What is the appropriate amikacin dose and dosing interval for a 70‑year‑old woman with impaired renal function (serum creatinine 2.05 mg/dL, BUN 28 mg/dL)?

Amikacin Dosing in a 70-Year-Old Female with Renal Impairment

For this 70-year-old woman with significant renal impairment (creatinine 2.05 mg/dL, BUN 28 mg/dL), administer amikacin 10 mg/kg per dose (maximum 750 mg) given 2-3 times per week, not daily, with doses administered after dialysis if she is on hemodialysis. 1

Dose Calculation and Frequency

Age-Based Dose Reduction

• Patients over 59 years of age require a reduced dose of 10 mg/kg per day (maximum 750 mg) rather than the standard 15 mg/kg dose, regardless of renal function status. 1
• This age-based reduction is critical because elderly patients have increased risk of both ototoxicity and nephrotoxicity with aminoglycosides. 1

Renal Impairment Adjustment

• With a creatinine of 2.05 mg/dL, this patient has significant renal insufficiency requiring interval extension to 2-3 times per week rather than daily dosing. 1
• The individual dose should be maintained at 12-15 mg/kg per dose (but reduced to 10 mg/kg in this case due to age >59 years) to take advantage of the concentration-dependent bactericidal effect. 1
• Reducing the milligram dose below the recommended per-dose amount may reduce drug efficacy, so the strategy is to extend the interval, not reduce the individual dose. 1

Practical Dosing Regimen

• Calculate the dose as 10 mg/kg based on actual body weight (e.g., if she weighs 70 kg, give 700 mg per dose). 1
• Administer this dose 2-3 times per week (e.g., Monday-Wednesday-Friday or Tuesday-Thursday-Saturday). 1
• If the patient is on hemodialysis, always give amikacin after the dialysis session to prevent premature drug removal and facilitate directly observed therapy. 1

Therapeutic Drug Monitoring

Target Levels

• Peak (Cmax) levels should be 35-45 μg/mL with daily dosing or 65-80 μg/mL with intermittent dosing. 1
• Trough (Cmin) levels must remain <5 μg/mL to avoid toxicity. 1
• Measure peak levels 1 hour after infusion completion and trough levels immediately before the next dose. 1

Monitoring Schedule

• Obtain amikacin levels on day 3 and day 7 of therapy, then weekly if treatment continues beyond 10 days. 2
• Monitor serum creatinine daily to detect nephrotoxicity early. 1, 2
• Perform baseline audiogram and vestibular testing before starting therapy, then monthly assessments with questioning about auditory or vestibular symptoms. 1

Critical Safety Considerations

Nephrotoxicity Risk

• Amikacin may be more nephrotoxic than streptomycin, with renal impairment occurring in 8.7% of patients overall and higher rates in those with baseline elevated creatinine. 1
• This patient's baseline creatinine of 2.05 mg/dL places her at increased risk, necessitating careful monitoring. 1
• Concurrent use of other nephrotoxic agents (NSAIDs, contrast dye, vancomycin, loop diuretics) significantly increases nephrotoxicity risk. 1

Ototoxicity Risk

• High-frequency hearing loss occurred in 24% of patients in one study, with higher rates in those receiving longer treatment and/or higher doses. 1
• Ototoxicity is more common with concurrent use of loop diuretics. 1
• Elderly patients have increased risk of eighth nerve toxicity, making audiometric monitoring essential in this 70-year-old patient. 1

Drug Accumulation in Renal Impairment

• Amikacin half-life can increase dramatically during therapy in patients with renal insufficiency, even when serum creatinine remains stable. 3
• In one study, mean half-life increased from 11.2 hours to 21.5 hours during treatment in patients with moderate to severe renal insufficiency. 3
• This accumulation occurs due to decreased amikacin-to-creatinine clearance ratio, not just reduced GFR, emphasizing the need for therapeutic drug monitoring. 3

Common Pitfalls to Avoid

Dosing Errors

• Never give daily dosing in patients with renal impairment – this leads to drug accumulation and toxicity. 1
• Never reduce the individual dose below 10 mg/kg in this elderly patient – maintain the per-dose amount and extend the interval instead. 1
• Never administer amikacin before dialysis if the patient is on hemodialysis – always give after dialysis to prevent premature drug removal. 1

Monitoring Failures

• Do not rely solely on serum creatinine to assess renal function during therapy – amikacin clearance can decrease even with stable creatinine. 3
• Do not skip therapeutic drug monitoring – serum levels should be measured to avoid both toxicity and subtherapeutic dosing. 1
• Do not continue therapy beyond 10 days without reassessing – if treatment must continue, intensify monitoring of drug levels, renal function, and auditory/vestibular function. 1, 4

Treatment Duration

• Limit treatment duration to 7-10 days whenever feasible to minimize toxicity risk. 4
• If treatment beyond 10 days is necessary, re-evaluate the indication and intensify monitoring of amikacin serum levels, renal function, and auditory/vestibular function. 1, 4

Alternative Dosing Calculation Method

Creatinine-Based Interval Extension

• An alternative approach is to calculate the dosing interval by multiplying the serum creatinine by 9. 4
• For this patient with creatinine 2.05 mg/dL: 2.05 × 9 = 18.45 hours, which approximates to dosing every 18-24 hours. 4
• However, the guideline-recommended approach of 2-3 times weekly dosing is preferred for patients with significant renal impairment to better prevent accumulation. 1