Azithromycin in Pregnancy
Direct Answer
Azithromycin is safe to use during pregnancy, including the first trimester, and is the CDC's preferred macrolide antibiotic for pregnant women requiring treatment for bacterial infections. 1, 2, 3
Safety Classification and Evidence Base
The FDA classifies azithromycin as Pregnancy Category B, meaning animal reproduction studies at doses up to 4 times (rats) and 2 times (mice) the human daily dose of 500 mg showed no evidence of fetal harm. 4 However, as with all medications, adequate and well-controlled studies in pregnant women are lacking, so use should be reserved for when clearly needed. 4
The CDC specifically designates azithromycin as the drug of choice during pregnancy due to its superior safety profile compared to other macrolide agents, with no conclusive evidence that azithromycin causes adverse fetal outcomes. 1, 2, 3
Clinical Evidence Supporting Safety
A prospective cohort study of 123 pregnant women exposed to azithromycin (71.6% during first trimester) found no statistically significant increase in major malformations compared to disease-matched controls (3.4% vs 2.3%) or non-teratogen controls (3.4%), which is within the baseline population risk of 1-3%. 5
A large randomized controlled trial (A-PLUS) involving 29,278 pregnant women at ≥28 weeks gestation who received a single 2-g oral dose of azithromycin showed no increase in adverse neonatal outcomes (stillbirth, neonatal death, or sepsis occurred in 10.5% vs 10.3% in placebo), while significantly reducing maternal sepsis or death (1.6% vs 2.4%, relative risk 0.67). 6
Pharmacokinetic studies demonstrate that pregnancy increases the volume of distribution by 86% without significantly changing the area under the curve, suggesting no dose adjustment is needed during pregnancy. 7
Approved Indications During Pregnancy
For chlamydial infections: 1 g orally as a single dose 8, 2, 3
For atypical pneumonia (Mycoplasma, Chlamydia, Legionella): 500 mg on day 1, followed by 250 mg daily for days 2-5 1, 3
For pertussis treatment or prophylaxis: Azithromycin is the preferred macrolide, particularly in the third trimester 3
For community-acquired respiratory infections: When macrolide coverage is needed 3
For inpatient pneumonia management: Azithromycin combined with a beta-lactam antibiotic (ampicillin or ceftriaxone) for severe presentations 1
Critical Safety Distinction: Never Substitute Clarithromycin
Do not use clarithromycin as an alternative to azithromycin during pregnancy. The CDC classifies clarithromycin as DIII (should not be used) due to demonstrated teratogenic effects in animal studies and possible increased risk of spontaneous abortion in human studies. 1, 2, 3 Despite both being macrolides, they are not interchangeable in pregnancy. 3
Common Pitfalls to Avoid
Do not withhold azithromycin in the first trimester out of excessive caution when clinically indicated—the CDC specifically recommends its use throughout pregnancy. 1, 3
Do not substitute doxycycline (the typical non-pregnant first-line for chlamydia and atypical pneumonia), as it causes fetal tooth discoloration, bone effects, and hepatotoxicity risk. 1, 3
Do not use azithromycin for syphilis treatment in pregnancy—it has insufficient efficacy data and penicillin remains the only proven effective treatment. 2
Standard Monitoring and Precautions
Monitor for standard azithromycin adverse effects applicable to all patients, including pregnant women: 1, 3, 4
- QT prolongation risk
- Hepatotoxicity (monitor liver enzymes)
- Clostridium difficile-associated diarrhea (can occur up to 2 months after last dose)
- Hearing impairment (rare but documented)
For pneumonia treatment after 20 weeks gestation, monitor for preterm labor, as pneumonia itself increases this risk. 1, 3
If treating with warfarin concurrently, carefully monitor prothrombin times, as post-marketing reports suggest azithromycin may potentiate oral anticoagulant effects. 4
Alternative Antibiotics When Azithromycin Cannot Be Used
Erythromycin is an acceptable macrolide alternative, though it causes more gastrointestinal side effects. 3
Amoxicillin is the safest first-line choice for typical bacterial lower respiratory tract infections throughout pregnancy. 3
Fluoroquinolones (levofloxacin) can be used for serious life-threatening infections when other options fail, with approximately 400 documented cases in pregnancy showing no increased arthropathy or birth defects. 1
Breastfeeding Considerations
It is unknown whether azithromycin is excreted in human milk, so caution should be exercised when administering to nursing women, as many drugs are excreted in breast milk. 4