FAMOTIDINE

Fetal Risk Summary

Famotidine, a reversible histamine H2-receptor antagonist that is more potent than either cimetidine or ranitidine, is used in the treatment of gastric and duodenal ulcers and in the therapy of pathologic hypersecretory conditions, such as Zollinger-Ellison syndrome.

Studies in rats and rabbits, using oral doses up to 2000 mg/kg/day and IV doses of 100–200 mg/kg/day, found no evidence of impaired fertility, fetotoxic effects, teratogenicity, or changes in postnatal behavior attributable to famotidine (1,2).

The drug is known to cross the term human placenta based on in vitro studies (3). No published reports on the use of famotidine in human pregnancy have appeared in the medical literature.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 33 newborns had been exposed to famotidine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Two (6.1%) major birth defects were observed (one expected). No anomalies were observed in six defect categories (cardiovascular defects, oral clefts, spina bifida, polydactyly, limb reduction defects, and hypospadias) for which specific data were available. The number of exposures is too small to draw any conclusions.

Breast Feeding Summary

Famotidine is concentrated in breast milk, but to a lesser degree than either cimetidine or ranitidine (4). Following a single 40-mg dose administered to eight postpartum women who were not breast-feeding, the mean milk:plasma ratios at 2, 6, and 24 hours were 0.41, 1.78, and 1.33, respectively (4). The mean peak milk concentration, 72 ng/mL, occurred at 6 hours compared to 2 hours for plasma (mean 75 ng/mL). Exposure of the nursing infant to famotidine via milk has not been reported. Although a potential risk may exist for adverse effects, another drug in this class, cimetidine, is considered to be compatible with breast feeding by the American Academy of Pediatrics (5). A 1991 Reference source suggested that because famotidine and two other similar histamine H2-receptor antagonists (i.e., nizatidine and roxatidine) are less concentrated in milk, they may be preferred in the nursing woman in place of cimetidine or ranitidine (6).

References

1. Burek JD, Majka JA, Bokelman DL. Famotidine: summary of preclinical safety assessment. Digestion 1985;32(Suppl 1):7–14.
2. Shibata M, Kawano K, Shiobara Y, Yoshinaga T, Fujiwara M, Uchida T, Odani Y. Reproductive studies on famotidine (YM 11170) in rats and rabbits. Oyo Yakuri 1983;26:489–97, 543–78, 831–40. As cited in Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD:Johns Hopkins University Press, 1989:273.
3. Dicke JM, Johnson RF, Henderson GI, Kuehl TJ, Schenker S. A comparative evaluation of the transport of H2-receptor antagonists by the human and baboon placenta. Am J Med Sci 1988;295:198–206.
4. Courtney TP, Shaw RW, Cedar E, Mann SG, Kelly JG. Excretion of famotidine in breast milk. Br J Clin Pharmacol 1988;26:639P.
5. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.
6. Anderson PO. Drug use during breast-feeding. Clin Pharm 1991;10:594–624.