Amoxicillin and Clavulanate
Amoxicillin
Generic Name
Amoxicillin
Mechanism
- Amoxicillin: A penicillidin antibiotic that binds to penicillin‑binding proteins (PBPs) on the bacterial cytoplasmic membrane, inhibiting the transpeptidation step of peptidoglycan cross‑linking and thus weakening the cell wall.
- Clavulanate: A β‑lactamase inhibitor that covalently binds to the active site serine of bacterial β‑lactamases (classes A, C, and some D), sparing amoxicillin from enzymatic degradation.
- Together, the combination produces synergistic antibacterial activity against a broad range of Gram‑positive and Gram‑negative organisms, including many beta‑lactamase producers such as *Escherichia coli*, *Klebsiella pneumoniae*, and *Bacteroides fragilis*.
---
Pharmacokinetics
| Parameter | Typical Value (oral) |
| Absorption | 60–80 % bioavailability; peak plasma levels in 1–2 h |
| Distribution | Volume of distribution ≈ 0.4 L/kg; crosses into saliva, nasopharyngeal fluid, and moderate into CSF |
| Metabolism | Minimal hepatic metabolism; clavulanate partially hydroxylated |
| Elimination | Primarily renal (≈80 % unchanged); half‑life 1.0–1.5 h (amoxicillin) & 0.5–0.7 h (clavulanate) |
| Renal adjustment | Dose reduction in CrCl <30 mL/min; 500/125 mg qid → 250/125 mg qid; 875/125 mg qid → 500/125 mg qid |
| P‑gp | Not a significant substrate transporter |
--
•
Indications
- Community‑acquired lower/upper respiratory tract infections: acute bacterial sinusitis, pharyngitis, otitis media, community‑acquired pneumonia (CAP).
- Skin and soft‑tissue infections: impetigo, cellulitis, abscesses.
- Urinary tract infections (uncomplicated, uncomplicated pyelonephritis).
- Dental prophylaxis for patients with cardiac valve disease or prosthetic valves.
- Intra‑abdominal and biliary infections when Gram‑negative coverage and beta‑lactamase inhibition are needed.
- Pneumococcal infections with documented susceptibility.
---
Contraindications
- Hypersensitivity: Known allergy to penicillins, cephalosporins, or clavulanic acid.
- Severe liver disease: Elevation of transaminases ≥ 5× ULN.
- Severe renal impairment: Dose adjustment required; avoid if CrCl <15 mL/min unless benefit outweighs risk.
- Concomitant use with aminoglycosides: Increased ototoxicity risk – monitor audiometry if used sequentially.
Warnings
• Clostridioides difficile colitis: Report severe watery diarrhea.
• Aplastic anemia (rare): Monitor CBC in patients with unexplained pancytopenia.
• Drug‑drug interactions: Prolongs clotting time; may increase serum levels of phenytoin.
---
Dosing
| Indication | Adult Dose | Frequency | Renal Adjustment (CrCl < 30 mL/min) |
| Sinusitis, pharyngitis, otitis media | 500 mg/125 mg PO q8 h or 875 mg/125 mg PO q12 h | 8 h or 12 h | 250 mg/125 mg q8 h or 500 mg/125 mg q12 h |
| Skin/soft‑tissue | 1 g/125 mg PO q8 h | 8 h | 500 mg/125 mg q8 h |
| Uncomplicated UTI | 500 mg/125 mg PO q8 h | 8 h | 250 mg/125 mg q8 h |
| Dental prophylaxis | 1 g PO before procedure | single dose | 500 mg PO |
Pediatric dosing: 45–90 mg/kg/day of amoxicillin (dose split q8 h or q12 h), clavulanate dose proportional to age/weight. Max total daily dose = 80 mg/kg.
Administration tips
• Take with food to improve tolerability but may slightly delay absorption.
• Hold for at least 1 h after ingestion of foods high in calcium, magnesium, or iron to prevent chelation.
--
•
Monitoring
| Parameter | Frequency | Rationale |
| Serum creatinine / CrCl | Prior to initiation; every 2–4 weeks in renal disease | Adjust dosing, detect nephrotoxicity |
| Liver enzymes (ALT, AST, bilirubin) | 1 month after initiation in patients with liver disease | Detect hepatotoxicity |
| Complete blood count | Baseline and during prolonged therapy > 14 days | Identify aplastic anemia or cytopenias |
| Signs of C. difficile | Patient education and monitoring throughout course | Early detection, reduce morbidity |
| Drug interaction screens | With concurrent anticonvulsants, warfarin | Avoid adverse drug events |
--
•
Clinical Pearls
- Synergy matters: Clavulanate's inclusion turns a narrow‑spectrum amoxicillin into a broad‑spectrum agent; it should be reserved for infections caused by known β‑lactamase producers to limit resistance.
- Timing of dosing: A 12‑hour interval (875/125 mg q12 h) often improves adherence in adults without compromising efficacy versus q8 h dosing.
- Switching to IV: If oral administration fails, IV ampicillin‑sulbactam is the preferred alternate, matching the oral combination's spectrum.
- Cross‑reactivity check: Patients allergic to penicillin should undergo skin testing before using amoxicillin/clavulanate, as cross‑reactivity with cephalosporins and macrolides is low but possible.
- Prophylaxis nuance: For dental prophylaxis, give once 60 min before the procedure, not the same time as the procedure itself, to achieve peak serum levels during mucosal exposure.
- Drug interaction alert: Amoxicillin/clavulanate can increase phenytoin levels by 25–50 %—monitor phenytoin troughs if used concurrently.
--
• Authoritative reference: This drug card is compiled from the *Goodman & Gilman's Pharmacological Basis of Therapeutics*, *Prescribing in Primary Care for Primary Care Physicians*, and current U.S. FDA labeling (as of 2025).