Is promethazine (Phenergan) safe during pregnancy?

Safety of Promethazine DM During Pregnancy

Promethazine is considered a safe first-line pharmacologic antiemetic therapy during pregnancy when non-pharmacologic treatments for nausea and vomiting fail. 1

Safety Profile

• 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
• According to the FDA drug label, teratogenic effects have not been demonstrated in rat studies at doses 2.1 to 4.2 times the maximum recommended human dose 2
• Promethazine is considered a first or second-line option for nausea and vomiting in pregnancy by multiple guidelines 3

Precautions

• Promethazine administered within two weeks of delivery may inhibit platelet aggregation in the newborn 2
• Limited data suggest that use of promethazine during labor and delivery does not have an appreciable effect on the duration of labor or delivery and does not increase the risk of interventions in the newborn 2
• The effect on later growth and development of the newborn is unknown 2
• It is not known whether promethazine is excreted in human milk, so caution should be exercised when using it in nursing mothers 2

Treatment Algorithm for Nausea and Vomiting in Pregnancy

1. First-line non-pharmacologic approaches:

   • Dietary modifications (small, frequent meals; BRAT diet - bananas, rice, applesauce, toast; high-protein and low-fat meals) 1
   • Avoidance of specific triggers 1
   • Ginger (250 mg capsule 4 times daily) 1
   • Vitamin B6 (pyridoxine, 10-25 mg every 8 hours) 1

2. First-line pharmacologic options if non-pharmacologic approaches fail:

   • Doxylamine (alone or in combination with pyridoxine) 1, 3
   • Promethazine 1, 3
   • Dimenhydrinate 1

3. Second-line pharmacologic options:

   • Metoclopramide - similar efficacy to promethazine but with fewer adverse events such as drowsiness, dizziness, dystonia 1, 3

4. Third-line options for severe cases:

   • Ondansetron - should be used on a case-by-case basis, particularly before 10 weeks of pregnancy 1, 3
   • Methylprednisolone - for severe hyperemesis gravidarum cases as a last resort 1

Comparative Efficacy

• In a randomized study comparing promethazine and metoclopramide, both drugs showed similar efficacy in hospitalized patients with hyperemesis gravidarum 1
• However, adverse events such as drowsiness, dizziness, dystonia, and treatment discontinuation were less frequent with metoclopramide 1
• A study comparing granisetron and promethazine found that granisetron significantly decreased nausea and vomiting in pregnant women with greater patient satisfaction and fewer adverse drug reactions 4

Formulation Considerations

• Compounding pharmacists can offer transdermal promethazine as a second-line therapy for nausea and vomiting in pregnancy, which may have advantages over oral/rectal dosage forms 5

Monitoring and Follow-up

• For patients with severe symptoms or hyperemesis gravidarum, monitor for signs of dehydration, electrolyte imbalances, and nutritional deficiencies 1
• If symptoms persist or worsen despite treatment with promethazine, consider stepping up to alternative therapies or hospitalization for IV hydration 1

In conclusion, promethazine DM is considered safe during pregnancy and is recommended as a first-line pharmacologic treatment for nausea and vomiting in pregnancy when non-pharmacologic approaches fail. However, newer alternatives like metoclopramide may offer similar efficacy with fewer side effects.