What is the appropriate dosing of Amikacin (an aminoglycoside antibiotic) for an adult patient with impaired renal function, who has undergone radical nephrectomy for adult cystic nephroma?

Amikacin Dosing in Adult Patients with Impaired Renal Function Post-Nephrectomy

For an adult patient with impaired renal function following radical nephrectomy, amikacin should be dosed at 12-15 mg/kg per dose administered 2-3 times weekly rather than daily, maintaining the full per-dose amount while extending the dosing interval to prevent toxic accumulation while preserving concentration-dependent bactericidal activity. 1

Critical Dosing Principle in Renal Impairment

The dose per administration must NOT be reduced below 12-15 mg/kg, as smaller doses compromise the concentration-dependent killing effect of aminoglycosides and may reduce efficacy. 1 Instead, the dosing frequency is decreased to allow adequate drug clearance between doses. 1

Specific Dosing Recommendations

For Creatinine Clearance <30 mL/min or Hemodialysis Patients

• Dose: 12-15 mg/kg per administration 1
• Frequency: 2-3 times weekly (NOT daily) 1
• Timing: Administer after hemodialysis if applicable 1, 2

For Patients >59 Years of Age with Normal Renal Function

• Dose: 10 mg/kg per day (maximum 750 mg) 1, 3
• This reduced dose accounts for age-related decline in renal function 1, 3

Alternative Interval-Based Dosing Method

If using fixed intervals with reduced frequency, calculate the interval by multiplying the serum creatinine (mg/100 mL) by 9. 2 For example, if serum creatinine is 2 mg/100 mL, administer the normal dose (7.5 mg/kg) every 18 hours. 2

Mandatory Therapeutic Drug Monitoring

Serum amikacin concentrations MUST be monitored to avoid toxicity, particularly in renal impairment. 1, 2

Target Levels

• Trough: <5 mg/L 1, 3
• Peak: 25-35 mg/L (daily dosing) or 65-80 mg/L (three times weekly dosing) 1

Monitoring Frequency

• Peak levels: Within the first week, repeat if poor response 1
• Trough levels: Weekly for 4 weeks, then fortnightly when stable 1
• Renal function: Twice weekly during month 1, weekly during month 2, then fortnightly 1

Ototoxicity Monitoring Requirements

Baseline audiometry is mandatory before initiating therapy in all testable patients. 3 Monthly audiometry should continue throughout treatment. 1, 3

Ototoxicity Definition and Action

• Ototoxicity is defined as 20 dB loss from baseline at any one test frequency OR 10 dB loss at any two adjacent frequencies 1, 3
• Immediately discontinue amikacin if ototoxicity is detected 3
• Hearing loss is typically irreversible once it occurs 1, 3

Critical Pitfalls to Avoid

Do NOT Reduce the Milligram Dose

Reducing the dose below 12-15 mg/kg compromises efficacy by failing to achieve adequate peak concentrations needed for concentration-dependent bacterial killing. 1 The American Thoracic Society explicitly warns that smaller doses may reduce drug efficacy. 1

Do NOT Combine with Loop Diuretics

Concurrent use of furosemide or other loop diuretics potentiates ototoxicity. 1, 3 This combination should be avoided. 1, 3

Do NOT Use Standard Daily Dosing in Renal Impairment

Standard daily dosing (15 mg/kg/day) in patients with creatinine clearance <30 mL/min leads to toxic accumulation. 1 The half-life of amikacin increases 5-10 fold in renal insufficiency. 4, 5

Do NOT Administer Before Hemodialysis

Approximately 40% of the dose is removed during hemodialysis if given before the session. 1 Always administer after dialysis to prevent premature drug removal and facilitate directly observed therapy. 1, 3

Additional Risk Factors Requiring Enhanced Monitoring

Patients with the following characteristics require more intensive monitoring: 3, 6

• Pre-existing renal insufficiency 3, 6
• Concurrent nephrotoxic agents (vancomycin, cisplatin) 3, 6
• Volume depletion or hemodynamic instability 6
• Hepatic disease (predisposes to hepatorenal syndrome) 1, 6
• Diabetes or immunocompromised state 3
• Previous aminoglycoside exposure 3

Duration Considerations

For serious infections, a minimum of 4 months of therapy may be necessary for cure, with 6 months recommended for bone infections. 1 However, treatment beyond 10 days requires re-evaluation with monitoring of serum levels, renal function, and auditory/vestibular function. 2

Practical Loading Dose Strategy

Administer a normal loading dose of 7.5 mg/kg initially, then adjust maintenance dosing based on renal function. 2 This ensures adequate initial drug exposure while preventing subsequent accumulation. 2