Is azithromycin (Zithromax) safe to use during pregnancy?

Azithromycin Safety in Pregnancy

Azithromycin is safe to use during pregnancy and is the CDC's preferred macrolide antibiotic for pregnant women, with no conclusive evidence of adverse fetal outcomes. 1, 2

FDA Classification and Safety Profile

• Azithromycin is FDA Pregnancy Category B, with animal reproduction studies showing no evidence of fetal harm at doses up to 4 times (rats) and 2 times (mice) the human daily dose of 500 mg 2, 3
• The CDC specifically recommends azithromycin as the drug of choice during pregnancy due to its superior safety profile compared to other macrolide agents 1, 2
• No conclusive evidence exists that azithromycin use during pregnancy causes adverse fetal outcomes 1, 2

Clinical Indications During Pregnancy

For Chlamydial Infections:

• The CDC recommends azithromycin 1g orally as a single dose as first-line treatment for chlamydial cervicitis in pregnancy, with cure rates of 94-100% 2, 4
• Clinical trials demonstrate superior tolerability compared to erythromycin, with 0% gastrointestinal side effects versus 100% with erythromycin 5, 6
• Repeat testing 3 weeks after completion of therapy is mandatory for all pregnant women to ensure cure 4

For Respiratory Infections:

• Azithromycin is recommended for atypical pneumonia (Mycoplasma, Chlamydia, Legionella): 500mg day 1, then 250mg daily for days 2-5 1
• The CDC recommends azithromycin for pertussis treatment or prophylaxis in pregnant women, especially in the third trimester 1, 2
• For community-acquired respiratory infections requiring macrolide coverage, azithromycin is the preferred agent 1

For Other Infections:

• The CDC specifically recommends azithromycin as the drug of choice for MAC (Mycobacterium avium complex) prophylaxis in HIV-infected pregnant women 2

Critical Safety Distinction: Avoid Clarithromycin

• The CDC advises against substituting clarithromycin for azithromycin during pregnancy due to clarithromycin's demonstrated teratogenic effects in animal studies 1, 2
• Azithromycin and clarithromycin are not interchangeable in pregnancy despite both being macrolides 1

Monitoring and Precautions

• Standard azithromycin precautions apply: monitor for QT prolongation risk, hepatotoxicity, and Clostridium difficile-associated diarrhea 1
• If treating pneumonia after 20 weeks gestation, monitor for preterm labor as pneumonia itself increases this risk 1
• Prothrombin times should be carefully monitored in patients receiving azithromycin and oral anticoagulants concomitantly 3

Alternative Antibiotics When Azithromycin Cannot Be Used

• Amoxicillin 500 mg orally three times daily for 7 days is an effective alternative for chlamydia with fewer gastrointestinal side effects than erythromycin 4
• Erythromycin base is an acceptable macrolide alternative, though it causes significantly more gastrointestinal side effects (58-100% versus 0-12% with azithromycin) 1, 5, 6
• Amoxicillin is the safest first-line choice for typical bacterial lower respiratory tract infections throughout pregnancy 1

Absolute Contraindications to Avoid

• Doxycycline and other tetracyclines are contraindicated due to tooth discoloration and bone effects 1, 4
• Fluoroquinolones (levofloxacin, ofloxacin) are contraindicated unless maternal necessity justifies fetal exposure for life-threatening infections 1, 4
• Erythromycin estolate is absolutely contraindicated during pregnancy due to drug-related hepatotoxicity 4, 3

Common Pitfalls to Avoid

• Do not use azithromycin for syphilis treatment in pregnancy—it has insufficient efficacy data and penicillin remains the only proven effective treatment 2
• Do not withhold azithromycin during the first trimester out of caution when treatment is clinically indicated—this approach is not evidence-based 2
• Ensure sexual partners are evaluated, tested, and treated if they had sexual contact during the 60 days preceding diagnosis 4
• Patients should abstain from sexual intercourse until 7 days after single-dose therapy or after completion of multi-day regimens 4