Ethambutol

Drug Levels and Effects:




Summary of Use during Lactation:


Limited information indicates that maternal doses of ethambutol up to 15 mg/kg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. The amount of ethambutol in milk is insufficient to treat tuberculosis in the breastfed infant. The Centers for Disease Control and Prevention and other professional organizations state that breastfeeding should not be discouraged in women taking ethambutol.[1][2][3]


Drug Levels:


Maternal Levels.

Information available on ethambutol excretion into breastmilk is limited to 2 cases which were originally reported only as personal communications. One mother had milk levels measured twice while taking ethambutol 15 mg/kg daily. Milk levels were 1.5 mg/L 3 hours after the dose and 1.4 mg/L during a 2-hour period after the dose, but collection methods were not stated. Another woman reportedly had a milk level of 4.6 mg/L which was similar to her plasma level, but her dosage and the milk collection time were not stated. Using these data, reviewers estimated that a breastfed infant would receive 0.51 to 0.86 mg/kg daily which is 3.4 to 5.7% of an infant's therapeutic dose.[4] Using the above sparse data, some authors have estimated that a fully breastfed infant would receive a maximum dose of 0.69 mg/kg daily[5] which is 4.6% of the maternal weight-adjusted dosage.

Infant Levels.

Relevant published information was not found as of the revision date.


Effects in Breastfed Infants:


In one uncontrolled study, 6-beta-hydroxycortisol levels were measured in 10 male infants whose mothers had tuberculosis and took ethambutol 1 gram daily plusisoniazid300 mg daily and the infants of mothers (apparently without tuberculosis) who took no chronic drug therapy. The infants of mothers taking the antituberculars had consistently lower 6-beta-hydroxycortisol levels on 8 occasions at 15-day intervals from 90 to 195 days of age, but these differences were statistically significant on days 120 and 195 only. The authors attributed the lower levels to inhibition of hepatic metabolism of cortisol to 6-beta-hydroxycortisol by the antitubercular drugs in milk.[6] However, ethambutol is not known to inhibit drug metabolism, so if the effect occurs it is more likely caused byisoniazid.

One woman takingrifampin450 mg,isoniazid300 mg and ethambutol 1200 mg daily during pregnancy andrifampin450 mg andisoniazid300 mg for the first 7 months of lactation (extent not stated). The infant was born with mildly elevated serum liver enzymes which persisted for to 1 (alanine transferase) to 2 years (aspartate transaminase), but had no other adverse reactions.[7]

Ethambutol was used as part of a seven-drug regimen to treat a pregnant woman with multidrug-resistant tuberculosis during the second and third trimesters of pregnancy and postpartum. The infant was breastfed (extent and duration not stated). At age 4.6 years, the child was developing normally except for a mild speech delay.[8]


Possible Effects on Lactation:


Relevant published information was not found as of the revision date.


References:


1. Blumberg HM, Burman WJ, Chaisson RE et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med. 2003;167:603-62. PMID:12588714
2. Anon. Treatment of tuberculosis. MMWR Recomm Rep. 2003;52:1-77. PMID:12836625
3. Bartlett JG. Guidelines section. Infect Dis Clin Pract. 2002;11:467-71.
4. Snider DE Jr, Powell KE. Should women taking antituberculosis drugs breast-feed? Arch Intern Med. 1984;144:589-90. PMID:6367682
5. Fulton B, Moore LL. Antiinfectives in breastmilk. Part III: Antituberculars, quinolones and urinary germicides. J Hum Lact. 1993;9:43-6. PMID:8489724
6. Toddywalla VS , Patel SB, Betrabet SS et al. Can chronic maternal drug therapy alter the nursing infant's hepatic drug metabolizing enzyme pattern? J Clin Pharmacol. 1995;35:1025-9. PMID:8568011
7. Peters C, Nienhaus A. [Case report--tuberculosis in a health care worker during pregnancy]. Pneumologie. 2008;62:695-8. PMID:18855309
8. Drobac PC, del Castillo H, Sweetland A et al. Treatment of multidrug-resistant tuberculosis during pregnancy: long-term follow-up of 6 children with intrauterine exposure to second-line agents. Clin Infect Dis. 2005;40:1689-92. PMID:15889370



Substance Identification:




Substance Name:

Ethambutol

CAS Registry Number:

74-55-5

Drug Class:


  • Antitubercular Agents


  • Administrative Information:




    LactMed Record Number:


    460


    Last Revision Date:


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