Posology : מינונים

4.2 Posology and method of administration
Levosimendan MBI is for in-hospital use only. It should be administered in a hospital setting where adequate monitoring facilities and expertise with the use of inotropic agents are available.

Posology
The dose and duration of treatment should be individualised according to the patient's clinical condition and response.

The treatment should be initiated with a loading dose of 6-12 microgram/kg infused over 10 minutes followed by a continuous infusion of 0.1 microgram/kg/min (see section 5.1). The lower loading dose of 6 microgram/kg is recommended for patients on concomitant intravenous vasodilators or inotropes or both at the start of the infusion. Higher loading doses within this range will produce a stronger haemodynamic response but may be associated with a transient increased incidence of adverse reactions. The response of the patient should be assessed with the loading dose or within 30 to 60 minutes of dose adjustment and as clinically indicated. If the response is deemed excessive (hypotension, tachycardia), the rate of the infusion may be decreased to 0.05 microgram/kg/min or discontinued (see section 4.4). If the initial dose is tolerated and an increased haemodynamic effect is required, the rate of the infusion can be increased to 0.2 microgram/kg/min.
The recommended duration of infusion in patients with acute decompensation of severe chronic heart failure is 24 hours. No signs of development of tolerance or rebound phenomena have been observed following discontinuation of levosimendan infusion. Haemodynamic effects persist for at least 24 hours and may be seen up to 9 days after discontinuation of a 24- hour infusion (see section 4.4).

Experience of repeated administration of levosimendan is limited. Experience with concomitant use of vasoactive agents, including inotropic agents (except digoxin) is limited.
In the REVIVE programme, a lower loading dose (6 micrograms/kg) was administered with baseline concomitant vasoactive agents (see sections 4.4, 4.5 and 5.1).

Monitoring of treatment
Consistent with current medical practice, ECG, blood pressure and heart rate must be monitored during treatment and the urine output measured. Monitoring of these parameters for at least 3 days after the end of infusion or until the patient is clinically stable is recommended (see section 4.4). In patients with mild to moderate renal or mild to moderate hepatic impairment monitoring is recommended for at least 5 days.

Elderly
No dose adjustment is required for elderly patients.

Renal impairment
Levosimendan MBI must be used with caution in patients with mild to moderate renal impairment. Levosimendan MBI should not be used in patients with severe renal impairment (creatinine clearance <30 ml/min) (see sections 4.3, 4.4 and 5.2).

Hepatic impairment
Levosimendan MBI must be used with caution in patients with mild to moderate hepatic impairment although no dose adjustment appears necessary for these patients. Levosimendan MBI should not be used in patients with severe hepatic impairment (see section 4.3, 4.4 and 5.2).

Paediatric population
Levosimendan MBI should not be administered to children and adolescents under 18 years of age (see sections 4.4 and 5.2).

Method of administration
Levosimendan MBI is to be diluted prior to administration (see section 6.6).

The infusion is for intravenous use only and can be administered by the peripheral or central route.


The following table provides detailed infusion rates for both the loading and maintenance infusion doses of a 0.05 mg/ml preparation of Levosimendan MBI infusion: Patient's   Loading dose is given as     Continuous infusion rate (ml/h) weight      an infusion over 10
(kg)        minutes with the infusion rate (ml/h) below
Loading        Loading       0.05             0.1              0.2 dose 6         dose 12       microgram/kg/    microgram/kg/    microgram/kg/ microgram/ microgram/        minute           minute           minute kg             kg
40          29             58            2                5                10
50          36             72            3                6                12 60          43             86            4                7                14 70          50             101           4                8                17 80          58             115           5                10               19 90          65             130           5                11               22 100         72             144           6                12               24 110         79             158           7                13               26 120         86             173           7                14               29 

The following table provides detailed infusion rates for both the loading and maintenance infusion doses for a 0.025 mg/ml preparation of Levosimendan MBI infusion: 
Patient's   Loading dose is given as     Continuous infusion rate (ml/h) weight      an infusion over 10 min
(kg)        with the infusion rate
(ml/h) below
Loading        Loading       0.05             0.1              0.2 dose 6         dose 12       microgram/kg/    microgram/kg/    microgram/kg/ microgram/ microgram/        minute           minute           minute kg             kg
40          58             115           5                10               19
50          72             144           6                12               24 60          86             173           7                14               29 70          101            202           8                17               34 80          115            230           10               19               38 90          130            259           11               22               43 100         144            288           12               24               48 110         158            317           13               26               53 120         173            346           14               29               58