What is the recommended dosing frequency of Amikacin (once daily (OD) or twice daily (BD)) in adults with normal renal function?

Amikacin Dosing Frequency in Adults

Amikacin should be administered once daily (OD) in adults with normal renal function at a dose of 15 mg/kg/day, given as a single daily dose 5-7 days per week initially. 1, 2, 3

Standard Dosing Algorithm

Initial Intensive Phase

• Administer 15 mg/kg/day as a single daily dose (maximum 1 gram/day) for the first 2-4 months or until culture conversion 1, 2
• Give 5-7 days per week during this initial phase 1, 2
• The once-daily regimen achieves therapeutic peak concentrations more reliably than divided dosing (100% vs 48% of patients achieving therapeutic peaks) 4

Continuation Phase

• After 2-4 months or culture conversion, reduce frequency to 2-3 times weekly while maintaining the same mg/kg dose 1, 2
• This takes advantage of the concentration-dependent bactericidal effect of aminoglycosides 1, 5

Why Once Daily is Superior

The FDA label technically allows divided dosing (7.5 mg/kg q12h or 5 mg/kg q8h), but once-daily dosing is strongly preferred based on pharmacokinetic principles: 3

• Once-daily dosing produces higher peak concentrations (essential for concentration-dependent killing) while allowing longer drug-free intervals that reduce toxicity risk 4
• Trough concentrations are significantly lower with once-daily dosing, reducing nephrotoxicity and ototoxicity risk 4
• Clinical efficacy is equivalent or superior: 83.1% primary success rate with once-daily 15 mg/kg dosing in severe infections 6

Age-Specific Modifications

• For patients >59 years old: reduce dose to 10 mg/kg/day (maximum 750 mg) given once daily, as elderly patients have increased risk of ototoxicity and nephrotoxicity 1, 2, 5
• Elderly patients often have reduced creatinine clearance even with normal serum creatinine 7

Renal Impairment Adjustments

Critical principle: maintain the mg/kg dose but extend the dosing interval 1, 5

• Give 12-15 mg/kg per dose, but reduce frequency to 2-3 times weekly 1, 5
• Never reduce the milligram dose—this is a common pitfall that risks treatment failure 5
• Administer after dialysis to facilitate directly observed therapy and avoid premature drug removal 5

Monitoring Requirements

Baseline Assessment

• Audiogram, vestibular testing, Romberg testing, and serum creatinine 1, 2, 5

During Therapy

• Monthly renal function assessment and questioning about auditory/vestibular symptoms 1, 2, 5
• Target peak levels: 25-35 mg/L for daily dosing (measured 30-90 minutes post-infusion) 5, 3
• Target trough levels: <5 mg/L to prevent toxicity 5
• Peak concentrations above 35 mcg/mL and trough concentrations above 10 mcg/mL should be avoided 3

Common Pitfalls to Avoid

• Do not use fixed 500 mg doses regardless of weight—this risks underdosing in heavier patients and treatment failure 5
• Do not divide the daily dose into twice-daily or three-times-daily regimens unless specifically indicated by the FDA label for certain situations, as this increases trough levels and toxicity risk 4
• Do not continue therapy beyond 10 days without reassessing drug levels and monitoring for toxicity 5
• Do not reduce the mg/kg dose in renal impairment; instead extend the dosing interval 1, 5

Duration of Therapy

• Usual duration is 7-10 days for most infections 3
• For tuberculosis, continue for 2-4 months or until culture conversion 1, 2
• If treatment beyond 10 days is required, re-evaluate the need for amikacin and intensify monitoring of serum levels, renal function, and auditory/vestibular function 3

Special Considerations

• Pregnancy: absolutely contraindicated due to risk of fetal nephrotoxicity and congenital hearing loss 5
• CNS infections: poor CSF penetration even with meningitis, which may necessitate higher systemic doses 2, 5
• Obese patients: adjust dose using ideal body weight plus 40% of excess weight 5