Target Trough Levels for Amikacin

The target trough level for amikacin should be less than 5 mg/L to minimize toxicity while maintaining therapeutic efficacy. 1

Standard Trough Monitoring Targets

Trough concentrations must be maintained below 5 mg/L to prevent drug accumulation and reduce the risk of nephrotoxicity and ototoxicity 1, 2
The FDA label specifies that trough concentrations (measured just prior to the next dose) above 10 mg/L should be avoided 3
For pediatric patients receiving amikacin for synergy (such as in infective endocarditis), a more stringent target of <1 μg/mL is recommended 1

Trough levels should be measured predose, with the first check recommended 1 week after starting therapy 1
Peak serum levels should be measured within the first week, and trough levels should be measured weekly for 4 weeks, then every 2 weeks when stable 2
In research settings, trough levels measured after 72 hours of therapy have been used to assess early drug accumulation 4

Elevated trough levels (>5 mg/L) are directly associated with increased risk of nephrotoxicity and ototoxicity 1
Research demonstrates a positive correlation between elevated amikacin trough levels and post-dose serum creatinine elevation (r = 0.48, P < 0.05) 4
In a controlled trial, individualized pharmacokinetic dosing targeting trough levels <1 μg/mL reduced nephrotoxicity from 21% to 5% (P = 0.03) 5
The highest drug concentration 12 hours after administration was significantly associated with development of toxicities (adjusted OR 1.862, P = 0.047) 6

If trough levels are high (>5 mg/L), extend the dosing interval rather than reducing the dose 1
This approach maintains the concentration-dependent bactericidal effect while allowing more time for drug elimination 7
In patients with renal impairment, dosing frequency should be reduced (every 2-3 days) while maintaining the dose at 12-15 mg/kg 2, 7

For ESRD patients, dosing frequency should be reduced to two or three times per week at 12-15 mg/kg 7
Administration should occur after dialysis to prevent premature drug removal 7
Standard trough targets of <5 mg/L still apply 1

Preterm infants demonstrate significantly higher trough levels compared to term infants (median 11.33 vs 8.5 μg/mL, P < 0.01) at standard dosing 4
62% of preterm infants developed toxic trough levels with standard 15 mg/kg dosing, compared to 21% in term infants 4
More frequent therapeutic drug monitoring is essential in this population 4

Failure to monitor trough levels leads to drug accumulation and increased toxicity, particularly in patients with renal impairment 1
Elderly patients are particularly susceptible to nephrotoxicity and ototoxicity and require closer monitoring 1
Concomitant use of other nephrotoxic medications (vancomycin, amphotericin B, loop diuretics) increases the risk of adverse effects 1, 3
Administering amikacin before dialysis in ESRD patients will result in premature drug removal and treatment failure 7

Monthly renal function assessments are recommended (more frequent if renal impairment is present) 1
Auditory and vestibular monitoring is necessary as ototoxicity is a significant risk with amikacin therapy 1
Blood urea nitrogen, serum creatinine, or creatinine clearance should be measured periodically 3
Serial audiograms should be obtained where feasible, particularly in high-risk patients 3