From the FDA Drug Label
Data obtained from patients with severe renal impairment (creatinine clearance = 0 to 30 mL/min) but without congestive heart failure have demonstrated that the presence of renal impairment significantly increases the terminal elimination half-life of milrinone lactate. Reductions in infusion rate may be necessary in patients with renal impairment For patients with clinical evidence of renal impairment, the recommended infusion rate can be obtained from the following table: Creatinine Clearance (mL/min/1.73m 2) Infusion Rate (mcg/kg/min) 5 0.2 10 0.23 20 0.28 30 0.33 40 0.38 50 0.43
The milrinone dose should be adjusted in patients with renal disease. Reductions in infusion rate may be necessary in patients with renal impairment. The recommended infusion rate can be determined based on the patient's creatinine clearance, with lower infusion rates recommended for patients with more severe renal impairment 1.
- For patients with a creatinine clearance of 5 mL/min/1.73m², the recommended infusion rate is 0.2 mcg/kg/min.
- For patients with a creatinine clearance of 10 mL/min/1.73m², the recommended infusion rate is 0.23 mcg/kg/min.
- For patients with a creatinine clearance of 20 mL/min/1.73m², the recommended infusion rate is 0.28 mcg/kg/min.
- For patients with a creatinine clearance of 30 mL/min/1.73m², the recommended infusion rate is 0.33 mcg/kg/min.
- For patients with a creatinine clearance of 40 mL/min/1.73m², the recommended infusion rate is 0.38 mcg/kg/min.
- For patients with a creatinine clearance of 50 mL/min/1.73m², the recommended infusion rate is 0.43 mcg/kg/min.
From the Research
Milrinone dosing should be reduced in patients with renal impairment, with adjustments based on creatinine clearance (CrCl) to prevent drug accumulation and potential adverse effects. For patients with CrCl 50 mL/min or greater, no adjustment is needed to the standard loading dose of 50 mcg/kg over 10 minutes followed by maintenance infusion of 0.375-0.75 mcg/kg/min. For CrCl 30-49 mL/min, reduce the maintenance dose by 30-50% (to approximately 0.2-0.43 mcg/kg/min) while keeping the same loading dose. For CrCl less than 30 mL/min, reduce the maintenance dose by 50-70% (to approximately 0.12-0.37 mcg/kg/min) with the same loading dose.
These adjustments are necessary because milrinone is primarily eliminated by the kidneys, with approximately 80-85% excreted unchanged in urine, as noted in studies such as 2. Without dose adjustment in renal impairment, drug accumulation can occur, potentially leading to excessive vasodilation, hypotension, and arrhythmias. Close hemodynamic monitoring is essential during milrinone administration in all patients, but particularly those with renal dysfunction, as emphasized in 3 and 4. Dose titration should be based on clinical response and tolerance, with careful attention to blood pressure, heart rate, and cardiac output.
Key considerations in managing patients with renal impairment include:
- Monitoring renal function and adjusting drug dosages accordingly, as discussed in 5 and 6
- Avoiding potential nephrotoxins and adjusting drug dosing to prevent adverse effects, as noted in 4
- Close monitoring of patients with renal dysfunction to prevent complications, as emphasized in 3 and 4
Overall, careful management of milrinone dosing in patients with renal impairment is crucial to prevent adverse effects and ensure optimal treatment outcomes, as supported by the most recent and highest quality studies, including 3 and 4.