CEFOTETAN

Fetal Risk Summary

Cefotetan is a parenteral, semisynthetic cephalosporin antibiotic. Reproduction studies in rats and monkeys found no evidence of impaired fertility or fetal harm at doses up to 20 times the human dose (1). Cephalosporins are usually considered safe to use during pregnancy.

A 1985 study measured the placental passage of the drug when administered just prior to cesarean section (2). Twenty women received a single, 1-g IV bolus dose of the antibiotic at intervals of 1–4 hours before surgery. The peak maternal plasma level obtained was 28 µg/mL. Cord blood concentrations progressively increased depending on the length of time after a mother received a dose, and were highest (12.5 µg/mL) when she received the drug 4 hours prior to surgery. Similarly, a progressive increase in amniotic fluid concentrations was observed with values of 5.1, 7.5, and 8.1 µg/mL measured at 2, 3, and 4 hours, respectively. The increases in the level of antibiotic in the amniotic fluid paralleled those in the cord blood.

Three Japanese studies reported placental passage of cefotetan (3,4 and 5). Cord blood levels almost double those measured above, 24.7 µg/mL, were reported 1 hour after a 1.0-g IV dose (3). This value was 15.4% of the peak maternal serum level, indicating that the peak maternal level was about 160 µg/mL. The amniotic fluid concentration was 12.3% of the mother's level, or approximately 20 µg/mL. A confirming study also found high cord blood levels after a single 1-g IV dose with the highest value of 29.0 µg/mL measured 3.6 hours after the maternal dose (4). The highest amniotic fluid level, however, was 8.6 µg/mL, which was also observed at 3.6 hours. The third study measured cord serum concentrations of 15, 31.4, and 3.5 µg/mL at 0.85, 3.75, and 16 hours, respectively, after a 1-g IV dose (5). Amniotic fluid concentrations ranged from 1.18 to 13.6 µg/mL up to 16 hours after a dose.

Breast Feeding Summary

Small amounts of cefotetan are excreted into human breast milk (5,6). A 1982 Reference reported milk levels ranging from 0.22 to 0.34 µg/mL 1–6 hours after a 1-g IV dose (5). In six women treated with cefotetan 1 g IM every 12 hours, mean milk levels 4–10 hours after a dose varied from 0.29 to 0.59 µg/mL (6). No accumulation in the milk was observed as evidenced by a steady milk:plasma ratio. The mean ratio 10 hours after the first dose was 0.05 compared to 0.07, 10 hours after the fifth dose.

Even though the amounts of antibiotic are very small, and no reports of adverse effects in a nursing infant have been located, three potential problems exist for the infant exposed to cefotetan in milk: 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 cefotetan, the American Academy of Pediatrics classifies other cephalosporin antibiotics as compatible with breast feeding (7).

References

1. Product information. Cefotan. Zeneca Pharmaceuticals, 1997.
2. Bergogne-Berezin E, Berthelot O, Ravina JH, Yernant D. Study of placental transfer of cefotetan (abstract). Program and Abstracts of the 25th Interscience Conference on Antimicrobial Agents and Chemotherapy, Minneapolis, MN, September 29-October 2, 1985, p 144.
3. Takase Z, Fujiwara M, Kawamoto Y, Seto M, Shirafuji H, Uchida M. Laboratory and clinical studies of cefotetan (YM09330) in the field of obstetrics and gynecology (English abstract). Chemotherapy (Tokyo) 1982;30(Suppl 1):869–81.
4. Motomura R, Teramoto C, Souda Y, Fujita A, Chiyoda R, Mori H, Yamabe T. Fundamental and clinical study of cefotetan (YM09330) in the field of obstetrics and gynecology (English abstract). Chemotherapy (Tokyo) 1982;30(Suppl 1):882–7.
5. Cho N, Fukunaga K, Kunii K. Fundamental and clinical studies on cefotetan (YM09330) in the field of obstetrics and gynecology (English abstract). Chemotherapy (Tokyo) 1982;30(Suppl 1):832–42.
6. Novelli A, Mazzei T, Ciuffi M, Nicoletti P, Buzzoni P, Reali EF, Periti P. The penetration of intramuscular cefotetan disodium into human extra-vascular fluid and maternal milk secretion. Chemioterapia 1983;2:337–42.
7. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.