Is Azithromycin (Zithromax) Safe During Pregnancy?
Yes, azithromycin is safe to use during pregnancy and is the preferred macrolide antibiotic when treatment is indicated. 1, 2
FDA Classification and Safety Profile
Azithromycin is classified as FDA Pregnancy Category B, meaning animal reproduction studies have shown no evidence of harm to the fetus at doses up to 4 times (rats) and 2 times (mice) the human daily dose of 500 mg. 1, 3
The CDC specifically designates azithromycin as the drug of choice during pregnancy among all macrolide antibiotics, based on animal studies showing no teratogenic effects and no conclusive evidence of adverse fetal outcomes in human use. 2, 4
Clinical Evidence Supporting Safety
A prospective cohort study of 123 pregnant women exposed to azithromycin found no increased risk of major malformations (3.4% in exposed group vs. 2.3% in disease-matched controls vs. 3.4% in non-teratogen controls), with 71.6% of exposures occurring during the first trimester. 5
No adequate and well-controlled studies exist in pregnant women, but extensive clinical experience and animal data support its safety profile. 3
Multiple studies have yielded conflicting results regarding risks of spontaneous miscarriage, congenital malformations, preterm birth, and low birth weight, but there is no conclusive evidence that azithromycin causes adverse offspring outcomes. 6
When to Use Azithromycin in Pregnancy
Azithromycin is recommended for:
- Sexually transmitted infections (including chlamydia) during pregnancy 2
- Respiratory infections including atypical pneumonia (Mycoplasma, Chlamydophila) 4
- Pertussis treatment and prophylaxis 1
- MAC (Mycobacterium avium complex) prophylaxis in HIV-infected pregnant women 2
- Preterm pre-labor rupture of membranes and adjunctive prophylaxis for cesarean delivery 6
Dosing in Pregnancy
Standard adult dosing applies:
- 500 mg on day 1, followed by 250 mg daily on days 2-5 1, 4
- For chlamydia: 1g orally as a single dose 2
Critical Safety Distinctions
Do NOT substitute clarithromycin for azithromycin:
- Clarithromycin has demonstrated teratogenic effects in animal studies and possible increased risk of spontaneous abortion in humans 2, 4
- The CDC classifies clarithromycin as DIII (should not be used) in pregnancy 4
Avoid erythromycin in neonates <1 month:
- Erythromycin is associated with infantile hypertrophic pyloric stenosis (IHPS) in neonates 1
- Azithromycin is the preferred macrolide for this age group 1
Common Pitfalls to Avoid
Do not withhold azithromycin during the first trimester out of excessive caution - it is specifically recommended for use throughout pregnancy when clinically indicated. 4
Do not confuse azithromycin with clarithromycin - they have distinctly different safety profiles in pregnancy. 2, 4
Monitor for known side effects including gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain), QT prolongation, hepatotoxicity, and Clostridium difficile-associated diarrhea. 1, 4, 3
Avoid concurrent use with aluminum- or magnesium-containing antacids as they reduce azithromycin absorption. 1
Special Monitoring Considerations
For pregnant women >20 weeks gestation being treated for early syphilis, consider fetal and contraction monitoring for 24 hours after treatment initiation due to risk of Jarisch-Herxheimer reaction precipitating preterm labor. 1
For pneumonia in pregnancy, monitor for preterm labor after 20 weeks gestation, as pneumonia increases risk of preterm delivery. 4
Monitor prothrombin times if co-administered with oral anticoagulants, as post-marketing reports suggest azithromycin may potentiate anticoagulant effects. 3