The Effect of Hemodialysis on Isoniazid, Rifampin,  Pyrazinamide, and Ethambutol

Malone, Rebecca S.; Fish, Douglas N.; Spiegel, David; Childs, James M.; Peloquin, Charles A.

doi:10.1164/ajrccm.159.5.9810034

Cited by 67 publications

(42 citation statements)

References 26 publications

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“…The concentration of ethambutol in the dialysate fluid sampled in week 2 was 274 g/liter, whereas the predialysis level was 1,496 g/liter. These findings, although not directly comparable to results obtained by authors who calculated clearance rates previously (12, 13), make it highly likely that the ELISIO-19H dialyzer gives a significantly higher clearance rate than the 1.5% quoted by Malone et al (13).…”

contrasting

confidence: 73%

“…Two earlier studies gave conflicting results (12,13). One reported only 1.5% clearance with a high-flux dialysis membrane (13). The other showed higher clearance values of 34 Ϯ 5.3 to 52 Ϯ 1.5 ml/min for ethambutol with various older dialyzers that were in use in 1975.…”

mentioning

confidence: 99%

“…Two earlier studies gave conflicting results (12,13). One reported only 1.5% clearance with a high-flux dialysis membrane (13).…”

mentioning

confidence: 99%

“…It is likely that the type of dialyzer influences clearance (12), but no recent studies have been conducted using contemporary high-flux dialyzers. Furthermore, while most authors agree that a dose of 15 to 25 mg/kg thrice weekly in hemodialysis patients is appropriate (14), they disagree on whether to give ethambutol before or after dialysis (13,(15)(16)(17). One local guideline from the United Kingdom recommends a prehemodialysis trough concentration of Ͻ1 mg/liter and administration of ethambutol postdialysis, aiming for a peak concentration of 2 to 6 mg/liter (18).…”

mentioning

confidence: 99%

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Ethambutol Is Cleared by a Contemporary High-Flux Hemodialyzer, and Drug Monitoring Ensures Safety and Therapeutic Effect

Chew

Jongbloed

Jegatheesan

et al. 2017

Antimicrob Agents Chemother

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It is uncertain, given the lack of recent data and the inconclusive nature of previous data, whether ethambutol is cleared by hemodialysis using contemporary dialyzers. We measured serum ethambutol concentrations before, during, and 1 h after hemodialysis in a 75-year-old Caucasian man receiving ethambutol for disseminated Bacille Calmette-Guérin infection. There was a mean 41% decrease in serum ethambutol concentration during dialysis, confirming the hemodialyzability of ethambutol and the utility of drug monitoring in ensuring safety.KEYWORDS drug monitoring, ethambutol, hemodialysis E thambutol, a dextro-2,2=-(ethylenediimino)-di-1-butanol dihydrochloride with a molecular weight of 277.23, is highly active against Mycobacterium tuberculosis, Mycobacterium bovis, and certain nontuberculous mycobacteria but not against Mycobacterium simiae, Mycobacterium ulcerans, or Mycobacterium haemophilum (1). The hydrochloride salt has two apparent dissociation constants of 6.35 and 9.35 pKa, and the monohydrochloride predominates in solution at neutrality (2). The logarithm of its partition coefficient (log P) is Ϫ0.14 (2).The MIC of ethambutol for wild-type M. tuberculosis is 0.5 to 2 mg/liter (3), while the MIC for Bacille Calmette-Guérin (BCG) strains of M. bovis is 2 to 4 mg/liter (4, 5). Ethambutol is used as part of the primary treatment regimens for tuberculosis and systemic BCG infection but has significant potential side effects. The most serious adverse effect of ethambutol is optic neuritis, which is dose related (3, 6). A study by Griffith et al. (7) found that the incidence of optic neuritis when ethambutol was taken for Ͼ2 months at a dose of 25 mg/kg daily was 5% to 6%, whereas with a dose of 15 mg/kg daily, it was 1%.Eighty percent of absorbed ethambutol is excreted unchanged by the kidney, with the remainder excreted as inactive metabolites, also in the urine (8). Given its high degree of renal clearance, the risk of ocular toxicity is increased with impaired renal function (9), especially as the half-life of 4 h may be more than doubled in end-stage renal disease (10). This poses a serious problem in patients on hemodialysis who require treatment with ethambutol, particularly because there is an increased risk of tuberculosis in this population (11). While the risk of toxicity with ethambutol is dose dependent, the doses at which adverse events occur vary with individual patients and the rates at which they clear the drug. Therefore, the exact dose adjustment to be made should be guided by therapeutic drug monitoring to suit the individual pharmacokinetics of ethambutol for a particular patient with end-stage renal disease.

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contrasting

confidence: 73%

mentioning

confidence: 99%

“…Two earlier studies gave conflicting results (12,13). One reported only 1.5% clearance with a high-flux dialysis membrane (13).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Ethambutol Is Cleared by a Contemporary High-Flux Hemodialyzer, and Drug Monitoring Ensures Safety and Therapeutic Effect

Chew

Jongbloed

Jegatheesan

et al. 2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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“…[6][7][8] Thus, among these patients, TST may not be helpful in diagnosis. [9,10] ESRF patients undergoing hemodialysis (HD) treatment has a 10-25-time greater risk than the general population for developing tuberculosis. [4,11] The incidence of TB in the various HD populations of the world (Canada, Poland, and Saudi Arabia) varies from 1.6% to 28%.…”

Section: Introductionmentioning

confidence: 99%