MILRINONE

For intravenous administration only. 6. Extravenous administration must be avoided. For prevention of local irritation the largest vein should be used. e. serum creatinine). g. life-threatening ventricular arrhythmias). The infusion rate should be adjusted according to haemodynamic response.

Length of treatment should be determined on the basis of clinical response. 4). 5 μg/kg/min) according to haemodynamic response and the possible onset of undesirable effects such as hypotension and arrhythmias. 13mg/kg/day total dose.

The following provides a guide to maintenance infusion delivery rate based upon a solution containing milrinone 200μg/ml prepared by adding 400ml diluent per 100ml solution for injection (40ml diluent per 10ml ampoule or respectively 80ml per an ampoule of 20ml).

22 Solutions of different concentrations may be used according to patient fluid requirements. The duration of therapy should depend upon the patient's response.

Elderly:

Experience so far suggests that no special dosage recommendations are necessary in patients with normal renal function. Renal clearance may be reduced in elderly patients, and lower Milrinone doses may be required in such cases.

Renal Impairment:

Dosage adjustment required. Dosage adjustment in patients with renal impairment is based on data obtained from patients with severe renal impairment but without congestive heart failure, who show significant increases to the terminal elimination half-life of milrinone.

13 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. 75 μg/kg/min for a period up to 35 hours. 75 μg/kg/min infusion for 35 hours significantly reduced the risk of development of low cardiac output syndrome.

2) have to be taken into consideration. 4). 3).

Adverse reactions have been ranked under heading of system-organ class and frequency using the following convention: very common (>= 1/10); common (>= 1/100, <1/10); uncommon (>= 1/1,000, <1/100); rare (>= 1/10,000, <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

System Organ Class Very common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1,000 to <1/100) Rare (≥1/10,00 0 to <1/1,000) Very rare (<1/10,000) Not known (cannot be estimated from the available data) Blood and the lymphati c system disorders : Thrombocyto penia* Immune system disorder: Anaphylactic shock Metaboli sm and nutrition disorders : hypokalemia Nervous system disorders : Headaches, usually mild to moderate in severity Tremor Cardiac disorders : Ventricular ectopic activity Ventricular tachycardia (non sustained or sustained) Supra– ventricular arrhythmias Ventricular fibrillation Angina pectoris/chest pain Torsades de pointes System Organ Class Very common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1,000 to <1/100) Rare (≥1/10,00 0 to <1/1,000) Very rare (<1/10,000) Not known (cannot be estimated from the available data) Hypotension Respirato ry, thoracic and mediastin al disorders : Bronchospas m Hepato- biliary disorders : Liver function tests abnormal Skin and subcutan eous tissue disorders : Skin reactions such as rash.

General disorders and administr ation site condition s:

Infusion site reaction *In infants and children, risk of thrombocytopenia increased significantly with duration of infusion. 4). No relationship has been established between the incidence of supraventricular or ventricular arrhythmias, and the plasma level of milrinone.

g. hypokalemia), elevated serum digoxin levels or catheter insertion. Clinical data suggest that milrinone-related arrhythmias are less common in children than in adults. 3) ***The critical consequences of the patent ductus arteriosus are related to a combination of pulmonary overcirculation with consecutive pulmonary oedema and haemorrhage and of reduced organ perfusion with consecutive intraventricular haemorrhage and necrotizing enterocolitis with possible fatal outcome as described in literature.

Milrinone is not recommended immediately following acute myocardial infarction until safety and efficacy have been established in this situation. The use of positive inotropic agents such as Milrinone in the acute phase of post myocardial infarction may lead to an undesirable increase in myocardial oxygen consumption (MVO2).

Heightened caution is needed in patients in the acute phase of myocardial infarction in spite of milrinone not increasing MVO2 in patients with chronic heart failure. e. serum creatinine). g. life-threatening ventricular arrhythmias). In patients with severe obstructive aortic or pulmonary valvular disease, or hypertrophic subaortic stenosis (KMP), milrinone should not be used in place of surgical relief of the obstruction.

As with other drugs with inotropic / vasodilator properties, it may aggravate outflow obstruction in these conditions. Supraventricular and ventricular arrhythmias have been observed in the high- risk population treated with Milrinone.

In some patients an increase in ventricular ectopy including non-sustained ventricular tachycardia has been observed. As the potential for arrhythmia, already prevalent in heart failure, may be increased by many drugs or combination of drugs, patients receiving milrinone should be closely monitored during infusion and the infusion should be stopped if arrhythmias develop.

There is possibility of an increased ventricular response rate in patients with flutter or fibrillation. In these patients, prior digitalisation or treatment with other agents to prolong atrio-ventricular node conduction time should be considered, as Milrinone produces a slight enhancement in A-V node conduction.

Milrinone may induce hypotension as a consequence of its vasodilatory activity, therefore caution should be exercised when Milrinone is administered to patients who are hypotensive prior to treatment. In patients showing excessive decreases in blood pressure after Milrinone administration, the treatment should be discontinued until the hypotensive effect has been resolved and then resumed, if necessary, at a lower rate of infusion.

1 - Severe hypovolemia.