Is azithromycin safe for use during pregnancy?

Azithromycin Safety in Pregnancy

Azithromycin is safe to use during pregnancy and is classified as a preferred macrolide antibiotic by the CDC, with FDA Pregnancy Category B designation indicating no evidence of fetal harm in animal studies. 1, 2

Safety Classification and Regulatory Status

• The FDA classifies azithromycin as Pregnancy Category B, with animal reproduction studies at doses up to 4 times (rats) and 2 times (mice) the human daily dose of 500 mg showing no evidence of harm to the fetus. 2
• The European Respiratory Society categorizes azithromycin as B1, meaning it has been taken by a limited number of pregnant women without an increase in the frequency of fetal malformation or harmful effects, and is classified as "Probably safe." 3
• The CDC specifically recommends azithromycin as the drug of choice during pregnancy due to its safety profile compared to other macrolide agents. 1

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 rate of 1-3%. 4
• No conclusive evidence exists that azithromycin use during pregnancy causes adverse fetal outcomes, according to the CDC. 1
• Human data from multiple studies suggest low risk, though some conflicting results exist regarding spontaneous miscarriage, congenital malformations, and preterm birth in certain studies. 5

Recommended Clinical Applications During Pregnancy

• Chlamydial infections: The CDC recommends azithromycin 1g orally as a single dose as an alternative treatment option during pregnancy. 1
• Pertussis treatment and prophylaxis: Azithromycin is the preferred macrolide, particularly for infants <1 month and by extension for pregnant women. 1
• MAC prophylaxis: For HIV-infected pregnant women requiring Mycobacterium avium complex prophylaxis, the CDC specifically recommends azithromycin as the drug of choice. 1
• Respiratory infections: Azithromycin can be used for management of respiratory infections during pregnancy when clinically indicated. 1

Pharmacokinetic Considerations

• Pregnancy increases the volume of distribution of the central compartment by 86% without significantly changing the area under the curve (AUC), suggesting no dose adjustment is necessary. 6
• Non-African American pregnant women may experience 21-42% higher dose-adjusted azithromycin AUC compared to nonpregnant women, though clinical significance remains unclear. 7
• The terminal elimination half-life is approximately 77-78 hours in both pregnant and nonpregnant women. 6

Breastfeeding Safety

• An epidemiological study suggests a very low risk of hypertrophic pyloric stenosis in infants exposed to macrolides during the first 13 days of breastfeeding (not after 2 weeks). 3
• It is not known whether azithromycin is excreted in human milk, and caution should be exercised when administered to nursing women. 2

Critical Contraindications and Pitfalls

• Do not confuse azithromycin with clarithromycin, which has been demonstrated to be a teratogen in animals and should be used with caution during pregnancy. 1
• Azithromycin has insufficient efficacy data for syphilis treatment in pregnancy and should not be used; penicillin remains the only proven effective treatment. 1
• Azithromycin should only be used during pregnancy when clinically indicated, as the benefits of treatment must outweigh potential risks. 5

Monitoring Considerations

• Close monitoring for known side effects of azithromycin, such as liver enzyme abnormalities and hearing impairment, is warranted during pregnancy. 2
• Prothrombin times should be carefully monitored if azithromycin is co-administered with oral anticoagulants, as spontaneous post-marketing reports suggest potential potentiation of anticoagulant effects. 2