Drugs That Are Both Nephrotoxic and Ototoxic
The aminoglycoside antibiotics (streptomycin, amikacin, kanamycin) and capreomycin are the primary drugs that cause both nephrotoxicity and ototoxicity, with cisplatin and carboplatin also exhibiting both toxicities. 1, 2
Aminoglycosides
Streptomycin
- Ototoxicity is the most important adverse reaction, affecting both vestibular and auditory function 1
- Nephrotoxicity occurs less commonly than with other aminoglycosides, requiring discontinuation in approximately 2% of patients 1
- Risk increases with age, cumulative doses above 100-120g, and concurrent loop diuretics 1
Amikacin and Kanamycin
These closely related drugs demonstrate higher nephrotoxicity than streptomycin 1:
- Nephrotoxicity: Renal impairment occurs in 8.7% of patients receiving amikacin, with 3.4% in those without risk factors 1
- Ototoxicity: High-frequency hearing loss occurred in 24% of patients in one report, though they cause less vestibular dysfunction than streptomycin 1
- Both toxicities are irreversible, particularly the vestibulocochlear nerve damage 2
Capreomycin
This second-line injectable agent shows the highest rates of both toxicities 1:
- Nephrotoxicity: Significant renal toxicity requiring discontinuation occurs in 20-25% of patients 1
- Ototoxicity: Vestibular disturbances, tinnitus, and deafness occur more frequently in elderly patients or those with preexisting renal impairment 1
- Proteinuria is common, along with potassium and magnesium depletion 1
Platinum Compounds
Cisplatin
- Ototoxicity: Affects 20-75% of patients with irreversible bilateral sensorineural hearing loss 3
- Nephrotoxicity: Results from accumulation in proximal tubule cells causing necrosis and apoptosis 4
- Both toxicities result from reactive oxygen species and protein dysregulation 4
Carboplatin
- Causes ototoxicity in approximately 5% of patients 3
- Also demonstrates nephrotoxic potential, though less severe than cisplatin 5
Critical Monitoring Requirements
For aminoglycosides, baseline and monthly monitoring must include 1:
- Audiogram and vestibular testing
- Serum creatinine and renal function assessment
- Serum drug concentration monitoring to avoid toxicity
For amikacin specifically 2:
- Renal function: twice weekly during month 1, weekly during month 2, then fortnightly
- Audiometry: baseline, then monthly until treatment cessation, with final review 2 months after last dose
- Ototoxicity defined as 20 dB loss at any frequency or 10 dB loss at two adjacent frequencies
Dose Adjustments in Renal Impairment
All these drugs require mandatory dose adjustments in renal insufficiency 1:
- Reduce dosing frequency to 2-3 times weekly
- Maintain the milligram dose at 12-15 mg/kg to preserve concentration-dependent bactericidal effect
- Administer after dialysis to facilitate directly observed therapy and avoid premature drug removal
- Monitor serum drug concentrations to prevent further toxicity
Common Pitfall
Never combine aminoglycosides with other nephrotoxic agents (capreomycin, cephalosporins, ciclosporin, colistimethate, tacrolimus) or loop diuretics, as this dramatically increases both nephrotoxicity and ototoxicity risk 2. There is no clinical benefit to prescribing multiple aminoglycosides simultaneously 2.