Medically reviewed on March 25, 2018
(MIL ri none)
- Milrinone Lactate
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
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)
- Phosphodiesterase-3 Enzyme Inhibitor
A selective phosphodiesterase inhibitor in cardiac and vascular tissue, resulting in vasodilation and inotropic effects with little chronotropic activity.
Infants (after cardiac surgery): 0.9 ± 0.4 L/kg (Ramamoorthy 1998)
Children (after cardiac surgery): 0.7 ± 0.2 L/kg (Ramamoorthy 1998)
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
Hepatic (minor); majority is not metabolized (Rocci 1987)
Urine (83% as unchanged drug; 12% as 0-glucuronide metabolite); active tubular secretion is a major elimination pathway for milrinone (Rocci 1987)
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)
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
Infants (after cardiac surgery): 3.15 ± 2 hours (Ramamoorthy 1998)
Children (after cardiac surgery): 1.86 ± 2 hours (Ramamoorthy 1998)
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)
Use: Labeled Indications
Inotropic support in heart failure: Short-term IV therapy of acutely-decompensated heart failure (HF)
Heart failure: 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 (ACCF/AHA [Yancy 2013]).
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.
The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) heart failure guidelines and an American Heart Association scientific statement on management of cardiogenic shock recommend milrinone to maintain systemic perfusion and preserve end-organ performance in HF patients with reduced ejection fraction presenting with cardiogenic shock [ACCF/AHA [Yancy 2013]], [AHA [van Diepen 2017]].
Palliation of symptoms in end-stage heart failure
Based on the American College of Cardiology Foundation/American Heart Association guidelines for the management of heart failure, long-term, continuous use of positive inotropic drugs is acceptable for palliation of patients with end-stage heart failure (ie, stage D) who cannot be stabilized with standard medical treatment, including device therapy, and are not eligible for either mechanical circulatory support or cardiac transplantation.
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.
Hypersensitivity to milrinone or any component of the formulation
Inotropic support in heart failure: IV: Loading dose (optional, not recommended by ACCF/AHA 2013 heart failure guidelines; also see "Note"): 50 mcg/kg administered over 10 minutes followed by a maintenance dose titrated according to hemodynamic and clinical response; Maintenance dose: IV infusion: 0.375 to 0.75 mcg/kg/minute; lower initial doses of 0.1 mcg/kg/minute (with final maintenance doses of 0.2 to 0.3 mcg/kg/minute) have also been recommended (HFSA [Lindenfeld 2010]). The ACCF/AHA 2013 heart failure guidelines recommend a maintenance dose of 0.125 to 0.75 mcg/kg/minute (ACCF/AHA [Yancy 2013]).
Note: When initiating an infusion of 0.5 mcg/kg/minute without a loading dose, significant hemodynamic changes seen at 30 minutes with similar effects on pulmonary capillary wedge pressure and cardiac index seen at 2 and 3 hours, respectively, compared to loading dose regimen (Baruch 2001).
Bridge to heart transplantation (off-label use): IV: 0.1 to 0.75 mcg/kg/minute; titrate to optimize clinical condition (Aranda 2003; Bhat 2006; Upadya 2004)
Cardiogenic shock (off-label use): IV: 0.125 to 0.75 mcg/kg/minute (AHA [van Diepen 2017])
Postoperative inotropic support in heart transplant recipients (off-label use): IV: 0.375 to 0.75 mcg/kg/minute; use the lowest effective dose and wean as tolerated over the first 3 to 5 days (ISHLT [Costanzo 2010]).
Refer to adult dosing.
PALS Guidelines (cardiac output maintenance and postresuscitation stabilization) (off-label use): Infants, Children, and Adolescents: IV, IO: Loading dose: 50 mcg/kg over 10 to 60 minutes followed by a maintenance infusion of 0.25 to 0.75 mcg/kg/minute (AHA [Kleinman 2010])
Dosing: Renal Impairment
Manufacturer recommended adjustment:
CrCl 50 mL/minute/1.73 m2: Administer 0.43 mcg/kg/minute
CrCl 40 mL/minute/1.73 m2: Administer 0.38 mcg/kg/minute
CrCl 30 mL/minute/1.73 m2: Administer 0.33 mcg/kg/minute
CrCl 20 mL/minute/ 1.73 m2: Administer 0.28 mcg/kg/minute
CrCl 10 mL/minute/1.73 m2: Administer 0.23 mcg/kg/minute
CrCl 5 mL/minute/1.73 m2: Administer 0.2 mcg/kg/minute
Starting dose (mcg/kg/minute)
1Based on expert opinion
Consider alternative therapy
Consider alternative therapy
Consider alternative therapy
Table has been converted to the following text.
Alternative Dosing Adjustments in Patients with Renal Impairment (based on expert opinion)
Starting dose: 0.375 mcg/kg/minute:
CrCl 50 mL/minute: 0.25 mcg/kg/minute
CrCl 40 mL/minute: 0.125 mcg/kg/minute
CrCl 30 mL/minute: 0.0625 mcg/kg/minute
CrCl ≤20 mL/minute: Consider alternative therapy
Starting dose: 0.5 mcg/kg/minute:
CrCl 50 mL/minute: 0.375 mcg/kg/minute
CrCl 40 mL/minute: 0.25 mcg/kg/minute
CrCl 30 mL/minute: 0.125 mcg/kg/minute
CrCl 20 mL/minute: 0.0625 mcg/kg/minute
CrCl ≤10 mL/minute: Consider alternative therapy
Starting dose: 0.75 mcg/kg/minute:
CrCl 50 mL/minute: 0.5 mcg/kg/minute
CrCl 40 mL/minute: 0.375 mcg/kg/minute
CrCl 30 mL/minute: 0.25 mcg/kg/minute
CrCl 20 mL/minute: 0.125 mcg/kg/minute
CrCl 10 mL/minute: 0.0625 mcg/kg/minute
CrCl 5 mL/minute: Consider alternative therapy
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer’s labeling.
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).
IV: For IV use only. Administer loading dose (optional) undiluted slowly over 10 minutes. Infuse maintenance dose via continuous infusion pump.
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).
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
>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
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.
• 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).
• 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]).
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 Risk Factor
Adverse events have not been observed in animal reproduction studies; however, increased resorption was reported in some studies.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Have patient report immediately to prescriber tachycardia, severe dizziness, passing out, or abnormal heartbeat (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
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- Drug class: inotropic agents
- Milrinone Lactate (AHFS Monograph)
- Milrinone (FDA)
- Milrinone Dextrose (FDA)
- Milrinone Injection (FDA)
- Milrinone Lactate in Dextrose Injection (FDA)
Other brands: Primacor