What are the guidelines for using prochlorperazine (antiemetic medication) in pregnancy?

Prochlorperazine Use in Pregnancy

Prochlorperazine can be used during pregnancy for severe, intractable nausea and vomiting that has not responded to safer first-line therapies, but it should be reserved as a second- or third-line option due to potential risks of extrapyramidal symptoms in both mother and neonate. 1, 2

Treatment Algorithm for Nausea and Vomiting in Pregnancy

First-Line Therapies (Use These First)

• Vitamin B6 (pyridoxine) 10-25 mg every 8 hours is the recommended initial pharmacologic treatment 3
• Doxylamine-pyridoxine combination (10 mg/10 mg or 20 mg/20 mg) is FDA-approved and should be used before prochlorperazine 3, 1
• H1-receptor antagonists (doxylamine, promethazine, dimenhydrinate) are considered safer alternatives 3

Second-Line Therapies (If First-Line Fails)

• Metoclopramide 10 mg IV or orally has similar efficacy to phenothiazines but with fewer adverse events and no increased risk of congenital defects 1, 4
• Prochlorperazine 5-10 mg every 6-8 hours or 25 mg suppository every 12 hours can be considered at this stage for severe cases 3

Third-Line Therapies (For Hospitalized Severe Cases)

• Ondansetron 8 mg sublingual every 4-6 hours, particularly for cases requiring hospitalization, though use caution before 10 weeks gestation 3, 1

Safety Profile of Prochlorperazine

Maternal Risks

• Extrapyramidal symptoms including akathisia, dystonic reactions, and oculogyric crisis can occur, especially when combined with other antiemetics like ondansetron and metoclopramide 5
• Central nervous system depression, anticholinergic effects, and drug-induced leukopenia or neutropenia are documented adverse effects 3
• Risk of neuroleptic malignant syndrome, though rare 3, 2

Fetal and Neonatal Risks

• The FDA label states safety has not been established in pregnancy and recommends use only when potential benefits outweigh risks in severe, intractable cases 2
• Neonates exposed in the third trimester are at risk for extrapyramidal symptoms and withdrawal symptoms including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorders 2
• Some studies suggest a possible 52% increased risk of congenital malformations (OR 1.52,95% CI 1.05-2.19), primarily cardiovascular defects like atrial or ventricular septal defects, though causality is uncertain 6
• Prolonged jaundice, extrapyramidal signs, and hyperreflexia or hyporeflexia have been reported in newborns 2

Clinical Considerations

When Prochlorperazine May Be Appropriate

• Severe hyperemesis gravidarum unresponsive to first-line therapies (vitamin B6, doxylamine, dietary modifications) 1, 2
• Cases requiring drug intervention where the physician judges potential benefits outweigh possible hazards 2
• Second and third trimester use may be safer than first trimester, though risks persist throughout pregnancy 1

Important Precautions

• Monitor for extrapyramidal symptoms closely, particularly if combining with other antiemetics 5
• Avoid in patients with history of leukopenia, neutropenia, dementia, glaucoma, or seizure disorders 3
• Counsel patients about potential neonatal complications requiring intensive care and prolonged hospitalization 2
• Consider that prochlorperazine is excreted in breast milk, requiring caution during lactation 2

Comparative Effectiveness

• In emergency department settings, prochlorperazine showed similar time to disposition as ondansetron for nausea and vomiting of pregnancy, though ondansetron was associated with longer ED stays in adjusted analyses 7
• No definitive drug specificity has been identified for the increased malformation risk seen with antipsychotics, suggesting underlying pathology or confounding may contribute 6, 8

Key Pitfall to Avoid

Do not use prochlorperazine as a first-line agent. The evidence consistently supports exhausting safer alternatives (vitamin B6, doxylamine-pyridoxine, metoclopramide) before resorting to phenothiazines like prochlorperazine 3, 1, 4. The potential for maternal extrapyramidal reactions and neonatal complications makes this a reserve option only for severe, refractory cases where the severity of maternal symptoms justifies the risk 2.