Amikacin Dosing in a 60-Year-Old Male with Renal Impairment
For this patient with a creatinine of 1.6 mg/dL, you must first calculate creatinine clearance using the Cockcroft-Gault equation to determine the appropriate amikacin dose, as serum creatinine alone significantly underestimates the degree of renal impairment and will lead to dangerous overdosing. 1, 2, 3
Step 1: Calculate Creatinine Clearance
Using the Cockcroft-Gault equation for this 60-year-old, 70 kg male with creatinine 1.6 mg/dL:
CrCl = [(140 - 60) × 70] / (72 × 1.6) = 48.6 mL/min
This represents moderate renal impairment (Stage 3 CKD), despite the creatinine being only mildly elevated. 2, 3 Patients can have significantly decreased GFR with near-normal serum creatinine values, particularly in older adults, making recognition of renal dysfunction more difficult if you rely on creatinine alone. 2
Step 2: Determine Loading Dose
Administer a loading dose of 7.5 mg/kg = 525 mg (approximately 500 mg) as the initial dose. 1 The loading dose remains the same regardless of renal function because it is needed to rapidly achieve therapeutic concentrations. 1
Step 3: Calculate Maintenance Dosing Interval
With a CrCl of 48.6 mL/min, you have two FDA-approved options:
Option A: Normal Dose at Prolonged Intervals (Preferred)
Administer 7.5 mg/kg (525 mg) every 14-15 hours. 1
The FDA label provides a simple calculation: multiply the serum creatinine by 9 to get the dosing interval in hours. 1 For this patient: 1.6 × 9 = 14.4 hours, which can be rounded to every 12-15 hours in practice. 1
Option B: Reduced Dose at Fixed Intervals
Administer a reduced maintenance dose every 12 hours, calculated as:
Maintenance Dose = (Observed CrCl / Normal CrCl) × Loading Dose 1 = (48.6 / 100) × 525 mg = 255 mg every 12 hours 1
Critical Monitoring Requirements
The half-life of amikacin increases dramatically during therapy in patients with renal insufficiency, even when serum creatinine remains stable. 4 In patients with creatinine >1.5 mg/dL, amikacin half-life nearly doubles from 11.2 hours to 21.5 hours during treatment, requiring dose reduction as therapy continues. 4
Measure peak and trough concentrations after the loading dose and before the second maintenance dose. 5 Target peak concentration should be ≥8 times the MIC of the pathogen (typically 40-60 mcg/mL for most susceptible organisms). 5 Trough concentrations >5 mg/L are associated with nephrotoxicity and mandate dose adjustment. 5
Reassess creatinine clearance every 2-3 days during therapy. 4, 5 The ratio of amikacin clearance to creatinine clearance decreases during treatment due to aminoglycoside accumulation in deep compartments, necessitating further dose reductions even if serum creatinine remains unchanged. 4
Common Pitfalls to Avoid
Do not dose based on serum creatinine alone—this patient's creatinine of 1.6 mg/dL appears only mildly elevated, but his actual CrCl of 48.6 mL/min represents moderate renal impairment requiring significant dose adjustment. 2, 3 Using standard dosing (7.5 mg/kg every 12 hours) would result in toxic accumulation. 1, 4
Do not use eGFR for aminoglycoside dosing—the Cockcroft-Gault equation using actual body weight is the validated method for aminoglycoside dose adjustment. 3, 6
Do not exceed 1.5 grams total daily dose regardless of calculated doses. 1
Limit treatment duration to 7-10 days whenever feasible. 1 If treatment beyond 10 days is required, amikacin serum levels and renal, auditory, and vestibular functions must be monitored closely. 1
Practical Recommendation
Start with 500 mg IV loading dose, then 500 mg every 15 hours (or 250 mg every 12 hours), with mandatory therapeutic drug monitoring after the first dose to guide subsequent adjustments. 1, 5 This approach balances the need for rapid therapeutic concentrations against the substantial risk of nephrotoxicity in a patient with pre-existing renal impairment. 4, 5