Co-amoxiclav (Amoxicillin/Clavulanic Acid) Use in Pregnancy
Co-amoxiclav is safe to use throughout pregnancy for appropriate bacterial infections, with the important exception that it should be avoided in women at risk of preterm delivery due to a documented association with necrotizing enterocolitis in neonates. 1, 2
Safety Classification and Evidence Base
Co-amoxiclav is classified as Pregnancy Category B, meaning reproduction studies in animals (rats and mice at doses up to 1,200 mg/kg/day) showed no evidence of fetal harm, though adequate well-controlled studies in pregnant women are lacking 2
The amoxicillin component alone carries Category A designation (the highest safety rating), while the combination formulation is Category B1, both indicating extensive human data showing no increased risk of congenital malformations, premature births, stillbirths, spontaneous abortions, or low birth weight 1
Multiple professional societies including the American College of Obstetricians and Gynecologists classify amoxicillin-clavulanate as "Compatible" for use throughout all trimesters 1
Clinical Indications During Pregnancy
Co-amoxiclav is recommended for:
Urinary tract infections: 500 mg IV/PO every 8 hours for 3-7 days 1
Bacterial respiratory tract infections when beta-lactam coverage is appropriate for the suspected pathogen 3, 1
Inflammatory bowel disease complications including perianal Crohn's disease and intra-abdominal abscesses from fistulizing disease 1
Salmonella gastroenteritis to prevent extraintestinal spread that could lead to placental and amniotic fluid infection 3
Critical Contraindication: Preterm Delivery Risk
Avoid co-amoxiclav in women at risk of preterm delivery or with preterm prelabor rupture of membranes 1, 2
A 2001 study reported increased risk of necrotizing enterocolitis in neonates when mothers received amoxicillin-clavulanate prophylactically for preterm prelabor rupture of membranes 2, 4
While subsequent studies between 2001-2008 did not confirm this finding and the original study had methodological limitations, the Centers for Disease Control and Prevention recommend considering alternative antibiotics (such as amoxicillin alone) in women with threatened preterm labor 1, 4
In women with threatened preterm labor requiring antibiotic coverage, use amoxicillin alone, ampicillin, cefotaxime, or ceftriaxone instead 3
Advantages Over Alternative Antibiotics
Co-amoxiclav is preferred over several other antibiotic classes:
Unlike fluoroquinolones, which should be avoided entirely during pregnancy, beta-lactam antibiotics including co-amoxiclav have not been associated with teratogenicity or increased toxicity 3
Unlike tetracyclines (including doxycycline), which are contraindicated due to increased hepatotoxicity and staining of fetal teeth and bones, co-amoxiclav has no such risks 3
Unlike clarithromycin, which showed increased risk for birth defects in animal studies and increased spontaneous abortion in one human study, co-amoxiclav has superior safety data 3
Co-amoxiclav is preferred over azithromycin due to its superior safety classification when both would provide adequate coverage 1
Dosing and Administration
Standard dosing during pregnancy:
500 mg IV/PO every 8 hours for urinary tract infections 1
Duration typically 7-14 days depending on infection type and severity 5
Breastfeeding Compatibility
Co-amoxiclav is compatible with breastfeeding 1, 2
Penicillins are excreted in breast milk but only at low concentrations 1, 2
The Academy of Breastfeeding Medicine and World Health Organization recommend monitoring breastfed infants for gastrointestinal effects due to potential alteration of intestinal flora, though serious adverse events are rare 1
Caution should be exercised as amoxicillin use by nursing mothers may lead to sensitization of infants 2
Important Drug Interactions During Pregnancy
Oral contraceptives: Amoxicillin may affect intestinal flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral contraceptives (relevant for postpartum contraception planning) 6
Hormonal effects: Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone and estradiol has been noted; this effect may also occur with co-amoxiclav 2
Common Pitfalls to Avoid
Do not confuse co-amoxiclav's safety profile with absolutely contraindicated antibiotics: Tetracyclines and fluoroquinolones are contraindicated in pregnancy, while co-amoxiclav is safe except in the specific context of threatened preterm delivery 5, 7
Do not use co-amoxiclav for prophylaxis in preterm prelabor rupture of membranes; use amoxicillin alone, ampicillin, or cephalosporins instead 3, 1
Do not assume all beta-lactams are interchangeable: While amoxicillin alone is Category A, the combination with clavulanic acid is Category B due to the specific concern in preterm delivery scenarios 1, 2