Anti-infective (Antituberculosis)
PREGNANCY RECOMMENDATION: Human Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
Although the animal reproductive suggest risk, the human data suggest that the risk probably is low. If indicated, the drug should not be withheld because of pregnancy.
FETAL RISK SUMMARY
The oral anti-infective agent, ethionamide, is indicated for the treatment of tuberculosis when Mycobacterium tuberculosis is resistant to isoniazid or rifampin, or when the patient is intolerant to other drugs. Although it apparently has not been studied, the relatively low molecular weight (about 166) suggests that it is transferred to the fetus.
Ethionamide was teratogenic in rats and rabbits at doses higher than those used in humans (1). Nishimura and Tanimura (2), Shepard (3), and Schardein (4) reviewed nine animal studies involving pregnant mice, rats, and rabbits. All of the studies, except one, showed various developmental anomalies.
Five human studies describing the outcome of pregnancies exposed to ethionamide have been briefly reviewed in three sources (2–4). Only one of the studies found an increased incidence of birth defects, reporting 7 cases, 2 of which were Down’s syndrome, from 23 exposed infants (2–4). The other reports found no association with congenital malformations (4).
A 2003 study reported the outcomes of seven pregnancies treated for multidrug-resistant tuberculosis (5). The seven women received multiple anti-infective agents. Two patients (one throughout and one postpartum) were treated with ethionamide. In 2005, the same group reported the long-term follow-up of six of the offspring; a seventh child, not exposed to ethionamide was lost to follow-up (6). The average age of the children was 3.7 years and each underwent a comprehensive clinical evaluation. None had hearing loss and all had normal vision and neurologic analysis. Of the two exposed to ethionamide (current age and time of exposure) one had mild speech delay (4.6 years; throughout and postpartum) and one was hyperactive (5.1 years; postpartum only). Both infants were breastfed (6). Neither of the two conditions appears to be related to ethionamide.
BREASTFEEDING SUMMARY
One report mentioned that two mothers were taking ethionamide and other antitubercular medications while breastfeeding their infants (6). However, no reports have been located that measured the drug in milk. The relatively low molecular weight (about 166) suggests that ethionamide will be excreted into breast milk. The effect of this exposure on a nursing infant is unknown.
References
1.Product information. Trecator. Wyeth-Ayerst Pharmaceuticals, 2001.
2.Nishimura H, Tanimura T. Clinical Aspects of the Teratogenicity of Drugs. Amsterdam: Excerta Medica, 1976:139–41.
3.Shepard TH. Catalog of Teratogenic Agents. 9th ed. Baltimore, MD: The Johns Hopkins University Press, 1998:188.
4.Schardein JL. Chemically Induced Birth Defects. 3rd ed. New York, NY: Marcel Dekker, 2000:393–4.
5.Shin S, Guerra D, Rich M, Seung K, Mukherjee J, Joseph K, Hurtado R, Alcantara F, Bayona J, Bonilla C, Farmer P, Furin J. Treatment of multidrug-resistant tuberculosis during pregnancy: a report of 7 cases. Clin Infect Dis 2003;36:996–1003.
6.Drobac PC, Castillo HD, Sweetland A, Anca G, Joseph JK, Furin J, Shin S. 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.