What are the safety and usage guidelines for Macrobid (nitrofurantoin) and Phenergan (promethazine) during pregnancy?

Macrobid (Nitrofurantoin) and Phenergan (Promethazine) in Pregnancy

Macrobid (Nitrofurantoin) in Pregnancy

Nitrofurantoin is safe and appropriate for treating urinary tract infections during the second and third trimesters of pregnancy, and remains acceptable in the first trimester when no suitable alternatives exist, though it should be avoided near term (after 36 weeks) due to risk of neonatal hemolysis. 1, 2

First Trimester Use

• Nitrofurantoin is recommended as a first-line antibiotic for UTIs during the first trimester according to European Urology guidelines, with fosfomycin as an acceptable alternative 1
• The American College of Obstetricians and Gynecologists states that prescribing nitrofurantoin in the first trimester is appropriate when no other suitable alternative antibiotics are available 2
• A 2025 cohort study of 42,402 nitrofurantoin-exposed pregnancies found no elevated risk of congenital malformations compared to β-lactam antibiotics (RR 1.12; 95% CI 0.99-1.26) 3
• Meta-analysis of cohort studies involving 9,275 exposed infants showed no increased risk of major malformations (RR 1.01; 95% CI 0.81-1.26) 4

Second and Third Trimester Use

• Nitrofurantoin may continue to be used as a first-line agent during the second and third trimesters for treatment and prevention of UTIs 2
• Treatment duration should be 7-14 days to ensure complete eradication of infection 1
• Nitrofurantoin should NOT be used for suspected pyelonephritis as it does not achieve therapeutic concentrations in the bloodstream 1

Critical Timing Restriction

• Avoid nitrofurantoin after 36 weeks gestation and during labor due to risk of hemolytic anemia in newborns with immature enzyme systems 1

Alternative Options When Nitrofurantoin is Contraindicated

• Cephalexin 500 mg four times daily for 7-14 days is the preferred alternative 1
• Fosfomycin single 3g dose for uncomplicated lower UTIs 1
• Amoxicillin-clavulanate if pathogen is susceptible 1

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Phenergan (Promethazine) in Pregnancy

Promethazine is acceptable for use during pregnancy when benefits outweigh risks, particularly for severe nausea and vomiting, though it carries FDA Pregnancy Category C designation and requires caution within two weeks of delivery due to potential neonatal effects. 5

Safety Profile and Indications

• The American Gastroenterological Association recognizes promethazine as having similar efficacy to metoclopramide for hyperemesis gravidarum, though metoclopramide causes less drowsiness, dizziness, and dystonia 6
• A Cochrane review and meta-analysis of 25 studies found no significant difference in efficacy among metoclopramide, ondansetron, and promethazine for hyperemesis gravidarum 6
• European Association for the Study of the Liver guidelines recommend phenothiazines (including promethazine) as first-line pharmacologic treatment for hyperemesis gravidarum 6

FDA Pregnancy Category C Designation

• The FDA label states there are no adequate and well-controlled studies in pregnant women, and promethazine should be used only if potential benefit justifies potential risk to the fetus 5
• Teratogenic effects have not been demonstrated in rat studies at doses 2.1 to 4.2 times the maximum recommended human dose 5
• Daily doses of 25 mg/kg intraperitoneally produced fetal mortality in rats 5

Timing-Specific Concerns

• Promethazine administered within two weeks of delivery may inhibit platelet aggregation in the newborn 5
• Limited data suggest use during labor and delivery does not appreciably affect duration of labor or increase risk of need for intervention in the newborn 5
• The effect on later growth and development of the newborn is unknown 5

Important Adverse Effects to Monitor

• Drug-induced extrapyramidal adverse effects may occur with phenothiazines, and the drug should be withdrawn if patients report such symptoms 6
• Promethazine may cause excessive sedation, particularly when combined with other CNS depressants 5
• May cause false-negative or false-positive pregnancy test results based on HCG immunological reactions 5

Clinical Decision Algorithm

• For mild to moderate nausea and vomiting: Start with vitamin B6 (pyridoxine) as first-line 6
• For persistent symptoms requiring pharmacotherapy: Consider promethazine, metoclopramide, or doxylamine-pyridoxine combinations as first-line options 6
• Avoid use within two weeks of expected delivery unless benefits clearly outweigh the risk of neonatal platelet dysfunction 5
• Monitor for extrapyramidal symptoms and discontinue if they occur 6