NIZATIDINE

Fetal Risk Summary

Nizatidine is an H2-receptor antagonist that inhibits gastric acid secretion. In pregnant rats and rabbits given oral doses up to 506 mg/kg/day, no adverse effects were observed on fertility, and no teratogenic effects occurred with doses up to 1500 mg/kg/day, although some abortions occurred in rabbits, but not rats, at the highest dose (1). In reproduction studies reported by the manufacturer, no evidence of impaired fertility or fetal harm was observed in rats given oral doses up to 1500 mg/kg/day (40.5 times the recommended human dose based on body surface area [RHD]) or rabbits at doses up to 275 mg/kg/day (14.6 times the RHD) (2).

A single cotyledon perfusion model was used to determine the placental transfer of nizatidine in both term human and preterm baboon placentas (3). In both systems, nizatidine was transferred at about 40% of the freely diffusable Reference compound. Nizatidine transfer across the placentas was the same in both directions (i.e., mother-to-fetus and fetus-to-mother).

Based on studies in male humans (4) and animals (5,6), nizatidine does not appear to have antiandrogenic effects like those observed with cimetidine (see Cimetidine). Reversible impotence, however, has been described in men treated with nizatidine for therapeutic indications (7).

A genetic counselor was consulted about a woman who had taken nizatidine during the 14th through the 16th postconception weeks (TM Gardner, personal communication, Jefferson Medical College, 1996). The woman delivered a healthy, 7 pound 13 ounce male infant at 37 weeks' gestation who was doing well at 1 month of age.

Breast Feeding Summary

Small amounts of nizatidine are excreted into human breast milk (8). Three women, who had been breast-feeding for 3–8 months, were administered nizatidine (150 mg) as a single dose and as multiple doses given every 12 hours for five doses. Serum and milk samples from both breasts were collected at intervals up to 12 hours after a dose. The mean total amount of drug measured in the milk from both breasts during a 12-hour interval was 96.1 ± 31.0 µg. This amount represented 0.064 ± 0.021% of the maternal dose. Peak concentrations of the drug in milk occurred between 1 and 2 hours after a dose.

Although the infants were not allowed to breast-feed during the above study, the small amounts excreted into the milk are probably not significant. Other drugs in this class are excreted into milk (see Cimetidine and Ranitidine). The American Academy of Pediatrics considers one of these agents, cimetidine, to be compatible with breast feeding (9).

References

1. Morton DM. Pharmacology and toxicology of nizatidine. Scand J Gastroenterol 1987;22(Suppl 136):1–8.
2. Product information. Axid. Eli Lilly, 2000.
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. Van Thiel DH, Gavaler JS, Heyl A, Susen B. An evaluation of the anti-androgen effects associated with H2 antagonist therapy. Scand J Gastroenterol 1987;22(Suppl 136):24–8.
5. Neubauer BL, Goode RL, Best KL, Hirsch KS, Lin T-M, Pioch RP, Probst KS, Tinsley FC, Shaar CJ. Endocrine effects of new histamine H2-receptor antagonist, nizatidine (LY139037), in the male rat. Toxicol Appl Pharmacol 1990;102:219–32.
6. Probst KS, Higdon GL, Fisher LF, McGrath JP, Adams ER, Emmerson JL. Preclinical toxicology studies with nizatidine, a new H2-receptor antagonist: acute, subchronic, and chronic toxicity evaluations. Fundam Appl Toxicol 1989;13:778–92.
7. Kassianos GC. Impotence and nizatidine. Lancet 1989;1:963.
8. Obermeyer BD, Bergstrom RF, Callaghan JT, Knadler MP, Golichowski A, Rubin A. Secretion of nizatidine into human breast milk after single and multiple doses. Clin Pharmacol Ther 1990;47:724–30.
9. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.