Posology : מינונים

4.2   Posology and method of administration

For intravenous administration

Adults:
Primacor Injection should be given as a loading dose of 50µg/kg administered over a period of 10 minutes usually followed by a continuous infusion at a dosage titrated between 0.375 µg/kg/min and 0.75 µg /kg/min according to haemodynamic and clinical response, but should not exceed 1.13mg/kg/day total dose.

The following provides a guide to maintenance infusion delivery rate based upon a solution containing milrinone 200 µg /ml prepared by adding 40ml diluent per 10ml ampoule (400ml diluent per 100ml Primacor Injection). 0.45% saline, 0.9% saline or 5% dextrose may be used as diluents.

Primacor Injection Dose                                 Infusion
(µg /kg/min)                                Delivery Rate (ml/kg/h)
0.375                                             0.11
0.400                                             0.12
0.500                                             0.15
0.600                                             0.18
0.700                                             0.21
0.750                                             0.22

Solutions of different concentrations may be used according to patient fluid requirements.
The duration of therapy should depend upon the patient’s response. In congestive cardiac failure, patients have been maintained on the infusion for up to 5 days, although the usual period is 48 to 72 hours. In acute states following cardiac surgery, it is unlikely that treatment need be maintained for more than 12 hours.

Renal Impairment:
Dosage adjustment required (see section 4.4).
Data obtained from patients with severe renal impairment but without heart failure have demonstrated that the presence of renal impairment significantly increases the terminal elimination half-life of milrinone. For patients with clinical evidence of renal impairment, the loading dose is not affected, but the following maintenance infusion rates are recommended using the infusion solution described above.

Creatinine Clearance           Primacor Injection Dose           Maintenance Infusion Delivery (ml/min/1.73m2)                   (µg /kg/min)                        Rate (ml/kg/h) 5                             0.20                                 0.06 10                             0.23                                 0.07 20                             0.28                                 0.08 30                             0.33                                 0.10 40                             0.38                                 0.11 50                             0.43                                 0.13 
The infusion rate should be adjusted according to haemodynamic response.

Elderly: Experience so far suggests that no special dosage recommendations are necessary.

Pediatric population:
In published studies selected doses for infants and children were:
• Intravenous loading dose: 50 to 75 μg/kg administered over 30 to 60 minutes.
• Intravenous continuous infusion: To be initiated on the basis of hemodynamic response and the possible onset of undesirable effects between 0.25 to 0.75 μg/kg/min for a period up to 35 hours.

In clinical studies on low cardiac output syndrome in infants and children under 6 years of age after corrective surgery for congenital heart disease 75 μg/kg loading dose over 60 minutes followed by a 0.75 μg/kg/min infusion for 35 hours significantly reduced the risk of development of low cardiac output syndrome.

Results of pharmacokinetic studies (see section 5.2) have to be taken into consideration.

Renal impairment in pediatric population:
Due to lack of data the use of milrinone is not recommended in pediatric population with renal impairment (for further information please see section 4.4).

Patent ductus arteriosus:
If the use of milrinone is desirable in preterm or term infants at risk of/with patent ductus arteriosus, the therapeutic need must be weighed against potential risks (see section 4.4, 4.8, 5.2, and 5.3).