Risk Factor: B
Class: Anti-infectives/ Antituberculosis
Fetal Risk Summary
No reports linking the use of ethambutol with congenital defects have been located. The drug crosses the placenta to the fetus (1,2). In a woman who delivered at 38 weeks’ gestation, ethambutol concentrations in the cord and maternal blood 30 hours after an 800-mg (15 mg/kg) dose were 4.1 and 5.5 ng/mL, respectively, a cord:maternal serum ratio of 0.75 (1). The amniotic fluid ethambutol level was 9.5 ng/mL (1). These levels were within the range (15 ng/mL) required to inhibit the growth of Mycobacterium tuberculosis (1).
The literature supports the safety of ethambutol in combination with isoniazid and rifampin during pregnancy (3,4,5,6 and 7). One investigator studied 38 patients (42 pregnancies) receiving antitubercular therapy (3). The minor abnormalities noted were within the expected frequency of occurrence. Another researcher observed six aborted fetuses at 512 weeks of age (4). Embryonic optic systems were specifically examined and were found to be normal. Most reviewers consider ethambutol, along with isoniazid and rifampin, to be the safest antituberculosis therapy (8,9). However, long-term follow-up examinations for ocular damage have not been reported, causing concern among some clinicians (10).
Breast Feeding Summary
Ethambutol is excreted into human milk. Milk concentrations in two women (unpublished data) were 1.4 g/mL (after an oral dose of 15 mg/kg) and 4.60 g/mL (dosage not given) (11). Corresponding maternal serum levels were 1.5 g/mL and 4.62 g/mL, respectively, indicating milk:serum ratios of approximately 1:1. The American Academy of Pediatrics considers ethambutol to be compatible with breast feeding (12).
- Shneerson JM, Francis RS. Ethambutol in pregnancy-foetal exposure. Tubercle 1979;60:1679.
- Holdiness MR. Transplacental pharmacokinetics of the antituberculosis drugs. Clin Pharmacokinet 1987;13:1259.
- Bobrowitz ID. Ethambutol in pregnancy. Chest 1974;66:204.
- Lewit T, Nebel L, Terracina S, Karman S. Ethambutol in pregnancy: observations on embryogenesis. Chest 1974;66:256.
- Snider DE, Layde PM, Johnson MW, Lyle MA. Treatment of tuberculosis during pregnancy. Am Rev Respir Dis 1980;122:6579.
- Brock PG, Roach M. Antituberculous drugs in pregnancy. Lancet 1981;1:43.
- Kingdom JCP, Kennedy DH. Tuberculous meningitis in pregnancy. Br J Obstet Gynaecol 1989;96:2335.
- American Thoracic Society. Treatment of tuberculosis and tuberculosis infection in adults and children. Am Rev Respir Dis 1986;134:35563.
- Medchill MT, Gillum M. Diagnosis and management of tuberculosis during pregnancy. Obstet Gynecol Surv 1989;44:814.
- Wall MA. Treatment of tuberculosis during pregnancy. Am Rev Respir Dis 1980;122:989.
- Snider DE Jr, Powell KE. Should women taking antituberculosis drugs breast-feed? Arch Intern Med 1984;144:58990.
- Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.