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Milrinone

Medically reviewed by Drugs.com. Last updated on Sep 20, 2020.

Pronunciation

(MIL ri none)

Index Terms

  • Milrinone Lactate
  • Primacor

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Generic: 200 mcg/mL (100 mL, 200 mL); 10 mg/10 mL (10 mL); 20 mg/20 mL (20 mL); 50 mg/50 mL (50 mL)

Solution, Intravenous [preservative free]:

Generic: 200 mcg/mL (100 mL, 200 mL); 10 mg/10 mL (10 mL); 20 mg/20 mL (20 mL); 50 mg/50 mL (50 mL)

Pharmacologic Category

  • Inotrope
  • Phosphodiesterase-3 Enzyme Inhibitor

Pharmacology

A selective phosphodiesterase inhibitor in cardiac and vascular tissue, resulting in vasodilation and inotropic effects with little chronotropic activity.

Distribution

Vd beta:

Infants (after cardiac surgery): 0.9 ± 0.4 L/kg (Ramamoorthy 1998)

Children (after cardiac surgery): 0.7 ± 0.2 L/kg (Ramamoorthy 1998)

Adults:

After cardiac surgery: 0.3 ± 0.1 L/kg (Ramamoorthy 1998)

Heart failure (with single injection): 0.38 L/kg

Heart failure (with infusion): 0.45 L/kg

Metabolism

Hepatic (minor); majority is not metabolized (Rocci 1987)

Excretion

Urine (83% as unchanged drug; 12% as 0-glucuronide metabolite); active tubular secretion is a major elimination pathway for milrinone (Rocci 1987)

Clearance:

Infants (after cardiac surgery): 3.8 ± 1 mL/kg/minute (Ramamoorthy 1998)

Children (after cardiac surgery): 5.9 ± 2 mL/kg/minute (Ramamoorthy 1998)

Children (with septic shock): 10.6 ± 5.3 mL/kg/minute (Lindsay 1998)

Adults:

After cardiac surgery: 2 ± 0.7 mL/kg/minute (Ramamoorthy 1998)

Heart failure: 2.2 to 2.3 mL/kg/minute

Onset of Action

IV: 5 to 15 minutes

Half-Life Elimination

Infants (after cardiac surgery): 3.15 ± 2 hours (Ramamoorthy 1998)

Children (after cardiac surgery): 1.86 ± 2 hours (Ramamoorthy 1998)

Adults:

Heart failure: 2.3 to 2.4 hours; renal impairment prolongs half-life (Rocci 1987)

Severe heart failure undergoing continuous venovenous hemofiltration (CVVH): 20.1 ± 3.3 hours (Taniguchi 2000)

Protein Binding

Plasma: ~70%

Use: Labeled Indications

Heart failure with reduced ejection fraction: Short-term IV therapy for patients with acute decompensated heart failure with reduced ejection fraction in need of inotropic support.

Off Label Uses

Bridge to heart transplantation

Data from several prospective trials and one observational study support the use of milrinone in patients awaiting heart transplant [Aranda 2003], [Bhat 2006], [Brozena 2004], [Upadya 2004]. Additional trials may be necessary to further define the role of milrinone in this setting.

Postoperative inotropic support for heart transplant recipients

Based on The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients, milrinone given for the perioperative inotropic support of heart transplant recipients is suggested as a therapeutic option in this setting.

Contraindications

Hypersensitivity to milrinone or any component of the formulation

Dosing: Adult

Heart failure with reduced ejection fraction:

Note: Reserve use for decompensated patients with low cardiac output or evidence of end organ hypoperfusion, in combination with standard therapies (ACCF/AHA [Yancy 2013]).

Continuous IV infusion: Initial: 0.125 mcg/kg/minute; dosing range: 0.125 to 0.75 mcg/kg/minute; titrate based on clinical response and hemodynamic end points. Use the lowest effective dose to minimize adverse effects (eg, arrhythmia, hypotension) (ACCF/AHA [Yancy 2013]).

Note: Loading doses are frequently not recommended (ACCF/AHA [Yancy 2013]), but may consider administering 50 mcg/kg over 10 minutes followed by a continuous infusion.

Bridge to heart transplantation (off-label use):

Continuous IV infusion: Initial: 0.125 mcg/kg/minute; dosage range: 0.1 to 0.75 mcg/kg/minute; titrate based on clinical response and hemodynamic end points. Use the lowest effective dose to minimize adverse effects (eg, arrhythmia, hypotension) (ACCF/AHA [Yancy 2013]; Aranda 2003; Bhat 2006; Upadya 2004).

Postoperative inotropic support in heart transplant recipients (off-label use):

Continuous IV infusion: Usual dose range: 0.375 to 0.75 mcg/kg/minute; titrate to the lowest effective dose based on clinical response and hemodynamic end points; wean as tolerated over the first 3 to 5 days following surgery (ISHLT [Costanzo 2010]).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Hemodynamic support (eg, acute decompensated heart failure, cardiogenic shock, septic shock): Limited data available; optimal dosing not established: Note: Dosing should be individualized and titrated to effect due to interpatient variability in clearance, with or without low cardiac output syndrome or acute kidney injury (Bailey 2004; Garcia Guerra 2013; Gist 2015; Vogt 2014):

Infants, Children, and Adolescents: IV, Intraosseous: Loading dose (optional): 50 mcg/kg administered over 10 to 60 minutes followed by a continuous IV or intraosseous infusion; infusion dose range: 0.25 to 0.75 mcg/kg/minute; titrate dose to effect (PALS [Kleinman 2010]). Due to the risk of hypotension, some centers do not utilize a loading dose (ACCM [Davis 2017]).

Low cardiac output syndrome (LCOS) following CHD corrective surgery, prevention: Limited data available: Infants and Children: IV: Loading dose: 25 or 75 mcg/kg administered over 60 minutes followed by a continuous IV infusion of 0.25 or 0.75 mcg/kg/minute (Hoffman 2003). Dosing based on a double-blind, placebo-controlled trial which randomized 227 postoperative cardiac surgery patients (age range: 2 days to 6.9 years, median: 3 months) at high risk for LCOS to low-dose milrinone (loading dose: 25 mcg/kg, continuous infusion: 0.25 mcg/kg/minute), high-dose milrinone (loading dose: 75 mcg/kg, continuous infusion: 0.75 mcg/kg/minute), and placebo; results showed patients in the high-dose milrinone group had a 64% relative risk reduction for the development of LCOS compared to placebo; the low-dose milrinone group had a statistically insignificant trend toward reducing the development of LCOS (Hoffman 2003).

Reconstitution

Loading dose (optional): May administer undiluted; diluting to a rounded total volume of 10 or 20 mL may simplify the visualization of the injection rate.

Maintenance dose: For a final concentration of 0.2 mg/mL: Dilute 1 mg/mL (20 mL) with 80 mL diluent (final volume: 100 mL) of 1/2NS, NS or D5W. May also dilute 1 mg/mL (10 mL) with 40 mL diluent (final volume: 50 mL).

Administration

IV: For IV use only. Administer loading dose (optional) undiluted slowly over 10 minutes; diluting to a rounded total volume of 10 or 20 mL may simplify the visualization of the injection rate. Infuse maintenance dose via continuous infusion pump.

Storage

Store at 20°C to 25°C (68°F to 77°F); avoid freezing. Minimize exposure to heat; avoid excessive heat. Brief exposure up to 40°C (104°F) will not adversely affect drug. Stable at 0.2 mg/mL in 1/2NS, NS, or D5W for 72 hours at room temperature in normal light (Wilson 1986).

Drug Interactions

Anagrelide: May enhance the adverse/toxic effect of Milrinone. Avoid combination

Riociguat: Milrinone may enhance the hypotensive effect of Riociguat. Management: Riociguat is contraindicated with nonselective phosphodiesterase (PDE) inhibitors and PDE type 5 inhibitors. Other types of PDE inhibitors are not contraindicated, but caution is advised and patients should be monitored for hypotension. Monitor therapy

Adverse Reactions

>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%, postmarketing, and/or case reports: Anaphylaxis, atrial fibrillation, bronchospasm, hepatic insufficiency, hypokalemia, injection site reaction, myocardial infarction, skin rash, thrombocytopenia, torsades de pointes, tremor

Warnings/Precautions

Concerns related to adverse effects:

• Arrhythmias: Ventricular arrhythmias, including nonsustained ventricular tachycardia and supraventricular arrhythmias, have been reported. Observe closely for arrhythmias in this very high-risk patient population; sudden cardiac death has been observed. Due to the prolonged half-life as compared to other inotropic agents, ventricular or atrial arrhythmias may persist even after discontinuation of milrinone especially in patients with renal dysfunction (Cox 2013; Leier 1998). Ensure that ventricular rate is controlled in atrial fibrillation/flutter before initiating; may increase ventricular response rate. In heart transplant candidates, institute appropriate measures to protect patient against risks of sudden cardiac death (Brozena 2004).

• Hypotension: Hypotension may occur. Monitor blood pressure closely. Hypotension may be prolonged especially in patients with renal dysfunction (Cox 2013; Leier 1998). Vigorous diuresis may contribute to hypotension; cautious administration of fluids may be required to prevent hypotension. Omitting the bolus dose may decrease the risk of hypotension (Baruch 2001; Cuffe 2002). If hypotension occurs, consider dose reduction or temporary discontinuation.

Disease-related concerns:

• Cardiovascular disease: Avoid use in patients with severe obstructive aortic or pulmonic valvular disease in lieu of surgical relief of the obstruction; may aggravate outflow tract obstruction in hypertrophic cardiomyopathy with outflow tract obstruction.

• Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy to minimize the risk of arrhythmias.

• Renal impairment: Use with caution in patients with renal impairment; reduction in infusion rate recommended. Hypotension may be prolonged in patients with renal dysfunction (Cox 2013; Leier 1998).

Other warnings/precautions:

• Appropriate use: A facility for immediate treatment of potential cardiac events, including life-threatening ventricular arrhythmias, must be available. Safe and effective use beyond 48 hours (prolonged use) has not been demonstrated. An increased risk of death and hospitalization has been observed with prolonged use in NYHA Class III/IV heart failure patients. Sudden cardiac death has been reported with prolonged use. Continuous electrocardiographic monitoring is recommended.

• Long-term therapy: According to the ACCF/AHA 2013 heart failure guidelines, long-term use of intravenous inotropic therapy without a specific indication or for reasons other than palliation is potentially harmful (ACCF/AHA [Yancy 2013]).

Monitoring Parameters

Platelet count, electrolytes (especially potassium and magnesium) and fluid status, renal function; ECG, blood pressure, heart rate; infusion site

If pulmonary artery catheter is in place, monitor cardiac index, stroke volume, systemic vascular resistance, pulmonary capillary wedge pressure and pulmonary vascular resistance.

Consult individual institutional policies and procedures.

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies; however, increased resorption was reported in some studies.

Patient Education

What is this drug used for?

• It is used to treat heart failure (weak heart).

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Fast heartbeat

• Severe dizziness

• Passing out

• Abnormal heartbeat

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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