Ethambutol is a Dialysable Drug, and Drug Monitoring Ensures Safety and Therapeuticity

Background: Ethambutol is renally cleared, but whether it is removed by haemodialysis is uncertain. No consensus guidelines exist on dosing ethambutol in the haemodialysis-dependent patient despite the potential for toxicity, in particular optic neuritis. To address this problem and ascertain if ethambutol is dialysable, we measured serum ethambutol levels in such a patient. We aimed for a trough (pre-dialysis) level of <1000 µg/l, and a peak level of 2000-6000 µg/l.

Methods: A 79-year old Caucasian male was diagnosed with delayed disseminated Bacille Calmette-Guérin infection (BCG) secondary to intravesical BCG immunotherapy for bladder cancer 12 months prior. He was on thrice-weekly haemodialysis. Rifampicin, isoniazid and ethambutol were commenced for 6 months, with cessation of ethambutol after 2 months. Ethambutol was dosed post-dialysis. Levels were taken at 0, 1, 2, and 3 hours into a 4-hour dialysis session, and at 1 hour post-dialysis, once weekly for 5 weeks. Additionally, a random dialysate level was measured during dialysis in week 2. Regular assessments of colour vision were undertaken during the period of treatment with ethambutol.

Results: A clear decline in ethambutol concentration during each dialysis session was observed (Figure 1). There was a significant concentration of ethambutol in the dialysate fluid (274 μg/l; pre-dialysis level 1496 µg/l). The target trough and peak levels were, in the main, achieved. As there were concerns regarding patient compliance, directly-observed therapy immediately after dialysis was commenced in week 3, and levels measured 1 hour post-dialysis showed clear peaks (Figure 1). No abnormalities of colour vision were detected, and the patient did not complain of any visual symptoms.

Conclusion: Ethambutol is a dialysable drug. Therapeutic drug monitoring, at the very least with pre- and post-dialysis levels, aids in dosing the drug so as to maintain concentrations in the therapeutic range. Finally, because ethambutol should be dosed after dialysis, directly-observed therapy may help patient compliance.   

Figure 1. Serum ethambutol concentrations before, during, and 1 hour after, haemodialysis.