Can Azithromycin Be Given in Pregnancy?

Yes, azithromycin is safe and recommended for use during pregnancy and is the preferred macrolide antibiotic in this population. 1, 2, 3

FDA Classification and Safety Profile

Azithromycin is classified as FDA 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 harm to the fetus. 4
Animal studies demonstrated no teratogenic effects, and extensive clinical experience supports its safety throughout pregnancy, including the first trimester. 2, 3
Human studies with over 100 women exposed during the first trimester did not demonstrate an increased risk of birth defects or specific pattern of malformations. 5

Azithromycin 1 g orally as a single dose is the recommended first-line treatment for chlamydial infection in pregnant women, with cure rates of 94-100% and excellent compliance. 1, 2
This regimen is superior to erythromycin-based alternatives, which have significantly lower efficacy (64-77%) and higher rates of gastrointestinal side effects. 2, 6
Mandatory follow-up testing 3 weeks after completion of therapy is required to ensure therapeutic cure, given the serious maternal and neonatal consequences of persistent infection. 1, 2

Azithromycin is the preferred macrolide for primary and secondary prophylaxis of Mycobacterium avium complex (MAC) disease in HIV-infected pregnant women. 1, 3
For secondary prophylaxis (chronic maintenance therapy), azithromycin plus ethambutol are the preferred drugs. 1

Azithromycin is useful for treating sexually transmitted diseases, toxoplasmosis, malaria, and bacterial respiratory infections during pregnancy. 7
It is also used in the management of preterm pre-labor rupture of membranes and adjunctive prophylaxis for cesarean delivery. 7

Doxycycline, ofloxacin, and levofloxacin are absolutely contraindicated during pregnancy due to potential fetal harm. 1, 2, 6
Erythromycin estolate is contraindicated due to drug-related hepatotoxicity in pregnancy. 1, 2, 6

Do not confuse azithromycin with clarithromycin, which demonstrated teratogenic effects in animal studies with increased risk for birth defects and spontaneous abortion. 1, 2, 3
Clarithromycin is not recommended as first-line therapy for MAC prophylaxis or treatment during pregnancy. 1

Azithromycin has good oral bioavailability and transplacental transfer, making it suitable for treating maternal-fetal infections. 7
The drug's convenient dosing regimen (often single-dose) enhances compliance, which is particularly important in pregnancy. 2, 8

Meta-analysis of randomized controlled trials demonstrated azithromycin had similar effectiveness but fewer adverse events compared with erythromycin or amoxicillin in pregnant women with chlamydial infection. 8
Decades of clinical experience with macrolides have documented their overall safety profile in pregnancy, though data on newer macrolides like azithromycin were initially limited. 9
A prospective cohort study of 123 pregnant women (71.6% exposed during first trimester) found no statistically significant increase in major malformations (3.4%) compared to disease-matched controls (2.3%) or non-teratogen controls (3.4%). 5

Never withhold azithromycin during the first trimester when clinically indicated—this approach is not evidence-based, as the drug has demonstrated safety throughout pregnancy. 3
Always ensure test of cure 3 weeks post-treatment for chlamydial infections, as untreated maternal infection leads to perinatal transmission resulting in neonatal conjunctivitis (5-12 days after birth) and subacute pneumonia (1-3 months of age). 1, 2, 6
Treat sexual partners concurrently and instruct patients to abstain from sexual intercourse until both partners complete treatment (7 days after single-dose or completion of 7-day regimen). 1, 2, 6
Monitor for drug interactions when co-administering with nelfinavir, warfarin, or other medications, though azithromycin has modest effects on most drug pharmacokinetics. 4

HIV-positive pregnant women should receive the same azithromycin treatment regimen as HIV-negative women for chlamydial infections. 1, 2, 6
Pregnant women under 25 years of age are at higher risk for chlamydial infection and should be targeted for screening. 2, 6
Nursing mothers should exercise caution, as it is unknown whether azithromycin is excreted in human milk, though many drugs are. 4

While there is no conclusive evidence that azithromycin causes adverse fetal outcomes, some studies have reported conflicting results regarding risks of spontaneous miscarriage, major congenital malformations, preterm birth, and low birth weight. 7
Azithromycin should only be used during pregnancy when clinically indicated, if the benefits of treatment are expected to outweigh potential risks. 7