Amoxicillin-Clavulanic Acid

ADMINISTRATION ROUTE:

PO, NG, IV

ALTERNATIVE NAMES:

Alpha-amoxyclav, augmentin, synermox.

ICU INDICATIONS:

1. Treatment of infections caused by susceptible organisms

Note: IV amoxicillin-clavulanic acid (Augmentin) in Wellington ICU is always prescribed as 'boosted'. This means additional amoxicillin is added between doses. See DOSAGE below for details

PRESENTATION AND ADMINISTRATION:

IV:

600 mg and 1.2 gm vials (powder). Contain 500 mg or 1 gm amoxicillin and 100 mg or 200 mg clavulanic acid. Reconstitute by adding 10 mL of water for injection to 600 mg vial (final volume 10.5 mL) or 20 mL to 1.2 gm vial (final volume 20.9 mL) and agitating until dissolved.

If less than 600 mg is required, add 11.5 mL of diluent to 600 mg vial to give a solution with a concentration of 50 mg/mL. Inject slowly over 3-4 minutes or administer in 100 mL of compatible fluid over 30-40 minutes.

Compatible for 4 hours with Normal saline, 3 hours with Hartmanns.

Note: amoxicillin and clavulanic acid is less stable in solutions that contain glucose so these solutions should be avoided for intermittent infusions.

Store at room temperature.

PO / NG:

Alpha-amoxyclav 625mg (500 mg amoxicillin, 125mg clavulanic acid) white tablets

Augmentin 500 (500 mg amoxicillin, 125mg clavulanic acid) white tablets

Synermox (500 mg amoxicillin, 125mg clavulanic acid ) white tablets

Alpha-amoxyclav 125mg/5 mL suspension (125mg amoxicillin, 31.25mg clavulanic acid)

Alpha-amoxyclav 250 mg/5 mL (250 mg amoxicillin, 62.5mg clavulanic acid)

Augmentin forte syrup 250 (250 mg amoxicillin, 62.5mg clavulanic acid)

Augmentin forte syrup 125 (125mg amoxicillin, 31.25mg clavulanic acid)

Amoxicillin and clavulanate potassium are well absorbed from the gastrointestinal tract after oral administration of augmentin. Augmentin can be given without regard to meals. Liquid is available for NG administration.

DOSAGE:

IV:

1.2 gm IV TDS amoxicilln-clavulanic acid AND 1 gm IV TDS amoxicillin

Doses must be staggered at 4-hour intervals i.e.give Augmentin 1.2 gm IV at 0800, amoxicillin 1gm IV at 1200, Augmentin 1.2 gm IV at 1600, amoxicillin 1 gm IV at 2000 etc.

PO:

500 mg/125mg PO TDS

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY (for IV dosing):

Dose in renal impairment

Dose in renal replacement therapy

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:

Augmentin 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:

1. History of allergic reaction to any of the penicillins.

2. 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:

Body as a Whole:

Serum sickness like reactions, Anaphylaxis

Digestive System:

Nausea, vomiting, diarrhoea, and haemorrhagic/pseudomembranous colitis. 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 and urticaria have been reported

Haematological System:

Anaemia, including haemolytic anaemia, thrombocytopaenia, thrombocytopaenic purpura, eosinophilia, leukopaenia, and agranulocytosis have been reported during therapy with penicillins