Interventions for Tuberculosis Control and Elimination 2002

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Ethambutol penetrates tissues rapidly and in high concentrations, including
lung, liver and kidney in experimental tuberculosis. 352,353 It has poor penetration
into cerebrospinal fluid and brain. 352 Renal failure decreases body
clearance and increases serum half-life, and dose adjustment in such patients
is mandatory. 354 High-fat meals alter the pharmacokinetics of ethambutol
somewhat, but probably not importantly. 355
Dosage. Although 15 mg/kg body weight in the continuation phase and
25 mg/kg body weight in the intensive phase have been recommended, 356
international consensus recommends 15 mg/kg (range 15 to 20 mg/kg)
throughout 8,13 to obviate operational difficulties in changing the dosage and
to further reduce toxicity.
Adverse drug events (table 5). The most important adverse drug event of
ethambutol is ocular toxicity, first reported in 1962, 357 and followed by
numerous accounts. 358-376 It is postulated that many instances of ethambutol’s
ocular toxicity might be explained by its binding to zinc or copper.
152,377 Two types of ocular toxicity (optic neuropathy) from ethambutol
have been described. 372,378 The more common form is a noninflammatory
axial fiber disease involving central fibers of the optic nerve. 378 Patients
with central or axial toxicity have reduced visual acuity, central scotoma,
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Figure 21. Pharmacokinetics of ethambutol in healthy volunteers. Reproduced
from 349 by the permission of the publisher American Thoracic Society at the American
Lung Association.