Ethambutol Use in Patients with Renal Impairment
Ethambutol requires dose adjustment in patients with renal impairment as it is primarily cleared by the kidneys, with increased risk of optic neuritis in renal insufficiency. 1
Pharmacokinetic Considerations
- Ethambutol is primarily excreted by the kidneys, with elimination half-life significantly prolonged in patients with renal dysfunction 2, 3
- In patients with normal renal function, no drug accumulation occurs with consecutive daily doses of 25 mg/kg 2
- However, marked accumulation has been demonstrated in patients with renal insufficiency 2, 3
- The terminal phase elimination rate constant correlates significantly with creatinine clearance and the reciprocal of serum creatinine 3
Dosing Recommendations
- Dose or dosing interval should be adjusted when creatinine clearance is less than 70 ml/minute 1
- For patients with end-stage renal disease on dialysis, ethambutol should be administered at 15-20 mg/kg three times weekly after dialysis 1
- Serum ethambutol levels should be monitored in patients with renal dysfunction when possible 4, 3
Increased Risk of Toxicity
- Renal insufficiency significantly increases the risk of optic toxicity 4, 5
- Patients with end-stage renal disease may develop severe and potentially irreversible optic neuritis even with adjusted dosing 5, 6
- Cases of complete vision loss have been reported in dialysis patients despite discontinuation of ethambutol 5
- Patients with renal impairment may also experience increased risk of peripheral neuritis 4, 6
Monitoring Recommendations
- Baseline visual acuity testing (Snellen chart) and color discrimination testing (Ishihara tests) are essential before starting treatment 1, 4
- Monthly testing of visual acuity and color discrimination is recommended for all patients with renal insufficiency 1, 4
- At each visit, patients should be questioned regarding visual disturbances including blurred vision or scotomata 1
- Patients should be instructed to contact their physician immediately if they experience any change in vision 1, 4
- Renal function should be monitored regularly during treatment 4, 7
Management of Toxicity
- Ethambutol should be discontinued immediately and permanently at the first sign of visual toxicity 1, 8
- Visual changes may be irreversible, especially in patients with renal impairment, even after prompt discontinuation 5, 6
- Consider alternative anti-tuberculosis regimens in patients with severe renal impairment if possible 8
Clinical Pearls and Pitfalls
- Creatinine clearance or serum creatinine serves as a useful predictor for a patient's capacity to eliminate ethambutol 3
- Concomitant use of other nephrotoxic drugs should be avoided when possible 7
- Avoid concurrent administration of ethambutol with aluminum hydroxide-containing antacids for at least 4 hours following ethambutol administration 2
- Unlike ethambutol, hepatic function does not affect dosing requirements as the drug can be used safely in patients with hepatic disease 1