DRUGS, PREGNANCY, AND LACTATION.

[Histamine.sub.2] Blockers and Proton Pump Inhibitors

None of the four [histamine.sub.2] blockers currently available are teratogenic or carcinogenic in animals, nor are they mutagenic. They are rated pregnancy category B drugs, but there are limited or no human data for two of the agents.

There is no evidence that cimetidine (Tagamet) is teratogenic in humans, based on data from a Michigan Medicaid study and studies from Sweden, Italy, and England.

What sets cimetidine apart from the other [H.sub.2] blockers is that it has weak antiandrogenic activity in both humans and animals, and it also reduces cytochrome P450 pathway metabolism, raising concerns about the potential risks of feminization in males and significant drug interactions. Therefore, cimetidine would not be the best [H.sub.2] blocker to use during pregnancy.

Cimetidine is concentrated in human breast milk at up to seven times plasma levels, which doesn't appear to have any clinical significance. The American Academy of Pediatrics (AAP) considers this drug to be compatible with breast-feeding.

Famotidine (Pepcid) is associated with few, if any drug interactions. There is also no evidence that famotidine is teratogenic in humans, but this is based on very few human data. It also concentrates in breast milk, but to a much lesser degree than cimetidine or ranitidine (Zantac), so it would be preferred during breast-feeding.

Nizatidine (Axid) has few, if any drug interactions, but there are almost no pregnancy or breast-feeding data on this drug in humans. Based on animal data and human data on the other [H.sub.2] blockers, nizatidine is probably safe during pregnancy and lactation. If a woman becomes pregnant while taking this drug, there would certainly be little reason for concern.