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10 x 10 ml x 1 mg/ml
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.
Use in elderly patients: Experience so far suggests that no special dosage recommendations are necessary.
Renal impairment in paediatric population: Due to lack of data the use of milrinone is not recommended in paediatric population with renal impairment.
– Refractory heart failure immediately (up to 72 hours) following cardiac surgery. – For the short-term (up to 48 hours) I.V. therapy of severe refractory congestive heart failure.
– In pediatric population Primacor is indicated for the short-term treatment (up to 35 hours) of severe congestive heart failure unresponsive to conventional
maintenance therapy (glycosides, diuretics, vasodilators and/or
angiotensin converting enzyme (ACE) inhibitors), and for the short-term treatment (up to 35 hours) of pediatric patients with acuts heart failure, including low output states following cardiac surgery.
The use of inotropic agents such as milrinone during the acute phase of a myocardial infarction may lead to an undesirable increase in myocardial oxygen consumption (MVO2). Primacor Injection is not recommended immediately following acute myocardial infarction until safety and efficacy have been established in this situation. Careful monitoring should be maintained during Primacor Injection therapy including blood pressure, heart rate, clinical state, electro-cardiogram, fluid balance, electrolytes and renal function (i.e. serum creatinine). In patients with severe obstructive aortic or pulmonary valvular disease or hypertrophic subaortic stenosis, Primacor Injection should not be used in place of surgical relief of the obstruction. In these conditions it is possible that a drug with inotropic / vasodilator properties might aggravate outflow obstruction.
For full details see presctibing information.
The use of inotropic agents such as milrinone during the acute phase of a myocardial infarction may lead to an undesirable increase in myocardial oxygen consumption (MVO2). Primacor Injection is not recommended immediately following acute myocardial infarction until safety and efficacy have been established in this situation. Careful monitoring should be maintained during Primacor Injection therapy including blood pressure, heart rate, clinical state, electro-cardiogram, fluid balance, electrolytes and renal function (i.e. serum creatinine). In patients with severe obstructive aortic or pulmonary valvular disease or hypertrophic subaortic stenosis, Primacor Injection should not be used in place of surgical relief of the obstruction. In these conditions it is possible that a drug with inotropic / vasodilator properties might aggravate outflow obstruction. Supraventricular and ventricular arrhythmias have been observed in the high risk population treated with milrinone. In some patients an increase in ventricular ectopy including nonsustained ventricular tachycardia has been observed which did not affect patient safety or outcome. The potential for arrhythmia, present in heart failure itself, may be increased by many drugs or a combination of drugs. Patients receiving Primacor Injection should be closely monitored during infusion and the infusion should be stopped if arrhythmias develop. As milrinone produces a slight enhancement in A-V node conduction, there is a possibility of an increased ventricular response rate in patients with uncontrolled atrial flutter / fibrillation. Consideration should therefore be given to digitalisation or treatment with other agents to prolong A-V node conduction time prior to starting Primacor Injection therapy, and to discontinuing the therapy if arrhythmias occur. Milrinone may induce hypotension as a consequence of its vasodilatory activity, therefore caution should be exercised when Primacor Injection is administered to patients who are hypotensive prior to treatment. The rate of infusion should be slowed or stopped in patients showing excessive decreases in blood pressure. 3 If prior vigorous diuretic therapy is suspected of having caused significant decreases in cardiac filling pressure, Primacor Injection should be cautiously administered while monitoring blood pressure, heart rate and clinical symptomatology. Improvement in cardiac output with resultant diuresis may necessitate a reduction in the dose of diuretic. Potassium loss due to excessive diuresis may necessitate a reduction in the dose of diuretic. Potassium loss due to excessive diuresis may predispose digitalised patients to arrhythmias. Therefore, hypokalaemia should be corrected by potassium supplementation in advance of, or during, the use of Primacor Injection. Decrease in haemoglobin, including anaemia, often takes place in the setting of cardiac failure. Due to the risk of thrombocytopenia or anaemia, careful monitoring of the corresponding laboratory parameters is required in patients with decreased platelet count or decreased haemoglobin. There is no experience in controlled trials with infusions of milrinone for periods exceeding 48 hours. Cases of infusion site reaction have been reported with Primacor injection. Consequently, careful monitoring of the infusion site should be maintained so as to avoid possible extravasation. Use in the elderly: There are no special recommendations for elderly patients. No agerelated effects on the incidence of adverse reactions have been observed. Controlled pharmacokinetic studies have not shown changes in the pharmacokinetic profile of milrinone in the elderly. In patients with severe renal impairment dosage adjustment is required. Paediatric population: The following should be considered in addition to the warnings and precautions described for adults: In neonates, following open- heart surgery during Primacor therapy, monitoring should include heart rate and rhythm, systemic arterial blood pressure via umbilical artery catheter or peripheral catheter, central venous pressure, cardiac index, cardiac output, systemic vascular resistance, pulmonary artery pressure, and atrial pressure. Laboratory values that should be followed are platelet count, serum potassium, liver function, and renal function. Frequency of assessment is determined by baseline values, and it is necessary to evaluate the neonate’s response to changes in therapy. Literature revealed that in paediatric patients with impaired renal function, there were marked impairment of milrinone clearance and clinically significant side effects, but the specific creatinine clearance at which doses must be adjusted in paediatric patients is still not clear, therefore the use of milrinone is not recommended in this population. In paediatric patients milrinone should be initiated only if the patient is hemodynamically stable. Caution should be exercised in neonates with risk factors of intraventricular haemorrhage (i.e. preterm infant, low birth weight) since milrinone may induce thrombocytopenia. In clinical studies in paediatric patients, risk of thrombocytopenia increased significantly with duration of infusion. Clinical data suggest that milrinone-related thrombocytopenia is more common in children than in adults. In clinical studies milrinone appeared to slow the closure of the ductus arteriosus in paediatric population. Therefore, 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.
Furosemide or bumetanide should not be administered in intravenous lines containing milrinone lactate in order to avoid precipitation.Milrinone should not be diluted in sodium bicarbonate intravenous infusion. Whilst there is a theoretical potential interaction with calcium channel blockers, there has been no evidence of a clinically significant interaction to date. Milrinone has a favourable inotropic effect in fully digitalised patients without causing signs of glycoside toxicity. Fluid and electrolyte changes, as well as serum creatinine levels, should be carefully monitored during treatment with milrinone. Improvement in cardiac output and consequently, diuresis, may require reduction in the dose of a diuretic agent. Potassium loss due to excessive diuresis may predispose digitalised patients to arrhythmias. Therefore, hypokalaemia should be corrected by potassium supplementation in advance of, or during milrinone use.
Pregnancy and Lactation
Pregnancy : Although animal studies have not revealed evidence of drug-induced foetal damage or other deleterious effects on reproductive function, the safety of milrinone in human pregnancy has not yet been established. It should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Lactation: There is insufficient information on the excretion of milrinone in human milk. A decision must be made whether to discontinue breast-feeding or to discontinue milrinone therapy taking into account the benefit of breast feeding for a child and the benefit of therapy for the woman.
Overdose of intravenous Primacor may produce hypotension (because of its vasodilatory effect) and cardiac arrhythmia. If this occurs, Primacor 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.