Is co-amoxiclav (amoxicillin and clavulanic acid) safe to use in pregnant women?

Co-amoxiclav Safety in Pregnancy

Co-amoxiclav (amoxicillin-clavulanic acid) is safe to use throughout pregnancy, including immediately before delivery, with no evidence of increased teratogenic risk or major congenital malformations. 1, 2, 3

Evidence Supporting Safety

Guideline Consensus

• Multiple international guidelines classify amoxicillin-clavulanic acid as "Compatible" for use during pregnancy across all trimesters 1, 2
• The European Respiratory Society/Thoracic Society of Australia and New Zealand (2020) explicitly lists co-amoxiclav as compatible with pregnancy, with only a very low theoretical risk of oral clefts during organogenesis 1
• The American Gastroenterological Association (2024) states that amoxicillin-clavulanic acid is safe and can be administered during pregnancy for inflammatory bowel disease-related infections 1
• The FDA drug label classifies co-amoxiclav as Pregnancy Category B, meaning animal reproduction studies showed no fetal harm and no adequate well-controlled human studies have demonstrated risk 3

Addressing the Necrotizing Enterocolitis Concern

• A single 2001 study raised concern about necrotizing enterocolitis (NEC) in neonates when co-amoxiclav was given for preterm prelabor rupture of membranes 1
• This concern has NOT been confirmed in subsequent research - three studies published between 2001-2008 failed to replicate these findings 4
• A 2022 French review concluded that available data do not support an increased NEC risk with co-amoxiclav use in late pregnancy 4
• The European Respiratory Society guidelines note this is a "very low risk" and recommend co-amoxiclav not be used specifically in women at risk of preterm delivery, but this is a precautionary measure rather than evidence-based contraindication 1

Clinical Applications During Pregnancy

Approved Indications

• Inflammatory bowel disease complications: pouchitis, perianal Crohn's disease, or intra-abdominal abscesses from fistulizing Crohn's disease 1
• Respiratory tract infections: upper and lower respiratory infections in pregnant women with airways disease 1
• Skin and soft tissue infections: including hangnail infections and other bacterial skin infections 2
• Urinary tract infections: as an alternative first-line agent 2, 5

Dosing Recommendations

• Standard adult dosing applies during pregnancy: 500 mg amoxicillin/125 mg clavulanic acid orally every 8 hours 2
• No dose adjustment needed based on trimester 3
• Can be used immediately before delivery without restriction 4

Breastfeeding Compatibility

• Co-amoxiclav is compatible with breastfeeding 1, 2
• Ampicillin-class antibiotics are excreted in breast milk, but at levels considered safe for the infant 3
• Limited human data support safety during lactation, with no significant adverse effects reported in breastfed infants 1
• Monitor breastfed infants for potential gastrointestinal effects (diarrhea, altered intestinal flora) 1

Critical Pitfalls to Avoid

When to Exercise Caution

• Women at high risk of preterm delivery: While not contraindicated, consider alternative antibiotics (amoxicillin alone, cephalexin) if equally effective for the indication 1
• Penicillin allergy: Do not use in women with history of anaphylaxis, angioedema, respiratory distress, or urticaria to penicillins 5
• Hepatotoxicity risk: The clavulanic acid component has been associated with cholestatic hepatitis in non-pregnant populations; monitor for signs of liver dysfunction 3

Common Prescribing Errors

• Do not confuse with erythromycin estolate, which is contraindicated in pregnancy due to hepatotoxicity 1
• Do not substitute with tetracyclines or fluoroquinolones, which are contraindicated after week 5 of pregnancy due to fetal harm 1, 5, 6
• Do not avoid use solely based on the 2001 NEC study - this concern has been adequately addressed by subsequent research showing no increased risk 4

Advantages Over Alternative Antibiotics

• Broader spectrum than amoxicillin alone: Covers beta-lactamase-producing organisms that would otherwise be resistant 7, 8
• Safer than fluoroquinolones: No risk of fetal cartilage damage 1, 5
• Safer than tetracyclines: No risk of tooth discoloration or bone growth suppression 1, 5, 6
• Safer than trimethoprim-sulfamethoxazole: No increased risk of neural tube defects, kernicterus, or preterm birth 1, 5, 6

When Co-amoxiclav is the Preferred Choice

• Beta-lactamase-producing bacterial infections where amoxicillin alone would be ineffective 7, 8
• Mixed aerobic-anaerobic infections including intra-abdominal abscesses 1
• Prophylaxis after operative vaginal delivery - a 2019 randomized controlled trial showed significant reduction in maternal infection (11% vs 19%, RR 0.58) with a single intravenous dose 9
• Patients requiring broader coverage than amoxicillin but who cannot tolerate cephalosporins 2, 5