Version October 2024
Acute decompensated heart failure:
Note: May consider for short-term use in patients with low cardiac index and hypotension or end-organ hypoperfusion (Ref).
Continuous infusion: IV: Initial: 0.125 to 0.25 mcg/kg/minute; titrate based on clinical end point (eg, systemic perfusion or end organ perfusion); usual dosage range: 0.125 to 0.75 mcg/kg/minute. Note: IV bolus loading doses are not recommended due to risk of hypotension (Ref).
Postoperative inotropic support, 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 (Ref).
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 end points. Monitor closely for adverse effects, such as arrhythmias and hypotension, which may occur more frequently with kidney dysfunction (Ref).
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 kidney impairment is generally not recommended due to likelihood for accumulation (Ref).
CrCl <10 mL/minute: Not established; consider alternative therapy (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
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 (Ref). During therapy, clinicians should not change dosing weight from one weight metric to another (ie, actual body weight to/from ideal body weight) (Ref). 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 kidney dysfunction (Ref).
Refer to adult dosing.
(For additional information see "Milrinone: Pediatric drug information")
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 (Ref).
Hemodynamic support (eg, acute decompensated heart failure, cardiogenic shock, fluid-refractory, catecholamine-resistant septic shock): Limited data available:
Infants, Children, and Adolescents:
Loading dose (optional): IV, Intraosseous: 50 mcg/kg administered over 10 to 60 minutes followed by a continuous IV or intraosseous infusion (Ref). Note: Due to the risk of hypotension, some centers do not utilize a loading dose (Ref).
Continuous IV or intraosseous infusion: Dose range: 0.25 to 0.75 mcg/kg/minute; titrate dose to effect (Ref).
Low cardiac output syndrome (LCOS) following congenital heart disease (CHD) corrective surgery, prevention: Limited data available:
Infants and Children: IV: Loading dose: 75 mcg/kg administered over 60 minutes followed by a continuous IV infusion of 0.75 mcg/kg/minute (Ref).
Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling. 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 (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%: Cardiovascular: Ventricular arrhythmia (nonsustained ventricular tachycardia [3%], ventricular ectopy [9%], ventricular fibrillation [<1%], ventricular tachycardia [1%])
1% to 10%:
Cardiovascular: Angina pectoris (≤1%), chest pain (≤1%), hypotension (3%), supraventricular cardiac arrhythmia (4%)
Nervous system: Headache (3%)
<1%:
Endocrine & metabolic: Hypokalemia
Hematologic & oncologic: Thrombocytopenia
Nervous system: Tremor
Postmarketing:
Cardiovascular: Atrial fibrillation (Kaakeh 2012), tachycardia, (Alhashemi 1998), torsades de pointes
Dermatologic: Skin rash
Hepatic: Abnormal hepatic function tests
Hypersensitivity: Anaphylactic shock
Local: Infusion-site reaction
Respiratory: Bronchospasm
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 kidney 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 kidney 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.
• Kidney impairment: Use with caution in patients with kidney impairment; reduction in infusion rate recommended. Hypotension may be prolonged in patients with kidney 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 heart failure guidelines, long-term use of IV inotropic therapy without a specific indication or for reasons other than palliation is potentially harmful (AHA/ACC/HFSA [Heidenreich 2022]).
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)
Yes
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): $0.47 - $0.97
20 mg/20 mL (per mL): $0.33 - $1.02
50 mg/50 mL (per mL): $0.41 - $0.96
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as lactate:
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.
IV, Intraosseous:
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 (Ref) or the loading dose may be divided into five equal doses and each dose is administered over 10 minutes if blood pressure remains within an acceptable range (Ref).
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 (Ref). 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 (Ref).
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: 100 mcg/mL, 200 mcg/mL.
Acute decompensated heart failure: Short-term IV therapy for patients with acute decompensated heart failure with reduced ejection fraction in need of inotropic support.
Postoperative inotropic support, heart transplant recipients
Primacor may be confused with Primaxin
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (inotropic medications, IV) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care Settings).
None known.
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 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.
BP, heart rate, ECG, hemodynamic parameters as appropriate (eg, CVP, RAP, MAP, CI, PCWP, SVR, ScvO2 or SvO2); intravascular volume status; kidney function; urine output; electrolytes (especially potassium and magnesium); platelet count.
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:
Term neonate (primary pulmonary hypertension of the newborn): Vd: 0.56 ± 0.19 L/kg (McNamara 2013).
Infants (after cardiac surgery): Vβ: 0.9 ± 0.4 L/kg (Ramamoorthy 1998).
Children (after cardiac surgery): Vβ: 0.7 ± 0.2 L/kg (Ramamoorthy 1998).
Adults: Vd:
After cardiac surgery: 0.31 L/kg (Das 1994).
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).
Half-life elimination:
Preterm neonates: 10.3 hours (Paradisis 2007).
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; kidney 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).
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.
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