Ethambutol Complications
The most serious complication of ethambutol is retrobulbar (optic) neuritis causing vision loss that may be irreversible, particularly in patients with renal insufficiency who require dose adjustment to prevent drug accumulation and toxicity. 1
Primary Ocular Complications
Retrobulbar neuritis is the most concerning adverse effect and manifests as:
- Decreased visual acuity affecting one or both eyes 1
- Decreased red-green color discrimination 1
- Blurred vision and central scotomata 2
- Peripheral visual field defects 3
The risk is dose-dependent with minimal risk at 15 mg/kg daily (only 18% at doses >30 mg/kg/day), but dramatically increases in patients with renal insufficiency regardless of dose. 1
Critical Risk Factors for Toxicity
Patients with renal insufficiency face significantly elevated risk of all ethambutol complications due to reduced drug clearance: 1
- Ethambutol is cleared primarily by the kidneys 1, 2
- Drug accumulation occurs when creatinine clearance <70 mL/min 1, 4
- Marked accumulation documented in renal insufficiency patients 2
Additional risk factors include:
- Daily doses exceeding 15 mg/kg 1, 3
- Treatment duration >2 months 1, 3
- Elderly patients 1
- Inability to report visual changes (young children, cognitive impairment) 3
Other Significant Complications
Peripheral neuritis affecting the extremities with numbness and tingling, though rare 1, 2
Cutaneous reactions requiring drug discontinuation occur in 0.2-0.7% of patients 1
Hepatotoxicity including fatal cases has been reported 2
Hypersensitivity syndrome consisting of cutaneous reaction, eosinophilia, and potential hepatitis, pneumonitis, nephritis, myocarditis, or pericarditis 2
Gastrointestinal effects including anorexia, nausea, vomiting, and abdominal pain 2
Hematologic effects including thrombocytopenia, leukopenia, and neutropenia 2
Hyperuricemia with precipitation of acute gout 2
Mandatory Monitoring Protocol
Before initiating ethambutol: 1
- Baseline visual acuity testing using Snellen chart
- Color discrimination testing using Ishihara tests
- Renal function assessment (creatinine clearance)
- Question patients monthly about visual disturbances (blurred vision, scotomata)
- Monthly visual acuity and color discrimination testing required for:
- Doses >15-25 mg/kg
- Treatment duration >2 months
- Any patient with renal insufficiency (this is non-negotiable)
- Regular renal function monitoring in patients with pre-existing impairment
Dose Adjustments in Renal Disease
When creatinine clearance <70 mL/min: 1, 4
- Adjust dose or dosing interval immediately
- Consider therapeutic drug monitoring
For end-stage renal disease on dialysis: 1, 4
- Administer 15-20 mg/kg three times weekly (not daily)
- Give dose after dialysis session
- Never use standard daily dosing—this is a critical error leading to toxicity
Management of Visual Toxicity
Discontinue ethambutol immediately and permanently at the first sign of any visual symptoms or documented visual changes. 1, 3, 2 This is non-negotiable.
Recovery of visual acuity generally occurs over weeks to months after discontinuation, but may be irreversible if the drug is not stopped promptly. 2, 5
Common Pitfalls to Avoid
- Never use standard doses in renal impairment—this leads to drug accumulation and severe toxicity including potentially irreversible vision loss 4
- Never skip monthly visual monitoring in renal patients—they are at highest risk even with dose adjustment 1, 4
- Never continue ethambutol after visual symptoms develop—permanent discontinuation is required 1, 2
- Never use ethambutol in young children (<5 years) whose visual acuity cannot be monitored unless drug-resistant TB is suspected 1
Special Populations
Pregnancy: Ethambutol is considered safe for use 1
Hepatic disease: Can be used safely without dose adjustment 1
Renal disease: Requires mandatory dose adjustment and intensified monitoring as detailed above 1, 4