What are the potential side effects of amikacin, particularly in patients with pre-existing renal or hearing impairment?

Side Effects of Amikacin

Amikacin carries two major toxicity risks—ototoxicity (affecting up to 24% of patients with high-frequency hearing loss) and nephrotoxicity (occurring in 8.7% of patients overall)—with significantly higher rates in patients with pre-existing renal or hearing impairment, requiring mandatory baseline and monthly monitoring of renal function and audiometry. 1, 2

Primary Toxicity Concerns

Ototoxicity (Eighth Cranial Nerve Damage)

• Auditory toxicity is the predominant form, with high-frequency hearing loss occurring in up to 24% of patients, particularly those receiving higher cumulative doses 1, 3
• Hearing loss typically occurs first and is often permanent once established, detected by regular audiometric testing 4
• Vestibular symptoms include vertigo, loss of balance, and tinnitus, though these occur less frequently than auditory damage 4, 2
• Ototoxicity is defined audiometrically as a 20 dB loss from baseline at any one test frequency OR a 10 dB loss at any two adjacent test frequencies 4
• Risk increases with age (especially >59 years), concurrent loop diuretics, larger single doses, and cumulative doses exceeding 100-120 grams 1, 3

Nephrotoxicity

• Renal impairment occurs in 8.7% of patients overall, but rates increase dramatically to 24% in patients with baseline elevated creatinine 1, 5
• Patients with no risk factors have only a 3.4% nephrotoxicity rate 1
• Manifestations include elevated serum creatinine, albuminuria, presence of red and white cells, casts, azotemia, and oliguria 2
• Renal toxicity is usually reversible when the drug is discontinued, unlike ototoxicity 2
• Risk increases with concurrent nephrotoxic agents (capreomycin, cephalosporins, ciclosporin, colistimethate sodium, tacrolimus) and larger cumulative doses 4, 5

Neuromuscular Blockade

• Acute muscular paralysis and apnea can occur, particularly in patients with myasthenia gravis or parkinsonism 2
• Amikacin may aggravate muscle weakness due to its curare-like effect on the neuromuscular junction 2

Critical Monitoring Requirements

Baseline Assessment (Before Starting Therapy)

• Audiogram and vestibular testing 1, 3
• Romberg testing 1, 3
• Serum creatinine measurement 1, 3

During Treatment

• Monthly renal function monitoring—increase frequency if evidence of renal impairment develops 4
• Monthly questioning regarding auditory or vestibular symptoms 1, 3
• Audiogram and vestibular testing intermittently during treatment, with frequency based on perceived risk and symptoms 4
• Trough amikacin level 1 week after starting therapy (target: <5 mg/L) to ensure accumulation is not occurring 4

Action Thresholds

• If ototoxicity is detected on audiogram, amikacin should be discontinued or dosing frequency reduced to avoid further hearing loss, though existing hearing loss is likely permanent 4
• If signs of renal irritation appear (casts, white or red cells, albumin), increase hydration and consider dose reduction 2
• If azotemia increases or progressive decrease in urinary output occurs, stop treatment 2

High-Risk Populations Requiring Enhanced Vigilance

Patients with Pre-existing Renal Impairment

• Highest risk for both nephrotoxicity and ototoxicity 1, 5
• Elderly patients (>59 years) are at increased risk due to reduced renal reserve, even when routine screening tests (BUN, serum creatinine) appear normal 1, 2
• Creatinine clearance determination is more useful than standard screening in elderly patients 2

Patients on Hemodialysis or ESRD

• Nephrotoxicity occurs in 8.7% overall, with higher frequency in those with initially increased creatinine 5
• Ototoxicity (high-frequency hearing loss) occurs in up to 24% of patients receiving amikacin 5

Additional Adverse Effects

Common but Less Severe

• Circumoral paresthesias immediately after injection are relatively common 3
• Skin rash, drug fever, headache, paresthesia, tremor 2
• Nausea and vomiting 2
• Eosinophilia, arthralgia, anemia 2
• Hypotension and hypomagnesemia 2

Rare but Serious

• Macular infarction sometimes leading to permanent loss of vision has been reported following intravitreous administration 2
• Overgrowth of nonsusceptible organisms with prolonged use 2

Absolute Contraindications

• Pregnancy: Risk of fetal vestibular or auditory nerve damage if used in second or third trimester 4, 1
• Hypersensitivity to amikacin or other aminoglycosides 4
• Myasthenia gravis (amikacin may impair neuromuscular transmission) 4

Critical Drug Interactions Increasing Toxicity Risk

• Loop diuretics: Increased risk of ototoxicity—concurrent use should be avoided 4, 5
• Nephrotoxic agents: Increased nephrotoxicity with capreomycin, cephalosporins, ciclosporin, colistimethate sodium, and tacrolimus 4, 5
• Bisphosphonates: Increased risk of hypocalcaemia 4

Critical Pitfalls to Avoid in Patients with Renal Impairment

• Never reduce the milligram dose in renal impairment—this compromises concentration-dependent bactericidal activity; instead, extend the dosing interval 1, 5
• Patients with renal insufficiency should receive 12-15 mg/kg per dose at reduced frequency, not reduced dose 1
• Never administer before dialysis—this removes the drug prematurely and causes treatment failure 1, 5
• Administration should occur after dialysis 5