No

Phosphodiesterase Enzyme Inhibitor

Short-term I.V. therapy of congestive heart failure; calcium antagonist intoxication

C

Hypersensitivity to milrinone or any component; amrinone

Avoid in severe obstructive aortic or pulmonic valvular disease. It may aggravate outflow tract obstruction in hypertrophic subaortic stenosis. Supraventricular and ventricular arrhythmias have developed in high-risk patients. Monitor closely during the infusion. Ensure that ventricular rate controlled in atrial fibrillation/flutter before initiating. Not recommended for use in acute MI patients. Monitor and correct fluid and electrolyte problems. Adjust dose in renal dysfunction.

1% to 10%:

Cardiovascular: Arrhythmias, hypotension

Central nervous system: Headache

<1% (Limited to important or life-threatening symptoms): Ventricular fibrillation, chest pain, hypokalemia, thrombocytopenia

Hypotension should respond to I.V. fluids and Trendelenburg position; use of vasopressors may be required

When furosemide is admixed with milrinone, a precipitate immediately forms.

Colorless to pale yellow solution; store at room temperature and protect from light; stable at 0.2 mg/mL in 0.9% sodium chloride or D₅W for 72 hours at room temperature in normal light

Standardized dose: 20 mg in 80 mL of 0.9% sodium chloride or D₅W (0.2 mg/mL)

Phosphodiesterase inhibitor resulting in vasodilation

Serum level: I.V.: Following a 125 mcg/kg dose, peak plasma concentrations of ~1000 ng/mL were observed at 2 minutes postinjection, decreasing to <100 ng/mL in 2 hours

Therapeutic effect: Oral: Following doses of 7.5-15 mg, peak hemodynamic effects occurred at 90 minutes

Drug concentration levels:

Therapeutic:

Serum levels of 166 ng/mL, achieved during I.V. infusions of 0.25-1 mcg/kg/minute, were associated with sustained hemodynamic benefit in severe congestive heart failure patients over a 24-hour period

Maximum beneficial effects on cardiac output and pulmonary capillary wedge pressure following I.V. infusion have been associated with plasma milrinone concentrations of 150-250 ng/mL

Toxic: Serum concentrations >250-300 ng/mL have been associated with marked reductions in mean arterial pressure and tachycardia; however, more studies are required to determine the toxic serum levels for milrinone

Distribution: Not known if distributed into breast milk

V_d at steady-state following I.V. administration as a single bolus: 0.32 L/kg; not significantly bound to tissues

In patients with severe congestive heart failure (CHF), V_d has been 0.33-0.47 L/kg

Protein binding: ~70% in plasma

Metabolism: 12% hepatic

Half-life, elimination: I.V.: 136 minutes in patients with CHF; patients with severe CHF have a more prolonged half-life, with values ranging from 1.7-2.7 hours. Patients with CHF have a reduction in the systemic clearance of milrinone, resulting in a prolonged elimination half-life. Alternatively, one study reported that 1 month of therapy with milrinone did not change the pharmacokinetic parameters for patients with CHF despite improvement in cardiac function.

Elimination: Following I.V. administration, 85% of dose excreted unchanged in urine within 24 hours; active tubular secretion is a major elimination pathway for milrinone; bolus doses of I.V. milrinone produced systemic clearance values of 25.9±5.7 L/hour (0.37 L/hour/kg); however, in patients with severe congestive heart failure, the clearance is reduced to 0.11-0.13 L/hour/kg. The reduction in clearance may be a result of reduced renal function. Creatinine clearance values were 1/2 those reported for healthy adults in patients with severe congestive heart failure (52 vs 119 mL/minute).

Adults: I.V.: Loading dose: 50 mcg/kg administered over 10 minutes followed by a maintenance dose titrated according to the hemodynamic and clinical response See below:

Dose rate 0.375 mcg/kg/minute; total dose 0.59 mg/kg/24 hours

Standard: Maintenance dosage:

Dose rate 0.500 mcg/kg/minute; total dose 0.77 mg/kg/24 hours

Maximum: Maintenance dosage:

Dose rate 0.750 mcg/kg/minute; total dose 1.13 mg/kg/24 hours

Dosing adjustment in renal impairment:

Cl_cr 50 mL/minute/1.73 m²: Administer 0.43 mcg/kg/minute.

Cl_cr 40 mL/minute/1.73 m²: Administer 0.38 mcg/kg/minute.

Cl_cr 30 mL/minute/1.73 m²: Administer 0.33 mcg/kg/minute.

Cl_cr 20 mL/minute/1.73 m²: Administer 0.28 mcg/kg/minute.

Cl_cr 10 mL/minute/1.73 m²: Administer 0.23 mcg/kg/minute.

Cl_cr 5 mL/minute/1.73 m²: Administer 0.2 mcg/kg/minute.

Cardiac monitor and blood pressure monitor required; serum potassium

Toxic: Patients should be monitored for ventricular arrhythmias and exacerbation of anginal symptoms; during I.V. therapy with milrinone, blood pressure and heart rate should be monitored

Long-term use of phosphodiesterase enzyme inhibitor therapy in heart failure provides some symptomatic relief but is associated with clear cut increases in mortality. Milrinone has been used for short-term improvement in hemodynamics. Chronic administration of milrinone does not confer beneficial effects on cardiovascular morbidity and mortality.

None reported

None reported

No information available to require special precautions

No effects or complications reported

This drug can only be given intravenously. If you experience increased voiding call for assistance. Report pain at infusion site, numbness or tingling of extremities, or difficulty breathing. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Consult prescriber if breast-feeding.

Monitor closely, titrate to blood pressure cardiac index

Injection, as lactate: 1 mg/mL (5 mL, 10 mL, 20 mL)

Barton P, Garcia J, Kouatli A, et al, "Hemodynamic Effects of I.V. Milrinone Lactate in Pediatric Patients With Septic Shock. A Prospective Double-Blinded, Randomized, Placebo-Controlled, Interventional Study," Chest, 1996, 109(5):1302-12.

Chang AC, Atz AM, Wernovsky G, et al, "Milrinone: Systemic and Pulmonary Hemodynamic Effects in Neonates After Cardiac Surgery," Crit Care Med, 1995, 23(11):1907-14.

Lindsay CA, Barton P, Lawless S, et al, "Pharmacokinetics and Pharmacodynamics of Milrinone Lactate in Pediatric Patients With Septic Shock," J Pediatr, 1998, 132(2):329-34.

Ramamoorthy C, Anderson GD, Williams GD, et al, "Pharmacokinetics and Side Effects of Milrinone in Infants and Children After Open Heart Surgery," Anesth Analg, 1998, 86(2):283-9.