amoxicillin-clavulanate
Brand: Augmentin, Augmentin ES, Augmentin XR
Prototype: penicillin-g
Drug Class: antibiotic
Drug Family: antibiotic
Subclass: aminopenicillin + beta-lactamase inhibitor
Organ Systems: infectious-disease
Mechanism of Action
Amoxicillin inhibits PBPs; clavulanate is a suicide inhibitor of bacterial beta-lactamases (especially class A enzymes such as TEM-1, SHV-1), protecting amoxicillin from hydrolytic inactivation and extending spectrum to beta-lactamase-producing organisms.
penicillin-binding proteins (PBPs)beta-lactamase enzymes
Indications
- community-acquired pneumonia (mild-moderate)
- sinusitis (moderate-severe)
- otitis media (treatment failure)
- skin and soft tissue infections
- diabetic foot infections (mild-moderate)
- bite wounds (animal/human)
Contraindications
- penicillin allergy
- cholestatic jaundice/hepatic dysfunction from prior amoxicillin-clavulanate use
Adverse Effects
Common
- diarrhea (more common than amoxicillin alone due to clavulanate)
- nausea
- vomiting
- rash
Serious
- cholestatic hepatitis (clavulanate-associated; occurs more commonly in older adults and male patients)
- anaphylaxis
- C. difficile colitis
Pharmacokinetics (ADME)
| Absorption | Amoxicillin: ~80%; clavulanate: ~75%; take with food to improve tolerance and clavulanate absorption |
| Distribution | Both components widely distributed; similar Vd to amoxicillin |
| Metabolism | Both partially metabolized; clavulanate to inactive products |
| Excretion | Renal |
| Half-life | Amoxicillin: 1–1.5 hours; clavulanate: ~1 hour |
| Onset | 1–2 hours |
| Peak | 1–2.5 hours |
| Duration | 8–12 hours |
| Protein Binding | ~20% |
| Vd | ~0.3 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| warfarin | may increase INR via gut flora alteration | moderate |
| allopurinol | increased rash risk | moderate |
Nursing Considerations
- Administer with food to reduce GI side effects (nausea, diarrhea) from clavulanate — the most common reason for intolerance
- Note that Augmentin 250 mg and Augmentin 500 mg tabs contain the same amount of clavulanate (125 mg) — do NOT double up on 250 mg tablets to make an 'equivalent' of 500 mg; use the appropriate tablet size
- Monitor for jaundice or RUQ pain, especially in elderly male patients — hepatotoxicity can occur up to 6 weeks after completing the course
- Augmentin ES (600 mg/5 mL) is for resistant otitis media in children; Augmentin XR (2000/125 mg) is for community-acquired pneumonia — verify formulation and dose by indication
Clinical Pearls
- Clavulanate inhibits class A beta-lactamases but NOT AmpC (class C) or class B metallo-beta-lactamases — organisms like Pseudomonas and MRSA remain intrinsically resistant
- The diarrhea associated with Augmentin is partly due to clavulanate's prokinetic effects on gut motility, not just antibiotic-associated dysbiosis; can be partially mitigated by dosing with food
Safety Profile
Pregnancy generally-safe
Lactation safe
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.