Dosage Form: Tablets
Description: Broad spectrum beta-lactam antibiotic
Manufacturer: GlaxoSmithKline (GSK)
Tablets containing different ratios of Amoxycillin trihydrate to Potassium Clavulanate:
- 375 mg (2:1)
- 625 mg (4:1)
- 1 g (7:1)
Suspensions containing different ratios of Amoxycillin trihydrate to Potassium Clavulanate:
- 156.25 mg / 5 mL (4:1)
- 312.5 mg / 5 mL (4:1)
- 457 mg / 5 mL (7:1)
Augmentin (beta-lactam antibacterial penicillin co-formualted with a beta-lactamase inhibitor) is an antibiotic agent with a notably broad spectrum of activity against commonly occuring bacetrial pathogens in general practice and hospital. The beta-lactamase inhibitory action of Clavulante extends the spectrum of amoxycillin to embrace a wider range of organisms, including many resistant to other beta-lactam antibiotics.
Amoxycillin is a semisynthetic antibiotic with a broad spectrum of antibacterial activity against many gram-positive and gram-negative microogranisms. Amoxycillin is, however, susceptible to degradation by beta-lactamases and therefore the spectrum of acitivity of amoxycillin alone does not include organisms which produce these enzymes.
Clavulanic acid is a beta-lactam, structurally related to the penicillins, which possesses the ability to inactivate a wide range of beta-lactamase enzymes commonly found in micro-organisms resistant to penicillins and cephalosporins. In particular, it has good activity the clinically important plasmid mediated beta-lactamases frequently responsible for transferred drug resistance. It is generally less effective against chromosomally-meditated type 1 beta-lactamases.
The presence of clavulanic acid in Augmentin formulations protects amoxycillin from degradation by beta-lactamase enzymes and effectively extends the antibacterial spectrum of amoxycillin to include many bacteria normally resistant to amoxycillin and other penicillins and cephalosporins.Thus Augmentin possesses the distinctive properties of a broad spectrum antibiotic and a beta-lactamase inhibitor. Augmentin is bactericidal to a wide range of organisms.
Short term treatment of bacetrial infections at the following sites when caused by Augmentin sensitive organisms:
- Upper Respiratory Tract infections (including ENT): recurrent tonsilitis, sinusitis, otitis media typically caused by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes.
- Lower Respiratory Tract infections: acute exacerbations of chronic bronchitis, lobar and bronchopneumonia typically caused by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis.
- Gentio-urinary Tract infections: cystitis, urethritis, pyelonephritis, female genital infections typically caused by Enterobacteriaceae (mainly Escheria coli), Stayphylococcus saprophyticus and Enterococcus species; and gonorrhoea caused by Neisseria gonorrhoeae.
- Skin and soft tissue infections: typically caused by Staphylococcus aureus, Streptococcus pyogenes and Bacteriodes species.
The paediatric t.i.d. dosing regimen is also indicated for the following infections:
- Other infections: septic abortion, puerperal sepsis, intra-abdominal sepsis.
- Some members of these species of bacteria produce beta-lactamase, rendering them insensitive to amoxycillin alone.
Infections caused by amoxycillin-susceptible organisms are amenable to Augmentin treatment due to its amoxycillin content. Mixed infections caused by amoxycillin-susceptible organisms in conjunction with Augmentin-susceptible beta-lactamase-producing organisms may therefore be treated by Augmentin.
Amoxicillin-clavulanate is contraindicated in patients with a history of hypersensitivity to beta-lactams, e.g. penicillins and cephalosporins and in patients with a previous history of amoxicillin-clavulanate-associated jaundice/hepatic dysfunction.
Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxycillin. Concomintant use with Augmentin may result in increased and prolonged blood levels of amoxycillin but not of clavulanic acid.
Concomintant use of allopurinol during treatment with amoxycillin can increase the likelihood of allergic skin reactions 20, 21. There are no data on the concomitant use of Augmentin and allopurinol.
In common with other broad-spectrum antibiotics, Augmentin may reduce the efficacy of oral contraceptives and patients should be warned accordingly.
Mucocutaneous candidiasis, diarrhoea, nausea and vomitting, have been reported. Nause is more often associated with higher oral dosages. If gastrointestinal reactions are evident, they may be reduced by taking Agumentin at the start of a meal.
Uncommonly the following was reported:
- A moderate rise in AST and/or ALT has been noted in patients treated with beta-lactam class antibiotics
- Skin rase, pruritus and urticaria
- There have been rare findings of Reversible leucopenia (including neutropenia) and thrombocytopenia
- Erthema multiforme and very rarely reversible agranulocytosis and haemolytic anaemia
- Prolongation of bleeding time and prothrombin time
- Anginoneurotic oedema, anaphylaxis, serum sickness-like syndrome, hypersensitivity vasculitis
- Reversible hyperactivity and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses.
- Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis)
- Superficial tooh discoloration has been reported very rarely in children. Good oral hygiene may help to prevent tooth coloration as it can usually be removed by brushing
- Hepatitis and cholestatic jaundice
These events have been noted with other penicillins and cephalosporins. Stevens-Johnson syndrome, toxic empidermal necrolysis, bullous exofoliative-dermatitis, acute generalised exanthemous pustulosis (AGEP) Interstitial nephritis and crsytalluria.
Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment.
These events have been very rarely reported in children.
Sings and symptoms usually occur during or shortly after treatment but in some cases may not become apparent until several weeks after treatment has ceased. These are usually reversible.
Hepatic events may be severe and in extremely rare cirumstances, deaths have been reported. These have almost always occurred in patients with serious underlying disease or taking concomintant medications known to have the potential for hepatic effects.
Dosage and Administration:
Depends on the age, weight and renal function of the patient and the severity of the infection.
Dosages are expressed throughout in terms of amoxycillin/calvulanate content except when doses are stated in terms of an individual component.
- Dosage should be expressed in terms of the age of the child and either in mg/kg/day or mL of suspension per dose or equivalent for other presentations.
- Children weighing 40 kg and over should be dosed according to the adult recommendations.
- Children up to 12 years:
- t.i.d. (4:1 formulations), b.i.d. (7:1 forumlations)
- Lower dose (mg/kg/day) 20/5 – 40/10 25/3.6 – 45-6.4
- Higher dose (mg/kg/day) 40/10 – 60/15 45/6.4 – 70/10
- The lower dose is recommended for infections such as skin and soft tissue and recurrent tonsillitis.
- The higher dose is recommended for infections such as otitis media, sinusitis, LRTIE and UTI.
- No cilincal data are available on doses of these formulations higher than 40/10 mg/kg/day t.i.d. (4:1) or 45/6.4 mg/kg/day b.i.d. (7:1) in children under 2 years. There are no clinical data for the 7:1 formulation for patients under 2 months of age. Dosing recommendations in this population therefore cannot be made.
- For administration to children up to 2 years old, Augmentin suspensions may be diluted to half-strength using water.
- Creatinine clearance >30 ml/min: No adjustment necessary
- Creatnine clearance 10-30 ml/min: 15/3.75 mg/kg given b.i.d.
- Creatinine clearance <10 ml/min: 15/3.75 mg/kg given as a single daily dose
- In the majority of cases, parenteral therapy, where available, may be preferred.
- Dosing adjustments are based on the maximum recommended level of amoxycillin
- 15/3.75/kg/day given as a single daily dose
- Prior to hemodialysis one additional dose of 15/2.75 mg/kg should be administered. In order to restore circulating drug levels, another dose of 15/3.75 mg/kg should be administered after haemodialysis
- Mild to moderate infections: 375 mg given t.i.d. or 625 mg given b.i.d. or t.i.d. or 1 g given b.i.d.
- Severe infections: (including chronic and recurrent urinary tract infections and those of the lower respiratory tract) 2 times 375 mg given t.i.d. or 1-2 times 625 mg given t.i.d. or 1 g given t.i.d.
- 2 Augmentin 375 mg should not be substitiuted for one Augmentin 625 mg since they are not equivalent
- In case of renal impairment, dosing adjustments are based on the maximum recommended level of amoxycillin
- Creatinine clearance >30 ml/min: no adjustment necessary
- Creatnine clearance >10-30 ml/min: 1 times 625 given b.i.d. or 1-2 times 375 mg, depending upon severity of infections, given b.i.d.
- Creatnine clearance <10 ml/min: 1 times 625 given o.d; or 1-2 times 375 gm, depending upong severity of infections, given o.d.- Haemodialysis.
- 1 times 625 mg or 2 times 375 mg every 24 hours, PLUS 1 dose during dialysis, to be repeated at the end of dialysis (as serum concentrations of both amoxycillin and clavulanic acid are decreased). The 1 g presentation should only be used in patients with a creatinine clearance of >30 ml/min.
3. Hepatic Impairment:
- Dose with caution; monitor hepatic function at regular intervals
- There are insufficient data on which to base a dosage recommendation
4. Method of Administration:
- Oral route
- Administer at the start of a meal, in order to minimize potential gastrointestinal intolerance
- The absorption of Augmentin is optimised when taken at the start of a meal
- Treatment should not be extended beyond 14 days without review
- Therapy can be started parenterally and continued with an oral preparation
Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. They may be treated symptomatically, with attention to the water/electrolyte balance.
If amoxycillin crystalluria has been observed, Augmentin can be removed from the circulation by haemodialysis.
A prospective study of 51 paediatric patients at a poison control centre suggested that overdosages of less than 150 mg/kg of amoxycillin are not associated with significant clinical symptoms and do not require gastric emptying.
Pregnancy and Lactation:
Reproduction studies in animals (mice and rats at doses up to 10 times the human dose) with orally and parenterally administered Augmentin have shown no teratogenic effects. In a single study in women with preterm, premature rupture of the foetal membrane (pPROM), it was reported that prophylactic treatment with Augmentin may be associated with an increased risk of necrotising enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy, unless considered essential by the physician.
Augmentin may be admininstered during the period of lactaiton. With the exception of the risk of sensitization, associated with the excretion of trace quanitities in breast milk, there are no known detrimental effects for the breast-fed infant.
Before inititating therapy with Augmentin, careful enquiry should be made concerning previous
hypersensitivity reactions to penicillins, cephalosporins, or other allergens.
Serious and occasionally fatal hypersensitivity (anaphyalactoid) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivty. If an allergic reaction occurs, Augmentin therapy should be dicontinued and appropriate alternative therapy instituted. Serious anaphylactoid reactions require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids and airway management, including intubation may also be required. Augmenting should be avoided if infectious mononucleosis is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of amoxycillin.
Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.
In general, Augmentin is well tolerated and possesses the characteristic low toxicity of the penicillin group of antibiotics. Periodic assessement of organ system functions; including renal, hepatic and haematopoietic function is advisable during prolonged therapy.
Prolongation of prothrombin time has been reported rarely in patients receiving Augmentin. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly.
Augmentin should be used with caution in patients with evidence of hepatic dysfunction.
In patients with renal impairment, dosage should be adjusted according to the degree of impairment.
In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy. During the administration of high doses of amoxycillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxycillin crystalluria. Augmentin suspensions containing aspartame, which is a source of phenylalanine and so should be used with caution in patients with phenylketonuria.
Pack of 2 strips of 7 tablets each.
Store at room temperature, below 25°C.