PANTOPRAZOLE

Fetal Risk Summary

Pantoprazole is a proton pump inhibitor that blocks gastric acid secretion by a direct inhibitory effect on the gastric parietal cell (1). It is used in the short-term treatment of erosive esophagitis associated with gastroesophageal reflux disease (GERD).

Reproductive studies have been conducted in pregnant rats and rabbits at doses up to 88 and 16 times, respectively, the recommended human dose based on body surface area (1). No evidence was found at these doses of impaired fertility or fetal harm.

Similar to other proton pump inhibitors, pantoprazole is carcinogenic in mice and rats (gastrointestinal, liver, and thyroid) (1). The dose-related nature of the tumors and the presumable limited in utero exposure to the drug during human gestation probably indicates a negligible risk. In addition, positive results were seen with pantoprazole in the in vitro human lymphocyte chromosomal aberration assays, and in some mutagenic tests with mice, rats, and hamsters. However, negative results were obtained in the in vitro Ames mutation assay and in the mammalian cell-forward gene mutation assay, and in several other tests of mutagenicity (1).

It is not known if pantoprazole crosses the human placenta. The molecular weight (about 432 for the hydrated form) is low enough, however, that passage to the fetus should be expected. Another proton pump inhibitor, omeprazole, has a similar molecular weight (about 345) and chemical structure and it is known to cross the human placenta (see Omeprazole).

No reports describing the use of pantoprazole during human pregnancy have been located. Human pregnancy experience with two other proton pump inhibitors (see Lansoprazole and Omeprazole) have not shown a causal relationship with congenital malformations. In some cases, for both agents, malformations may have been missed because of the design and size of the studies. The animal and cell toxicity data are a potential concern, but the absence of follow-up studies prevents a risk assessment for exposed offspring. As with all drug therapy, avoidance of pantoprazole during pregnancy, especially during the 1st trimester, is the safest course. If pantoprazole is required or if inadvertent exposure does occur early in gestation, the known risk to the embryo/fetus for congenital defects, based on animal data for pantoprazole and the published experience for other proton pump inhibitors, appears to be low. Long-term follow-up of offspring exposed during gestation is warranted.

Breast Feeding Summary

No reports describing the use of pantoprazole during human lactation have been located. Both pantoprazole and the inactive metabolites are excreted into the milk of lactating rats (1). The animal data and the relatively low molecular weight (about 432 for the hydrated form) suggest that pantoprazole excretion into human milk should be expected. Because of the carcinogenicity and mutagenicity in animals, the chromosomal aberrations in human lymphocytes, and the potential for suppression of gastric acid secretion in the nursing infant, the use of pantoprazole during lactation should probably be avoided until clinical data are available.

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