Is it safe to administer promethazine (Phenergan) to a pregnant female at 8 weeks gestation?

From the Guidelines

Promethazine should be avoided during pregnancy, especially in the first trimester, unless the potential benefit clearly outweighs the risks. For a woman who is 8 weeks pregnant, alternative medications with better safety profiles should be considered first. According to the most recent study 1, the American College of Gastroenterology recommends a step-up approach for patients who do not respond to first-line therapy, and metoclopramide can be given for nausea and vomiting of pregnancy (NVP) and hyperemesis gravidarum (HG). Additionally, a study published in the Journal of Hepatology 1 lists doxylamine/pyridoxine as a first-line recommended treatment for management of Hyperemesis Gravidarum, which has a better safety profile compared to promethazine.

Some key points to consider when managing nausea and vomiting of pregnancy include:

• The first trimester is a critical period for fetal organ development, making medication exposure particularly concerning during this time.
• First-line treatments like vitamin B6 (pyridoxine), with or without doxylamine, have better safety data and should be tried before considering promethazine.
• Metoclopramide can be given for NVP and HG, and has not been associated with an increased risk of congenital defects.
• Ondansetron is given primarily in severe NVP that requires hospitalization, and has not been associated with an increased risk of stillbirth, spontaneous abortion, or major birth defects; however, some studies have reported cases of congenital heart defects when ondansetron is given in the first trimester.

If treatment with promethazine is absolutely necessary for severe nausea and vomiting of pregnancy or other conditions where benefits might outweigh risks, it should be prescribed at the lowest effective dose for the shortest duration possible, and only after consultation with an obstetrician 1.

From the FDA Drug Label

Teratogenic effects have not been demonstrated in rat-feeding studies at doses of 6.25 and 12.5 mg/kg of promethazine HCl. There are no adequate and well-controlled studies of promethazine hydrochloride tablets in pregnant women. Promethazine hydrochloride tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus

The administration of promethazine to a pregnant female at 8 weeks gestation is not recommended unless the potential benefit justifies the potential risk to the fetus 2.

• Key considerations:
  • No adequate and well-controlled studies in pregnant women
  • Potential risk to the fetus
  • Use only if potential benefit outweighs the risk It is essential to weigh the potential benefits against the potential risks before making a decision to administer promethazine to a pregnant woman at 8 weeks gestation.

From the Research

Safety of Promethazine in Pregnancy

• The safety of administering promethazine (Phenergan) to a pregnant female at 8 weeks gestation is a concern due to the potential risks to the fetus.
• According to a systematic review of treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy 3, antihistamines, including promethazine, were associated with improved symptoms compared to placebo for mild symptoms of nausea and emesis of pregnancy.
• However, the quality of evidence was low, and the review did not specifically address the safety of promethazine at 8 weeks gestation.
• A retrospective cohort study comparing antiemetics for nausea and vomiting of pregnancy in an emergency department setting found no difference in time from medication administration to disposition between women who received ondansetron and women who received promethazine or other antiemetics 4.
• Another study examining antiemetic use among pregnant women in the United States found that promethazine use decreased annually from 2006 to 2014, while ondansetron use increased 5.
• There is limited evidence on the safety of promethazine in pregnancy, and more research is needed to establish its efficacy and safety.

Comparison with Other Antiemetics

• Ondansetron was associated with improved symptoms for a range of symptom severity, and its use increased significantly between 2001 and 2014 5.
• Metoclopramide was also associated with improved symptoms, but its use decreased from 2006 to 2014 5.
• Pyridoxine-doxylamine was associated with greater benefit than placebo for moderate symptoms, but its use was relatively low compared to other antiemetics 3.

Considerations for Use in Pregnancy

• The use of any medication during pregnancy should be carefully considered, weighing the potential benefits against the potential risks to the mother and fetus.
• While promethazine may be effective in treating nausea and vomiting in pregnancy, its safety at 8 weeks gestation is not well established, and alternative antiemetics may be preferred.