MILNIRONE Solution for injection / infusion Ref.[8124] Active ingredients: Milrinone

For intravenous administration.

Adults

Milrinone 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 0.375μg/kg/min and 0.75μg/kg/min according to haemodynamic and clinical response, but should not exceed 1.13mg/kg/day total dose. For instructions on dilution of the product before administration and a guide to maintenance infusion delivery rates, see section 6.6.

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. 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 infusion rate should be adjusted according to haemodynamic response. Recommended maintenance infusion rates are provided in section 6.6.

Elderly

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

Paediatric 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

Due to lack of data the use of milrinone is not recommended in paediatric 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).

Overdose of intravenous milrinone may produce hypotension (because of its vasodilatory effect) and cardiac arrhythmia. If this occurs, Milrinone Injection administration should be reduced or temporarily discontinued until the patient’s condition stabilises. No specific antidote is known, but general measures for circulatory support should be taken.

3 years for the unopened product.

After dilution:

Chemical and physical in-use stability has been demonstrated for 48 hours at 5°C when diluted with 0.45% sodium chloride infusion, 0.9% sodium chloride infusion or 5% glucose infusion.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Store below 25°C. Do not freeze. Store in the original package.

For storage conditions of the medical product after dilution, please see section 6.3.

Milrinone 1mg/ml Solution for Injection is presented in 10ml clear, neutral glass (PhEur, Type I) ampoules. The ampoules are packed in a PVC tray and cardboard box in packs of 10.

Instructions for dilution

Infusion solutions should be freshly prepared before use. Parenteral drug products should be examined visually and should not be used if particulate matter or discolouration are present.

The following diluents may be used to prepare solutions for infusion:

• 0.45% sodium chloride infusion
• 0.9% sodium chloride infusion
• 5% glucose infusion

A solution containing 200 μg/ml milrinone should be prepared by taking the contents of a 10 ml ampoule and adding 40 ml of one of the above diluents (400 ml diluent per 100 ml Milrinone Injection).

For single use. Discard any unused solution.

Delivery rates

Adults

The following provides a guide to maintenance infusion delivery rate based upon a solution containing milrinone 200μg/ml, prepared as described above.

Renal impairment

The following maintenance infusion rates are recommended using the infusion solution described above.

The infusion rate should be adjusted according to haemodynamic response. See section 4.2.