ADMINISTRATION ROUTE:
PO, NG, IV
ALTERNATIVE NAMES:
Amoxiclav Devatis Forte, Augmentin, Co-amoxiclav, Curam
ICU INDICATIONS:
- Treatment of infections caused by susceptible organisms
Note: IV amoxicillin + clavulanic acid in Wellington ICU is always prescribed as 'boosted' for adult patients. This means additional amoxicillin is added between doses. See DOSAGE below for details.
For reconstitution and administration of amoxicillin doses, see separate amoxicillin monograph.
PRESENTATION AND ADMINISTRATION:
IV:
600 mg vials contain 500 mg amoxicillin and 100 mg clavulanic acid
1.2 g vials contain 1 g amoxicillin and 200 mg clavulanic acid
Reconstitution:
Reconstitute each 600 mg vial with 10 mL of water for injection, and each 1.2 g vial with 20 mL of water for injection. Administer within 20 minutes of reconstitution
Intermittent IV dose:
Inject the reconstituted solution slowly over 3-4 minutes
Alternatively, add doses below 600 mg to 50 mL and doses above 600 mg to 100 mL of compatible fluid and administer over 30-40 minutes
Compatible with the following IV fluids: Sodium chloride 0.9% (stable for 4 hours)
Note: amoxicillin + clavulanic acid is less stable in solutions that contain glucose so these solutions should be avoided
Store at room temperature
PO / NG:
Amoxicillin 500 mg + clavulanic acid 125 mg tablets Amoxicillin 250 mg/5 mL + clavulanic acid 62.5 mg/5 mL oral suspension Amoxicillin 125 mg/5 mL + clavulanic acid 31.25 mg/5 mL oral suspension
Amoxicillin and clavulanic acid are well absorbed from the gastrointestinal tract after oral administration of amoxicillin + clavulanic acid. Amoxicillin + clavulanic acid can be given without regard to meals
DOSAGE:
IV:
Amoxicillin + clavulanic acid 1.2 g TDS AND Amoxicillin 1 g TDS
Doses must be staggered at 4 hour intervals i.e. give
- Amoxicillin + clavulanic acid 1.2 g IV at 0000, 0800, 1600
- Amoxicillin 1 g IV at 0400, 1200, 2000
Unstagger doses prior to ICU discharge or as appropriate
PO:
500 mg / 125mg TDS
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:
Adjustment only applies to IV dosing. Oral administration does not require dose adjustment.
Dose in renal impairment
| GFR (ml/min) / CRRT mode | DOSE |
|---|---|
| ≥30 - <50 | dose as in normal renal function |
| <30 or CVVHDF | Amoxicillin + clavulanic acid 1.2 g BD AND Amoxicillin 1 g BD |
Doses must be staggered at 6 hour intervals i.e. give
- Amoxicillin + clavulanic acid 1.2 g IV at 0800, 2000
- Amoxicillin 1 g IV at 1400, 0200
Unstagger doses prior to ICU discharge or as appropriate
Dose in renal replacement therapy
When a patient is receiving intermittent haemodialysis or peritoneal dialysis, there is no need to boost amoxicillin + clavulanic acid
| MODALITY | AMOXICILLIN + CLAVULANIC ACID DOSE |
|---|---|
| CAPD | 1.2 g BD |
| HD | 1.2 g BD. On dialysis days, ensure 2nd dose is given after dialysis session |
DOSAGE IN PAEDIATRICS:
IV:
Severe infections:
1st week of life 50 mg/kg amoxicillin and 12.5 mg/kg clavulanic acid BD
Otherwise 50 mg/kg amoxicillin and 12.5 mg/kg clavulanic acid QID
CLINICAL PHARMACOLOGY:
Amoxicillin + clavulanic acid is an oral antibacterial combination consisting of the semisynthetic antibiotic amoxicillin and the lactamase inhibitor, clavulanate potassium. Clavulanic acid is active against the clinically important plasmid mediated beta-lactamases frequently responsible for transferred drug resistance to penicillins and cephalosporins. Amoxicillin is bactericidal against susceptible organisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell wall mucopeptide. Amoxicillin/ clavulanic acid has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections:
Gram-Positive Aerobes:
- Staphylococcus aureus (beta-lactamase and non-beta-lactamase producing)
Staphylococci which are resistant to methicillin/oxacillin must be considered resistant to amoxicillin/clavulanic acid.
Gram-Negative Aerobes:
-
Enterobacter species. Although most strains of Enterobacter species are resistant in vitro, clinical efficacy has been demonstrated with Augmentin in urinary tract infections caused by these organisms
-
Escherichia coli (beta-lactamase and non-beta-lactamase producing)
-
Haemophilus influenzae (beta-lactamase and non-beta-lactamase producing)
-
Klebsiella species (all known strains are beta-lactamase producing)
-
Moraxella catarrhalis (beta-lactamase and non-beta-lactamase producing)
Amoxicillin diffuses readily into most body tissues and fluids with the exception of the brain and spinal fluid. The results of experiments involving the administration of clavulanic acid to animals suggest that this compound, like amoxicillin, is well distributed in body tissues.
Note: additional organisms (not outlined above) which are adequately treated with amoxicillin alone should be treated with amoxicillin rather than Augmentin
CONTRAINDICATIONS:
-
History of allergic reaction to any of the penicillins.
-
Previous history of cholestatic jaundice/hepatic dysfunction associated with augmentin
WARNINGS:
Anaphylaxis
Penicillins are a common cause of anaphylactic reactions
Pseudomembranous colitis
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including amoxicillin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of antibacterial agents.
PRECAUTIONS:
General:
Prescribing amoxicillin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug resistant bacteria.
Laboratory Tests:
No tests in addition to routine ICU tests are required.
Drug/Laboratory Test Interactions:
None noted
IMPORTANT DRUG INTERACTIONS IN ICU:
None of significance
ADVERSE REACTIONS:
General:
Serum sickness like reactions, anaphylaxis
Gastrointestinal:
Nausea, vomiting, diarrhoea, and haemorrhagic/pseudomembranous colitis, Clostridium difficile colitis, dyspepsia, enterocolitis (including drug-induced enterocolitis syndrome), gastritis, glossitis, melanoglossia, mucocutaneous candidiasis, pancreatitis, black hairy tongue, stomatitis
Hepatobilary:
Hepatic dysfunction including cholestatic jaundice, hepatic cholestasis and acute cytolytic hepatitis have been reported
Nervous System:
Reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioural changes, and/or dizziness have been reported rarely
Skin:
Stevens-Johnson Syndrome, exfoliative dermatitus, toxic epidermal necrolysis, acute generalised exanthematous pustulosis, hypersensitivity vasculitis, urticaria, bullous dermatitis, erythema multiforme, exfoliative dermatitis, pruritis, toxic epidermal necrolysis have been reported
Haematological System:
Anaemia, including haemolytic anaemia, thrombocytopaenia, thrombocytopaenic purpura, eosinophilia, leukopaenia, and agranulocytosis have been reported during therapy with penicillins
Genitourinary:
Vaginal mycosis, vaginitis, crystaluria, haematuria
Renal:
Interstitial nephritis (including acute interstitial nephritis; can be haemorrhagic)