Erythromycin Safety in Pregnancy
Erythromycin is safe to use during pregnancy and is classified as FDA Pregnancy Category B, with no evidence of teratogenicity or adverse effects on reproduction in animal studies and human data suggesting low risk if any. 1
FDA Classification and Safety Profile
- Erythromycin is designated as FDA Pregnancy Category B, meaning animal reproduction studies have failed to demonstrate fetal risk, though adequate well-controlled studies in pregnant humans are lacking 1
- Animal studies at doses up to 350-700 mg/kg/day (approximately 1-3 times the maximum human dose) showed no evidence of teratogenicity or embryotoxicity in rats, mice, and rabbits 1
- A large Norwegian population-based registry study of 180,120 pregnancies found no increased risk of cardiovascular malformations (adjusted OR = 1.2 [95% CI 0.8,1.8]) or any other specific malformations with first-trimester erythromycin exposure 2
Clinical Guidelines for Pregnancy Use
- Erythromycin is recommended as the preferred macrolide for long-term suppression of Bartonella infection during pregnancy, as tetracyclines are contraindicated 3
- For syphilis treatment in pregnancy, erythromycin is specifically noted as not reliably curing fetal infection and should be avoided; penicillin with desensitization is required instead 3
- The 2020 ERS/TSANZ guidelines classify erythromycin as "probably safe" during pregnancy (Category A/B), noting that most human reports found no evidence of increased birth defects 3
Important Clinical Caveats
Infantile Hypertrophic Pyloric Stenosis (IHPS)
- Erythromycin use in newborns carries a risk of IHPS, with a 5% absolute risk in one cohort study (7 of 157 exposed infants) 3, 1
- The risk appears dose-dependent: 5.1% for 8-14 days of treatment and 10% for 15-21 days 1
- One epidemiological study suggested a very low risk of pyloric stenosis in infants exposed during the first 13 days of breastfeeding (not after 2 weeks) 3
- Parents should be counseled to contact their physician if vomiting or irritability with feeding occurs 1
Pharmacokinetic Considerations
- Serum erythromycin levels are significantly diminished in the third trimester, with delayed absorption and lower peak concentrations compared to non-pregnant patients 4
- In two pregnant women studied, erythromycin levels were undetectable throughout the 4-hour sampling period, both of whom experienced severe gastrointestinal symptoms 4
- Severe gastrointestinal adverse events may indicate subtherapeutic plasma concentrations, potentially compromising treatment efficacy 4
Comparative Efficacy in Pregnancy
- For chlamydial infection in pregnancy, amoxicillin demonstrated superior tolerability with a 2% failure rate versus 12% for erythromycin (p = 0.005) in a randomized controlled trial 5
- Severe gastrointestinal side-effects occurred in 31% of erythromycin-treated women versus 6% with amoxicillin (p < 0.001) 5
- Only 1% of amoxicillin-treated women discontinued therapy due to side effects compared to 12% with erythromycin (p = 0.002) 5
Specific Formulation Warning
- Erythromycin estolate should be avoided during pregnancy due to potential maternal hepatotoxicity 3
- Other erythromycin formulations (base, stearate, ethylsuccinate) are acceptable 3
Alternative Considerations
- Azithromycin is the preferred macrolide during pregnancy according to CDC guidelines, with a better safety profile and improved tolerability 6
- For conditions requiring macrolide therapy in pregnancy, azithromycin should be considered first-line over erythromycin when clinically appropriate 6
- Penicillins and cephalosporins remain first-line antibiotics during pregnancy when appropriate for the indication 7
Drug Interactions During Pregnancy
- Erythromycin is a CYP3A4 inhibitor and can increase levels of drugs metabolized by this pathway, including theophylline, digoxin, oral anticoagulants, and certain statins 1
- Concomitant use with cisapride, pimozide, astemizole, or terfenadine is contraindicated due to risk of QT prolongation and fatal arrhythmias 1