What is the recommended dosing regimen for amikacin (generic name) in patients with normal and impaired renal function?

Amikacin Dosing Regimen for Normal and Impaired Renal Function

For patients with normal renal function, amikacin should be administered at 15 mg/kg/day as a single daily dose (maximum 1.0 g/day), with dose reduction to 10 mg/kg/day (maximum 750 mg) for patients over 59 years of age. 1

Dosing in Normal Renal Function

Adults

• Single daily dosing: 15 mg/kg/day (maximum 1.0 g/day) 1
• Alternative regimen per FDA label: 15 mg/kg/day divided into 2-3 equal doses (7.5 mg/kg q12h or 5 mg/kg q8h) 2
• For patients >59 years: Reduce to 10 mg/kg/day (maximum 750 mg) 1
• For uncomplicated UTIs: 250 mg twice daily may be sufficient 2

Pediatric Patients

• Infants and children: 15-30 mg/kg/day as a single daily dose (maximum 1 g/day) 1
• Newborns: Loading dose of 10 mg/kg followed by 7.5 mg/kg every 12 hours 2

Single daily dosing is preferred as it provides higher peak concentrations that enhance concentration-dependent bactericidal effects while allowing longer drug-free periods to reduce toxicity 1.

Dosing in Impaired Renal Function

Patients with renal impairment require dose adjustment using one of two approaches:

1. Normal Dose at Prolonged Intervals

• Maintain dose at 12-15 mg/kg but extend interval between doses to 2-3 times per week 1
• If creatinine clearance is unavailable: Calculate dosing interval (hours) by multiplying serum creatinine by 9
  • Example: If serum creatinine is 2 mg/dL, administer normal dose every 18 hours 2

2. Reduced Dose at Fixed Intervals

• Maintenance dose (every 12 hours) = (observed CrCl / normal CrCl) × loading dose 2
• Alternative calculation: Divide normal dose by patient's serum creatinine 2

Therapeutic Drug Monitoring

Monitoring serum concentrations is crucial for optimal dosing:

• Target peak levels: 25-35 μg/mL (measured 30-90 minutes after injection) 1, 2
• Target trough levels: <5-10 μg/mL (measured just before next dose) 1, 2
• Peak levels >35 μg/mL and trough levels >10 μg/mL should be avoided 2

Administration Methods

• Intramuscular: Direct injection
• Intravenous: Dilute in 100-200 mL of compatible solution (0.9% sodium chloride or 5% dextrose) and infuse over 30-60 minutes 2
• For pediatric patients: Adjust fluid volume appropriately; infants should receive a 1-2 hour infusion 2

Monitoring Recommendations

• Baseline renal function tests before starting treatment 1
• Monthly assessment of renal function for all patients 1
• More frequent monitoring (every 1-2 weeks) for high-risk patients:
  • Those receiving aminoglycosides
  • Patients with baseline renal impairment
  • Elderly patients 1
• Regular monitoring of auditory and vestibular function 1

Common Pitfalls and Caveats

• Nephrotoxicity occurs in 2-25% of patients receiving aminoglycosides 1
• Risk factors for nephrotoxicity include:
  • Pre-existing renal impairment
  • Advanced age (>59 years)
  • Larger cumulative doses
  • Concurrent use of other nephrotoxic agents
  • Dehydration 1
• Amikacin is contraindicated in pregnancy due to risk of fetal nephrotoxicity and congenital hearing loss 1
• Avoid concurrent use with other aminoglycosides or nephrotoxic agents 1
• Treatment duration should be limited to 7-10 days when possible; extended treatment requires careful monitoring 2
• If no clinical response occurs within 3-5 days, therapy should be reassessed 2

While the FDA label suggests divided dosing 2, more recent guidelines from the American Thoracic Society and CDC support once-daily dosing 1, which provides optimal pharmacodynamics while potentially reducing toxicity.