Is amoxicillin-clavulanate (Augmentin) contraindicated in pregnancy and breastfeeding?

Amoxicillin-Clavulanate Safety in Pregnancy and Breastfeeding

Amoxicillin-clavulanate is NOT contraindicated during pregnancy and can be used safely throughout all trimesters when clinically indicated, with one specific exception: avoid use in women at high risk of preterm delivery due to a very low risk of necrotizing enterocolitis in the fetus. 1, 2

Safety Classification and Evidence

• The European Respiratory Society/Thoracic Society of Australia and New Zealand classifies amoxicillin-clavulanate as "Compatible" for use during pregnancy 1, 2
• The FDA categorizes it as Pregnancy Category B, meaning animal reproduction studies showed no fetal harm, though adequate human studies are limited 3
• Reproduction studies in pregnant rats and mice at doses up to 1200 mg/kg/day revealed no evidence of fetal harm 3

Use Across Pregnancy Trimesters

First Trimester:

• Safe to use when clinically indicated 2, 4
• A prospective controlled study of 191 women exposed to amoxicillin-clavulanate in the first trimester found major malformation rates (1.9%) comparable to controls (3%) and within baseline population risk 4
• There is a theoretical concern about oral clefts with exposure during organogenesis, but the absolute risk is very low 1

Second and Third Trimesters:

• Compatible and safe for use 1, 2
• Critical exception: Not recommended in women at risk of preterm delivery due to a very low risk of necrotizing enterocolitis in the fetus 1, 2
• This concern stems from a 2001 study on prophylactic antibiotics in preterm prelabor rupture of membranes, though subsequent studies between 2001-2008 failed to confirm this risk 5

At Delivery:

• Can be used when clinically necessary 5
• Recent evidence does not support an increased risk of necrotizing enterocolitis even when used just before delivery 5

Clinical Decision Algorithm for Pregnancy

1. Confirm bacterial infection requiring antibiotic therapy 2
2. Assess gestational age and preterm delivery risk:
   • If NOT at risk for preterm delivery → Amoxicillin-clavulanate is safe throughout pregnancy 1, 2
   • If at risk for preterm delivery → Consider alternative antibiotics (amoxicillin alone, cephalosporins) 1
3. Prescribe at standard therapeutic doses - the benefit of treating maternal infection outweighs theoretical fetal risks 2, 3

Use During Breastfeeding

Amoxicillin-clavulanate is compatible with breastfeeding. 1, 2

• Both amoxicillin and clavulanate are excreted in breast milk in small amounts 3
• The primary concern is potential sensitization of infants or mild gastrointestinal disturbance due to alteration of intestinal flora 1, 3
• Most systemic antibiotics present in breast milk could theoretically cause falsely negative cultures in febrile infants 1
• Medicines that are low risk in pregnancy are also low risk in breastfeeding and should be continued 1

Important Clinical Caveats

Common Pitfalls to Avoid:

• Do not withhold amoxicillin-clavulanate in pregnancy based on outdated concerns about necrotizing enterocolitis - this risk applies only to women at risk of preterm delivery 1, 5
• Do not confuse the safety profile with other antibiotics that ARE contraindicated in pregnancy (tetracyclines after 5 weeks, fluoroquinolones, sulfonamides in first trimester) 1
• The theoretical cleft palate risk is very low and should not prevent appropriate treatment of maternal infections 1, 6

When to Choose Alternatives:

• In women at high risk for preterm delivery, consider amoxicillin alone or cephalosporins (cefuroxime) as first-line alternatives 1
• For perianal sepsis in Crohn's disease during pregnancy, metronidazole and/or ciprofloxacin are suggested alternatives 1