasystoles, tachycardia, and headache.

There is no experience of using levosimendan in pregnant women. Animal studies have shown toxic effects on reproduction. Therefore, levosimendan should be used in pregnant women only if the benefits for the mother outweigh the possible risks to the foetus. It is not known whether levosimendan is excreted in human milk. Studies in rats have shown excretion of levosimendan in breast milk, therefore women receiving levosimendan should not breastfeed.

An initial haemodynamic efect of levosimendan may be a decrease in systolic and diastolic blood pressure, therefore, levosimendan should be used with caution in patients with low baseline systolic or diastolic blood pressure or those at risk for a hypotensive episode. More conservative dosing regimens are recommended for these patients. Physicians should tailor the dose and duration of therapy to the condition and response of the patient. Severe hypovolaemia should be corrected prior to levosimendan infusion. If excessive changes in blood pressure or heart rate are observed, the rate of infusion should be reduced or the infusion discontinued. The exact duration of all haemodynamic efects has not been determined, however, the haemodynamic effects, generally last for 7-10 days. This is partly due to the presence of active metabolites, which reach their maximum plasma concentrations about 48 hours after the infusion has been stopped. Non-invasive monitoring for at least 4-5 days after the end of infusion is recommended. Monitoring is recommended to continue until the blood pressure reduction has reached its maximum and the blood pressure starts to increase again, and may need to be longer than 5 days if there are any signs of continuing blood pressure decrease, but can be shorter than 5 days if the patient is clinically stable. In patients with mild to moderate renal or mild to moderate hepatic impairment an extended period of monitoring maybe needed. Levosimendan should be used cautiously in patients with mild to moderate renal impairment. Limited data on the elimination of the active metabolites are available in patients with impaired renal function. Impaired renal function may lead to increased concentrations of the active metabolites, which may result in a more pronounced and prolonged haemodynamic effect. Levosimendan should be used cautiously in patients with mild to moderate hepatic impairment. Impaired hepatic function may lead to prolonged exposure to the active metabolites, which may result in a more pronounced and prolonged haemodynamic effect. Levosimendan infusion may cause a decrease in serum potassium concentration. Thus, low serum potassium concentrations should be corrected prior to the administration of Levosimendan and serum potassium should be monitored during treatment. As with other medicinal products for heart failure, infusions of Levosimendan may be accompanied by decreases in haemoglobin and haematocrit and caution should be exercised in patients with ischaemic cardiovascular disease and concurrent anaemia. Levosimendan infusion should be used cautiously in patients with tachycardia atrial fibrillation with rapid ventricular response or potentially life-threatening arrhythmias. Experience with repeated administration of Levosimendan is limited. Experience with concomitant use of vasoactive agents, including inotropic agents (except digoxin), is limited. Benefit and risk should be assessed for the individual patient. Levosimendan should be used cautiously and under close ECG monitoring in patients with ongoing coronary ischaemia, long QTc interval regardless of etiology, or when given concomitantly with medicinal products that prolong the QTc interval. The use of levosimendan in cardiogenic shock has not been studied. No information is available on the use of Levosimendan in the following disorders: restrictive cardiomyopathy, hypertrophic cardiomyopathy, severe mitral valve insufficiency, myocardial rupture, cardiac tamponade, and right ventricular infarction Levosimendan should not be
administered to children as there is very limited experience of use in children and adolescent under 18 years of age. Limited experience is available on the use of Levosimendan in patients with heart failure after surgery, and insevere heart failure in patients awaiting heart transplantation.

Positive Inotropic drugs

Store in a refrigerator (2˚C-8˚C) Do not freeze. The color of the concentrate may turn to orange during storage, but there is no loss of potency and the product may be used until the indicated expiry date if storage instructions have been followed. For storage conditions of the diluted medicinal product.