Is azithromycin (Zithromax) safe to use during pregnancy?

Azithromycin Safety in Pregnancy

Azithromycin is considered safe and is recommended as the first-line treatment for chlamydial infections during pregnancy, with strong evidence supporting its safety profile compared to other macrolide antibiotics. 1

Safety Profile and Recommendations

• The Centers for Disease Control and Prevention (CDC) specifically recommends azithromycin 1g orally in a single dose as the first-line treatment for chlamydial infections in pregnant women 1

• This recommendation is based on:

  • High compliance rate (single-dose regimen)
  • Demonstrated safety in pregnancy
  • Proven efficacy against chlamydial infections

• The FDA pregnancy category for azithromycin is B, indicating that:

  • Animal reproduction studies have shown no evidence of harm to the fetus 2
  • No adequate and well-controlled studies in pregnant women have shown adverse effects

Evidence Supporting Safety

• Animal studies at doses up to 4 times the human daily dose of 500mg showed no evidence of harm to the fetus 2
• Azithromycin has good oral bioavailability and transplacental transfer, making it suitable for treating various infections during pregnancy 3
• In HIV-infected pregnant women, azithromycin is the drug of choice for MAC (Mycobacterium avium complex) prophylaxis based on animal studies and anecdotal evidence of safety in humans 4

Treatment Alternatives in Pregnancy

When azithromycin cannot be used, alternative regimens include:

• Amoxicillin 500mg orally three times daily for 7 days 1
• Erythromycin base 500mg orally four times a day for 7 days 4
• Erythromycin ethylsuccinate in various dosing regimens 4, 1

Important Contraindications

Several antibiotics are contraindicated during pregnancy:

• Doxycycline and fluoroquinolones (ofloxacin, levofloxacin) are contraindicated due to potential fetal harm 4, 1
• Erythromycin estolate is specifically contraindicated due to drug-related hepatotoxicity 4, 1
• Clarithromycin has been demonstrated to be a teratogen in animals and should be used with caution 4

Recent Research Findings

Recent studies have shown mixed but generally reassuring results:

• A 2022 comprehensive review found conflicting results regarding adverse offspring outcomes, with some studies reporting increased risks of spontaneous miscarriage, major congenital malformations, and preterm birth, while others found no such associations 3
• A 2023 multicountry randomized trial found that a single 2g oral dose of azithromycin during labor reduced maternal sepsis without increasing adverse neonatal outcomes 5
• A 2021 systematic review and meta-analysis found that prophylactic azithromycin during pregnancy reduced low birth weight and prematurity 6

Clinical Considerations

• Test of cure is recommended 3 weeks after treatment completion for pregnant women 1
• Sexual partners from the previous 60 days should be evaluated and treated to prevent reinfection 4, 1
• Patients should abstain from sexual intercourse until both they and their partners have completed treatment 4, 1

Drug Interactions

• Caution is advised when co-administering azithromycin with:
  • Nelfinavir (increased azithromycin serum concentrations) 2
  • Oral anticoagulants (may potentiate effects) 2
  • Protease inhibitors (may affect drug levels) 4

Conclusion

Based on the most recent and highest quality evidence, azithromycin is considered safe for use during pregnancy when clinically indicated. The benefits of treatment generally outweigh the potential risks, particularly for treating chlamydial infections and other susceptible bacterial infections.