Comparative Pharmacology
Head-to-head clinical analysis: AUGMENTIN 875 versus PROSTAPHLIN.
Peer-Reviewed Evidence
Head-to-head clinical analysis: AUGMENTIN 875 versus PROSTAPHLIN.
AUGMENTIN '875' vs PROSTAPHLIN
Head-to-head clinical comparison of therapeutic indices and safety profiles.
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.
Prostaphlin (oxacillin) is a penicillinase-resistant penicillin that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), specifically PBP1 and PBP3, leading to inhibition of transpeptidation and cell lysis. It is resistant to staphylococcal beta-lactamases.
Treatment of infections caused by susceptible strains such as lower respiratory tract infections, otitis media, sinusitis, skin and skin structure infections, and urinary tract infections due to beta-lactamase producing strains
Treatment of infections caused by penicillinase-producing staphylococci, including skin and soft tissue infections, pneumonia, osteomyelitis, endocarditis, and septicemiaOff-label: empiric therapy for suspected staphylococcal infections in hospitalized patients
One 875 mg amoxicillin/125 mg clavulanate tablet orally every 12 hours.
250-500 mg IM or IV every 4-6 hours for moderate to severe infections. For oral use: 250-500 mg every 6 hours on empty stomach.
None Documented
None Documented
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).
0.4-0.8 hours in adults with normal renal function; prolonged in renal impairment (up to 4-6 hours in anuria).
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.
Hepatic metabolism via hydrolysis and oxidation; minor renal excretion.
Amoxicillin: ~50-70% renal as unchanged drug, 10-20% biliary. Clavulanate: ~30-50% renal as unchanged, ~25% fecal.
Primarily renal (70-80% unchanged via glomerular filtration and tubular secretion); minor biliary/fecal elimination (<10%).
Amoxicillin: ~17-20% (albumin). Clavulanate: ~25-30% (albumin).
80-90% bound to serum albumin.
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.
0.3-0.4 L/kg (confined to extracellular fluid; poor CNS penetration unless meninges inflamed).
Oral: Amoxicillin 80-90%, Clavulanate ~60-70% (absorption enhanced with food).
Oral: 30-40% (due to acid lability and first-pass metabolism); IM: 70-80%.
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.
No dose adjustment for GFR >30 mL/min. For GFR 10-30 mL/min: 250-500 mg every 8 hours. For GFR <10 mL/min: 250-500 mg every 12 hours.
No specific adjustment required for mild-moderate hepatic impairment; contraindicated in severe hepatic impairment (Child-Pugh C) due to risk of hepatotoxicity.
No specific guidelines; use caution in severe hepatic impairment (Child-Pugh C) and monitor for toxicity.
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).
Infants and children: 50-100 mg/kg/day IM or IV divided every 6 hours. Neonates: 25-50 mg/kg/day divided every 8 hours.
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).
No specific adjustments required, but monitor renal function and adjust accordingly based on GFR.
No FDA black box warning.
No FDA black box warning.
["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"]
["Hypersensitivity reactions including anaphylaxis","Clostridioides difficile-associated diarrhea","Neutropenia and interstitial nephritis with prolonged use","Use with caution in patients with renal impairment"]
["Hypersensitivity to amoxicillin, clavulanate, or any beta-lactam antibiotic","History of cholestatic jaundice or hepatic dysfunction with prior Augmentin use"]
["Hypersensitivity to penicillins","History of severe penicillin allergy"]
Data Pending Review
Data Pending Review
Take with food or milk to minimize gastrointestinal distress. Avoid alcohol during treatment and for 48 hours after completion.
No significant food interactions. Take on an empty stomach or with food if gastrointestinal upset occurs. Avoid alcohol due to potential hepatotoxicity.
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.
Prostaphlin (oxacillin) is a penicillinase-resistant penicillin. Animal studies have not shown teratogenicity. There are no adequate and well-controlled studies in pregnant women. FDA Pregnancy Category B. Risk cannot be ruled out but is considered low. Use only if clearly needed.
Compatible with breastfeeding. M/P ratio unknown; amoxicillin and clavulanate are excreted into breast milk in low levels. Risk of infant diarrhea and candidiasis. Monitor infant for rash, diarrhea, or fungal infections.
Oxacillin is excreted into breast milk in small amounts (M/P ratio approximately 0.5). It is considered compatible with breastfeeding by the American Academy of Pediatrics. However, potential for infant sensitization and diarrhea exists. Monitor infant for rash or gastrointestinal disturbances.
Pharmacokinetic changes in pregnancy (increased renal clearance, volume of distribution) may reduce serum concentrations. Current evidence does not support routine dose adjustment; use standard dosing (875 mg amoxicillin/125 mg clavulanate twice daily) unless severe infection. Monitor clinical response.
Pregnancy-induced physiological changes (e.g., increased plasma volume, enhanced renal clearance) may require higher doses or more frequent administration to achieve therapeutic levels. No established formal dose adjustment guidelines; monitor clinical response and adjust as necessary.
Category C
Category C
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).
PROSTAPHLIN (oxacillin) is a penicillinase-resistant penicillin used for methicillin-susceptible Staphylococcus aureus (MSSA) infections. Administer IV via intermittent infusion over 30-60 minutes; avoid IM due to pain. Monitor hepatic function and CBC due to risk of neutropenia. Dose adjustment required in renal impairment (CrCl <10 mL/min). Use with caution in patients with penicillin allergy; cross-reactivity with cephalosporins is low but possible.
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).
Take exactly as prescribed; complete full course even if you feel better.Report any signs of allergic reaction: rash, itching, swelling, difficulty breathing.Notify doctor if you experience severe diarrhea, unusual bleeding/bruising, or yellowing of skin/eyes.Avoid alcohol while on this medication to reduce risk of hepatotoxicity.Inform your doctor about all other medications you are taking, especially methotrexate and anticoagulants.