Is azithromycin (Zithromax) safe to use during pregnancy?

Azithromycin Safety in Pregnancy

Azithromycin is considered safe and is recommended for use during pregnancy when clinically indicated, with evidence supporting its safety profile and efficacy for treating infections in pregnant women. 1, 2

Evidence Supporting Azithromycin Use in Pregnancy

Safety Profile

• FDA pregnancy category B medication, indicating animal reproduction studies have not demonstrated fetal risk, though adequate human studies are limited 3
• Reproductive studies in rats and mice at doses up to 4 times the human daily dose showed no evidence of harm to the fetus 3
• The 2025 North American clinical practice guidelines specifically recommend azithromycin as one of the safe systemic antibiotics for pregnant patients with hidradenitis suppurativa (conditional recommendation, moderate quality evidence) 2

Efficacy and Indications

• Azithromycin is the primary recommended treatment for chlamydial infection in pregnant women 1
• It can be used for treating various infections during pregnancy, including sexually transmitted infections, respiratory infections, and as prophylaxis in certain situations 1, 2

Clinical Recommendations for Use

Dosing and Administration

• For chlamydial infections: 1g orally in a single dose 2, 1
• For MAC prophylaxis in HIV-infected pregnant women: azithromycin is preferred over clarithromycin due to better safety profile 2
• For hidradenitis suppurativa: standard dosing can be used safely during pregnancy 2

Monitoring and Follow-up

• Test of cure is recommended 3 weeks after treatment completion for chlamydial infections during pregnancy 1
• Monitor for common side effects such as gastrointestinal symptoms, which are generally mild 3

Comparison with Alternative Antibiotics

Safer Alternatives to Avoid in Pregnancy

• Doxycycline: Contraindicated due to risk of tooth discoloration and potential bone growth suppression in the fetus 2, 1
• Erythromycin estolate: Contraindicated due to risk of maternal hepatotoxicity 2, 1
• Fluoroquinolones: Should be avoided due to potential fetal cartilage damage 2

Alternative Options When Azithromycin Cannot Be Used

• Amoxicillin 500 mg orally three times daily for 7 days (95% efficacy) 1
• Erythromycin base 500 mg orally four times daily for 7 days (64% efficacy) 1

Recent Research Findings

Recent studies have shown mixed but generally reassuring results regarding azithromycin use in pregnancy:

• A 2023 randomized controlled trial found that a single 2g oral dose of azithromycin in women planning vaginal delivery significantly reduced the risk of maternal sepsis without increasing adverse neonatal outcomes 4
• A 2021 systematic review and meta-analysis found that prophylactic azithromycin during pregnancy reduced the risk of low birth weight (Pooled RR 0.79; 95% CI 0.68-0.93) and prematurity (Pooled RR 0.87; 95% CI 0.78-0.98) 5
• A 2022 comprehensive review noted that while some studies reported increased risks of adverse outcomes, there is no conclusive evidence that azithromycin causes harm to offspring 6

Important Considerations and Precautions

• Azithromycin crosses the placenta, but pharmacokinetic studies show no need for dose adjustment during pregnancy 7
• The benefits of treating infections during pregnancy generally outweigh the potential risks of azithromycin exposure
• Partner treatment is essential when treating sexually transmitted infections to prevent reinfection 1

Clinical Decision Algorithm

1. Confirm need for antibiotic therapy in pregnant patient
2. Consider azithromycin as first-line if treating:
   • Chlamydial infection
   • Community-acquired pneumonia
   • MAC prophylaxis in HIV-infected women
   • Hidradenitis suppurativa requiring antibiotics
3. Check for contraindications:
   • History of allergic reaction to macrolides
   • Significant drug interactions with other medications
4. Administer appropriate dosage based on indication
5. Schedule follow-up for test of cure when treating STIs
6. Ensure partner treatment when treating sexually transmitted infections

In conclusion, current guidelines and evidence support azithromycin as a safe and effective antibiotic option during pregnancy when clinically indicated, with a favorable risk-benefit profile compared to many alternative antibiotics.