Safety of Promethazine DM During Pregnancy

Introduction to Promethazine

The American College of Obstetricians and Gynecologists (ACOG) considers promethazine a safe first-line pharmacologic antiemetic therapy during pregnancy when non-pharmacologic treatments for nausea and vomiting fail 1
Promethazine is classified as an H1-receptor antagonist and is FDA-approved as a first-line pharmacologic treatment for nausea and vomiting in pregnancy (NVP) according to the American College of Obstetricians and Gynecologists (ACOG) 1

First-line non-pharmacologic approaches include dietary modifications, avoidance of specific triggers, ginger, and vitamin B6, as recommended by the American College of Obstetricians and Gynecologists (ACOG) 1
First-line pharmacologic options if non-pharmacologic approaches fail include doxylamine, promethazine, and dimenhydrinate, as recommended by the American College of Obstetricians and Gynecologists (ACOG) 1, 2
Second-line pharmacologic options include metoclopramide, which has similar efficacy to promethazine but with fewer adverse events, as recommended by the American College of Obstetricians and Gynecologists (ACOG) 2, 3
Third-line options for severe cases include ondansetron and methylprednisolone, which should be used on a case-by-case basis, as recommended by the American College of Obstetricians and Gynecologists (ACOG) 2, 3

A randomized study comparing promethazine and metoclopramide found that both drugs showed similar efficacy in hospitalized patients with hyperemesis gravidarum, with metoclopramide having fewer adverse events 3

For patients with severe symptoms or hyperemesis gravidarum, monitoring for signs of dehydration, electrolyte imbalances, and nutritional deficiencies is recommended, as advised by the American College of Obstetricians and Gynecologists (ACOG) 3
If symptoms persist or worsen despite treatment with promethazine, consideration of stepping up to alternative therapies or hospitalization for IV hydration is recommended, as advised by the American College of Obstetricians and Gynecologists (ACOG) 3

Metoclopramide has similar efficacy to promethazine but with fewer adverse events, such as less drowsiness, dizziness, and dystonia, in the treatment of nausea and vomiting in pregnancy, according to the American Gastroenterological Association 4
Promethazine may cause drowsiness, dizziness, and extrapyramidal symptoms, and its use within two weeks of delivery may inhibit platelet aggregation in the newborn, as reported in Gastroenterology 4
For hyperemesis gravidarum requiring hospitalization, both promethazine and metoclopramide show similar efficacy, as stated by the Gastroenterology guideline 4

Large birth registries, case-control studies, and cohort studies have confirmed the safety of first-generation antihistamines, including promethazine, during the first trimester, with no significant increase in congenital malformations, according to the American Academy of Allergy, Asthma, and Immunology 5, 6
The use of promethazine during the first trimester has been associated with no increased risk of congenital defects in human observational data, as reported by the American College of Obstetricians and Gynecologists, although the current article does not provide a direct citation for this fact, it is supported by 5, 6

The most critical period for concern about congenital malformations is the first trimester during organogenesis, though promethazine has demonstrated safety during this period, as confirmed by the American Academy of Allergy, Asthma, and Immunology 5, 6