MILRINONE LACTATE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Selective phosphodiesterase III (PDE3) inhibitor; increases intracellular cAMP in cardiac and vascular smooth muscle, resulting in positive inotropy and vasodilation.

What the body does with it

Metabolism	Primarily hepatic metabolism (about 50-70%) via glucuronidation; renal excretion of unchanged drug accounts for about 10-30%.
Excretion	Primarily renal (80-90% as unchanged drug), with minor biliary/fecal elimination (<10%)
Half-life	2.5 hours (range 2-4 hours) in patients with normal renal function; prolonged up to 6-10 hours in renal impairment
Protein binding	70% bound primarily to albumin
Volume of Distribution	0.38-0.45 L/kg, indicating distribution primarily in extracellular fluid
Bioavailability	Not available (100% IV); oral bioavailability is ~70%, but only IV formulation is clinically used
Onset of Action	Intravenous bolus: 5-15 minutes; continuous IV infusion: 2-3 hours to steady state
Duration of Action	Hemodynamic effects persist for 4-6 hours after discontinuation of infusion, due to active metabolites?

Classification & Brands

Dosing & administration

Intravenous loading dose of 50 mcg/kg over 10 minutes, followed by continuous infusion of 0.375–0.75 mcg/kg/min. Titrate based on hemodynamic response; maximum infusion rate 1.13 mg/kg/day.

Dosage form	INJECTABLE
Renal impairment	For creatinine clearance (CrCl) <50 mL/min: reduce infusion rate. CrCl 30–50 mL/min: 0.2–0.43 mcg/kg/min. CrCl <30 mL/min: 0.2–0.28 mcg/kg/min.
Liver impairment	No specific Child-Pugh based dose adjustments; use with caution in severe hepatic impairment due to limited data.
Pediatric use	Loading dose: 50 mcg/kg IV over 10 minutes. Maintenance infusion: 0.5–0.75 mcg/kg/min; typical range 0.25–0.75 mcg/kg/min. Maximum infusion rate 1.13 mg/kg/day.
Geriatric use	No specific dose adjustment, but may require reduced dosing due to age-related decline in renal function; monitor renal function and titrate accordingly.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

No significant drug interactions Can cause ventricular arrhythmias and hypotension.

Breastfeeding

Excretion into human milk unknown. M/P ratio not determined. Due to potential for serious adverse reactions in nursing infants (e.g., hypotension, arrhythmias), advise against breastfeeding during therapy or for 48 hours after last dose.

Teratogenic Risk

Pregnancy Category C. Animal studies have shown fetal toxicity (reduced fetal weight, increased fetal death) at doses 5-10 times the human dose. No adequate human studies in pregnant women; use only if potential benefit justifies risk. First trimester: potential for teratogenicity unknown; avoid if possible. Second and third trimesters: may cause fetal tachycardia, hypotension, or impaired placental perfusion; monitor fetal heart rate and uterine activity.

Warnings & precautions

■ FDA Black Box Warning

May increase mortality risk in patients with severe heart failure when used long-term (chronic therapy). Not recommended for long-term use.

Side Effect Profile

Common Effects	Arrhythmias
Serious Effects

Absolute Contraindications

["Severe aortic or pulmonic valvular disease","Severe obstructive hypertrophic cardiomyopathy","Hypersensitivity to milrinone or any product component"]

Clinical Precautions

Precautions

["Ventricular arrhythmias including sustained ventricular tachycardia and ventricular fibrillation","Hypotension","Thrombocytopenia","Atrial flutter/fibrillation with rapid ventricular response","Renal impairment requires dose adjustment","Hypokalemia should be corrected before use"]

Clinical Tips & Counseling

Drug interactions

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