Is Azithromycin Safe in Pregnancy?
Yes, azithromycin is safe to use during pregnancy and is the preferred macrolide antibiotic when treatment is indicated. 1, 2
Guideline Recommendations
The CDC explicitly designates azithromycin as the drug of choice among macrolide antibiotics for pregnant women, based on animal studies and anecdotal human safety evidence. 1, 2 This recommendation applies across multiple clinical scenarios:
- For chlamydial infections: Azithromycin 1g orally as a single dose is a recommended first-line regimen during pregnancy 1
- For MAC prophylaxis in HIV-infected pregnant women: Azithromycin is specifically preferred over other macrolides 1
- For pertussis treatment/prophylaxis: Azithromycin is the recommended agent, particularly in infants and pregnant women 1
FDA Classification and Safety Data
Azithromycin is FDA Pregnancy Category B, meaning animal reproduction studies have shown no evidence of fetal harm at doses up to 4 times (rats) and 2 times (mice) the human daily dose of 500mg. 1, 3 The FDA label states: "There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, azithromycin should be used during pregnancy only if clearly needed." 3
Clinical Evidence on Fetal Outcomes
The research evidence shows no conclusive evidence that azithromycin causes adverse fetal outcomes: 4
- 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% vs 3.4%). 5
- The baseline rate of major malformations (1-3%) was not exceeded in azithromycin-exposed pregnancies 5
- Some observational studies have reported associations with spontaneous miscarriage, congenital malformations, preterm birth, and low birth weight, but these findings have not been consistently replicated 4
Pharmacokinetic Considerations
Pregnancy increases the volume of distribution of azithromycin by 86% without significantly changing the area under the curve (AUC), meaning therapeutic drug levels are maintained without dose adjustment. 6 Importantly:
- Repeated maternal intravenous dosing achieves significant fetal tissue uptake in the fetal lung and liver without evidence of fetal injury 7
- Good transplacental transfer occurs, making azithromycin suitable for treating intrauterine infections 7
Critical Comparison: Why Azithromycin Over Other Macrolides
Clarithromycin should be avoided or used with extreme caution in pregnancy because it has been demonstrated to be teratogenic in animal studies. 1, 2 This makes the choice between macrolides straightforward—azithromycin is clearly safer.
Erythromycin is associated with more frequent gastrointestinal side effects that may discourage compliance, and erythromycin estolate is contraindicated in pregnancy due to drug-related hepatotoxicity. 1
First Trimester Considerations
Some providers may choose to withhold prophylactic azithromycin during the first trimester out of general caution about drug exposure, but this is not evidence-based when treatment is clinically necessary. 1, 2 The available data, including 71.6% first-trimester exposures in one study, show no increased malformation risk. 5
Common Pitfalls to Avoid
- Do not confuse azithromycin with clarithromycin—the latter is teratogenic in animals and should be avoided 1, 2
- Do not withhold azithromycin when clinically indicated based on theoretical first-trimester concerns—the evidence supports its safety 2, 5
- Do not assume all macrolides are equivalent in pregnancy—azithromycin has the best safety profile 1, 2
- Counsel patients that azithromycin should only be used when clinically indicated, as with any medication in pregnancy, but reassure them that current evidence does not suggest fetal harm 4, 5
Practical Prescribing
When prescribing azithromycin in pregnancy:
- Use standard dosing regimens—no dose adjustment is needed 6
- For chlamydia: Single 1g dose 1
- For pertussis: 500mg day 1, then 250mg daily days 2-5 1
- Repeat testing 3 weeks after treatment completion is recommended for pregnant women with chlamydia to ensure therapeutic cure given potential maternal and neonatal sequelae 1