AUGMENTIN '500'
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AUGMENTIN '500' (AUGMENTIN '500').
Amoxicillin is a semisynthetic aminopenicillin that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidation and disrupting cell wall integrity, leading to bacteriolysis. Clavulanate is a beta-lactamase inhibitor that irreversibly binds to and inactivates a broad range of beta-lactamases, preventing degradation of amoxicillin and extending its spectrum to include beta-lactamase-producing bacteria.
| Metabolism | Amoxicillin is primarily excreted unchanged in urine via renal tubular secretion; minor hepatic metabolism to penicilloic acid. Clavulanate is extensively metabolized in the liver to 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one; both parent and metabolites are excreted in urine. |
| Excretion | Renal excretion 50-70% (amoxicillin) and 40-60% (clavulanate) as unchanged drug; tubular secretion and glomerular filtration. Fecal elimination <10%. |
| Half-life | Amoxicillin: 1-1.3 hours; clavulanate: 1 hour. In renal impairment (CrCl <30 mL/min): amoxicillin 7-20 hours, clavulanate 4-6 hours. Extends dosing interval. |
| 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. Distributes into interstitial fluid, tissues, and pus; low CSF penetration. |
| Bioavailability | Oral: 90% (amoxicillin), 60% (clavulanate) – enhanced by food. IV: 100%. |
| Onset of Action | Oral: 1-2 hours to bactericidal serum concentrations. IV: immediate peak levels after infusion. |
| Duration of Action | Oral: 6-8 hours (bactericidal levels). IV: 4-6 hours. Dosing every 8-12 hours based on infection severity. |
1 tablet (amoxicillin 500 mg / clavulanate 125 mg) orally every 8 hours or 1 tablet (amoxicillin 875 mg / clavulanate 125 mg) orally every 12 hours for mild to moderate infections. For severe infections, use 875 mg/125 mg every 12 hours.
| Dosage form | TABLET |
| Renal impairment | CrCl 10-30 mL/min: 250-500 mg amoxicillin every 12 hours. CrCl <10 mL/min: 250-500 mg amoxicillin every 24 hours. Hemodialysis: 250-500 mg amoxicillin per day, with an additional dose during and after dialysis. |
| Liver impairment | Child-Pugh Class A (mild): No adjustment required. Child-Pugh Class B (moderate): Use with caution; consider dose reduction or increased interval. Child-Pugh Class C (severe): Contraindicated due to risk of hepatotoxicity. |
| Pediatric use | For children >40 kg: same as adult dosing. For children <40 kg: based on amoxicillin component, 45 mg/kg/day divided every 12 hours or 40 mg/kg/day divided every 8 hours (using 125 mg/5 mL or 250 mg/5 mL suspension). For otitis media, 90 mg/kg/day divided every 12 hours (using 400 mg/5 mL suspension). |
| Geriatric use | No specific dose adjustment beyond renal function; assess creatinine clearance and adjust accordingly. Use lower end of dosing interval due to age-related renal decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AUGMENTIN '500' (AUGMENTIN '500').
| Breastfeeding | Excreted into breast milk in low concentrations (M/P ratio: amoxicillin 0.02-0.04, clavulanate unknown). Considered compatible with breastfeeding in most cases; theoretical risk of diarrhea, candidiasis, or allergic sensitization in infant. American Academy of Pediatrics considers amoxicillin compatible with breastfeeding. |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies reveal no evidence of fetal harm. No adequate, well-controlled studies in pregnant women. Amoxicillin-clavulanate crosses the placenta. First trimester: No increased risk of major congenital anomalies. Second/third trimester: Use only if clearly needed; potential association with necrotizing enterocolitis in neonates if maternal use near delivery. |
■ FDA Black Box Warning
None
| Common Effects | Vomiting Nausea Diarrhea Mucocutaneous candidiasis |
| Serious Effects |
["History of allergic reaction to any penicillin (e.g., anaphylaxis, urticaria, Stevens-Johnson syndrome).","History of cholestatic jaundice/hepatic dysfunction associated with amoxicillin-clavulanate.","Infectious mononucleosis (high incidence of maculopapular rash).","Phenylketonuria (for formulations containing aspartame); use caution with chewable tablets containing phenylalanine.","Severe renal impairment (CrCl < 30 mL/min) without dose adjustment."]
| Precautions | ["Serious hypersensitivity reactions (anaphylaxis, angioedema) may occur; contraindicated in patients with history of allergic reactions to penicillins, cephalosporins, or other beta-lactams.","Clostridium difficile-associated diarrhea (CDAD) reported; may range from mild diarrhea to fatal colitis.","Hepatic dysfunction (including hepatitis, cholestatic jaundice) occurs more frequently in elderly, males, and with prolonged use; discontinue if signs of hepatitis occur.","Renal impairment requires dose adjustment to avoid accumulation and neurotoxicity (seizures).","Prolonged therapy may result in overgrowth of non-susceptible organisms (e.g., Candida, Pseudomonas).","May prolong prothrombin time in patients receiving anticoagulants; monitor INR.","Decreased efficacy of oral contraceptives; consider additional contraception."] |
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| Fetal Monitoring | Monitor for signs of maternal allergic reaction (urticaria, anaphylaxis); prolonged use may alter maternal or neonatal gut flora. No specific fetal monitoring required; assess neonatal outcomes if used near term (potential for hemolytic anemia, neutropenia). |
| Fertility Effects | No known significant effects on fertility in either males or females based on animal studies. No human data available suggesting impaired fertility. |
| Food/Dietary | Take with food to reduce gastrointestinal discomfort. High-fat meals may slightly delay absorption but do not significantly affect overall exposure. Avoid alcohol? There is no direct interaction with alcohol, but alcohol can worsen GI side effects and impair liver function; caution is advised. |
| Clinical Pearls | Augmentin '500' refers to amoxicillin 500 mg/clavulanate 125 mg. Dosing is based on amoxicillin component. Twice-daily dosing is typical for most infections. Higher clavulanate doses (e.g., 125 mg per 500 mg amoxicillin) are used for enhanced beta-lactamase coverage. Avoid in patients with penicillin allergy, mononucleosis (causes rash), or history of cholestatic jaundice with Augmentin. Monitor for diarrhea, which may indicate C. difficile. Adjust dose in renal impairment (CrCl <30 mL/min). |
| Patient Advice | Take Augmentin exactly as prescribed, usually twice daily at evenly spaced intervals. · Complete the full course even if you feel better to prevent resistance. · May cause diarrhea; contact your doctor if it is severe or bloody. · Take with food to reduce stomach upset; avoid high-fat meals which may delay absorption. · Inform your doctor of any rash, itching, or difficulty breathing (signs of allergy). · If you have severe kidney disease, your dose may need adjustment. · Do not take if you have had an allergic reaction to penicillins or cephalosporins. · Avoid use if you have had liver problems from Augmentin before. |