CEPHRADINE

Fetal Risk Summary

Cephradine is an oral and parenteral cephalosporin antibiotic. The drug rapidly crosses the placenta throughout gestation (1,2,3 and 4). In the 1st and 2nd trimesters, IV or oral doses produce amniotic fluid levels in the 1 µg/mL range or less. Between 15 and 30 weeks of gestation, a 1-g IV dose produces therapeutic fetal levels peaking in 40–50 minutes (1). At term, oral doses of 2 g/day for 2 days or more allowed cephradine to concentrate in the amniotic fluid, producing levels in the range of 3–15 µg/mL (2,3). A 2-g IV dose 17 minutes prior to delivery produced high cord serum levels (29 µg/mL) but low amniotic fluid concentrations (1.1 µg/mL) (4). Serum samples taken from two of the newborns within 20 hours of birth indicated cephradine is excreted by the neonate (4). No other infant data were given in any of the studies. Cephalosporins are usually considered safe to use during pregnancy.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 339 newborns had been exposed to cephradine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 27 (8.0%) major birth defects were observed (14 expected). Specific data were available for six defect categories, including (observed/expected) 9/3 cardiovascular defects, 0/0.5 oral clefts, 0/0 spina bifida, 1/1 polydactyly, 0/0.5 limb reduction defects, and 1/1 hypospadias. The data for all defects and cardiovascular defects are suggestive of an association between cephradine and congenital defects, but other factors, such as the mother's disease, may be involved. However, similar findings were measured for cefaclor and cephalexin (see Cefaclor and Cephalexin). In contrast, other antiinfectives with large cohorts (see Ampicillin, Amoxicillin, Penicillin G, Erythromycin, and Tetracycline) were not associated with defects.

Breast Feeding Summary

Cephradine is excreted into breast milk in low concentrations. After 500 mg orally every 6 hours for 48 hours, constant milk concentrations of 0.6 µmg/mL were measured during 6 hours, a milk:plasma ratio of about 0.2 (2,3). Even though these levels are low, three potential problems exist for the nursing infant: modification of bowel flora, direct effects on the infant, and interference with the interpretation of culture results if a fever workup is required. Although not specifically listing cephradine, the American Academy of Pediatrics classifies other cephalosporin antibiotics as compatible with breast feeding (5).

References

1. Lange IR, Rodeck C, Cosgrove R. The transfer of cephradine across the placenta. Br J Obstet Gynaecol 1984;91:551–4.
2. Mischler TW, Corson SL, Bolognese RJ, Letocha MJ, Neiss ES. Presence of cephradine in body fluids of lactating and pregnant women. Clin Pharmacol Ther 1974;15:214.
3. Mischler TW, Corson SL, Larranaga A, Bolognese RJ, Neiss ES, Vukovich RA. Cephradine and epicillin in body fluids of lactating and pregnant women. J Reprod Med 1978;21:130–6.
4. Craft I, Forster TC. Materno-fetal cephradine transfer in pregnancy. Antimicrob Agents Chemother 1978;14:924–6.
5. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.