AUGMENTIN '250'
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AUGMENTIN '250' (AUGMENTIN '250').
Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), disrupting peptidoglycan cross-linking. Clavulanate is a beta-lactamase inhibitor that irreversibly binds to beta-lactamases, preventing hydrolysis of amoxicillin.
| Metabolism | Amoxicillin undergoes partial hepatic metabolism; clavulanate is extensively metabolized in the liver. Both are primarily excreted renally. |
| Excretion | Renal: ~50-70% as amoxicillin, ~25-40% as clavulanate unchanged; biliary/fecal: minor (10-15% combined). |
| Half-life | Amoxicillin: 1.0-1.3 hours; clavulanate: 1.0-1.5 hours; prolonged in renal impairment (up to 7 hours for amoxicillin in anuria). |
| Protein binding | Amoxicillin: 17-20%, clavulanate: 22-30%, primarily to albumin. |
| Volume of Distribution | Amoxicillin: 0.3-0.4 L/kg; clavulanate: 0.2-0.3 L/kg, indicating distribution into extracellular fluid and tissues. |
| Bioavailability | Oral: 70-90% for amoxicillin, ~60% for clavulanate; IV: 100%. |
| Onset of Action | Oral: 1-2 hours to therapeutic serum levels; IV: immediate. |
| Duration of Action | 6-8 hours; dosing interval 8-12 hours based on infection severity and renal function. |
| Molecular Weight | Amoxicillin: 365.4 Da; Clavulanate: 199.2 Da; Combination: average 282.3 Da. |
One 250 mg amoxicillin/125 mg clavulanate tablet orally every 8 hours for 7-10 days.
| Dosage form | TABLET |
| Renal impairment | CrCl 10-30 mL/min: 250 mg amoxicillin every 12 hours; CrCl <10 mL/min: 250 mg amoxicillin every 24 hours; hemodialysis: 250 mg amoxicillin after each dialysis session. |
| Liver impairment | Child-Pugh A (mild): no adjustment; Child-Pugh B (moderate): use with caution, reduce dose or increase interval; Child-Pugh C (severe): avoid use. |
| Pediatric use | Based on amoxicillin component: 20 mg/kg/day in divided doses every 8 hours for mild-to-moderate infections; 40 mg/kg/day in divided doses every 8 hours for severe infections (max 1.5 g/day). |
| Geriatric use | Assess renal function; adjust dose based on creatinine clearance; monitor for adverse effects such as diarrhea and rash. |
| 1st trimester | Use is generally avoided due to theoretical risk of teratogenicity; however, data do not suggest a significant increase in congenital malformations. Amoxicillin-clavulanate is only used if clearly needed. |
| 2nd trimester | Considered safe; amoxicillin-clavulanate is used when indicated. No known risk of fetal harm. |
| 3rd trimester | Considered safe; however, use near delivery may increase risk of neonatal jaundice or kernicterus due to displacement of bilirubin from albumin. |
Clinical note
Comprehensive clinical and safety monograph for AUGMENTIN '250' (AUGMENTIN '250').
| Placental transfer | Amoxicillin and clavulanate cross the placenta. Cord blood concentrations are approximately 20-30% of maternal serum concentrations. Fetal tissues achieve therapeutic levels. |
| Breastfeeding | Amoxicillin and clavulanate are excreted into breast milk in low levels. Adverse effects in the nursing infant are rare but may include diarrhea, rash, or thrush. Caution is advised in infants with preexisting gastrointestinal issues or allergies. Generally considered compatible with breastfeeding. |
■ FDA Black Box Warning
None
| Common Effects | Vomiting Nausea Diarrhea Mucocutaneous candidiasis |
| Serious Effects |
History of anaphylactic reaction to penicillins or cephalosporinsHistory of cholestatic jaundice or hepatic dysfunction associated with amoxicillin-clavulanate
| Precautions | Severe hypersensitivity reactions including anaphylaxis, Clostridium difficile-associated diarrhea, Hepatic dysfunction (more common in elderly or prolonged use), Risk of superinfection with prolonged therapy |
| Food/Dietary | Take with food to minimize gastrointestinal upset and improve absorption. Avoid high-fat meals as they may delay absorption. No specific food avoidance required. |
Loading safety data…
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | FDA Pregnancy Category B. Studies in animals have not demonstrated fetal risk. No adequate well-controlled studies in pregnant women. Avoid use in first trimester if possible; caution in second and third trimesters. No known teratogenicity. |
| Fetal Monitoring | Monitor maternal renal function and signs of hypersensitivity. Fetal monitoring not specifically required. |
| Fertility Effects | No studies on fertility effects in humans. Animal studies show no impairment of fertility. |
| Clinical Pearls | Augmentin '250' contains amoxicillin 250mg and clavulanate 125mg per 5mL suspension. Clavulanate inhibits β-lactamase, extending amoxicillin's spectrum to include β-lactamase-producing strains of H. influenzae, M. catarrhalis, and S. aureus (not MRSA). Administer every 12 hours with food to reduce GI upset and enhance absorption. Shake suspension well before use; refrigerate suspension to maintain potency. Not effective against MRSA or Pseudomonas. Monitor for diarrhea, rash, and hepatotoxicity (rare but serious). Dose adjustment required in renal impairment (CrCl <30 mL/min). |
| Patient Advice | Take this medication exactly as prescribed, every 12 hours, with a meal or snack. · Shake the suspension well before each dose and measure with the provided device. · Store the suspension in the refrigerator; discard after 10 days. · Complete the full course of treatment even if you feel better. · Inform your doctor if you develop severe diarrhea, rash, or yellowing of skin/eyes. · Do not use if you are allergic to penicillins or cephalosporins. · Check with doctor before use if you have kidney disease or are taking blood thinners. |