AUGMENTIN XR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AUGMENTIN XR (AUGMENTIN XR).
Amoxicillin is a beta-lactam antibacterial that 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, protecting amoxicillin from degradation.
| Metabolism | Amoxicillin is partially metabolized via hydrolysis to penicilloic acid; clavulanate is extensively metabolized via hydrolysis to 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and other metabolites. Both are primarily excreted renally. |
| Excretion | Amoxicillin: ~50-70% excreted unchanged in urine via glomerular filtration and tubular secretion; clavulanate: ~25-40% excreted unchanged in urine; both undergo minor biliary/fecal elimination (<10%). |
| Half-life | Amoxicillin: ~1.0-1.3 hours; clavulanate: ~0.9-1.2 hours; prolonged in renal impairment (creatinine clearance <30 mL/min: amoxicillin half-life up to 7-14 hours). |
| Protein binding | Amoxicillin: ~17-20% bound to serum proteins (mainly albumin); clavulanate: ~22-30% bound to albumin. |
| Volume of Distribution | Amoxicillin: ~0.3-0.4 L/kg; clavulanate: ~0.3-0.4 L/kg; distributes well into most body tissues and fluids, including lungs, sinus secretions, and pleural fluid, but limited CNS penetration unless meninges inflamed. |
| Bioavailability | Oral: Amoxicillin ~74-92% (dose-dependent, increased with extended-release); clavulanate ~60-75% (improved when taken with food). |
| Onset of Action | Oral: ~1-2 hours to peak plasma concentrations; clinical effect begins within 1-2 hours after administration. |
| Duration of Action | Typically 6-8 hours; extended-release formulation (2 g amoxicillin/125 mg clavulanate) maintains therapeutic concentrations for ~12 hours, allowing twice-daily dosing for indications like community-acquired pneumonia. |
| Brand Substitutes | Vamaxy 500mg/100mg Injection, Penom Clav 500 mg/100 mg Injection, PD Mox C 500mg/100mg Injection, MS Clav 500 mg/100 mg Injection, Clavunex 500mg/100mg Injection, Verclav 250 mg/50 mg Injection, Augclav 250 mg/50 mg Injection, Moxxil Duo 300mg Injection, Penom Clav 250 mg/50 mg Injection, PD Mox C 250mg/50mg Injection |
Adults and adolescents ≥16 years: 2 tablets (amoxicillin 1000 mg/clavulanate 62.5 mg per tablet) orally every 12 hours for 10 days.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | CrCl 10-30 mL/min: 1 tablet (amoxicillin 1000 mg/clavulanate 62.5 mg) every 12 hours. CrCl <10 mL/min: not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B or C: contraindicated due to increased risk of hepatotoxicity. |
| Pediatric use | Not approved for pediatric use. For children <16 years, use alternative formulations with weight-based dosing (e.g., amoxicillin 45 mg/kg/day divided every 12 hours, max 1750 mg/day, with clavulanate doses adjusted accordingly). |
| Geriatric use | Evaluate renal function; use recommended renal adjustment based on CrCl. No additional age-related adjustments required. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AUGMENTIN XR (AUGMENTIN XR).
| Breastfeeding | Excreted into breast milk in low concentrations (M/P ratio approximately 0.03-0.06). Considered compatible with breastfeeding; monitor infant for diarrhea and allergic reactions. |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies show no evidence of fetal harm. Limited human data in first trimester; no increased risk of major malformations reported. Potential for infantile diarrhea and allergic reactions with late pregnancy exposure. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: INCREASED RATE OF HEPATOTOXICITY. AUGMENTIN XR contains a higher dose of clavulanate (125 mg) compared to other amoxicillin/clavulanate formulations, which has been associated with an increased risk of hepatic adverse events, including jaundice and cholestatic hepatitis. Avoid use in patients with hepatic impairment.
| Serious Effects |
["Hypersensitivity to amoxicillin, clavulanate, or any other beta-lactam antibiotic (e.g., penicillins, cephalosporins)","History of cholestatic jaundice or hepatic dysfunction associated with amoxicillin/clavulanate","Severe renal impairment (creatinine clearance <30 mL/min) due to fixed dose ratio not adjustable"]
| Precautions | ["Hepatotoxicity: Increased risk of hepatic events, including jaundice and cholestatic hepatitis; avoid in patients with hepatic impairment.","Serious allergic reactions: Anaphylaxis, angioedema; discontinue if allergic reaction occurs.","Clostridioides difficile-associated diarrhea: May range from mild diarrhea to fatal colitis.","Seizures: May occur in patients with renal impairment or those receiving high doses.","Superinfection: Prolonged use may result in overgrowth of non-susceptible organisms."] |
| Food/Dietary |
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| Monitor for signs of hypersensitivity, diarrhea, and superinfection in mother and neonate. Assess renal function periodically due to potential for altered clearance in pregnancy. |
| Fertility Effects | No evidence of impaired fertility in animal studies. No human data on reproductive effects. |
| Take with a meal or snack to enhance absorption and reduce gastrointestinal distress. Avoid alcohol during treatment and for 48 hours after completion due to risk of disulfiram-like reaction. No other significant food interactions reported. |
| Clinical Pearls | Augmentin XR (amoxicillin/clavulanate) is an extended-release formulation dosed twice daily for community-acquired pneumonia and acute bacterial sinusitis. The clavulanate component inhibits beta-lactamase, extending amoxicillin's spectrum to include beta-lactamase-producing strains. Adjust dose for creatinine clearance <30 mL/min: avoid XR formulation; use immediate-release. Monitor for diarrhea, which is more common with clavulanate. Not for use in patients with severe renal impairment (CrCl <30 mL/min) or those on hemodialysis. |
| Patient Advice | Take with food to reduce stomach upset. · Swallow tablets whole; do not crush, chew, or split. · Complete the full course even if you feel better. · Shake oral suspension well before each use. · Store tablets at room temperature; refrigerate oral suspension (discard unused after 10 days). · Notify your doctor if you develop severe diarrhea, rash, or jaundice. |