Drug Class Description
Phosphodiesterase inhibitors.

Generic Name
Milrinone

Drug Description
Each ampoule contains 1mg/ml of the active substance Milrinone.

Presentation
Solution for Injection.Clear, colourless to pale yellow liquid.

Indications
Primacor Injection is indicated for the short-term treatment of severe congestive heart failure unresponsive to conventional maintenance therapy, and for the treatment of patients with acute heart failure, including low output states following cardiac surgery.

Adult Dosage
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 0.375µg/kg/min and 0.75µg/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 200µg/ml prepared by adding 40ml diluent per 10ml ampoule (400ml diluent per 100ml Primacor Injection). 0.45% saline, 0.9% saline or 5% glucose may be used as diluents.Primacor Injection Dose(µg/kg/min)InfusionDelivery Rate (ml/kg/hr)0.3750.4000.5000.6000.7000.7500.110.120.150.180.210.22Solutions 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 following maintenance infusion rates are recommended using the infusion solution described above.Creatinine Clearance(ml/min/1.73m2)Primacor Injection Dose(µg/kg/min)Maintenance Infusion Delivery Rate(ml/kg/hr)510203040500.200.230.280.330.380.430.060.070.080.100.110.13The infusion rate should be adjusted according to haemodynamic response.Elderly: Experience so far suggests that no special dosage recommendations are necessary.Children: Safety and effectiveness in children and adolescents under 18 years of age have not been established. Primacor Injection should be used only if the potential benefits outweigh the potential risks.

Child Dosage
Safety and effectiveness in children and adolescents under 18 years of age have not been established. Primacor Injection should be used only if the potential benefits outweigh the potential risks.

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

Contra Indications
• Hypersensitivity to milrinone or any of the excipients• Severe hypovolaemia.

Special Precautions
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 Primacor Injection. In some patients an increase in ventricular ectopy including non-sustained ventricular tachycardia has been observed which did not affect patient safety or outcome.As Primacor Injection 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.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.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.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.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

Interactions
None have been observed during Primacor Injection therapy.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.

Adverse Reactions
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).Blood and the lymphatic system disorders:• Uncommon: ThrombocytopeniaMetabolism and nutrition disorders:• Uncommon: HypokalaemiaNervous system disorders:• Common: Headaches, usually mild to moderate in severity• Uncommon: TremorCardiac disorders: • Common:- Ventricular ectopic activity- Non sustained or sustained ventricular tachycardia- Supraventricular arrhythmias- Hypotension• Uncommon:- Ventricular fibrillation- Angina/chest pain• Very rare: Torsades de pointesThe incidence of arrhythmias has not been related to dose or plasma levels of milrinone. These arrhythmias are rarely life threatening. If present, they are often associated with certain underlying factors such as pre-existing arrhythmias, metabolic abnormalities (e.g. hypokalaemia) abnormal digoxin levels and catheter insertion.Respiratory, thoracic and mediastinal disorders:• Very rare: BronchospasmHepato-biliary disorders:• Uncommon: Liver function tests abnormalSkin and subcutaneous tissue disorders:• Very rare: Skin reactions such as rash.General disorders and administration site conditions:• Very rare: Anaphylactic shock• Not known: Infusion site reaction

Manufacturer
sanofi-aventis

Drug Availability
(POM)

Updated
23 November 2011