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 inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidation and autolysin inhibitors. Clavulanate is a beta-lactamase inhibitor that binds to and inactivates beta-lactamases, protecting amoxicillin from hydrolysis.
| Metabolism | Amoxicillin is partially metabolized via hydrolysis of the beta-lactam ring to inactive penicilloic acid, minor hepatic metabolism; excreted primarily unchanged renally. Clavulanate is extensively metabolized in the liver, primarily to metabolites excreted in urine and feces. |
| Excretion | Amoxicillin: ~60% renal as unchanged drug via glomerular filtration and tubular secretion; Clavulanate: ~30-50% renal as metabolites and unchanged, remainder fecal. Approximately 50-70% of total dose excreted renally within 6 hours. |
| Half-life | Amoxicillin: ~1-1.3 hours in adults with normal renal function; Clavulanate: ~1 hour. Both prolonged in renal impairment (amoxicillin up to 7-20 hours with CrCl <10 mL/min). |
| Protein binding | Amoxicillin: ~17% bound to serum protein (primarily albumin); Clavulanate: ~25% bound to albumin. |
| Volume of Distribution | Amoxicillin: Vd ~0.3-0.4 L/kg; clavulanate: Vd ~0.3 L/kg. Distributes well into interstitial fluid, tissues, and bone; limited CNS penetration (10-20% of serum levels) unless inflamed meninges. |
| Bioavailability | Oral: 80-90% for both components; food does not significantly affect absorption (note: clavulanate is better absorbed with food, extended-release tab with food). |
| Onset of Action | Oral: 1-2 hours for peak serum concentrations; clinical improvement typically within 24-48 hours. IV: immediate onset after administration. |
| Duration of Action | Dosing interval 8-12 hours; bacteriostatic levels persist for 6-8 hours. Extended-release formulations (Augmentin XR) provide 12-hour coverage. |
| Molecular Weight | Amoxicillin trihydrate: 419.45 g/mol. Clavulanate potassium: 237.25 g/mol. Combined product is formulated at fixed ratios (most commonly 4:1 or 7:1 amoxicillin:clavulanate by weight). |
500 mg/125 mg orally every 8 hours or 875 mg/125 mg orally every 12 hours; intravenous: 1 g/0.2 g every 8 hours.
| Renal impairment | CrCl 30-50 mL/min: 500 mg/125 mg orally every 12 hours; CrCl 10-29 mL/min: 500 mg/125 mg orally every 24 hours; CrCl <10 mL/min: 500 mg/125 mg orally every 24 hours, supplement after dialysis. |
| Liver impairment | No specific adjustment recommended; use with caution in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | 3 months to 40 kg: 25-45 mg/kg/day of amoxicillin component in 2-3 divided doses; >40 kg: adult dosing. |
| Geriatric use | Adjust based on renal function; initiate with lower end of dosing due to age-related renal decline. |
| 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.
■ FDA Black Box Warning
None
| Serious Effects |
Known hypersensitivity (anaphylaxis, urticaria, or other IgE-mediated reactions) to amoxicillin-clavulanate, any penicillin, or any component of the formulation.History of amoxicillin-clavulanate-associated jaundice or hepatic dysfunction (cholestatic hepatitis) — risk of recurrence is high.Use for PPROM (preterm prelabour rupture of membranes) — contraindicated based on ORACLE I evidence; erythromycin must be substituted.Concomitant use with live oral typhoid vaccine (antibiotic activity may render vaccine ineffective — space by ≥3 days).Severe penicillin allergy with cross-reactivity concern: approximately 1–2% cross-reactivity with cephalosporins exists (lower with later-generation cephalosporins); in patients with prior anaphylaxis to penicillin, all beta-lactams should be used with extreme caution or avoided pending allergy evaluation.
| Precautions | Serious hypersensitivity reactions (anaphylaxis) can occur, Clostridium difficile-associated diarrhea (CDAD) risk, Hepatic dysfunction, including hepatitis and cholestatic jaundice, especially in elderly and patients with prior therapy, Renal impairment requires dose adjustment, Potential for superinfection with prolonged therapy |
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. |
| Lactation Rating | L1 — Safest (Hale's Lactation Risk Category). Compatible with breastfeeding. |
| Teratogenic Risk | FDA Category B. No evidence of teratogenicity in animal studies; human data do not indicate increased risk of major birth defects. However, use only when clearly needed in pregnancy, especially during first trimester. Theoretical risk of neonatal kernicterus if used near term due to bilirubin displacement from albumin. |
| Fetal Monitoring | Monitor for maternal allergic reactions, rash, gastrointestinal disturbances. No specific fetal monitoring required; standard prenatal care. In high-dose therapy, consider surveillance for Clostridioides difficile infection. |
| Fertility Effects | No known adverse effects on fertility in animal studies. Limited human data; unlikely to impair fertility. Antibiotics may transiently alter vaginal flora but no long-term reproductive impact. |
| Food/Dietary |
| May be taken with food to reduce GI irritation. No significant food interactions. Avoid high-fat meals if taking extended-release formulation (fat increases absorption variability). |
| Clinical Pearls | Administer with food to reduce GI upset. Monitor for rash, especially in patients with mononucleosis (EBV). Dose adjustment required for CrCl <30 mL/min. High dose (2000 mg amoxicillin) provides adequate coverage for penicillin-resistant S. pneumoniae. Avoid in penicillin allergy; cross-reactivity with cephalosporins is low but possible. |
| Patient Advice | Take with food or milk to minimize stomach upset. · Complete the full course even if you feel better. · Shake oral suspension well before each use. · Use backup contraception if on oral contraceptives. · Contact doctor if rash, watery diarrhea, or signs of liver problems (yellowing skin, dark urine). · Do not take if allergic to penicillin or cephalosporins. |