Is Azithromycin (Zithromax) safe to use during pregnancy?

Azithromycin Safety During Pregnancy

Azithromycin is generally considered safe to use during pregnancy when clinically indicated, as it has a favorable safety profile compared to other macrolide antibiotics. 1

Safety Classification and Evidence

• Azithromycin is classified as FDA Pregnancy Category B, indicating that animal reproduction studies have not demonstrated fetal risk, but adequate well-controlled studies in pregnant women are lacking 2
• Animal studies at doses up to 4 times the human daily dose showed no evidence of harm to the fetus due to azithromycin 2
• Current evidence does not conclusively demonstrate that azithromycin use during pregnancy causes adverse fetal outcomes 3
• The CDC considers azithromycin the preferred macrolide when treatment is necessary during pregnancy due to its pharmacokinetic properties and safety profile 1

Clinical Applications During Pregnancy

• Azithromycin is listed as an alternative treatment option for chlamydial infections during pregnancy (1g orally in a single dose) 4, 5
• For HIV-infected pregnant women requiring MAC (Mycobacterium avium complex) prophylaxis, azithromycin is specifically recommended as the drug of choice 1
• Azithromycin can be used in the management of respiratory infections during pregnancy when clinically indicated 4

Pharmacokinetics in Pregnancy

• Pregnancy increases the volume of distribution of azithromycin by approximately 86% relative to bioavailability, but without significant changes in the overall drug exposure (AUC) 6
• This pharmacokinetic change does not necessitate dose adjustments during pregnancy 6

Safety Considerations and Precautions

• A 2006 study of 123 women who took azithromycin during pregnancy (71.6% during first trimester) found no statistically significant increase in major malformations compared to control groups 7
• While some studies have reported potential risks of spontaneous miscarriage, major congenital malformations, and preterm birth, others have not confirmed these findings 3
• The CDC advises against confusing azithromycin with clarithromycin, which has been demonstrated to be a teratogen in animals 1

Recommendations for Clinical Practice

• Use azithromycin during pregnancy only when clinically indicated and when the benefits of treatment are expected to outweigh potential risks 3
• When treating chlamydial infections in pregnancy, azithromycin (1g orally in a single dose) may be considered as an alternative to first-line agents such as erythromycin or amoxicillin 4, 5
• For patients with cystic fibrosis who are on chronic azithromycin therapy and considering pregnancy, the potential risk to the infant must be weighed against the risk to the mother of treatment discontinuation 8
• Monitoring for known side effects of azithromycin, such as liver enzyme abnormalities, is warranted during pregnancy 2

Common Pitfalls

• Confusing azithromycin with clarithromycin, which has greater teratogenic potential in animal studies 1
• Discontinuing necessary antibiotic treatment due to unfounded concerns about safety, potentially leading to untreated maternal infections that could harm both mother and fetus 8
• Failing to consider that the benefits of treating serious maternal infections often outweigh the theoretical risks of azithromycin use during pregnancy 3