Is Compazine (prochlorperazine) safe to use during pregnancy and while breastfeeding?

Prochlorperazine (Compazine) in Pregnancy and Breastfeeding

Prochlorperazine is considered safe and appropriate for use during pregnancy, particularly for nausea and vomiting, and is compatible with all trimesters and breastfeeding according to current guidelines. 1

Safety Profile During Pregnancy

The 2023 EASL guidelines explicitly list prochlorperazine as compatible with periconception, first trimester, second/third trimester, and breastfeeding for the management of hyperemesis gravidarum. 1 This represents the most recent high-quality guideline evidence available.

First-Line Treatment Status

• Prochlorperazine is designated as a first-line pharmacologic antiemetic when non-pharmacologic treatments fail for nausea and vomiting in pregnancy. 2
• It is grouped with other safe first-line options including doxylamine, promethazine, and dimenhydrinate. 2
• The treatment algorithm begins with dietary modifications, trigger avoidance, ginger, and vitamin B6 before advancing to pharmacologic options. 2

Evidence Quality and Malformation Risk

• Large observational studies have not demonstrated a definitive association between prochlorperazine use during pregnancy and increased risk of birth defects. 3
• A Swedish registry study of 2,908 women using antipsychotics (predominantly prochlorperazine for nausea/vomiting) found a modest increased risk of congenital malformations (OR 1.52,95% CI 1.05-2.19), primarily cardiovascular defects. 4 However, this study could not establish drug specificity and suggested underlying pathology or confounding may explain the excess risk. 4
• The lack of drug specificity in the Swedish study and the inability to exclude confounding by indication means causality cannot be established. 4

FDA Classification and Prescribing Considerations

• The FDA label states that "safety for the use of prochlorperazine during pregnancy has not been established" and recommends use only for "severe nausea and vomiting that are so serious and intractable that, in the judgment of the physician, drug intervention is required and potential benefits outweigh possible hazards." 5
• However, this conservative FDA language predates the robust observational data and current guideline recommendations that support its safety profile. 1, 2

Critical Prescribing Caveats

Neonates exposed to prochlorperazine in the third trimester are at risk for extrapyramidal symptoms and/or withdrawal symptoms following delivery. 5 These may include:

• Agitation, hypertonia, hypotonia, tremor 5
• Somnolence, respiratory distress, feeding disorders 5
• Prolonged jaundice, hyperreflexia or hyporeflexia 5
• Symptoms range from self-limited to requiring intensive care unit support 5

Monitor all neonates exposed near delivery for these complications, which have varied in severity. 5

Breastfeeding Compatibility

• Prochlorperazine is explicitly listed as compatible with breastfeeding in the 2023 EASL guidelines. 1
• Phenothiazines are excreted in breast milk, so caution is advised, but the guideline designation supports its use. 5, 1
• Chlorpromazine (a related phenothiazine) has been reported to cause drowsiness and lethargy in breastfed infants, suggesting monitoring is prudent. 6

Alternative Treatment Options

When prochlorperazine is ineffective or not tolerated:

• Second-line: Metoclopramide has similar efficacy to prochlorperazine but with fewer adverse events (less drowsiness, dizziness, dystonia). 2
• Third-line: Ondansetron and methylprednisolone for severe cases, used on a case-by-case basis. 2
• All these alternatives are also considered compatible with pregnancy when clinically indicated. 1

Clinical Monitoring Recommendations

• For severe symptoms or hyperemesis gravidarum, monitor for dehydration, electrolyte imbalances, and nutritional deficiencies. 2
• If symptoms persist despite prochlorperazine, consider stepping up to alternative therapies or hospitalization for IV hydration. 2
• Use within two weeks of delivery may inhibit platelet aggregation in the newborn, requiring neonatal monitoring. 2

Risk-Benefit Framework

The key clinical decision point is severity of maternal symptoms: prochlorperazine should be reserved for nausea and vomiting that significantly impairs maternal nutrition, hydration, or quality of life, not for minor self-limited symptoms. 2 The extensive clinical experience with prochlorperazine for pregnancy-related nausea, combined with explicit guideline endorsement, supports its use when clinically indicated despite theoretical concerns raised by older observational data. 1, 4, 3