Augmentin® 125/31 SF Suspension

Augmentin 125/31 SF Suspension: When reconstituted each 5 ml contains co-amoxiclav 125/31.

The amoxicillin is present as amoxicillin trihydrate and the clavulanic acid is present as potassium clavulanate.

Augmentin 125/31 SF Suspension: Dry powder for reconstitution in water, at time of dispensing, to form an oral sugar-free suspension.

Augmentin is an antibiotic agent with a notably broad spectrum of activity against the commonly occurring bacterial pathogens in general practice and hospital. The ß-lactamase inhibitory action of clavulanate extends the spectrum of amoxicillin 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 when amoxicillin resistant beta-lactamase producing strains are suspected as the cause. In other situations, amoxicillin alone should be considered.

- Upper Respiratory Tract Infections (including ENT) in particular sinusitis, otitis media, recurrent tonsillitis. These infections are often caused by Streptococcus pneumoniae, Haemophilus influenzae*, Moraxella catarrhalis* and Streptococcus pyogenes.

- Lower Respiratory Tract Infections in particular acute exacerbations of chronic bronchitis (especially if considered severe), bronchopneumonia. These infections are often caused by Streptococcus pneumoniae, Haemophilus influenzae* and Moraxella catarrhalis*.

- Genito-urinary Tract and Abdominal Infections in particular cystitis (especially when recurrent or complicated - excluding prostatitis), septic abortion, pelvic or puerperal sepsis and intra-abdominal sepsis. These infections are often caused by Enterobacteriaceae* (mainly Escherichia coli*), Staphylococcus saprophyticus, Enterococcus species.*

- Skin and Soft Tissue Infections in particular cellulitis, animal bites and severe dental abscess with spreading cellulitis. These infections are often caused by Staphylococcus aureus*, Streptococcus pyogenes and Bacteroides species*.

- A comprehensive list of sensitive organisms is provided in Section 5.

* Some members of these species of bacteria produce beta-lactamase, rendering them insensitive to amoxicillin alone.

Mixed infections caused by amoxicillin-susceptible organisms in conjunction with Augmentin-susceptible beta-lactamase-producing organisms may be treated withAugmentin. These infections should not require the addition of another antibiotic resistant to beta-lactamases.

Usual dosages for the treatment of infection

Augmentin Suspension

* Each 25 mg Augmentin provides co-amoxiclav 20/5.

Dosage in renal impairment

Mild impairment (creatinine clearance>30 ml/min): no change in dosage.

Moderate to severe impairment (creatinine clearance <30 ml/min): A reduction in dosage should be made in proportion to the recommendation for adults.

Dosage in hepatic impairment

Dose with caution; monitor hepatic function at regular intervals.

There are, as yet, insufficient data on which to base a dosage recommendation.

Administration

Oral: Suspensions. 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.

Duration of therapy should be appropriate to the indication and should not exceed 14 days without review.

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.

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 several weeks after treatment has ceased.

In patients with renal impairment, dosage should be adjusted according to the degree of impairment (see Section 4.2).

In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy. During the administration of high doses of amoxicillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria (See Section 4.9 Overdose).

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 4.3).

Erythematous rashes have been associated with glandular fever in patients receiving amoxicillin.

Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.

Augmentin Suspensions contain 12.5 mg aspartame per 5 ml dose and therefore care should be taken in phenylketonuria.

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.

Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions. There are no data on the concomitant use of Augmentin and allopurinol.

Reproduction studies in animals (mice and rats) 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, 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 known detrimental effects for the breast-fed infant.

None known.

Side effects are uncommon and mainly of a mild and transitory nature.

Gastrointestinal reactions:

Diarrhoea, indigestion, nausea, vomiting, and mucocutaneous candidiasis have been reported. Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis) has been reported rarely. 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.

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.

Superficial tooth discolouration has been reported rarely, mostly with the suspension. It can usually be removed by brushing.

Renal and urinary tract disorders:

Crystalluria has been reported very rarely (See Section 4.9 Overdose).

Genito-urinary effects:

Vaginal itching, soreness and discharge may occur.

Hepatic effects:

Moderate and asymptomatic rises in AST and/or ALT and alkaline phosphatases have been reported occasionally. Hepatitis and cholestatic jaundice have been reported rarely. These hepatic reactions have been reported more commonly with Augmentin than with other penicillins.

After Augmentin hepatic reactions have been reported more frequently in males and elderly patients, particularly those over 65 years. The risk increases with duration of treatment longer than 14 days. These reactions have been very rarely reported in children.

Signs and symptoms usually occur during or shortly after treatment but in some cases may not occur until several weeks after treatment has ended. Hepatic reactions are usually reversible but they may be severe and,very rarely, deaths have been reported.

Hypersensitivity reactions:

Urticarial and erythematous skin rashes sometimes occur. Rarely erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalised exanthematous pustulosis (AGEP), serum sickness-like syndrome and hypersensitivity vasculitis have been reported. Treatment should be discontinued if one of these disorders occurs. In common with other ß-lactam antibiotics angioedema and anaphylaxis have been reported. Interstitial nephritis can occur rarely.

Haematological effects:

As with other ß-lactams transient leucopenia (including neutropenia and agranulocytosis), thrombocytopenia and haemolytic anaemia have been reported rarely. Prolongation of bleeding time and prothrombin time has also been reported rarely (see 4.5).

CNS effects:

CNS effects have been seen very rarely. These include reversible hyperactivity, dizziness, headache and convulsions. Convulsions may occur with impaired renal function or in those receiving high doses.

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.

Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see Section 4.4 Special Warnings and Special Precautions for Use)

Resistance to many antibiotics is caused by bacterial enzymes which destroy 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 amoxicillin's rapid bactericidal effect at concentrations readily attainable in the body.

Clavulanate by itself has little antibacterial activity; however, in association with amoxicillin as Augmentin, it produces an antibiotic agent of broad spectrum with wide application in hospital and general practice.

Augmentin is bactericidal to a wide range of organisms including:

Gram-positive

Aerobes: Enterococcus faecalis*, Enterococcus faecium*, 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*, Moraxella catarrhalis* (Branhamella catarrhalis), Escherichia coli*, Proteus mirabilis*, Proteus vulgaris*, Klebsiella species*, Salmonella species*, Shigella species*, Bordetella pertussis, Brucella species, Neisseria gonorrhoeae*, Neisseria meningitidis*, Vibrio cholerae, Pasteurella multocida.

Anaerobes: Bacteroides species* including B. fragilis.

* Some members of these species of bacteria produce beta-lactamase, rendering them insensitive to amoxicillin alone.

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 amoxicillin have low levels of serum binding; about 70% remains free in the serum.

Doubling the dosage of Augmentin approximately doubles the serum levels achieved.

Not relevant

Augmentin 125/31 SF Suspension

The powder contains xanthan gum, hydroxypropyl methylcellulose, aspartame, silicon dioxide, colloidal silica, succinic acid, raspberry, orange and golden syrup dry flavours.

None

Augmentin 125/31 SF Suspension Dry powder: 24 months

Reconstituted suspensions: 7 days

Augmentin 125/31 SF Suspension: the dry powder should be stored in a dry place. Reconstituted suspensions should be kept in a refrigerator (but not frozen) for up to 7 days.

Augmentin 125/31 SF Suspension: Clear glass bottles containing powder for reconstitution to 100 ml.

Augmentin 125/31 SF Suspension: At time of dispensing, the dry powder should be reconstituted to form an oral suspension as detailed below:

Beecham Group plc

980 Great West Road

Brentford, Middlesex TW8 9GS

Trading as

GlaxoSmithKline UK

Stockley Park West

Uxbridge

Middlesex UB11 1BT

PL 00038/0298

8 December 2003

15 August 2007

POM