Milrinone (Milrinone) - Indications and Dosage

INDICATIONS AND USAGE

Milrinone Lactate Injection is indicated for the short-term intravenous treatment of patients with acute decompensated heart failure. Patients receiving milrinone should be observed closely with appropriate electrocardiographic equipment. The facility for immediate treatment of potential cardiac events, which may include life-threatening ventricular arrhythmias, must be available. The majority of experience with intravenous milrinone has been in patients receiving digoxin and diuretics. There is no experience in controlled trials with infusions of milrinone for periods exceeding 48 hours.

DOSAGE AND ADMINISTRATION

Milrinone Lactate Injection should be administered with a loading dose followed by a continuous infusion (maintenance dose) according to the following guidelines:

LOADING DOSE

50 mcg/kg: Administer slowly over 10 minutes

The table below shows the loading dose in milliliters (mL) of milrinone (1 mg/mL) by patient body weight (kg).

Loading Dose (mL) Using 1 mg/mL Concentration
Patient Body Weight (kg)
kg	30	40	50	60	70	80	90	100	110	120
mL	1.5	2.0	2.5	3.0	3.5	4.0	4.5	5.0	5.5	6.0

The loading dose may be given undiluted, but diluting to a rounded total volume of 10 or 20 mL (see MAINTENANCE DOSE for diluents) may simplify the visualization of the injection rate.

MAINTENANCE DOSE
	Infusion Rate	Total Daily Dose (24 hours)
Minimum	0.375 mcg/kg/min	0.59 mg/kg	Administer as a continuous intravenous infusion.
Standard	0.50 mcg/kg/min	0.77 mg/kg
Maximum	0.75 mcg/kg/min	1.13 mg/kg

Milrinone Lactate Injection drawn from vials should be diluted prior to maintenance dose administration. The diluents that may be used are 0.45% Sodium Chloride Injection, USP; 0.9% Sodium Chloride Injection, USP; or 5% Dextrose Injection, USP. The table below shows the volume of diluent in milliliters (mL) that must be used to achieve 200 mcg/mL concentration for infusion, and the resultant total volumes.

Desired Infusion Concentration mcg/mL	Milrinone 1 mg/mL (mL)	Diluent (mL)	Total Volume (mL)
200	10	40	50
200	20	80	100

The infusion rate should be adjusted according to hemodynamic and clinical response. Patients should be closely monitored. In controlled clinical studies, most patients showed an improvement in hemodynamic status as evidenced by increases in cardiac output and reductions in pulmonary capillary wedge pressure.

Note: See “ Dosage Adjustment in Renally Impaired Patients.” Dosage may be titrated to the maximum hemodynamic effect and should not exceed 1.13 mg/kg/day. Duration of therapy should depend upon patient responsiveness.

The maintenance dose in mL/hr by patient body weight (kg) may be determined by reference to the following table.

Milrinone Infusion Rate (mL/hr) Using 200 mcg/mL Concentration
Maintenance Dose (mcg/kg/min)	Patient Body Weight (kg)
	30	40	50	60	70	80	90	100	110	120
0.375	3.4	4.5	5.6	6.8	7.9	9.0	10.1	11.3	12.4	13.5
0.400	3.6	4.8	6.0	7.2	8.4	9.6	10.8	12.0	13.2	14.4
0.500	4.5	6.0	7.5	9.0	10.5	12.0	13.5	15.0	16.5	18.0
0.600	5.4	7.2	9.0	10.8	12.6	14.4	16.2	18.0	19.8	21.6
0.700	6.3	8.4	10.5	12.6	14.7	16.8	18.9	21.0	23.1	25.2
0.750	6.8	9.0	11.3	13.5	15.8	18.0	20.3	22.5	24.8	27.0

When administering milrinone lactate by continuous infusion, it is advisable to use a calibrated electronic infusion device.

Intravenous drug products should be inspected visually and should not be used if particulate matter or discoloration is present.

Dosage Adjustment in Renally Impaired Patients

Data obtained from patients with severe renal impairment (creatinine clearance = 0 to 30 mL/min) but without congestive heart failure have demonstrated that the presence of renal impairment significantly increases the terminal elimination half-life of milrinone. Reductions in infusion rate may be necessary in patients with renal impairment. For patients with clinical evidence of renal impairment, the recommended infusion rate can be obtained from the following table:

Creatinine Clearance (mL/min/1.73 m2)	Infusion Rate (mcg/kg/min)
5	0.20
10	0.23
20	0.28
30	0.33
40	0.38
50	0.43

HOW SUPPLIED

Milrinone Lactate Injection, 1 mg/mL, is supplied as follows:

NDC Number	Contents	Packaged
NDC 0703-8005-03	10 mg/10 mL	Single-Dose, packaged in 10s
NDC 0703-8006-03	20 mg/20 mL	Single-Dose, packaged in 10s
NDC 0703-8008-01	50 mg/50 mL	Single-Dose, packaged individually

Each mL milrinone lactate equivalent to 1 mg milrinone and 47 mg dextrose, anhydrous, USP, in water for injection, USP. The pH is adjusted to between 3.2 and 4.0 with lactic acid or sodium hydroxide. The total concentration of lactic acid can vary between 0.95 mg/mL and 1.29 mg/mL. These vials require preparation of dilutions prior to administration to patients intravenously.

Store at controlled room temperature 15 ^°-30 ^°C (59 ^°-86 ^°F) [see USP].

Avoid freezing.

Issued: November 2003

SICOR Pharmaceuticals, Inc.

Irvine, CA 92618