Risk Factor: BM
Class: Anti-infectives/ Cephalosporins
Fetal Risk Summary
Cephalexin is an oral, semisynthetic cephalosporin antibiotic. Reproduction studies found no evidence in rats, at doses up to 500 mg/kg, found no evidence of impaired fertility or reproductive performance or, in mice and rats, of fetal harm (1).
Several published reports have described the administration of cephalexin to pregnant patients in various stages of gestation (2,3,4,5,6,7,8,9,10 and 11). None of these have linked the use of cephalexin with congenital defects or toxicity in the newborn. However, even though cephalosporins are usually considered safe to use during pregnancy, a surveillance study described below found results contrasting to the published data.
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 3,613 newborns had been exposed to cephalexin during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 176 (4.9%) major birth defects were observed (154 expected). Specific data were available for six defect categories, including (observed/expected) 44/36 cardiovascular defects, 11/5 oral clefts, 3/2 spina bifida, 3/10 polydactyly, 1/6 limb reduction defects, and 8/9 hypospadias. The data for total defects, cardiovascular defects, and oral clefts are suggestive of an association between cephalexin and congenital defects, but other factors, such as the mother’s disease, concurrent drug use, and chance, may be involved. However, similar findings were measured for another cephalosporin antibiotic with more than a thousand exposures (see Cefaclor). Positive results were also suggested for cephradine (339 exposures) but not for cefadroxil (722 exposures) (see Cephradine and Cefadroxil). In contrast, other antiinfectives with large cohorts (see Ampicillin, Amoxicillin, Penicillin G, Erythromycin, and Tetracycline) had negative findings.
Transplacental passage of cephalexin has been demonstrated only near term (2,3). Following a 1-g oral dose, peak concentrations for maternal serum, cord serum, and amniotic fluid were about 34 (1 hour), 11 (4 hours), and 13 mg/mL (6 hours), respectively (3). Patients in whom labor was induced were observed to have falling concentrations of cephalexin in all samples when labor was prolonged beyond 18 hours (4). In one report, all fetal blood samples gave a negative Coombs’ reaction (2).
The effect of postcoital prophylaxis with a single oral dose of either cephalexin (250 mg) or nitrofurantoin macrocrystals (50 mg) starting before or during pregnancy in 33 women (39 pregnancies) with a history of recurrent urinary tract infections was described in a 1992 Reference (11). A significant decrease in the number of infections was documented without fetal toxicity.
The manufacturer has unpublished information on 46 patients treated with cephalexin during pregnancy (C.L. Lynch, personal communication, Dista Products, 1981). Two of these patients received the drug from 12 months prior to conception to term. No effects on the fetus attributable to the antibiotic were observed. Follow-up examination on one infant at 2 months was normal.
Breast Feeding Summary
Cephalexin is excreted into breast milk in low concentrations. A 1-g oral dose given to six mothers produced peak milk levels at 45 hours averaging 0.51 mg/mL (range 0.240.85 mg/mL) (12). Mean milk:plasma ratios at 1, 2, and 3 hours were 0.008, 0.021, and 0.14, respectively. 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 cephalexin, the American Academy of Pediatrics classifies other cephalosporin antibiotics as compatible with breast feeding (13).
- Product information. Keflex. Dista Products, 1997.
- Paterson ML, Henderson A, Lunan CB, McGurk S. Transplacental transfer of cephalexin. Clin Med 1972;79:224.
- Creatsas G, Pavlatos M, Lolis D, Kaskarelis D. A study of the kinetics of cephapirin and cephalexin in pregnancy. Curr Med Res Opin 1980;7:436.
- Hirsch HA. Behandlung von harnwegsinfektionen in gynakologic und geburtshilfe mit cephalexin. Int J Clin Pharmacol 1969;2(Suppl):1213.
- Brumfitt W, Pursell R. Double-blind trial to compare ampicillin, cephalexin, co-trimoxazole, and trimethoprim in treatment of urinary infection. Br Med J 1972;2:6736.
- Mizuno S, Metsuda S, Mori S. Clinical evaluation of cephalexin in obstetrics and gynaecology. In Proceedings of a Symposium on the Clinical Evaluation of Cephalexin, Royal Society of Medicine, London, June 2 and 3, 1969.
- Guttman D. Cephalexin in urinary tract infections-preliminary results. In Proceedings of a Symposium on the Clinical Evaluation of Cephalexin, Royal Society of Medicine, London, June 2 and 3, 1969.
- Soto RF, Fesbre F, Cordido A, et al. Ensayo con cefalexina en el tratamiento de infecciones urinarias en pacientes embarazadas. Rev Obstet Ginecol Venez 1972;32:63741.
- Campbell-Brown M, McFadyen IR. Bacteriuria in pregnancy treated with a single dose of cephalexin. Br J Obstet Gynaecol 1983;90:10549.
- Jakobi P, Neiger R, Merzbach D, Paldi E. Single-dose antimicrobial therapy in the treatment of asymptomatic bacteriuria in pregnancy. Am J Obstet Gynecol 1987;156:114852.
- Pfau A, Sacks TG. Effective prophylaxis for recurrent urinary tract infections during pregnancy. Clin Infect Dis 1992;14:8104.
- Kafetzis D, Siafas C, Georgakopoulos P, Papadatos CJ. Passage of cephalosporins and amoxicillin into the breast milk. Acta Paediatr Scand 1981;70:2858.
- Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.