AUGMENTIN '400'
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AUGMENTIN '400' (AUGMENTIN '400').
Augmentin '400' 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 inactivation of amoxicillin.
| Metabolism | Amoxicillin is partially metabolized by hydrolysis to inactive penicilloic acid; clavulanate is extensively metabolized to 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one. |
| Excretion | Amoxicillin: ~50-70% renal (tubular secretion and glomerular filtration) as unchanged drug, remainder metabolized to penicilloic acid. Clavulanate: ~30-50% renal as unchanged drug, remainder metabolized and excreted via bile/feces. Total renal clearance accounts for ~60-80% of elimination for both components. |
| Half-life | Amoxicillin: 1-1.3 hours (prolonged to ~7 hours in renal impairment, e.g., CrCl <10 mL/min). Clavulanate: 1-1.2 hours (prolonged in renal impairment). Clinical context: Dosing interval adjustment required for CrCl <30 mL/min. |
| Protein binding | Amoxicillin: ~17-20% bound to albumin. Clavulanate: ~25% bound to albumin. Binding is non-saturable and clinically insignificant for distribution. |
| Volume of Distribution | Amoxicillin: 0.3-0.4 L/kg (primarily extracellular fluid; penetrates well into CSF with inflamed meninges). Clavulanate: 0.3-0.4 L/kg; limited CNS penetration unless meninges inflamed. |
| Bioavailability | Oral (tablet or suspension): Amoxicillin ~75-90% (food does not significantly affect absorption). Clavulanate ~60-70% (absorption may be slightly enhanced with food). The '400' formulation (e.g., 400 mg amoxicillin/57 mg clavulanate) provides proportional bioavailability. |
| Onset of Action | Oral (immediate-release): Therapeutic concentrations achieved in plasma within 1-2 hours; clinical effect (e.g., symptom relief in acute otitis media) typically begins within 24-48 hours of adequate dosing. |
| Duration of Action | Bactericidal levels persist for approximately 6-8 hours after a single oral dose. Twice-daily or three-times-daily dosing maintains effective concentrations for most susceptible pathogens. For β-lactamase-producing organisms, the clavulanate component ensures activity for the entire dosing interval. |
500 mg (amoxicillin 400 mg / clavulanate 57 mg) orally every 12 hours or 875 mg (amoxicillin 700 mg / clavulanate 100 mg) orally every 12 hours; usual duration 5-10 days.
| Dosage form | FOR SUSPENSION |
| Renal impairment | CrCl 10-29 mL/min: 250-500 mg every 12 hours. CrCl <10 mL/min: 250-500 mg every 24 hours. Hemodialysis: 250-500 mg every 24 hours, with an additional dose during and after dialysis. |
| Liver impairment | Child-Pugh Class A (mild): No adjustment. Child-Pugh Class B (moderate): Caution, consider reducing dose or extending interval; no specific guidelines. Child-Pugh Class C (severe): Avoid use due to potential hepatotoxicity. |
| Pediatric use | For children >40 kg: 500 mg (amoxicillin 400 mg / clavulanate 57 mg) every 12 hours or 875 mg every 12 hours. For children <40 kg: based on amoxicillin component, 45 mg/kg/day divided every 12 hours for mild to moderate infections; 80-90 mg/kg/day divided every 12 hours for severe infections. |
| Geriatric use | Monitor renal function; adjust dose based on CrCl as for adults. Consider lower end of dosing range due to increased risk of adverse effects (e.g., diarrhea, hepatotoxicity). Avoid in patients with hepatic impairment or history of jaundice with amoxicillin-clavulanate. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AUGMENTIN '400' (AUGMENTIN '400').
| Breastfeeding | Compatible with breastfeeding. Amoxicillin and clavulanate are excreted in breast milk in low levels (M/P ratio not established). Risk of diarrhea and allergic sensitization in infant. |
| Teratogenic Risk | Pregnancy category B. No evidence of teratogenicity in animal studies. Limited human data; avoid in first trimester unless clearly needed. Use only if benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["History of allergic reaction to penicillins or cephalosporins","History of cholestatic jaundice or hepatic dysfunction associated with amoxicillin/clavulanate","Mononucleosis (increased risk of rash)"]
| Precautions | ["Clostridium difficile-associated diarrhea","Hypersensitivity reactions (anaphylaxis)","Hepatic dysfunction (elevated liver enzymes, hepatitis, cholestatic jaundice)","Severe cutaneous adverse reactions (SJS, TEN, DRESS)","Antibiotic-associated colitis","Overgrowth of non-susceptible organisms","Renal impairment: dose adjustment required","Phenylketonurics: contains phenylalanine"] |
| Food/Dietary | No significant food interactions; may be taken with food to minimize gastrointestinal upset. Avoid high-fat meals that may delay absorption; overall bioavailability unaffected. |
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| Monitor for signs of hypersensitivity, diarrhea, and Clostridium difficile infection in mother. Fetal monitoring as per routine obstetric care; no specific monitoring required. |
| Fertility Effects | No known adverse effects on fertility. Standard use does not impair reproductive function. |
| Clinical Pearls | Augmentin '400' (amoxicillin/clavulanate 400 mg/57 mg per 5 mL) is a high-dose formulation for pediatric infections. Dosing is based on amoxicillin component: 45 mg/kg/day divided q12h for mild-moderate infections; for severe infections or otitis media, use 90 mg/kg/day divided q12h. Clavulanate dose (6.4 mg/kg/day) may limit maximum amoxicillin dose to 45 mg/kg/day in high-dose regimens; use 600 mg/42.9 mg per 5 mL formulation when higher clavulanate is needed. Caution in hepatic impairment: reported with cholestatic jaundice, especially in elderly and with prolonged use. Reconstituted suspension stable for 10 days refrigerated. |
| Patient Advice | Take every 12 hours with or without food; giving with food may reduce stomach upset. · Shake suspension well before each use; use dosing spoon or syringe for accuracy. · Complete entire course as prescribed, even if symptoms improve. · Stop and call if rash, severe diarrhea, or yellowing of skin/eyes occurs. · Refrigerate reconstituted suspension; do not freeze. Discard after 10 days. |