Milrinone

Dosage Forms & Strengths

infusion solution, in D5W

• 20mg/100mL
• 40mg/200mL

injectable solution

• 1mg/mL

Congestive Heart Failure

50 mcg/kg loading dose by IV push over 10 minutes, then 0.375-0.75 mcg/kg/min IV 

Maintenance: 1.13 mg/kg/day

Monitor electrolytes, renal function, blood pressure

Dosing Modifications

Renal impairment

• CrCl <50 mL/min: 0.43 mcg/kg/min  
• CrCl <40 mL/min: 0.38 mcg/kg/min
• CrCl <30 mL/min: 0.33 mcg/kg/min
• CrCl <20 mL/min: 0.28 mcg/kg/min
• CrCl <10 mL/min: 0.23 mcg/kg/min
• CrCl <5 mL/min: 0.2 mcg/kg/min

Not FDA-approved in children

Dosage Forms & Strengths

infusion solution, in D5W

• 20mg/100mL
• 40mg/200mL

injectable solution

• 1mg/mL

Low Cardiac Output, Septic Shock

50 mcg/kg loading dose by IV push over 10-60 minutes, then 0.25-0.75 mcg/kg/min IV 

Monitor electrolytes, renal function, blood pressure

Since milrinone is given by a healthcare professional, you are not likely to miss a dose.

Milrinone is a prescription medication used for short-term treatment of acute decompensated heart failure (a specific type of heart problem).  

Before taking milrinone, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to any ingredient in milrinone
• have or have had kidney problems
• have or have had liver problems
• have or have had problems with swelling or excess water
• are diabetic or hypoglycemic (have problems with your blood sugars)
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant.

In an emergency situation it may not be possible to tell your caregivers about your health conditions. Make sure any doctor caring for you afterward knows you have received this medicine.

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers at once if you have:

• chest pain;

• a light-headed feeling, like you might pass out;

• bronchospasm (wheezing, chest tightness, trouble breathing); or

• low potassium--leg cramps, constipation, irregular heartbeats, fluttering in your chest, extreme thirst, increased urination, numbness or tingling, muscle weakness or limp feeling.

Common side effects may include:

• headache;

• tremors; or

• easy bruising or bleeding.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Usual Adult Dose for Congestive Heart Failure:

Loading dose: 50 mcg/kg IV over 10 minutes.
Maintenance infusion: 0.375 to 0.75 mcg/kg/min.

Usual Pediatric Dose for Congestive Heart Failure:

less than 1 month:
Hemodynamic support: Full term neonates: Loading dose: 50 to 75 mcg/kg IV administered over 15 minutes followed by a continuous infusion of 0.5 mcg/kg/minute; titrate to effect; range: 0.25 to 0.75 mcg/kg/minute has been used by several centers. One report used a loading dose of 50 mcg/kg IV administered over 15 minutes, followed by a continuous infusion of 0.5 mcg/kg/minute for 30 minutes in 10 neonates (3 to 27 days old, median age: 5 days) with low cardiac output after cardiac surgery; results showed improved hemodynamic parameters and milrinone was well tolerated.
Prevention of postoperative low cardiac output syndrome (CHD corrective surgery): Full term neonates: Loading dose: 75 mcg/kg IV administered over 60 minutes followed by a continuous IV infusion of 0.75 mcg/kg/minute for 35 hours was used in a randomized, placebo controlled trial of 227 patients (age: 2 days to 6.9 years, median: 3 months) and showed 64% relative risk reduction for development of low cardiac output syndrome compared to placebo; a lower milrinone dose used in the study did not show a statistically significant relative risk reduction compared to placebo for the same endpoint.

1 month and older:
Loading dose: 50 mcg/kg IV over 15 minutes.
Maintenance infusion: 0.25-1 mcg/kg/min.

Milrinone lactate injection is a member of a new class of bipyridine inotropic/vasodilator agents with phosphodiesterase inhibitor activity, distinct from digitalis glycosides or catecholamines. Milrinone lactate is designated chemically as 1,6-dihydro-2-methyl-6-oxo-[3,4´-bipyridine]-5-carbonitrile lactate and has the following structure:

Milrinone is an off-white to tan crystalline compound with a molecular weight of 211.2 and a molecular formula of C12H9N3O. It is slightly soluble in methanol, and very slightly soluble in chloroform and in water. As the lactate salt, it is stable and colorless to pale yellow in solution. Milrinone lactate is available as sterile aqueous solutions of the lactate salt of Milrinone for injection or infusion intravenously.
Sterile, single-dose syringes: Single-dose syringes of 5 mL contain in each mL Milrinone lactate equivalent to 1 mg Milrinone USP 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 USP or sodium hydroxide NF. The total concentration of lactic acid USP can vary between 0.95 mg/mL and 1.29 mg/mL. These syringes require preparation of dilutions prior to administration to patients intravenously.

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.

Cardiovascular Effects

In patients receiving Milrinone in Phase II and III clinical trials, ventricular arrhythmias were reported in 12.1%: Ventricular ectopic activity, 8.5%; nonsustained ventricular tachycardia, 2.8%; sustained ventricular tachycardia, 1% and ventricular fibrillation, 0.2% (2 patients experienced more than one type of arrhythmia). Holter recordings demonstrated that in some patients injection of Milrinone increased ventricular ectopy, including nonsustained ventricular tachycardia. Life-threatening arrhythmias were infrequent and when present have been associated with certain underlying factors such as preexisting arrhythmias, metabolic abnormalities (e.g. hypokalemia), abnormal digoxin levels and catheter insertion. Milrinone was not shown to be arrhythmogenic in an electrophysiology study. Supraventricular arrhythmias were reported in 3.8% of the patients receiving Milrinone. The incidence of both supraventricular and ventricular arrhythmias has not been related to the dose or plasma Milrinone concentration.

Other cardiovascular adverse reactions include hypotension, 2.9% and angina/chest pain, 1.2%.

In the postmarketing experience, there have been rare cases of “torsades de pointes” reported.

CNS Effects

Headaches, usually mild to moderate in severity, have been reported in 2.9% of patients receiving Milrinone.

Other Effects

Other adverse reactions reported, but not definitely related to the administration of Milrinone include hypokalemia, 0.6%; tremor, 0.4%; and thrombocytopenia, 0.4%.

Isolated spontaneous reports of bronchospasm and anaphylactic shock have been received; and in the postmarketing experience, liver function test abnormalities and skin reactions such as rash have been reported.

Postmarketing Adverse Event Reports

In addition to adverse events reported from clinical trials, the following events have been reported from worldwide postmarketing experience with Milrinone:

Isolated spontaneous reports of bronchospasm and anaphylactic shock.

Liver function test abnormalities and skin reactions such as rash.

Administration site conditions: Infusion site reaction.

Inotropic support in heart failure: Short-term IV therapy of acutely-decompensated heart failure

American College of Cardiology/American Heart Association heart failure (HF) guideline recommendations (ACCF/AHA [Yancy 2013]): To maintain systemic perfusion and preserve end-organ performance in patients with cardiogenic shock; bridge therapy in stage D HF unresponsive to guideline-directed medical therapy and device therapy in patients awaiting heart transplant or mechanical circulatory support; short-term management of hospitalized patients with severe systolic dysfunction presenting with low blood pressure and significantly depressed cardiac output; long-term management (palliative therapy) in select patients with stage D HF unresponsive to guideline-directed medical therapy and device therapy who are not candidates for heart transplant or mechanical circulatory support.

Refer to adult dosing.

>10%: Cardiovascular: Ventricular arrhythmia (ventricular ectopy: 9%, nonsustained ventricular tachycardia: 3%, ventricular tachycardia: 1%, ventricular fibrillation: <1%)

1% to 10%:

Cardiovascular: Supraventricular cardiac arrhythmia (4%), hypotension (3%), angina pectoris (≤1%), chest pain (≤1%)

Central nervous system: Headache (3%)

<1% (Limited to important or life-threatening): Anaphylaxis, atrial fibrillation, bronchospasm, hepatic insufficiency, hypokalemia, injection site reaction, myocardial infarction, skin rash, thrombocytopenia, torsades de pointes, tremor

The maximum recommended daily dose is 1.13 mg/kg.

Experience with infusions of milrinone for periods exceeding 48 hours has not been documented.