Is Amoxyclav (amoxicillin/clavulanate) safe to use during pregnancy?

Amoxicillin/Clavulanate (Amoxyclav) Safety in Pregnancy

Amoxicillin/clavulanate is safe and compatible for use throughout all trimesters of pregnancy when clinically indicated for bacterial infections. 1

Safety Classification and Evidence Base

• Multiple international guidelines classify amoxicillin/clavulanate as "Compatible" for use during pregnancy, including the European Respiratory Society/Thoracic Society of Australia and New Zealand (ERS/TSANZ) task force 1

• The FDA categorizes this medication as Pregnancy Category B, meaning reproduction studies in pregnant rats and mice at doses up to 1200 mg/kg/day (approximately 4 times the maximum human dose for amoxicillin and 9 times for clavulanate based on body surface area) revealed no evidence of fetal harm 2

• The European Association for the Study of the Liver (EASL) 2023 guidelines support its use throughout pregnancy for appropriate maternal infections 3

Clinical Decision-Making Algorithm

When to prescribe:

• Confirm bacterial infection requiring antibiotic therapy based on clinical presentation or culture results 1
• Consider amoxicillin/clavulanate as a first-line safe option for appropriate infections during any trimester 1
• The benefit of treating maternal infections generally outweighs theoretical fetal risks 1

Critical contraindication:

• Do NOT use amoxicillin/clavulanate in women at risk of preterm delivery due to a very low but documented risk of necrotizing enterocolitis in the fetus 1
• This contraindication is supported by research showing higher rates of neonatal necrotizing enterocolitis when co-amoxiclav was used in women with preterm rupture of membranes 4

Evidence Quality and Nuances

Strong reassuring evidence:

• Animal reproduction studies specifically for the amoxicillin/clavulanate combination showed no increased occurrence of fetal malformations or harmful effects 1
• Beta-lactam antibiotics, including amoxicillin combinations, are generally considered safe and effective in pregnancy 5
• A large randomized controlled trial (n=3427) demonstrated safety when used prophylactically after operative vaginal delivery, with only one potentially causally-related serious adverse event in the antibiotic arm 6

Areas of uncertainty:

• One systematic review identified a possible association with cleft palate in one case-control study, though cohort studies did not reveal significant relationships with major congenital anomalies 7
• The absolute risk increase, if real, appears minimal, and the systematic review concluded that no major congenital anomalies were definitively linked to amoxicillin/clavulanate use 7

Breastfeeding Compatibility

• Amoxicillin/clavulanate is compatible with breastfeeding according to ERS/TSANZ guidelines 1, 8
• The American Academy of Dermatology recommends it as a safe and effective choice during breastfeeding (FDA Category B) 8
• Amoxicillin is excreted in human milk and may lead to infant sensitization, so monitor breastfed infants for gastrointestinal effects 2, 8

Common Pitfalls to Avoid

Critical error: Using amoxicillin/clavulanate in women with threatened preterm labor or preterm rupture of membranes—this specific population should receive alternative antibiotics (such as erythromycin for PROM) 1, 4

Monitoring considerations:

• While generally safe, the FDA label notes that oral ampicillin-class antibiotics are poorly absorbed during labor, though clinical significance is unclear 2
• No adequate well-controlled studies exist in pregnant women, so use only when clearly needed despite strong safety signals 2