Ethambutol Side Effects: Clinical Overview
The most serious side effect of ethambutol is retrobulbar neuritis, which can lead to vision loss that may be irreversible if the medication is not promptly discontinued when visual symptoms appear. 1
Major Side Effects
Ocular Toxicity
- Retrobulbar neuritis is the most severe and concerning adverse effect, which is usually dose-related 1
- Visual symptoms include decreased visual acuity, decreased red-green color discrimination, blurred vision, central scotomata, and peripheral visual field defects 1, 2
- Risk increases significantly with:
- Visual changes can be unilateral or bilateral 2
- While often reversible upon prompt discontinuation, irreversible blindness has been reported 2, 3
Neurological Effects
Dermatological Reactions
- Skin reactions requiring discontinuation occur in 0.2-0.7% of patients 1
- Rashes 1
- Hypersensitivity reactions including erythema multiforme and pruritus 2
Gastrointestinal Effects
Other Reported Effects
- Elevated serum uric acid levels with potential for acute gout 2
- Fever, malaise, headache, and dizziness 2
- Mental confusion, disorientation, and possible hallucinations 2
- Hematologic effects: thrombocytopenia, leucopenia, and neutropenia 2
- Liver toxicities (including fatalities) 2
- Hypersensitivity syndrome with cutaneous reaction, eosinophilia, and potential organ involvement 2
Risk Factors for Toxicity
- Renal insufficiency significantly increases risk of ocular toxicity 1, 4
- Doses exceeding 15 mg/kg/day 1
- Extended treatment duration 1, 3
- Obesity (when dosed based on total body weight rather than lean body mass) 5
- Age (elderly may be at higher risk) 1
- Inability to report visual changes (young children, cognitively impaired) 1
Monitoring Recommendations
- Baseline visual acuity testing (Snellen chart) and color discrimination testing (Ishihara tests) before starting treatment 1, 2
- Monthly monitoring of visual acuity and color discrimination for:
- Question patients at each visit about visual disturbances 1, 2
- Instruct patients to report immediately any changes in vision 1, 2
- Baseline and periodic assessment of hepatic function 2
- Renal function monitoring in patients with kidney disease 1
- Consider measuring serum ethambutol levels in patients with renal dysfunction 1
Management of Toxicity
- Discontinue ethambutol immediately and permanently at first sign of visual toxicity 1, 2
- Recovery of visual acuity generally occurs over weeks to months after drug discontinuation, but may be incomplete 2, 3
- In patients with renal disease, dose adjustment is required when creatinine clearance is <70 mL/minute 1
- For end-stage renal disease patients on dialysis, administer at 15-20 mg/kg three times weekly after dialysis 1
Contraindications
- Known hypersensitivity to ethambutol 1
- Pre-existing optic neuritis from any cause 1
- Inability to report symptomatic visual disturbances 1
- Creatinine clearance <50 mL/min 1
- Use with caution in children whose visual acuity cannot be monitored (generally <5 years of age) 1
Clinical Pearls
- Visual acuity must be tested for each eye separately and both eyes together 2
- If corrective glasses are used prior to treatment, these must be worn during visual acuity testing 2
- Testing visual acuity through a pinhole eliminates refractive error that may develop during treatment 2
- Visual symptoms may precede measurable decreases in visual acuity 2
- Ethambutol can be used safely in patients with hepatic disease 1
- Ethambutol is considered safe for use in pregnancy 1