Pregnancy Category of Azithromycin (Zithromax)
Azithromycin is classified as FDA Pregnancy Category B, indicating that animal reproduction studies have not demonstrated a fetal risk but there are no adequate and well-controlled studies in pregnant women. 1
Understanding Pregnancy Category B Classification
- Reproduction studies performed in rats and mice at doses up to moderately maternally toxic concentrations (200 mg/kg/day) showed no evidence of harm to the fetus due to azithromycin 1
- These animal study doses are estimated to be 4 times (rats) and 2 times (mice) the human daily dose of 500 mg, based on mg/m² calculations 1
- The FDA classification indicates that while animal studies are reassuring, there are insufficient well-controlled studies in pregnant women to definitively establish safety 1
Clinical Evidence Supporting Use in Pregnancy
- Azithromycin is considered the preferred macrolide antibiotic during pregnancy when treatment is necessary 2
- The CDC recommends azithromycin as the drug of choice for certain infections during pregnancy, including as prophylaxis for MAC (Mycobacterium avium complex) in HIV-infected pregnant women 3
- For treatment of chlamydial infections during pregnancy, azithromycin 1g orally in a single dose is recommended as first-line therapy due to its superior efficacy, safety profile, and excellent compliance 4
Safety Considerations
- Unlike clarithromycin (which has shown teratogenic effects in animal studies), azithromycin did not produce defects in animal studies 3
- Azithromycin is preferred over clarithromycin during pregnancy, particularly in the first trimester 3
- While human experience with azithromycin use during first trimester is limited, available data do not demonstrate an increase in or specific pattern of birth defects 3, 5
Research Findings and Limitations
- A study of 123 women exposed to azithromycin during pregnancy (with 71.6% exposed during first trimester) found no statistically significant increase in major malformations compared to control groups 5
- Some studies have reported conflicting results regarding risks of spontaneous miscarriage, major congenital malformations, and preterm birth, but there is no conclusive evidence establishing causality 6
- Recent animal studies have raised concerns about potential fetal developmental effects at high doses, but clinical significance remains unclear 7
Clinical Recommendations
- Azithromycin should only be used during pregnancy when clinically indicated and when the benefits of treatment are expected to outweigh potential risks 6
- When macrolide therapy is necessary during pregnancy, azithromycin is generally preferred over other macrolides due to its safety profile 2
- For pregnant women with certain conditions like cystic fibrosis who may be on chronic azithromycin therapy, the risks of discontinuation may outweigh potential risks to the fetus 8
Important Precautions
- As with all medications during pregnancy, use azithromycin only when clearly needed 1
- It is unknown whether azithromycin is excreted in human milk, so caution should be exercised when administering to nursing women 1
- Avoid concurrent administration with aluminum- or magnesium-containing antacids as they can reduce azithromycin absorption 3