Safety of Amoxicillin-Clavulanic Acid in Pregnancy
Amoxicillin-clavulanic acid is generally safe to use during pregnancy, including the first trimester, and is classified as FDA Pregnancy Category B, indicating no evidence of risk to the human fetus.
Evidence on Safety Profile
Amoxicillin-clavulanic acid has been extensively studied in pregnancy:
The FDA pregnancy classification of Category B indicates that animal reproduction studies have failed to demonstrate a risk to the fetus, though adequate and well-controlled studies in pregnant women are limited 1.
A prospective controlled study of 191 women exposed to amoxicillin-clavulanic acid during the first trimester found no significant difference in major malformation rates (1.9%) compared to controls exposed to amoxicillin alone (3%), and rates were within baseline risk for the general population 2.
Praxis Medical Insights notes that amoxicillin with clavulanic acid is considered "compatible" with pregnancy and is recommended as a first-choice medication during pregnancy by the European Respiratory Society/TSANZ task force 3.
Specific Considerations
First Trimester Use
- While there has been a theoretical concern about a possible very low risk of oral clefts when exposed during organogenesis, the evidence is not conclusive 3, 4.
- A systematic review examining amoxicillin use in pregnancy found that cohort studies did not reveal a significant relationship between amoxicillin use and major congenital anomalies 4.
Late Pregnancy Use
- There was historical concern about necrotizing enterocolitis in newborns when used in late pregnancy, based on a single clinical trial from 2001 3.
- However, more recent evidence does not support an increased risk of necrotizing enterocolitis with the use of amoxicillin-clavulanic acid in late pregnancy 5.
- Current guidance suggests it can be prescribed at any stage of pregnancy, including just before delivery 5.
Practical Recommendations
Standard dosing of amoxicillin-clavulanic acid can be used during pregnancy when clinically indicated 3.
For treating infections during pregnancy, beta-lactams including amoxicillin-clavulanic acid are generally considered safe and effective 6.
When prescribing amoxicillin-clavulanic acid during pregnancy, consider:
- Using the standard dose as clinically indicated
- The benefit of treating bacterial infections typically outweighs the minimal risks of amoxicillin with clavulanic acid use in pregnancy 3
- Monitoring for common side effects such as gastrointestinal disturbances
Important Considerations for Breastfeeding
- Amoxicillin-clavulanic acid is excreted in breast milk, but is generally considered safe during breastfeeding 1.
- Be aware that the presence of the antibiotic in breast milk could potentially:
- Cause falsely negative cultures in febrile infants
- Produce mild gastrointestinal effects due to alteration of intestinal flora 3
Conclusion
Based on the available evidence, amoxicillin-clavulanic acid appears to have a favorable safety profile for use during pregnancy, including the first trimester. The benefits of treating bacterial infections during pregnancy generally outweigh the potential risks associated with this antibiotic.