GI Agents: Part II

The second part of this three-part series examines the safety of drugs used to treat several gastrointestinal diseases that cause significant morbidity in pregnant women.

▸ Helicobacter pylori infection: Several studies have linked this infection to severe nausea/vomiting of pregnancy. Eradication regimens involve dual, triple, or quadruple therapy, typically for 2 weeks, combining one or two anti-infectives and an antisecretory agent. Bismuth and ranitidine bismuth citrate are sometimes added to the regimen.

If clinically acceptable, the best course is to delay therapy until after the first trimester. Of the four anti-infectives used (amoxicillin, clarithromycin, metronidazole, and tetracycline), only tetracycline clearly causes developmental toxicity, but the carcinogenic potential of metronidazole has not been tested adequately.

Two proton pump inhibitors, lansoprazole (Prevacid) and omeprazole (Prilosec, Zegerid), are the antisecretory agents of choice for H. pylori eradication as neither appears to pose significant risk in pregnancy. Although ranitidine (Zantac) is compatible with pregnancy, both the salt form ranitidine bismuth citrate (Tritec) and bismuth alone are best avoided because the limited human data prevent an accurate assessment of bismuth's risk to the embryo or fetus. Amoxicillin, clarithromycin, and tetracycline are compatible with breast-feeding. All of the other agents used for H. pylori infection are best avoided in lactation.

▸ Cholelithiasis: Only one gallstone-solubilizing agent, ursodiol (Actigall, Urso), is available in the United States. Reports of exposure to this agent early in pregnancy are limited, but there are more data on the second half of pregnancy, which indicate that the drug does not appear to represent a risk in pregnancy or lactation.

▸ Digestive enzymes: Two digestive pancreatic enzymes—pancreatin and pancrelipase—are used for various conditions that result in deficient pancreatic secretions, such as cystic fibrosis and chronic pancreatitis. Only fragments of pancreatin and pancrelipase are absorbed systemically. Human data are limited, but animal data suggest these enzymes are low risk in pregnancy and lactation. Of note, the enteric coating on many of these products is diethyl phthalate, and high doses of some phthalates may cause developmental toxicity, but the embryo or fetus is exposed to very small quantities.

▸ Ulcer prophylaxis: Sucralfate (Carafate) inhibits pepsin activity and protects against ulceration. Only very small amounts of the drug are absorbed systemically, and it is compatible in both pregnancy and lactation. The prostaglandin misoprostol (Cytotec) is also indicated for ulcer prophylaxis, but this use is contraindicated in pregnancy (see GI Agents: Part I, INTERNAL MEDICINE NEWS, Feb. 15, 2006, p. 47).

▸ Flatulence: Two antiflatulents available over the counter are the silicone product simethicone (multiple trade names) and activated charcoal. They also are combined in a single product (Flatulex). Because neither agent is absorbable, they present no risk to the embryo, fetus, or nursing infant.

▸ Obesity: There is no human pregnancy experience with the lipase inhibitor, orlistat (Xenical), which inhibits the absorption of dietary fats. The animal reproduction data and minimal systemic bioavailability suggest that the drug represents a low risk in pregnancy and lactation.

▸ Inflammatory bowel disease: Mesalamine (5-aminosalicylic acid, 5-ASA) (Asacol, Canasa, Pentasa, Rowasa) is compatible with pregnancy. Reports have described several hundred pregnant women who had taken the drug without apparent harm to embryo or fetus. Two other agents in this class, balsalazide (Colazal) and olsalazine (Dipentum), are broken down in the colon to 5-ASA. Both agents appear to be compatible with pregnancy.

A third drug, sulfasalazine (Azulfidine), is metabolized to 5-ASA plus sulfapyridine. Sulfapyridine readily crosses the placenta to the fetus. When sulfapyridine is used close to delivery, neonatal jaundice and/or kernicterus secondary to displacement of bilirubin from albumin is a theoretical concern but has not been reported. Although human experience is limited, sulfasalazine appears to be compatible with pregnancy.

All of the inflammatory bowel disease agents should be used cautiously during lactation. Multiple episodes of diarrhea were reported in one nursing infant that appeared to be related to the mesalamine rectal suppositories used by the mother. In another case, persistent bloody diarrhea was attributed to the mother's use of sulfasalazine. Because of these cases, close observation of the nursing infant is required if the mother is taking any of these agents.

The second part of this three-part series examines the safety of drugs used to treat several gastrointestinal diseases that cause significant morbidity in pregnant women.

▸ Helicobacter pylori infection: Several studies have linked this infection to severe nausea/vomiting of pregnancy. Eradication regimens involve dual, triple, or quadruple therapy, typically for 2 weeks, combining one or two anti-infectives and an antisecretory agent. Bismuth and ranitidine bismuth citrate are sometimes added to the regimen.

If clinically acceptable, the best course is to delay therapy until after the first trimester. Of the four anti-infectives used (amoxicillin, clarithromycin, metronidazole, and tetracycline), only tetracycline clearly causes developmental toxicity, but the carcinogenic potential of metronidazole has not been tested adequately.

Two proton pump inhibitors, lansoprazole (Prevacid) and omeprazole (Prilosec, Zegerid), are the antisecretory agents of choice for H. pylori eradication as neither appears to pose significant risk in pregnancy. Although ranitidine (Zantac) is compatible with pregnancy, both the salt form ranitidine bismuth citrate (Tritec) and bismuth alone are best avoided because the limited human data prevent an accurate assessment of bismuth's risk to the embryo or fetus. Amoxicillin, clarithromycin, and tetracycline are compatible with breast-feeding. All of the other agents used for H. pylori infection are best avoided in lactation.

▸ Cholelithiasis: Only one gallstone-solubilizing agent, ursodiol (Actigall, Urso), is available in the United States. Reports of exposure to this agent early in pregnancy are limited, but there are more data on the second half of pregnancy, which indicate that the drug does not appear to represent a risk in pregnancy or lactation.

▸ Digestive enzymes: Two digestive pancreatic enzymes—pancreatin and pancrelipase—are used for various conditions that result in deficient pancreatic secretions, such as cystic fibrosis and chronic pancreatitis. Only fragments of pancreatin and pancrelipase are absorbed systemically. Human data are limited, but animal data suggest these enzymes are low risk in pregnancy and lactation. Of note, the enteric coating on many of these products is diethyl phthalate, and high doses of some phthalates may cause developmental toxicity, but the embryo or fetus is exposed to very small quantities.

▸ Ulcer prophylaxis: Sucralfate (Carafate) inhibits pepsin activity and protects against ulceration. Only very small amounts of the drug are absorbed systemically, and it is compatible in both pregnancy and lactation. The prostaglandin misoprostol (Cytotec) is also indicated for ulcer prophylaxis, but this use is contraindicated in pregnancy (see GI Agents: Part I, INTERNAL MEDICINE NEWS, Feb. 15, 2006, p. 47).

▸ Flatulence: Two antiflatulents available over the counter are the silicone product simethicone (multiple trade names) and activated charcoal. They also are combined in a single product (Flatulex). Because neither agent is absorbable, they present no risk to the embryo, fetus, or nursing infant.

▸ Obesity: There is no human pregnancy experience with the lipase inhibitor, orlistat (Xenical), which inhibits the absorption of dietary fats. The animal reproduction data and minimal systemic bioavailability suggest that the drug represents a low risk in pregnancy and lactation.

▸ Inflammatory bowel disease: Mesalamine (5-aminosalicylic acid, 5-ASA) (Asacol, Canasa, Pentasa, Rowasa) is compatible with pregnancy. Reports have described several hundred pregnant women who had taken the drug without apparent harm to embryo or fetus. Two other agents in this class, balsalazide (Colazal) and olsalazine (Dipentum), are broken down in the colon to 5-ASA. Both agents appear to be compatible with pregnancy.

A third drug, sulfasalazine (Azulfidine), is metabolized to 5-ASA plus sulfapyridine. Sulfapyridine readily crosses the placenta to the fetus. When sulfapyridine is used close to delivery, neonatal jaundice and/or kernicterus secondary to displacement of bilirubin from albumin is a theoretical concern but has not been reported. Although human experience is limited, sulfasalazine appears to be compatible with pregnancy.

All of the inflammatory bowel disease agents should be used cautiously during lactation. Multiple episodes of diarrhea were reported in one nursing infant that appeared to be related to the mesalamine rectal suppositories used by the mother. In another case, persistent bloody diarrhea was attributed to the mother's use of sulfasalazine. Because of these cases, close observation of the nursing infant is required if the mother is taking any of these agents.

The second part of this three-part series examines the safety of drugs used to treat several gastrointestinal diseases that cause significant morbidity in pregnant women.

▸ Helicobacter pylori infection: Several studies have linked this infection to severe nausea/vomiting of pregnancy. Eradication regimens involve dual, triple, or quadruple therapy, typically for 2 weeks, combining one or two anti-infectives and an antisecretory agent. Bismuth and ranitidine bismuth citrate are sometimes added to the regimen.

If clinically acceptable, the best course is to delay therapy until after the first trimester. Of the four anti-infectives used (amoxicillin, clarithromycin, metronidazole, and tetracycline), only tetracycline clearly causes developmental toxicity, but the carcinogenic potential of metronidazole has not been tested adequately.

Two proton pump inhibitors, lansoprazole (Prevacid) and omeprazole (Prilosec, Zegerid), are the antisecretory agents of choice for H. pylori eradication as neither appears to pose significant risk in pregnancy. Although ranitidine (Zantac) is compatible with pregnancy, both the salt form ranitidine bismuth citrate (Tritec) and bismuth alone are best avoided because the limited human data prevent an accurate assessment of bismuth's risk to the embryo or fetus. Amoxicillin, clarithromycin, and tetracycline are compatible with breast-feeding. All of the other agents used for H. pylori infection are best avoided in lactation.

▸ Cholelithiasis: Only one gallstone-solubilizing agent, ursodiol (Actigall, Urso), is available in the United States. Reports of exposure to this agent early in pregnancy are limited, but there are more data on the second half of pregnancy, which indicate that the drug does not appear to represent a risk in pregnancy or lactation.

▸ Digestive enzymes: Two digestive pancreatic enzymes—pancreatin and pancrelipase—are used for various conditions that result in deficient pancreatic secretions, such as cystic fibrosis and chronic pancreatitis. Only fragments of pancreatin and pancrelipase are absorbed systemically. Human data are limited, but animal data suggest these enzymes are low risk in pregnancy and lactation. Of note, the enteric coating on many of these products is diethyl phthalate, and high doses of some phthalates may cause developmental toxicity, but the embryo or fetus is exposed to very small quantities.

▸ Ulcer prophylaxis: Sucralfate (Carafate) inhibits pepsin activity and protects against ulceration. Only very small amounts of the drug are absorbed systemically, and it is compatible in both pregnancy and lactation. The prostaglandin misoprostol (Cytotec) is also indicated for ulcer prophylaxis, but this use is contraindicated in pregnancy (see GI Agents: Part I, INTERNAL MEDICINE NEWS, Feb. 15, 2006, p. 47).

▸ Flatulence: Two antiflatulents available over the counter are the silicone product simethicone (multiple trade names) and activated charcoal. They also are combined in a single product (Flatulex). Because neither agent is absorbable, they present no risk to the embryo, fetus, or nursing infant.

▸ Obesity: There is no human pregnancy experience with the lipase inhibitor, orlistat (Xenical), which inhibits the absorption of dietary fats. The animal reproduction data and minimal systemic bioavailability suggest that the drug represents a low risk in pregnancy and lactation.

▸ Inflammatory bowel disease: Mesalamine (5-aminosalicylic acid, 5-ASA) (Asacol, Canasa, Pentasa, Rowasa) is compatible with pregnancy. Reports have described several hundred pregnant women who had taken the drug without apparent harm to embryo or fetus. Two other agents in this class, balsalazide (Colazal) and olsalazine (Dipentum), are broken down in the colon to 5-ASA. Both agents appear to be compatible with pregnancy.

A third drug, sulfasalazine (Azulfidine), is metabolized to 5-ASA plus sulfapyridine. Sulfapyridine readily crosses the placenta to the fetus. When sulfapyridine is used close to delivery, neonatal jaundice and/or kernicterus secondary to displacement of bilirubin from albumin is a theoretical concern but has not been reported. Although human experience is limited, sulfasalazine appears to be compatible with pregnancy.

All of the inflammatory bowel disease agents should be used cautiously during lactation. Multiple episodes of diarrhea were reported in one nursing infant that appeared to be related to the mesalamine rectal suppositories used by the mother. In another case, persistent bloody diarrhea was attributed to the mother's use of sulfasalazine. Because of these cases, close observation of the nursing infant is required if the mother is taking any of these agents.