Is erythromycin (macrolide antibiotic) safe to use during pregnancy?

Erythromycin Safety in Pregnancy

Erythromycin is generally safe to use during pregnancy and is classified as "probably safe" (FDA Category B) with most human studies showing no increased risk of birth defects, though azithromycin is now preferred due to better tolerability and safety profile. 1, 2

Safety Profile During Pregnancy

Erythromycin has a long-established safety record in pregnancy with no evidence of teratogenicity:

• The European Respiratory Society/Thoracic Society of Australia and New Zealand classify erythromycin as Category A/B ("probably safe"), noting that most reports in humans found no evidence of increased risk of birth defects 1
• A large Norwegian population-based study of 180,120 pregnancies found no increased risk of cardiovascular malformations (adjusted OR = 1.2 [95% CI 0.8,1.8]) or other specific malformations with first-trimester erythromycin exposure 3
• The FDA drug label notes that observational studies have reported cardiovascular malformations after exposure to erythromycin-containing products during early pregnancy, though causality remains uncertain 4

Clinical Indications in Pregnancy

Erythromycin remains indicated for specific infections during pregnancy:

• CDC guidelines recommend erythromycin base 500 mg orally four times daily for 7 days as an alternative regimen for chlamydial infections in pregnant women 1, 5
• Erythromycin is the preferred macrolide for long-term suppression of Bartonella infection during pregnancy, as tetracyclines are contraindicated 2
• Important exception: Erythromycin does NOT reliably cure fetal syphilis infection and should be avoided for this indication; penicillin with desensitization is required instead 2

Important Safety Concerns and Limitations

Several critical caveats limit erythromycin use:

Erythromycin Estolate Formulation

• Erythromycin estolate is specifically contraindicated during pregnancy due to potential maternal hepatotoxicity 1
• Use erythromycin base, stearate, or ethylsuccinate formulations instead 1

Gastrointestinal Tolerability

• Frequent gastrointestinal side effects (nausea, vomiting, abdominal pain, diarrhea) may discourage patient compliance 1
• Side effects are more frequent and severe with erythromycin compared to other macrolides 1
• Severe gastrointestinal symptoms in third-trimester patients may indicate subtherapeutic plasma concentrations, potentially compromising treatment efficacy 6

Pharmacokinetic Changes in Late Pregnancy

• Absorption is delayed and serum levels are diminished in third-trimester pregnancy compared to second trimester 6
• In some third-trimester patients, erythromycin serum levels may be undetectable, correlating with severe gastrointestinal symptoms 6

Neonatal Risks

• Infantile hypertrophic pyloric stenosis (IHPS) is a concern when erythromycin is used in newborns, with a 5% absolute risk (7 of 157 exposed infants) in one cohort study 1, 2, 4
• A dose-response effect exists: 5.1% risk for 8-14 days of treatment, 10% risk for 15-21 days 4
• During breastfeeding, there is a very low risk of pyloric stenosis in infants exposed during the first 13 days (not after 2 weeks) 1, 2

Preferred Alternative: Azithromycin

Azithromycin is now the preferred macrolide during pregnancy:

• CDC guidelines recommend azithromycin as the preferred macrolide with better safety profile and improved tolerability 2
• Azithromycin is FDA Pregnancy Category B with no adverse effects reported in studies of pregnant patients 1, 5
• For chlamydial infections in pregnancy, azithromycin 1 g orally as a single dose is a recommended first-line regimen 1, 5
• Azithromycin has superior gastrointestinal tolerability compared to erythromycin 1

Clinical Decision Algorithm

When considering macrolide therapy in pregnancy:

1. First choice: Use azithromycin for most indications requiring macrolide therapy 2, 5
2. Second choice: Use erythromycin base, stearate, or ethylsuccinate (never estolate) if azithromycin is unavailable or contraindicated 1
3. Monitor for: Gastrointestinal intolerance, which may indicate subtherapeutic levels, especially in third trimester 6
4. Avoid for: Syphilis treatment (use penicillin instead) 2
5. Counsel patients: About gastrointestinal side effects and importance of completing therapy despite discomfort 1