Gastrointestinal agents during pregnancy and breastfeeding
Overview
FDA pregnancy categories prior to 2014, figure (1). Gastroesophageal reflux disease (GERD) occurs in up to 80%, of pregnancies and peaks in the third trimester. The exact mechanism and pathogenesis of this condition associated with pregnancy is likely multifactorial "table 1".
Gastrointestinal agents
Antacids (H2RA and PPI)
H2 receptor antagonists. Histamine 2-receptor blockers include (all 4 are Pregnancy Category B): cimetidine (Tagamet), ranitidine (Zantac), nizatidine (Nizatect), famotidine (Antodine). H2RA can be used during any trimester of pregnancy without risk of anomalies. They are recommended in pregnant women whose symptoms cannot be controlled with lifestyle modification and antacids. Ranitidine may be preferable to cimetidine for chronic use. Cimetidine and ranitidine reach relatively high concentrations in mother’s milk then nizatidine. Famotidine is secreted to milk with very low concentrations. Famotidine is the H2 blocker of choice during breastfeeding.
Proton pump inhibitors. PPI can be used during any trimester of pregnancy without risk of anomalies. PPIs as a class are Pregnancy Category B, including esomeprazole (Nexium), rabeprazole (Pariet, Bepra), lansoprazole (Zoton Fast) and omeprazole (Losec) is Pregnancy Category C but is considered safe during pregnancy. Omeprazole, pantoprazole are secreted to milk with very low concentrations. Pantoprazole and omeprazole are the PPI of choice during breastfeeding.
| Table (1). Antacids (H2 blockers and PPIs) during pregnancy and breastfeeding | ||||
|---|---|---|---|---|
| Drug | Previous FDA classification | Breast-feeding | Clinical risk summary | |
| Famotidine | B |
Probably compatible Secreted less than other H2 blockers Considered low risk |
Crosses placenta with no fetal toxicity or teratogenicity in animal studies | |
| Ranitidine | B |
Probably compatible Considered low risk |
Crosses placenta with no toxicity or teratogenicity in animal studies; considered H2 blocker of choice due to efficacy and safety data Withdrawal from market 2020 |
|
| Cimetidine | B |
Compatible Has antiandrogenic activity, so use with caution |
Crosses placenta with no toxicity in animal studies, has some weak anti-androgenic activity that could result in feminism of male fetuses but no documented cases in humans | |
| Omeprazole | C |
Compatible (Pantoprazole and omeprazole are the PPI of choice during breastfeeding) |
||
| Esomeprazole | B (esomeprazole magnesium) |
Potential toxicity Wait 5–7.5 hr after dose for breast-feeding to limit exposure |
||
| Lansoprazole | B |
Potential toxicity Should be avoided |
Unknown whether crosses placenta but likely; carcinogenic in animals and should be avoided in first trimester | |
| Pantoprazole | B |
Compatible (Pantoprazole and omeprazole are the PPI of choice during breastfeeding) |
||
Antiemetic medications
Nausea and vomiting occur in up to 80% of all pregnant women between 6 and 12 weeks of gestation, but these symptoms are usually self-limiting. One-third of women with nausea and vomiting of pregnancy have clinically significant symptoms, and 1% will progress to hyperemesis gravidarum, which poses health risks to the mother and fetus "table 2".
- Pyridoxine (Vitamin B6), Doxylamine-Pyridoxine Combination. Pyridoxine has been used alone and in combination for the treatment of nausea and vomiting of pregnancy. Combination therapy of doxylamine and pyridoxine was recently approved by the FDA for the treatment of nausea and vomiting of pregnancy.
- Phenothiazines. Phenothiazines, such as metoclopramide, prochlorperazine, and promethazine, are dopamine antagonists commonly used in the treatment of nausea and vomiting during pregnancy. Although there have been reports of increased risk of cardiac defects, these reports did not consider other factors, such as the mother's health, when the drug was reviewed. The American Academy of Pediatrics (AAP) cautions against their use in nursing mothers because they may cause sedation and other untoward effects.
- Serotonin 5-HT3 receptor antagonists. Dolasetron, granisetron, and ondansetron have not been linked to any fetal malformations, although experience with the newer agents remains limited. Recent studies of ondansetron have suggested a low teratogenic risk; however, an increased risk for a cardiac septum defect is possible, but data are inconsistent, but this has not been confirmed in other studies. The AAP considers these agents compatible with breast-feeding.
- Domperidone and metoclopramide may be used during breastfeeding (preferably after complete initiation of lactation and/or measuring of plasma prolactin levels). Galactagogue medication should never replace evaluation and counseling on modifiable factors that affect milk production.
| Table (2). Antiemetics during pregnancy and breastfeeding | |||
|---|---|---|---|
| Drug | Previous FDA classification | Breast-feeding | Clinical risk summary |
| Pyridoxine | A |
Compatible Excreted in breast milk |
High doses pose little risk to fetus; vitamin B6 deficiency common during pregnancy—pyridoxine required for good maternal and fetal health |
| Doxylamine, pyridoxine | A (FDA-approved for use in nausea, vomiting in pregnancy) | Probably compatible, but sedative and antihistamine actions are potential concern | Safe in pregnancy, including first trimester |
| Metoclopramide | B |
Potential toxicity Concern for CNS effects but data lacking |
Safe in pregnancy |
| Prochlorperazine | C |
Potential toxicity Use caution—may cause sedation, lethargy in infant |
Safe in pregnancy |
| Promethazine | C |
Probably compatible May cause sedation in infant |
Safe in pregnancy May cause platelet aggregation in newborn if given within 2 wk of delivery, of unknown clinical significance |
| Ondansetron | B |
Probably compatible Unknown safety |
Safe in pregnancy |
Summary note
See additional notes, "General approach for treatment of nausea and vomiting" and "Nausea and vomiting in general practice".
- First-line treatments of nausea and vomiting in pregnancy include pyridoxine (vitamin B6) 10-25 mg every 8 hours alone or in combination with doxylamine 12.5-25 mg every 8 hours. If symptoms do not resolve after first-line therapies, consider adjunct therapy with any of the following:
- Promethazine 12.5-25 mg intramuscularly, orally, or rectally every 4-6 hours.
- Dimenhydrinate 50-100 mg orally or rectally every 4-6 hours.
- Diphenhydramine 25-50 mg orally every 4-6 hours.
- Prochlorperazine 25 mg rectally every 12 hours.
- For women with nausea and vomiting of pregnancy but without dehydration, if symptoms do not resolve after addition of adjunct therapy to first-line therapies, consider addition of any of the following:
- Metoclopramide (Primpran) 5-10 mg intramuscularly or orally every 6-8 hours.
- Ondansetron (Zofran) 4-8 mg orally disintegrating tablet every 6-8 hours.
- Trimethobenzamide 200-300 mg intramuscularly or orally every 6-8 hours.
References
- Niebyl JR, Briggs GG. The pharmacologic management of nausea and vomiting of pregnancy. J Fam Pract. 2014;63(2 Suppl): S31-S37.
- Thélin CS, Richter JE. Review article: the management of heartburn during pregnancy and lactation. Aliment Pharmacol Ther. 2020;51(4):421-434.
