Note: Dosing should be individualized and titrated to desired effect due to interpatient variability in milrinone clearance, with or without low cardiac output syndrome or acute kidney injury (Ref).
Hemodynamic support (eg, fluid-refractory, catecholamine-resistant septic shock, cardiogenic shock, acute decompensated heart failure): Limited data available:
Neonates:
Loading dose (optional): IV: 50 mcg/kg administered over 10 to 60 minutes followed by continuous IV infusion (Ref). Note: Loading doses have been associated with hypotension and, as a result, some experts recommend against the use, especially in patients with renal dysfunction; eliminating the loading dose may not dramatically alter the time to therapeutic effect (Ref).
Continuous IV infusion: 0.25 to 0.75 mcg/kg/minute; titrate to effect (Ref).
Low cardiac output syndrome (LCOS) following congenital heart disease (CHD) corrective surgery, prevention: Limited data available:
Term neonates: IV: Loading dose: 75 mcg/kg administered over 60 minutes followed by a continuous IV infusion of 0.75 mcg/kg/minute (Ref).
Persistent pulmonary hypertension of the newborn (PPHN), treatment: Very limited data in preterm neonates, limited data available in term neonates: Note: May be used in combination with nitric oxide or sildenafil.
Preterm and term neonates:
Loading dose (optional): IV: 50 mcg/kg over 60 minutes; dosing based on one open-label study in late preterm and term neonates (n=11; median GA: 39.2 ± 1.3 weeks) (Ref).
Continuous IV infusion: Initial: 0.25 to 0.5 mcg/kg/minute; titrate as needed; maximum rate: 1 mcg/kg/minute (Ref). Note: Diastolic hypotension was reported following milrinone initiation in neonates with persistent respiratory failure and hypoxic ischemic encephalopathy receiving therapeutic hypothermia and inhaled nitric oxide; may consider dose reduction in these patients (Ref).
Postligation cardiac syndrome, prevention: Very limited data available: Note: Dosing based on a pharmacokinetic study of 10 preterm neonates at risk of postligation cardiac syndrome based on post-procedure echocardiography (Ref).
Preterm neonates:
PMA <27 weeks: Continuous IV infusion: 0.5 mcg/kg/minute for 3 hours then decrease to 0.15 mcg/kg/minute for 21 hours.
PMA ≥27 to 30 weeks: Continuous IV infusion: 0.5 mcg/kg/minute for 3 hours then decrease to 0.2 mcg/kg/minute for 21 hours.
Note: A slightly different regimen has been utilized to prevent low superior vena cava flow in preterm neonates (<30 weeks GA) (Ref).
Dosing: Altered kidney function: Neonatal:
Hemodynamic support, cardiac dysfunction with increased systemic vascular resistance (eg, fluid-refractory, catecholamine-resistant septic shock, cardiogenic shock, acute decompensated heart failure):
Term neonates: Note: Use modified Schwartz equation to calculate CrCl.
CrCl >30 mL/minute/1.73 m2: No adjustment necessary (Ref).
CrCl ≤30 mL/minute/1.73 m2: Loading dose: IV: 25 mcg/kg over 30 minutes, followed by continuous IV infusion at 0.25 mcg/kg/minute (Ref).
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.
(For additional information see "Milrinone: Drug information")
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 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
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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, 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).
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.
Note: Premixed solutions available.
IV infusion: 100 mcg/mL, 200 mcg/mL.
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).
Short-term treatment of acute decompensated heart failure (FDA approved in adults); has also been used for treatment of shock (eg, cardiogenic and septic) and persistent pulmonary hypertension of the newborn (PPHN), and prevention of postoperative low cardiac output syndrome (LCOS).
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.
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 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.
Blood pressure, heart rate, ECG, hemodynamic parameters as appropriate (eg, central venous pressure [CVP], right atrial pressure [RAP], mean arterial pressure [MAP], cardiac index [CI], pulmonary capillary wedge pressure [PCWP], systemic vascular resistance [SVR], ScvO2 or SvO2); platelet count, electrolytes (especially calcium, potassium, and magnesium) and fluid status, renal function; infusion site.
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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