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 heart failure therapies as tolerated (ACCF/AHA [Yancy 2013]).
Continuous infusion: IV: Initial: 0.125 mcg/kg/minute; dosing range: 0.125 to 0.75 mcg/kg/minute; titrate based on clinical end point (eg, end organ perfusion). Use the lowest effective dose to minimize adverse effects (eg, arrhythmia, hypotension) (ACCF/AHA [Yancy 2013]).
Note: Loading doses are usually not recommended due to excess risk of hypotension (ACCF/AHA [Yancy 2013]), but if used, the manufacturer labeling suggests 50 mcg/kg over 10 minutes followed by a continuous infusion.
Postoperative inotropic support in heart transplant recipients (off-label use):
Continuous infusion: IV: 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]).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Conservative initial doses should be utilized, as clearance is highly dependent on kidney function. Titrate dose based on clinical response and hemodynamic end points. Monitor closely for adverse effects, such as arrhythmias and hypotension, which may occur more frequently with kidney dysfunction (ACCF/AHA [Yancy 2013]; Charisopoulou 2014; Chong 2018; Cox 2013; Hasei 2008; Majure 2011).
CrCl 10 to 50 mL/minute: Initial: 0.0625 to 0.125 mcg/kg/minute depending on indication and degree of kidney impairment; titrate cautiously, especially with worsening kidney function. Titrating to >0.375 mcg/kg/minute in significant renal impairment is generally not recommended due to likelihood for accumulation (Rodgers 2016; expert opinion).
CrCl <10 mL/minute: Not established; consider alternative therapy (Chong 2018).
There are no dosage adjustments provided in the manufacturer’s labeling.
(For additional information see "Milrinone: Pediatric drug information")
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).
Infants, Children and Adolescents: Specific recommendations for dosing adjustments in pediatric patients are lacking. Milrinone clearance is significantly reduced and other pharmacokinetic parameters (eg volume of distribution) have shown a high degree of interpatient variability in pediatric patients with acute kidney injury; doses should be individualized and titration based upon hemodynamic and clinical response rather than an algorithmic approach based upon dose adjustment for estimated creatinine clearance (Gist 2015, Vogt 2014).
There are no dosage adjustments provided in the manufacturer’s labeling.
Refer to adult dosing.
The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.
Class 1, 2, or 3 obesity (BMI ≥30 kg/m2):
Continuous infusion: IV: Use ideal body weight for initial weight-based dosing, then titrate to hemodynamic effect and clinical response (expert opinion). During therapy, clinicians should not change dosing weight from one weight metric to another (ie, actual body weight to/from ideal body weight) (Erstad 2021; expert opinion). Refer to adult dosing for indication-specific doses.
Rationale for recommendations: There is a paucity of studies evaluating the influence of obesity on milrinone dosing or pharmacokinetics. Milrinone has a small Vd; clearance is affected by kidney dysfunction and milrinone is typically titrated to clinical end points (eg, end organ perfusion, cardiac output/index). Adverse effects may be more frequent with higher doses and/or renal dysfunction (expert opinion).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous, as lactate:
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); 20 mg/100 mL in Dextrose 5% (100 mL); 40 mg/200 mL with Dextrose 5% (200 mL)
Solution, Intravenous, as lactate [preservative free]:
Generic: 200 mcg/mL (100 mL [DSC], 200 mL [DSC]); 10 mg/10 mL (10 mL); 20 mg/20 mL (20 mL); 50 mg/50 mL (50 mL); 20 mg/100 mL in Dextrose 5% (100 mL); 40 mg/200 mL with Dextrose 5% (200 mL)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Generic: 1 mg/mL (10 mL, 20 mL)
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.
Loading dose: Administer undiluted or diluted by slow IV push over at least 10 minutes; to minimize hypotension, slower infusion rates up to 60 minutes may also be used (PALS [Kleinman 2010]) or the loading dose may be divided into two or more doses and each dose is administered over 10 minutes if blood pressure remains within an acceptable range (ACCM [Davis 2017]).
Continuous IV or Intraosseous infusion: Administer as a continuous IV infusion with the use of an infusion pump or syringe pump or an intraosseous infusion until IV access can be obtained in pediatric patients (PALS [Kleinman 2010]). Avoid extravasation; administration into a large vein may help prevent the possibility of extravasation; some suggest central-line administration is preferred, especially in neonates; administration into an umbilical arterial catheter is not recommended (Eichenwald 2017).
Note: Premixed solutions available
IV infusion: 20 mg in 100 mL (total volume) (concentration: 200 mcg/mL) of D5W
Note: Premixed solutions available
IV infusion: 200 mcg/mL
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.
Postoperative inotropic support for heart transplant recipients
Primacor may be confused with Primaxin
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>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
Hypersensitivity to milrinone or any component of the formulation
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]).
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Anagrelide: May enhance the adverse/toxic effect of Milrinone. Risk X: 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. Risk C: Monitor therapy
Adverse events have not been observed in animal reproduction studies; however, increased resorption was reported in some studies.
It is not known if milrinone is present in breast milk. The manufacturer recommends that caution be exercised when administering milrinone to breastfeeding women.
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.
A selective phosphodiesterase inhibitor in cardiac and vascular tissue, resulting in vasodilation and inotropic effects with little chronotropic activity.
Onset of action: IV: 5 to 15 minutes
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)
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
Protein binding, plasma: ~70%
Metabolism: Hepatic (minor); majority is not metabolized (Rocci 1987)
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)
Excretion: 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
Solution (Milrinone Lactate in Dextrose Intravenous)
20 mg/100 mL 5% (per mL): $0.18 - $0.40
40 mg/200 mL 5% (per mL): $0.18 - $0.41
Solution (Milrinone Lactate Intravenous)
10 mg/10 mL (per mL): $0.48 - $4.80
20 mg/20 mL (per mL): $0.33 - $4.74
50 mg/50 mL (per mL): $0.42 - $3.72
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