Ethambutol Dosing in Renal Failure
For patients with renal failure, ethambutol dosing should be adjusted by increasing the dosing interval to three times weekly (not daily) at 20-25 mg/kg/dose when creatinine clearance is <30 mL/min or for patients on hemodialysis. 1
Pharmacokinetic Considerations
- Ethambutol is approximately 80% cleared by the kidneys and may accumulate in patients with renal insufficiency 1
- In renal failure, ethambutol's elimination half-life is prolonged (7.4 to 11.8 hours compared to normal) and total body clearance is decreased 2
- Terminal phase elimination rate correlates significantly with creatinine clearance and the reciprocal of serum creatinine, making these useful predictors for ethambutol elimination capacity 2
Dosing Recommendations Based on Renal Function
For Patients with CrCl <30 mL/min or on Hemodialysis:
- Change frequency from daily to three times weekly 1
- Use 20-25 mg/kg/dose three times weekly (not daily) 1
- Administer medications after hemodialysis on dialysis days to avoid premature clearance 1
For Patients with CrCl 30-50 mL/min:
- Standard doses can be used, but measurement of serum concentrations 2 and 6 hours after administration is recommended to optimize dosing 1
- Close monitoring for toxicity is essential 1
Monitoring Recommendations
- Measure serum ethambutol levels in patients with renal dysfunction 1
- Monitor serum drug concentrations to ensure adequate absorption without excessive accumulation 1
- Assess visual acuity and color vision before starting treatment 1
- Regular ophthalmologic monitoring is crucial as ethambutol can cause optic neuritis and retrobulbar neuritis 1
- Instruct patients to stop treatment immediately and inform their provider if they develop changes in visual acuity or color vision 1
Clinical Considerations and Pitfalls
- Decreasing the dose (rather than extending the interval) lowers peak serum drug concentrations and can compromise treatment efficacy 1
- Simply reducing the dose is not recommended as it may lead to subtherapeutic levels and treatment failure 1
- Failure to adjust ethambutol dosing in renal failure can lead to drug accumulation and increased risk of ocular toxicity 3
- A case report described a dialysis patient who developed bilateral optic nerve atrophy after receiving standard ethambutol dosing (17.9 mg/kg/day) for 8-9 months 3
- For patients on peritoneal dialysis, begin with doses recommended for hemodialysis patients and verify adequacy using serum concentration monitoring 1
Special Populations
- For obese patients, careful consideration of dosing is needed as ethambutol systemic clearance follows fractal geometry-based laws, potentially leading to reduced drug exposure in obesity 4
- In patients with both renal failure and extremes of body mass, the estimated glomerular filtration rate may need to be adjusted for body surface area 5
By following these evidence-based dosing recommendations and implementing appropriate monitoring, clinicians can optimize ethambutol therapy while minimizing the risk of toxicity in patients with renal failure.