Amikacin: Indications, Dosing, and Adverse Effects
Primary Indications
Amikacin is indicated for serious gram-negative bacterial infections, particularly those caused by organisms resistant to gentamicin and tobramycin, and as part of combination therapy for non-tuberculous mycobacterial (NTM) pulmonary disease. 1, 2
Specific Clinical Scenarios
Gram-negative infections: Highly effective against most gram-negative bacteria including gentamicin- and tobramycin-resistant strains, with documented efficacy in genitourinary infections (90% cure rate), septicemia (85%), and respiratory tract infections (69%). 3, 4
Non-tuberculous mycobacterial disease: Used as part of multi-drug regimens for MAC (Mycobacterium avium complex) and other NTM infections, particularly in extensive or fibrocavitary disease and in patients who have failed prior therapy. 2
Febrile neutropenia: Preferred aminoglycoside for empiric therapy in immunocompromised hosts due to enhanced activity against organisms commonly encountered in this population. 4
Gentamicin-resistant infections: Amikacin achieved 88% efficacy in treating infections caused by gentamicin-resistant pathogens. 3
Dosing Regimens
Standard Adult Dosing (Normal Renal Function)
Daily dosing: 15 mg/kg once daily (maximum 1.5 g/day) administered IV over 30-60 minutes or IM, given 5-7 days per week initially. 1, 5
Divided dosing: Alternative regimens include 7.5 mg/kg every 12 hours or 5 mg/kg every 8 hours. 1, 5
Duration: Typical treatment course is 7-10 days; if therapy beyond 10 days is required, reassess necessity and intensify monitoring. 1
Intermittent (Thrice-Weekly) Dosing
After 2-4 months of therapy or culture conversion in NTM disease, reduce frequency to 15-25 mg/kg three times weekly while maintaining the mg/kg dose. 5, 2
Target peak concentrations for intermittent dosing: 65-80 mg/L. 5
Age-Related Adjustments
Elderly patients (>59 years): Reduce to 10 mg/kg once daily (maximum 750 mg) due to substantially increased risk of ototoxicity and nephrotoxicity. 5, 6
Pediatric patients: 15-30 mg/kg once daily (maximum 1 g/day). 5
Newborns: Loading dose of 10 mg/kg, then 7.5 mg/kg every 12 hours. 1
Renal Impairment Adjustments
Critical principle: Never reduce the mg/kg dose in renal impairment; instead extend the dosing interval to preserve concentration-dependent bactericidal activity. 5, 7
Maintain dose at 12-15 mg/kg but administer 2-3 times per week according to renal function. 5, 7
Practical calculation: Multiply serum creatinine (mg/dL) by 9 to obtain dosing interval in hours. Example: creatinine 2 mg/dL → dose every 18 hours. 5, 1
Hemodialysis patients: Administer 12-15 mg/kg 2-3 times weekly after dialysis to prevent premature drug removal. 5, 7
Obesity Adjustments
Calculate dosing weight as ideal body weight (IBW) + 40% of excess weight. 5
IBW formulas: Male = 50 kg + 2.3 × (height in cm − 152.4)/2.54; Female = 45.5 kg + 2.3 × (height in cm − 152.4)/2.54. 5
Nebulized Amikacin (for NTM Disease)
Standard dose: 500 mg twice daily via nebulizer with filter attachment. 2
Reduced dose: 250-500 mg once or twice daily if intolerance develops after initial period. 2
Preparation: Use 250 mg/mL injection diluted to 4 mL with 0.9% sodium chloride. 2
Pre-treatment: Administer bronchodilator (e.g., salbutamol) before nebulization to reduce coughing and bronchospasm. 2
Therapeutic Drug Monitoring
Target Levels
Peak concentrations: 25-35 mg/L for daily dosing; 65-80 mg/L for thrice-weekly dosing. 5, 1
Peak levels above 35 mcg/mL and trough levels above 10 mcg/mL should be avoided. 1
Sampling Timing
Peak: Draw 60-120 minutes after infusion ends (or 30-90 minutes per FDA label). 5, 1
Trough: Draw immediately before next dose. 5
Monitoring Frequency
Peak levels: Measure during first week; repeat if clinical response is poor. 5
Trough levels: Weekly for first 4 weeks, then every two weeks once stable. 5
For nebulized amikacin, check trough level 1 week after starting to ensure no systemic accumulation. 2
Major Adverse Effects
Ototoxicity (Most Important)
Ototoxicity is the most clinically significant adverse effect, characterized by irreversible hearing loss and vestibular dysfunction. 2
Incidence: High-frequency hearing loss occurs in 1.5-24% of patients, with higher rates in longer treatment courses and higher doses. 5
Audiologic definition: Loss of 20 dB at any single frequency or 10 dB at two adjacent frequencies on audiogram. 2
Clinical manifestations: Hearing loss (usually occurs first), tinnitus, vertigo, loss of balance, and auditory disturbances. 2
Risk factors: Advanced age, prolonged use, concurrent loop diuretics (markedly increases risk), cumulative doses above 100-120 g, and previous aminoglycoside exposure. 2, 6
Irreversibility: Hearing loss that has occurred is likely permanent even after discontinuation. 2
Nephrotoxicity
Incidence: Occurs in 8.7% of patients overall, but only 3.4% in those without risk factors. 5
Risk factors: Pre-existing renal impairment, prolonged use, concurrent nephrotoxic agents (capreomycin, cephalosporins, ciclosporin, colistimethate, tacrolimus), dehydration, and advanced age. 2
Monitoring: Nephrotoxicity is generally less common with amikacin than with other aminoglycosides but requires vigilant monitoring. 8
Other Adverse Effects
Circumoral paresthesias: Relatively common immediately after injection. 6
Neuromuscular blockade: Risk of impaired neuromuscular transmission, particularly concerning in myasthenia gravis. 2
Hypocalcemia: Increased risk when combined with bisphosphonates. 2
Overall tolerability: No side effects reported in 80.6% of patients in large clinical trials. 3
Safety Monitoring Protocol
Baseline Assessment
Audiogram and vestibular testing (including Romberg test). 5, 6
Serum creatinine and calculation of creatinine clearance. 1
Complete blood count, liver function tests. 2
During Therapy
Renal function monitoring:
Intensive phase: Twice weekly during month 1, weekly during month 2. 2
Continuation phase: Every 2 weeks thereafter; increase frequency if renal impairment emerges. 2, 5
For nebulized amikacin: Monthly monitoring (or more frequently if impairment develops). 2
Ototoxicity monitoring:
Baseline audiometry, then monthly audiometry until aminoglycoside therapy ceases. 2
Final audiometry review 2 months after final dose. 2
Question patients at each visit about tinnitus, hearing changes, vertigo, or balance problems. 5, 6
Repeat audiogram and vestibular testing immediately if any symptoms develop. 6
For nebulized amikacin:
- Initial supervised test dose with pre- and post-dose lung function monitoring. 2
Contraindications
Absolute Contraindications
Hypersensitivity to amikacin or other aminoglycosides. 2
Pregnancy: Risk of fetal nephrotoxicity and congenital hearing loss (vestibular or auditory nerve damage to fetus if used in second or third trimester). 2, 5
Myasthenia gravis: Amikacin impairs neuromuscular transmission. 2
Drug Interactions
High-Risk Interactions
Loop diuretics: Markedly increased risk of ototoxicity. 2, 5
Nephrotoxic agents: Increased nephrotoxicity risk with capreomycin, cephalosporins, ciclosporin, colistimethate sodium, and tacrolimus. 2
Bisphosphonates: Increased risk of hypocalcemia. 2
Aminoglycoside Redundancy
- No clinical benefit in prescribing amikacin with capreomycin, kanamycin, or streptomycin simultaneously. 2
Admixture Compatibility
Amikacin for injection may only be mixed with 0.9% sodium chloride. 2
Must not be nebulized as a mixture with other drugs (salbutamol, dornase alfa, or other nebulized antibiotics). 2
Amikacin is the aminoglycoside least inactivated by semisynthetic penicillins, an advantage over gentamicin and tobramycin. 4
Critical Clinical Pitfalls
Dosing Errors
Never reduce the mg/kg dose in renal impairment—always extend the dosing interval instead to maintain concentration-dependent killing. 5, 7
Avoid fixed 500 mg doses regardless of patient weight, as this causes underdosing in larger patients and treatment failure. 5
Monitoring Failures
Do not continue therapy beyond 10 days without reassessing drug levels and intensifying toxicity monitoring. 1
Do not administer before dialysis in ESRD patients, as this results in premature drug removal and treatment failure. 7