What are the recommended dosing, renal dose adjustments, therapeutic drug monitoring parameters, and contraindications for amikacin in adults and children?

Amikacin Dosing, Monitoring, and Safety Guidelines

Adult Dosing

For adults with normal renal function, administer amikacin 15 mg/kg/day intravenously or intramuscularly, either as a single daily dose or divided into 2-3 doses (7.5 mg/kg every 12 hours or 5 mg/kg every 8 hours), with a maximum total daily dose not exceeding 15 mg/kg/day or 1.5 grams/day. 1

• Once-daily dosing is preferred because aminoglycosides exhibit concentration-dependent killing and a prolonged post-antibiotic effect, and this approach may reduce both nephrotoxicity and ototoxicity compared to divided dosing. 2

• For patients older than 50-59 years, reduce the dose to 10 mg/kg/day (approximately 750 mg) due to age-related decline in renal function. 3, 4

• Administer intravenously over 30-60 minutes when using the IV route. 1

Pediatric Dosing

For infants and children with normal renal function, administer 15-22.5 mg/kg/day divided every 8 hours (5-7.5 mg/kg every 8 hours), or alternatively 15-20 mg/kg once daily. 5

Neonatal Dosing (Weight and Age-Stratified):

• Neonates <1200 grams, ≤7 days old: 7.5 mg/kg every 18-24 hours 5
• Neonates 1200-2000 grams, >7 days old: 7.5-10 mg/kg every 8-12 hours 5
• Newborns (general recommendation): Loading dose of 10 mg/kg, then 7.5 mg/kg every 12 hours 1

Critical Pediatric Pitfall:

• Never use fixed 500 mg doses in children—this ignores weight entirely and risks treatment failure. Always calculate doses based on actual body weight. 5, 2

Renal Dose Adjustments

In renal impairment, do NOT reduce the mg/kg dose; instead, maintain the full 12-15 mg/kg dose and extend the dosing interval (e.g., every 2-3 days) to preserve peak concentrations while limiting toxicity. 4

• For patients on hemodialysis: Administer 12-15 mg/kg per dose after dialysis, given 2-3 times weekly. 4

• Alternative method for stable patients: Calculate the dosing interval in hours by multiplying the serum creatinine (mg/dL) by 9. For example, if serum creatinine is 2 mg/dL, give the normal dose every 18 hours. 1

• Reduced dosage at fixed intervals (when interval extension is not feasible): After a loading dose of 7.5 mg/kg, calculate maintenance doses using: Maintenance Dose = (observed creatinine clearance/normal creatinine clearance) × loading dose, administered every 12 hours. 1

Therapeutic Drug Monitoring (TDM)

Target Levels for Once-Daily Dosing:

• Peak concentration: 25-35 mg/L for daily dosing, or 65-80 mg/L when dosing three times weekly 4
• Trough concentration: <5 mg/L 4, 2
• Measure peak levels 30-90 minutes after infusion completion 1

Target Levels for Divided Dosing:

• Peak concentration: 30-40 mg/L (measured 30-90 minutes after infusion) 4
• Trough concentration: <10 mg/L 4
• Avoid peak concentrations >35 mg/L and trough concentrations >10 mg/L 1

Monitoring Schedule:

• Obtain a peak level within the first week of therapy 4
• Measure trough levels weekly for the first 4 weeks, then every 2 weeks once stable 4
• Whenever possible, measure both peak and trough concentrations intermittently during therapy 1

Baseline and Ongoing Safety Monitoring

Before Starting Therapy:

• Obtain audiogram, vestibular testing, Romberg testing, and serum creatinine 4, 2

During Therapy:

• Monthly monitoring: Reassess renal function (serum creatinine), inquire about auditory or vestibular symptoms 3, 4
• Repeat audiogram and vestibular testing if any eighth-nerve toxicity symptoms develop 4
• For nebulized amikacin in NTM disease, perform monthly renal, auditory, and vestibular monitoring 3

Ototoxicity Definition:

• 20 dB loss from baseline at any one test frequency, OR 10 dB loss at any two adjacent test frequencies 3, 2
• If this occurs, discontinue amikacin or reduce dosing frequency; hearing loss is likely permanent 3

Toxicity Profiles

Ototoxicity:

• Occurs in approximately 24% of patients 4
• Risk increases with cumulative doses >100-120 grams and concurrent loop diuretics 4
• High-frequency hearing loss occurs first; amikacin causes less vestibular dysfunction than streptomycin 4

Nephrotoxicity:

• Overall incidence is 8.7%, dropping to 3.4% in patients without risk factors 4
• Risk factors include pre-existing elevated creatinine, larger total doses, and concurrent nephrotoxic agents 4
• Amikacin may be more nephrotoxic than streptomycin but comparable to gentamicin and tobramycin 4, 6

Contraindications

Pregnancy is an absolute contraindication due to risk of fetal nephrotoxicity and congenital hearing loss (vestibular or auditory nerve damage to fetus if used in second or third trimester). 3, 4, 2

• Hypersensitivity to amikacin or other aminoglycosides 3
• Myasthenia gravis: Amikacin may impair neuromuscular transmission 3

Drug Interactions

Increased Toxicity Risk:

• Ototoxicity: Loop diuretics 3
• Nephrotoxicity: Capreomycin, cephalosporins, ciclosporin, colistimethate sodium, tacrolimus 3
• Hypocalcemia: Bisphosphonates 3

Critical Interaction Note:

• No clinical benefit in prescribing amikacin AND capreomycin, kanamycin, or streptomycin simultaneously 3

Duration of Therapy

• Standard infections: 7-10 days; limit duration to short-term whenever feasible 1
• Complicated intra-abdominal infections: 4-7 days unless source control is inadequate 3, 4
• Serious M. abscessus infections: Minimum 4 months; 6 months for bone infections 3
• Uncomplicated UTIs: 250 mg twice daily may be used 1

Special Clinical Situations

M. abscessus Infections:

• IV amikacin: 10-15 mg/kg daily (lower dose for patients >50 years or therapy ≥3 weeks) to achieve peak serum levels of approximately 20 mg/L 3
• Three-times-weekly dosing: 25 mg/kg may be used but difficult to tolerate beyond 3 months 3
• Combine with high-dose cefoxitin (up to 12 g/day) or imipenem (500 mg 2-4 times daily) for initial therapy (minimum 2 weeks) 3

Nebulized Amikacin for NTM:

• Adults and children: 500 mg twice daily (nebulized); may reduce to 250-500 mg once or twice daily if intolerance occurs 3
• Use 250 mg/mL injection diluted to 4 mL with 0.9% sodium chloride 3
• Administer bronchodilator prior to reduce coughing and bronchospasm 3
• Perform supervised test dose with pre- and post-dose lung function monitoring 3

Febrile Neutropenic or Cystic Fibrosis Patients:

• May require initial doses of 30 mg/kg/day divided every 8 hours based on documented need from serum levels 5

Key Clinical Pitfalls to Avoid

• Do not reduce the mg/kg dose in renal impairment—extend the interval instead to maintain therapeutic peaks 4, 2
• Do not use fixed doses (e.g., 500 mg) without weight-based calculation 5, 2
• Do not continue beyond 10 days without re-evaluation and monitoring of serum levels, renal function, and auditory/vestibular function 1
• Do not combine with other aminoglycosides (capreomycin, kanamycin, streptomycin) as there is no added benefit 3
• Once-daily dosing has not been fully evaluated in pregnant women, children, elderly persons, and critically ill patients—use caution in these populations 2