Augmentin (GlaxoSmithKline) — US, UK, EU; most widely recognised brand · Clavulin (Canada) · Augmentin ES-600 (paediatric high-dose oral suspension) · Augmentin XR (extended-release 1000/62.5 mg — not recommended in pregnancy due to limited data) · Timentim / Timentin (ticarcillin-clavulanate — IV formulation, different antibiotic component; do not confuse) · Co-amoxiclav (INN/BAN generic term widely used in UK and Commonwealth countries) · Amoclan, Amoxyclav, Curam (various generic manufacturers)
Clinical safety rating: caution
Human studies have proved safety
Amoxicillin is a semi-synthetic aminopenicillin that exerts bactericidal activity by irreversibly binding to penicillin-binding proteins (PBPs 1A, 1B, 2, and 3) in the bacterial cell wall, inhibiting transpeptidation (cross-linking) of peptidoglycan strands, thereby disrupting cell wall synthesis and leading to osmotic lysis. Clavulanic acid is a suicide inhibitor of class A and class C beta-lactamases (including TEM-1, TEM-2, SHV-1). It contains a beta-lactam ring and binds irreversibly to the active site of these enzymes, preventing them from hydrolysing the amoxicillin beta-lactam ring and extending amoxicillin's spectrum to include beta-lactamase-producing strains of H. influenzae, M. catarrhalis, S. aureus (MSSA), E. coli, Klebsiella spp., and anaerobes. Clavulanate has minimal intrinsic antibacterial activity at clinical concentrations.
| Metabolism | Amoxicillin: Minimally metabolised hepatically (~10%). Approximately 60–70% is excreted unchanged in urine via glomerular filtration and tubular secretion. A small fraction undergoes penicilloic acid formation. Renal clearance is the dominant elimination pathway, making amoxicillin levels highly sensitive to changes in GFR — relevant in pregnancy given physiological increase in GFR (~50% above baseline). Clavulanate: Extensively metabolised, primarily in the liver, to inactive metabolites (1-amino-4-hydroxy-butan-2-one and related compounds). Approximately 25–40% is excreted unchanged in urine. Clavulanate metabolism is not significantly affected by pregnancy, though increased renal clearance modestly reduces urinary clavulanate exposure. CYP450 involvement: Negligible for both components. Neither amoxicillin nor clavulanate are substrates, inhibitors, or inducers of CYP enzymes — the basis for the relatively clean drug interaction profile. |
Dosing varies by indication and patient profile. Always follow your institution's current prescribing guidelines.
| Renal impairment | Consult protocols for adjustment. |
| Liver impairment | Consult protocols for adjustment. |
| 1st trimester | Safe for standard infections (UTI, skin and soft tissue, respiratory, dental). No increased risk of major congenital malformations based on large epidemiological cohorts. Preferred over fluoroquinolones, tetracyclines, and trimethoprim (theoretical folate antagonism in T1). GI side effects may worsen pregnancy-related nausea — take with food. |
| 2nd trimester | Safe for standard infections. Effective for asymptomatic bacteriuria and acute cystitis where local resistance patterns permit. Avoid for PPROM (typically a second-trimester complication at borderline viability) — use erythromycin per ORACLE I evidence and ACOG guidance. Monitor for vulvovaginal candidiasis, which is more prevalent in mid-pregnancy. |
| 3rd trimester | Safe for standard infections including pyelonephritis (IV formulation), UTI, and skin infections. Strictly avoid for PPROM due to demonstrated NEC risk in the preterm neonate (ORACLE I). May be used intrapartum for chorioamnionitis (in combination with gentamicin and metronidazole per ACOG protocol, though ampicillin is more commonly used in that regimen). Near-term use has no established fetal structural risk, but neonatal GI colonisation effects are theoretically possible. |
Clinical note
Amoxicillin-clavulanate is a broad-spectrum oral antibiotic combining a penicillin with a beta-lactamase inhibitor. It is generally considered safe in pregnancy for standard indications such as urinary tract infections, skin and soft tissue infections, and community-acquired respiratory infections. However, the landmark ORACLE I randomised controlled trial (Kenyon et al., Lancet 2001) demonstrated a statistically significant increase in necrotising enterocolitis (NEC) in neonates born to mothers who received co-amoxiclav for preterm prelabour rupture of membranes (PPROM). Consequently, erythromycin (or azithromycin) is the preferred antibiotic for PPROM latency therapy. Outside the PPROM context, the overall risk-benefit profile remains favourable in pregnancy.
nausea
Loading safety data…
| Placental transfer | Yes — amoxicillin crosses the placenta readily by passive diffusion. Cord blood concentrations are approximately 25–30% of maternal serum concentrations. Clavulanate also crosses the placenta, though data are more limited; placental transfer appears similar in proportion. Fetal tissue concentrations are sufficient for therapeutic effect against susceptible organisms in fetal compartments (e.g., chorioamnionitis treatment). This transplacental transfer is the mechanism underlying neonatal gut microbiome disruption postulated in the ORACLE I NEC signal. |
| Breastfeeding | Amoxicillin-clavulanate is excreted into breast milk in low concentrations. Amoxicillin milk levels are typically 0.1–1.5 mg/L; clavulanate milk levels are negligible. The relative infant dose (RID) for amoxicillin is estimated at <1% of the maternal weight-adjusted dose, well below the 10% threshold of concern. Monitor the nursing infant for GI effects (diarrhoea, loose stools, candidal diaper rash) and possible, though rare, allergic sensitisation. Diarrhoea in the infant is the most commonly reported adverse effect. Premature or neonates with compromised renal function warrant closer observation. Temporary interruption of breastfeeding is not necessary. |
