Antibiotic (Antituberculosis)
PREGNANCY RECOMMENDATION: Limited Human Data—No Relevant Animal Data
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of capreomycin during human pregnancy have been located. A 1992 review of tuberculosis and pregnancy stated that the safety of capreomycin in pregnancy was not established, but cited no references of its use (1). Two other sources, one published in 1995 and the other in 1996, concluded that capreomycin should be avoided, if possible, because of the potential for ototoxicity and deafness (2,3). Neither source cited pregnancy data involving capreomycin.
FETAL RISK SUMMARY
Capreomycin is a polypeptide antibiotic isolated from Streptomyces capreolus. The antibiotic is a mixture of four active components consisting of capreomycin IA and IB (a combined total of at least 90% of the product) and capreomycin IIA and IIB. Capreomycin is given by IM injection. Less than 1% is absorbed orally. It is indicated, in combination with other antituberculosis agents, as an alternate drug when the primary agents are ineffective or cannot be used because of toxicity. Because the toxicity of capreomycin is similar to aminoglycosides (e.g., cranial nerve VIII and renal), it should not be used with these agents (4).
Capreomycin caused a low incidence of wavy ribs in rats given doses 3.5 times the human dose (1). No studies have been conducted on the effects of the antibiotic on fertility, carcinogenicity, or mutagenicity (4).
It is not known if capreomycin crosses the human placenta. The molecular weight (about 653–669) suggests that the drug will cross to the embryo–fetus.
A 2003 report described the use of capreomycin in a pregnant woman with multidrug-resistant tuberculosis (5). A 22-year-old woman was diagnosed with the infection at 23 weeks’ gestation and daily treatment was initiated with rifampin (600 mg), isoniazid (300 mg), and ethambutol (700 mg). Because of lack of response, her therapy was changed after 3 weeks to capreomycin (IV 1000 mg 5 days/week), cycloserine (750 mg/day), levofloxacin (1000 mg/day), para-aminosalicylic acid (12 g/day), and pyrazinamide (1500 mg/day). After spontaneous rupture of the membrane, she gave birth at 35 weeks’ gestation to a healthy, 2003-g infant. The results of a tuberculin skin test and three nasogastric aspiration cultures were negative, as were a neurologic examination and electrophysiology hearing studies. The infant was kept separated from the mother (5).
A 2003 study reported the outcomes of seven pregnancies treated for multidrug-resistant tuberculosis (6). The seven women received multiple anti-infective agents. Three patients (one throughout, one in 1st trimester, and one postpartum) were treated with IV capreomycin. In 2005, the same group reported the long-term follow-up of six of the offspring; a seventh child, not exposed to capreomycin, was lost to follow-up (7). 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 three exposed to capreomycin (current age and time of exposure), one had mild speech delay (4.6 years; throughout and postpartum), one was hyperactive (5.1 years; postpartum only), and one had no abnormalities (1.25 years; 1st trimester only). All three were breastfed (7). Neither of the two conditions appears to be related to capreomycin.
BREASTFEEDING SUMMARY
No studies reporting the excretion of capreomycin into breast milk have been located. One report mentioned that two infants whose mothers were receiving IV capreomycin and other antituberculosis agents were breastfed (7). No other details were available, but the long-term follow-up revealed no evidence of capreomycin-induced toxicity (see above).
The molecular weight (about 653–669) suggests that the drug will be excreted into breast milk.
The effect on a nursing infant from this exposure is unknown. Although the systemic absorption of capreomycin in a neonate has not been studied, <1% of an oral dose is absorbed by adults, so the risk, if any, to a nursing infant appears to be minimal.
References
1.Hamadeh MA, Glassroth J. Tuberculosis and pregnancy. Chest 1992;101:1114–20.
2.Davidson PT. Managing tuberculosis during pregnancy. Lancet 1995;346:199–200.
3.Robinson CA, Rose NC. Tuberculosis: current implications and management in obstetrics. Obstet Gynecol Surv 1996;51:115–24.
4.Product information. Capastat. 1990.
5.Klaus-Dieter KLL, Qarah S. Multidrug-resistant tuberculosis in pregnancy—case report and review of the literature. Chest 2003;123:953–6.
6.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.
7.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.