AUGMENTIN ES-600
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AUGMENTIN ES-600 (AUGMENTIN ES-600).
AUGMENTIN ES-600 is a combination of amoxicillin, a beta-lactam antibiotic, and clavulanate, a beta-lactamase inhibitor. Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), while clavulanate irreversibly inhibits beta-lactamase enzymes, preventing degradation of amoxicillin.
| Metabolism | Amoxicillin is partially metabolized to penicilloic acid; clavulanate is extensively metabolized. Both are primarily excreted renally. |
| Excretion | Amoxicillin: ~50-70% excreted unchanged renally via glomerular filtration and tubular secretion; clavulanate: ~25-40% excreted unchanged renally. Combined: renal excretion accounts for ~60-80% of elimination, with minor biliary/fecal elimination (approx 5-15% for amoxicillin). |
| Half-life | Amoxicillin: ~1.0-1.5 hours in adults with normal renal function; clavulanate: ~1.0-1.2 hours. In renal impairment, half-life prolongs significantly (amoxicillin up to 7-20 hours in ESRD). |
| Protein binding | Amoxicillin: ~17-20% bound to albumin; clavulanate: ~22-30% bound to albumin. |
| Volume of Distribution | Amoxicillin: ~0.3-0.4 L/kg; clavulanate: ~0.2-0.3 L/kg. Indicates distribution into extracellular fluid, with moderate tissue penetration. |
| Bioavailability | Oral: ~70-90% for amoxicillin; clavulanate is well absorbed (~60-70%) but subject to some first-pass metabolism. Food does not affect absorption of AUGMENTIN ES-600 but may reduce peak concentration slightly. |
| Onset of Action | Oral administration: peak serum concentrations reached ~1-2 hours; bacteriostatic/bactericidal effects begin within 1-2 hours after absorption. |
| Duration of Action | Approximately 6-8 hours for susceptible organisms, consistent with every 12-hour dosing for AUGMENTIN ES-600. Clinical duration may extend to 12 hours based on MIC and dosing interval. |
| Molecular Weight | Amoxicillin: 365.4 Da; Clavulanate: 199.16 Da. Augmentin ES-600 is a combination; individual molecular weights are relevant. |
90 mg/kg/day orally divided every 12 hours (based on amoxicillin component). Maximum 4000 mg amoxicillin/600 mg clavulanate per day.
| Dosage form | FOR SUSPENSION |
| Renal impairment | CrCl <30 mL/min: Do not use this formulation. For CrCl 30-49 mL/min: Adjust dose interval to every 12 hours; for CrCl 10-29 mL/min: every 24 hours; for CrCl <10 mL/min: avoid use. |
| Liver impairment | No specific Child-Pugh adjustments. Caution in severe hepatic impairment; monitor for hepatotoxicity. |
| Pediatric use | Weight ≥40 kg: 2000 mg amoxicillin/200 mg clavulanate every 12 hours. Weight <40 kg: 45 mg amoxicillin/kg/day divided every 12 hours (Augmentin ES-600 contains 600 mg amoxicillin/42.9 mg clavulanate per 5 mL; use 90 mg/kg/day of amoxicillin divided every 12 hours per guidelines). |
| Geriatric use | No specific dose adjustment except based on renal function. Monitor renal function and adjust accordingly. |
| 1st trimester | Penicillins are generally considered safe during pregnancy. Augmentin ES-600 (amoxicillin/clavulanate) is classified as FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, but adequate human studies in first trimester are lacking. Use only if clearly needed. |
| 2nd trimester | Safe for use. No known teratogenic effects documented. Can be used for indicated infections during second trimester. |
| 3rd trimester | Safe for use. No known adverse fetal or neonatal effects. However, caution near term due to theoretical risk of kernicterus or altered gut flora in neonate. |
Clinical note
Comprehensive clinical and safety monograph for AUGMENTIN ES-600 (AUGMENTIN ES-600).
| Placental transfer | Amoxicillin crosses the placenta with fetal serum levels approximately 30-50% of maternal levels. Clavulanate also crosses but to a lesser extent (fetal levels about 10-20% of maternal). Transfer is moderate and consistent with other penicillins. |
| Breastfeeding |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Vomiting Nausea Diarrhea Mucocutaneous candidiasis |
| Serious Effects |
Known hypersensitivity to any penicillin or beta-lactam antibioticPrevious history of cholestatic jaundice or hepatic dysfunction associated with amoxicillin/clavulanateHistory of penicillin-associated anaphylaxisPhenylketonuria (due to aspartame content in oral suspension; not applicable to all formulations)
| Precautions | Hypersensitivity reactions including anaphylaxis, Severe cutaneous adverse reactions (SCARs), Clostridium difficile-associated diarrhea (CDAD), Hepatic dysfunction (elevated liver enzymes, hepatitis, cholestatic jaundice), Potential for microbial overgrowth with prolonged use, Increased risk of rash with concomitant allopurinol |
| Food/Dietary |
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| Amoxicillin and clavulanate are excreted into breast milk in small amounts (<0.25% of maternal dose for amoxicillin; <0.1% for clavulanate). These levels are unlikely to cause adverse effects in nursing infants, except for rare cases of diarrhea, rash, or candidiasis. Benefits outweigh risks for standard indications; monitor infant for gastrointestinal disturbances. American Academy of Pediatrics considers penicillins compatible with breastfeeding. |
| Lactation Rating | L1 (Safe) |
| Teratogenic Risk | Augmentin ES-600 (amoxicillin/clavulanate) is classified as FDA Pregnancy Category B. Animal studies have not demonstrated fetal harm, and there are no adequate and well-controlled studies in pregnant women. The risk of teratogenicity is considered low across all trimesters, but use only when clearly needed. |
| Fetal Monitoring | Monitor for maternal hypersensitivity reactions (rash, anaphylaxis), gastrointestinal disturbances (diarrhea, C. difficile colitis). No specific fetal monitoring required, but assess fetal well-being if maternal infection is severe or prolonged. |
| Fertility Effects | No known adverse effects on fertility. Animal studies have not shown impairment of fertility. No human data on fertility impact. |
| Administer with food to enhance absorption and reduce gastrointestinal side effects. Avoid high-fat meals immediately before dosing as they may delay absorption. No specific food restrictions; however, maintaining consistent timing with meals is recommended. |
| Clinical Pearls | AUGMENTIN ES-600 (amoxicillin/clavulanate) is specifically formulated for pediatric patients with persistent or recurrent acute otitis media. Each 5 mL suspension contains 600 mg amoxicillin and 42.9 mg clavulanate, allowing higher amoxicillin dosing (90 mg/kg/day) while maintaining clavulanate at standard levels. For optimal absorption, administer at the start of a meal. Shake suspension vigorously before each use. Use within 10 days of reconstitution; refrigerate but do not freeze. |
| Patient Advice | Take this medication exactly as prescribed, at evenly spaced intervals. · Complete the full course even if symptoms improve; do not skip doses. · Administer with food to reduce stomach upset and enhance absorption. · Shake the suspension well before measuring each dose; use the provided dosing device. · Refrigerate the suspension; discard any unused portion after 10 days. · Do not take if allergic to penicillins or cephalosporins. · Report any signs of allergic reaction (rash, itching, difficulty breathing) immediately. · May cause diarrhea; contact doctor if severe or persistent. |