Is Azithromycin (macrolide antibiotic) safe to use during the first trimester of pregnancy?

Azithromycin Safety in First Trimester of Pregnancy

Azithromycin is generally considered safe during the first trimester of pregnancy and is the preferred macrolide antibiotic when treatment is needed during this period. 1

Safety Profile

• Azithromycin is classified as an FDA Pregnancy Category B drug, indicating that animal reproduction studies have not demonstrated fetal risk, but there are no adequate well-controlled studies in pregnant women 2
• Animal studies and anecdotal evidence of safety in humans suggest that among available macrolide agents, azithromycin is the drug of choice during pregnancy 1
• Unlike clarithromycin (which has been demonstrated to be a teratogen in animals), azithromycin has not shown evidence of harm to the fetus in animal reproduction studies 2, 1

Clinical Evidence

• A study comparing pregnancy outcomes in women exposed to azithromycin versus those exposed to non-teratogenic antibiotics found no statistically significant differences in rates of major malformations (3.4% in the azithromycin group versus 2.3% in the control group) 3
• The majority of women in this study (71.6%) took azithromycin during the first trimester, providing specific evidence for first-trimester safety 3
• While some studies have reported conflicting results regarding potential risks of spontaneous miscarriage, major congenital malformations, and cardiovascular malformations, there is currently no conclusive evidence that azithromycin use during pregnancy causes adverse fetal outcomes 4

Recommendations for Use During Pregnancy

• For HIV-infected pregnant women requiring MAC (Mycobacterium avium complex) prophylaxis, guidelines specifically recommend azithromycin as the drug of choice during pregnancy 1
• While some healthcare providers may choose to withhold medications during the first trimester due to general concerns about drug exposure during this critical period of organogenesis, azithromycin is considered the preferred macrolide when treatment is necessary 1
• Azithromycin's pharmacokinetic properties make it particularly suitable during pregnancy, as it is not affected by the cytochrome P450 system and can be used safely without concerns for drug interactions that might affect other antibiotics 1

Clinical Considerations

• When prescribing azithromycin during pregnancy, the benefits of treatment should be weighed against potential risks, particularly when treating serious infections 4
• Pharmacokinetic studies in pregnant women have shown that pregnancy increases the volume of distribution of azithromycin relative to bioavailability, but this does not necessitate dose adjustments 5
• Azithromycin has good transplacental transfer, making it suitable for treating infections that could affect the fetus 4, 6

Common Pitfalls and Caveats

• 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
• While azithromycin is generally considered safe, it should still only be used when clinically indicated during pregnancy 4
• Be aware that some providers may choose to withhold any medication during the first trimester out of an abundance of caution, but this approach is not evidence-based when azithromycin treatment is clinically necessary 1