Is Phenergan (promethazine) safe to use during pregnancy?

Promethazine (Phenergan) Safety During Pregnancy

Promethazine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, as it is classified as FDA Pregnancy Category C. 1

Safety Profile and Classification

Promethazine (Phenergan) is classified as FDA Pregnancy Category C, indicating that:

• Teratogenic effects have not been demonstrated in rat studies at doses 2.1-4.2 times the maximum recommended human dose 1
• However, daily doses of 25 mg/kg intraperitoneally have been found to produce fetal mortality in rats 1
• There are no adequate well-controlled studies in pregnant women 1

Clinical Guidelines for Use During Pregnancy

The European Association for the Study of the Liver (EASL) and American College of Obstetricians and Gynecologists (ACOG) recommend:

• Phenothiazines like promethazine are considered first-line pharmacologic treatments for hyperemesis gravidarum (severe nausea and vomiting in pregnancy) 2
• Promethazine should be used after trying non-pharmacological approaches and safer first-line options like vitamin B6 (pyridoxine) 2
• Caution is warranted as drug-induced extrapyramidal adverse effects may occur with phenothiazines, and the drug should be withdrawn if such symptoms appear 2

Efficacy and Comparative Safety

• In a randomized study comparing promethazine and metoclopramide for hospitalized hyperemesis gravidarum patients, both drugs showed similar efficacy 2
• However, drowsiness, dizziness, dystonia, and discontinuation due to adverse events were more frequent with promethazine compared to metoclopramide 2
• Recent trends show decreasing use of promethazine in pregnancy (from 16.0% in 2006 to 8.0% in 2014) with concurrent increases in ondansetron use 3

Specific Concerns and Precautions

When using promethazine during pregnancy:

1. Timing considerations:

   • Use should be minimized during the first trimester when risk of congenital malformations is greatest 2
   • If used within two weeks of delivery, promethazine may inhibit platelet aggregation in the newborn 1

2. Monitoring:

   • Monitor for extrapyramidal symptoms and discontinue if they occur 2
   • Be aware that promethazine may affect laboratory test results, including false-negative or false-positive pregnancy tests 1

3. Breastfeeding:

   • It is unknown whether promethazine is excreted in human milk 1
   • A decision should be made whether to discontinue nursing or the medication based on importance to the mother 1

Alternative Options

For nausea and vomiting in pregnancy, consider these alternatives in order of preference:

1. First-line options:

   • Non-pharmacological approaches
   • Vitamin B6 (pyridoxine) alone or with doxylamine 2

2. Second-line options:

   • Metoclopramide (similar efficacy to promethazine but fewer side effects) 2
   • Ondansetron (for severe cases, but use with caution before 10 weeks gestation) 2

3. Last resort:

   • Methylprednisolone (for severe hyperemesis gravidarum) 2

Bottom Line

While promethazine has been used in pregnancy for decades and major teratogenic effects have not been established, it should be reserved for cases where the benefit outweighs potential risks. When needed for severe nausea and vomiting in pregnancy, it remains a reasonable option after first-line therapies have failed, but patients should be monitored for adverse effects.