AUGMENTIN Amoxycillin + Clavulanate-potassium     DESCRIPTION Augmentin 375 mg tablets: White oval film-coated tablets engraved. Augmentin on one side. Each tablet contains 250 mg amoxycillin and 125 mg clavulanic acid. Augmentin 625 mg tablets : White oval film-coated tablets engraved. Augmentin. Each tablet contains 500 mg amoxycillin and 125 mg clavulanic acid. Augmentin 156 mg syrup : Bottles of powder for the preparation of fruit flavoured syrup. When reconstituted each 5 ml contains 125 mg amoxycillin and 31.25 mg clavulanic acid. Augmentin 312 mg syrup : Bottles of powder for the preparation of fruit flavoured syrup. When reconstituted each 5 ml contains 250 mg amoxycillin and 62.5 mg clavulanic acid. Not all presentations are available in every country. The amoxycillin is present as amoxycillin trihydrate and the clavulanic acid is present as potassium clavulanate. Augmentin 156 mg and 312 mg syrups contain aspartame. Augmentin presentations do not contain sucrose, tartrazine or any other azo dyes and Augmentin Syrups do not contain preservatives.     USES Augmentin is an antibiotic agent with a notably broad spectrum of activity against the commonly occurring bacterial pathogens in general practice and hospital. The β-lactamase inhibitory action of clavulanate extends the spectrum of amoxycillin to embrace a wider range of organisms, including many resistant to other ß-lactam antibiotics. Augmentin oral preparations are indicated for short-term treatment of bacterial infections at the following sites: Upper respiratory tract infections (including ENT) e.g. tonsillitis, sinusitis, otitis media. Lower respiratory tract infections e.g. acute and chronic bronchitis, lobar and bronchopneumonia. Genito-urinary tract infections e.g. cystitis, urethritis, pyelonephritis. Skin and soft tissue infections, e.g. boils, abscesses, cellulitis, wound infections. Bone and joint infections e.g. osteomyelitis. Dental infections e.g. dentoalveolar abscess. Other infections e.g. septic abortion, puerperal sepsis, intra-abdominal sepsis. Augmentin is bactericidal to a wide range of organisms including: Gram-positive : Aerobes: Enterococcus faecalis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, *Staphylococcus aureus, *Coagulase negative staphylococci (including staphylococcus epidermidis), Corynebacterium species, Bacillus anthracis, Listeria monocytogenes. Anaerobes: Clostridium species, Peptococcus species, Peptostreptococcus. Gram-negative : Aerobes: *Haemophilus influenzae, *Escherichia coli, *Proteus mirabilis, *Proteus vulgaris, *Klebsiella species,*Moraxella catarrhalis, *Salmonella species, *Shigella species, Bordetella pertussis, Brucella species, *Neisseria gonorrhoeae, Neisseria meningitidis, Vibrio cholerae, Pastuerella multocida. Anaerobes : *Bacteroides spp. including B. fragilis * including ß-lactamase producing strains resistant to ampicillin and amoxycillin.     DOSAGE & ADMINISTRATION Usual dosages for the treatment of infection Adults and children over 12 years Mild - Moderate infections One Augmentin 375 mg tablet three times a day Severe infections One Augmentin 625 mg tablet three times a day. Where the 625 mg tablet is not available, a dose of two Augmentin 375 mg tablets three times a day may be taken. Therapy can be started parenterally and continued with an oral preparation. The Augmentin 625 mg tablet is not available in all countries. Children: The usual recommended daily dosage is 25 mg/kg/dayo in divided doses every eight hours. The table below presents guidance for children. Under 1 year 25 mg/kg/day, for example a 7.5 kg child would require 2 ml Augmentin 156 mg syrup three times a day. 1 - 6 year (10-18 kg) 5 ml Augmentin 156 mg syrup three times a day. Over 6 years (18-40 kg) 5 ml Augmentin 312 mg syrup three times a day. In more serious infections the dosage may be increased up to 50 mg/kg/day in divided doses every eight hours. * Each 25 mg Augmentin provides 20 mg amoxycillin and 5 mg clavulanic acid. Augmentin 375 mg and 625 mg tablets are not recommended in children of 12 years and under. Dosage in dental infections (e.g. dentoalveolar abscess) Adults and children over 12 years : One Augmentin 375 mg tablet three times a day for five days. Dosage in renal impairment Adults: Dosage in hepatic impairment Dose with caution; monitor hepatic function at regular intervals. Each Augmentin 375 mg tablet contains 0.63 mmol (25 mg) of potassium. Oral Administration To minimise potential gastrointestinal intolerance, administer at the start of a meal. The absorption of Augmentin is optimised when taken at the start of a meal. Treatment should not be extended beyond 14 days without review. Contra-indications, warnings, etc. Contra-indications: Penicillin hypersensitivity. Attention should be paid to possible cross-sensitivity with other ß-lactam antibiotics, e.g. cephalosporins. A previous history of Augmentin - or penicillin-associated jaundice/hepatic dysfunction. Precautions: Changes in liver function tests have been observed in some patients receiving Augmentin. The clinical significance of these changes is uncertain but Augmentin should be used with caution in patients with evidence of hepatic dysfunction. Cholestatic jaundice, which may be severe, but is usually reversible, has been reported rarely. Signs and symptoms may not become apparent for up to six weeks after treatment has ceased. In patients with moderate or severe renal impairment Augmentin dosage should be adjusted as recommended in the Dosage and administration section. Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity (see Contra-indications). Erythematous rashes have been associated with glandular fever in patients receiving amoxycillin. Prolonged use may also occasionally result in overgrowth of non-susceptible organisms. Augmentin Suspensions contain 12.5mg aspartame per 5ml dose and therefore care should be taken in phenylketonuria. Interactions: Prolongation of bleeding time and prothrombin time have been reported in some patients receiving Augmentin. Augmentin should be used with care in patients on anti-coagulation therapy. In common with other broad-spectrum antibiotics, Augmentin may reduce the efficacy of oral contraceptives and patients should be warned accordingly. Use in pregnancy and lactation: Reproduction studies in animals (mice and rats) with orally and parenterally administered Augmentin have shown no teratogenic effects. There is limited experience of the use of Augmentin in human pregnancy. As with all medicines, use should be avoided in pregnancy, especially during the first trimester, unless considered essential by the physician. Augmentin may be administered during the period of lactation. With the exception of the risk of sensitisation, associated with the excretion of trace quantities in breast milk, there are no detrimental effects for the infant.     SIDE EFFECTS Side effects, as with amoxycillin, are uncommon and mainly of a mild and transitory nature. Diarrhoea, indigestion, nausea, vomiting, pseudomembranous colitis, and candidiasis have been reported. Nausea, although uncommon, is more often associated with higher oral dosages. If gastrointestinal side effects occur with oral therapy they may be reduced by taking Augmentin at the start of meals. A moderate rise in AST and/or ALT has been noted in patients with semi-synthetic penicillins but the significance of these findings is unknown. Hepatitis and cholestatic jaundice have been reported rarely with Augmentin. They may however be severe and continue for several months. They are reported as occuring predominantly in adult or elderly patients and slightly more frequently in males. Signs and symptoms may occur during treatment but are more frequently reported after cessation of therapy with a delay of up to six weeks. The hepatic events are usually reversible. However, in extremely rare circumstances, deaths have been reported. These have aalways been cases associated with serious underlying disease or concomitant medications. Urticarial and erythematous rashes sometimes occur. Rarely erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis and exfoliative dermatitis have been reported. Treatment should be discontinued if one of these types of rash appears. In common with other ß-lactam antibiotics angioedema and anaphylaxis have been reported. Interstitial nephritis can occur rarely. As with other antibiotics the incidence of gastrointestinal side effects may be raised in children under 2 years. In clinical trials, however, only 4% of children under 2 years were withdrawn from treatment. As with other ß-lactams transient leucopenia, thrombocytopenia and haemolytic anaemia have been reported rarely.     OVERDOSAGE Problems of overdosage with Augmentin are unlikely to occur; if encountered 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. Augmentin may be removed from the circulation by haemodialysis. Pharmaceutical precautions Augmentin oral presentations should be stored in a dry place at 25°C or below. Bottles of Augmentin Tablets should be kept tightly closed and the tablets dispensed in moisture-proof containers. Once reconstituted, Augmentin syrup must be stored in a refrigerator (but not frozen) and used within 7 days. Further information Resistance to many antibiotics is caused by bacterial enzymes which destory the antibiotic before it can act on the pathogen. The clavulanate in Augmentin anticipates this defence mechanism by blocking the ß-lactamase enzymes, thus rendering the organisms sensitive to amoxycillin's rapid bactericidal effect at concentrations readily attainable in the body. Clavulanate by itself has little antibacterial activity; however, in association with amoxycillin as Augmentin it produces an antibiotic agent of broad spectrum with wide application in hospital and general practice. The pharmacokinetics of the two components of Augmentin are closely matched. Peak serum levels of both occur about 1 hour after oral administration. Absorption of Augmentin is optimised at the start of a meal. Both clavulanate and amoxycillin have low levels of serum binding; about 70% remains free in the serum. Doubling the dosage of Augmentin approximatedly doubles the serum levels achieved. Augmentin is also available as Augmentin Intravenous for the short-term treatment of bacterial infections and for prophylaxis against infection which may be associated with major surgical procedures. Augmentin Intravenous is described in a separate Pack Insert.