AUGMENTIN '875'
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AUGMENTIN '875' (AUGMENTIN '875').
Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). Clavulanate is a beta-lactamase inhibitor that irreversibly binds to and inactivates beta-lactamase enzymes, preventing degradation of amoxicillin.
| Metabolism | Amoxicillin is partially metabolized to 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. Both are excreted renally. |
| Excretion | Amoxicillin: ~50-70% renal as unchanged drug, 10-20% biliary. Clavulanate: ~30-50% renal as unchanged, ~25% fecal. |
| Half-life | Amoxicillin: 1-1.5 hours (may extend to 7-13 hours in renal impairment). Clavulanate: ~1 hour (may extend to 2.5-4.5 hours in renal impairment). |
| Protein binding | Amoxicillin: ~17-20% (albumin). Clavulanate: ~25-30% (albumin). |
| Volume of Distribution | Amoxicillin: 0.3-0.4 L/kg; distributes well into tissues, low CNS penetration unless inflamed. Clavulanate: 0.2-0.3 L/kg; distributes into tissues but limited CNS. |
| Bioavailability | Oral: Amoxicillin 80-90%, Clavulanate ~60-70% (absorption enhanced with food). |
| Onset of Action | Oral: 1-2 hours for peak serum concentrations; clinical effect within 24-48 hours for susceptible infections. |
| Duration of Action | Amoxicillin: 6-8 hours (bactericidal levels). Clavulanate: 6-8 hours (beta-lactamase inhibition). Dosing interval: q12h for Augmentin '875'. |
| Molecular Weight | 419.45 |
One 875 mg amoxicillin/125 mg clavulanate tablet orally every 12 hours.
| Dosage form | TABLET |
| Renal impairment | CrCl 10-30 mL/min: 875 mg amoxicillin/125 mg clavulanate every 12 hours; CrCl <10 mL/min: 875 mg amoxicillin/125 mg clavulanate every 24 hours; hemodialysis: dose after dialysis on dialysis days. |
| Liver impairment | No specific adjustment required for mild-moderate hepatic impairment; contraindicated in severe hepatic impairment (Child-Pugh C) due to risk of hepatotoxicity. |
| Pediatric use | For children ≥40 kg: same as adult dose; for <40 kg: use weight-based suspension (amoxicillin 45 mg/kg/day divided every 12 hours for mild-moderate infections or 90 mg/kg/day divided every 12 hours for severe infections). |
| Geriatric use | No specific dose adjustment solely for age; monitor renal function and adjust dose based on CrCl as above; consider increased risk of adverse effects (e.g., diarrhea, rash). |
| 1st trimester | No increased risk of major malformations; use if clearly needed. |
| 2nd trimester | Safe; commonly used for infections. |
| 3rd trimester | Safe; avoid high doses near term due to risk of kernicterus (theoretical). |
Clinical note
Comprehensive clinical and safety monograph for AUGMENTIN '875' (AUGMENTIN '875').
| Placental transfer | Crosses placenta; achieves therapeutic levels in fetal circulation. |
| Breastfeeding | Excreted into breast milk in low levels; considered compatible with breastfeeding. Monitor infant for diarrhea or rash. |
| Lactation Rating | L1 |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to penicillinsHistory of cholestatic jaundice/hepatic dysfunction with amoxicillin-clavulanatePrevious immediate hypersensitivity reaction to beta-lactam
| Precautions | Serious hypersensitivity reactions including anaphylaxis, Clostridium difficile-associated diarrhea, Hepatotoxicity (elevated liver enzymes, hepatitis, cholestatic jaundice), Overgrowth of non-susceptible organisms, Potential for seizures with high doses or renal impairment |
| Food/Dietary | Take with food or milk to minimize gastrointestinal distress. Avoid alcohol during treatment and for 48 hours after completion. |
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| Teratogenic Risk | FDA Pregnancy Category B. No evidence of teratogenicity in animal studies. Limited human data; no increased risk of major birth defects reported. Avoid in first trimester if possible due to theoretical risk of neural tube defects from folate antagonism. |
| Fetal Monitoring | Monitor for signs of hypersensitivity, diarrhea, and superinfection. In pregnancy, assess for premature rupture of membranes or chorioamnionitis if used for UTI. Fetal monitoring not routinely required unless maternal infection poses risk. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies show no impairment of fertility. |
| Clinical Pearls |
| Monitor renal function; adjust dose for CrCl <30 mL/min. High-dose amoxicillin (875 mg) may cause crystalluria, ensure adequate hydration. Increases INR with warfarin. False-positive urine glucose tests (Clinitest). |
| Patient Advice | Take with food to reduce GI upset. · Complete full course even if feeling better. · Shake suspension well before each use. · Report rash, diarrhea, or severe abdominal pain. · Avoid alcohol (may cause disulfiram-like reaction). |