Risk Factor: BM
Class: Anti-infectives/ Cephalosporins
Fetal Risk Summary
Cefoxitin is a parenteral, semisynthetic cephalosporin antibiotic. Reproduction studies found no evidence in rats of impaired fertility or reproductive performance at doses three times the maximum recommended human dose (MRHD) or, in mice and rats, fetal harm (other than a slight decrease in fetal weight) or teratogenesis at doses up to approximately 7.5 times the MRHD (1).
Multiple reports have described the transplacental passage of cefoxitin (2,3,4,5,6,7,8,9,10,11,12,13 and 14). Two patients were given 1 g IV just prior to therapeutic abortion at 9 and 10 weeks’ gestation (10). At 55 minutes, the serum level in one woman was 10.5 g/mL while none was found in the fetal tissues. In the second patient, at 4.25 hours the maternal serum was nil, while the fetal tissue level was 35.7 g/mL.
At term, following IM or rapid IV doses of 1 or 2 g, cord serum levels up to 22 mg/mL (11%90%) of maternal levels have been measured (7,8,9 and 10). Amniotic fluid concentrations peaked at 23 hours in the 3 to 15 mg/mL range (7,8,10,11,14). No apparent adverse effects were noted in any of the newborns. Cephalosporins are usually considered safe to use during pregnancy.
Breast Feeding Summary
Cefoxitin is excreted into breast milk in low concentrations (6,10,12,13,15). Up to 2 g/mL has been detected in the milk of women receiving therapeutic doses (J.J. Whalen, personal communication, Merck, Sharpe & Dohme, May 13, 1981). No data on the infants were given. Following prophylactic administration of 24 g of cefoxitin to 18 women during and following cesarean section, milk samples were collected a mean 25 hours (range 956 hours) after the last dose of antibiotic (15). Only one sample, collected 19 hours after the last dose, contained measurable concentrations of cefoxitin (0.9 g/mL). Although 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. The American Academy of Pediatrics considers the drug to be compatible with breast feeding (16).
- Product information. Mefoxin. Merck & Company, 1997.
- Bergone-Berezin B, Kafe H, Berthelot G, Morel O, Benard Y. Pharmacokinetic study of cefoxitin in bronchial secretions. In Current Chemotherapy: Proceedings of The 10th International Congress of Chemotherapy, Zurich, Switzerland, September 1823, 1977. Washington, DC:American Society for Microbiology, 1978.
- Aokawa H, Minagawa M, Yamamiohi K, Sugiyama A. Studies on cefoxitin. Chemotherapy (Tokyo) 1977;(Suppl):394.
- Matsuda S, Tanno M, Kashiwakura S, Furuya H. Basic and clinical studies on cefoxitin. Chemotherapy (Tokyo) 1977;(Suppl):396.
- Berthelot G, Bergogne-Berezin B, Morel O, Kafe H, Benard Y. Cefoxitin: pharmacokinetic study in bronchial secretions-transplacental diffusion (abstract No. 80). Paper presented at 10th International Congress of Chemotherapy, Zurich, Switzerland, September 1823, 1977.
- Mashimo K, Mihashi S, Fukaya I, Okubo B, Ohgob M, Saito A. New drug symposium IV. Cefoxitin. Chemotherapy (Tokyo) 1978;26:1149.
- Matsuda S, Tanno M, Kashiwakura T, Furuya H. Laboratory and clinical studies on cefoxitin in the field of obstetrics and gynecology. Chemotherapy (Tokyo) 1978;26(Suppl 1):4607.
- Cho N, Ubhara K, Suigizaki K, et al. Clinical studies of cefoxitin in the field of obstetrics and gynecology. Chemotherapy (Tokyo) 1978;26(Suppl 1):46875.
- Seiga K, Minagawa M, Yamaji K, Sugiyama Y. Study on cefoxitin. Chemotherapy (Tokyo) 1978;26(Suppl 1):491501.
- Takase Z, Shirafuji H, Uchida M. Clinical and laboratory studies on cefoxitin in the field of obstetrics and gynecology. Chemotherapy (Tokyo) 1978;26(Suppl 1):5025.
- Bergogne-Berezin B, Lambert-Zeohovsky N, Rouvillois JL. Placental transfer of cefoxitin (abstract No.314). Paper presented at the 18th Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, Georgia, October 14, 1978.
- Brogden RN, Heel RC, Speight TM, Avery GS. Cefoxitin: a review of its antibacterial activity, pharmacological properties and therapeutic use. Drugs 1979;17:137.
- Dubois M, Delapierre D, Demonty J, Lambotte R, Dresse A. Transplacental and mammary transfer of cefoxitin (abstract No. 118). Paper presented at 11th International Congress of Chemotherapy and 19th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, Massachusetts, October 15, 1979.
- Bergogne-Berezin B, Morel O, Kafe H, et al. Pharmacokinetic study of cefoxitin in man: diffusion into the bronchi and transfer across the placenta. Therapie 1979;34:34554.
- Roex AJM, van Loenen AC, Puyenbroek JI, Arts NFT. Secretion of cefoxitin in breast milk following short-term prophylactic administration in caesarean section. Eur J Obstet Gynecol Reprod Biol 1987;25:299302.
- Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.