SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT Augmentin 100 mg/12.5 mg/ml powder for oral suspension 2. QUALITATIVE AND QUANTITATIVE COMPOSITION When reconstituted, every ml of oral suspension contains amoxicillin trihydrate equivalent to 100 mg amoxicillin and potassium clavulanate equivalent to 12.5 mg of clavulanic acid. Excipients with known effect Every ml of oral suspension contains 3.2 mg aspartame (E951). The flavouring in Augmentin contains maltodextrin (glucose) (see section 4.4). This medicine contains 1.7 mg sodium benzoate (E211) per ml. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Powder for oral suspension. Off-white powder. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Augmentin is indicated for the treatment of the following infections in adults and children (see sections 4.2, 4.4 and 5.1): Acute bacterial sinusitis (adequately diagnosed) Acute otitis media Acute exacerbations of chronic bronchitis (adequately diagnosed) Community acquired pneumonia Cystitis Pyelonephritis Skin and soft tissue infections in particular cellulitis, animal bites, severe dental abscess with spreading cellulitis Bone and joint infections, in particular osteomyelitis. Consideration should be given to official guidance on the appropriate use of antibacterial agents. 4.2 Posology and method of administration Posology Doses are expressed throughout in terms of amoxicillin/clavulanic acid content except when doses are stated in terms of an individual component. The dose of Augmentin that is selected to treat an individual infection should take into account: The expected pathogens and their likely susceptibility to antibacterial agents (see section 4.4) 2 The severity and the site of the infection The age, weight and renal function of the patient as shown below. The use of alternative presentations of Augmentin (e.g. those that provide higher doses of amoxicillin and/or different ratios of amoxicillin to clavulanic acid) should be considered as necessary (see sections 4.4 and 5.1). For children < 40 kg, this formulation of Augmentin provides a maximum daily dose of 1600-3000 mg amoxicillin/200-400 mg clavulanic acid, when administered as recommended below. If it is considered that a higher daily dose of amoxicillin is required, it is recommended that another preparation of Augmentin is selected in order to avoid administration of unnecessarily high daily doses of clavulanic acid (see sections 4.4 and 5.1). The duration of therapy should be determined by the response of the patient. Some infections (e.g. osteomyelitis) require longer periods of treatment. Treatment should not be extended beyond 14 days without review (see section 4.4 regarding prolonged therapy). Adults and children 40 kg should be treated with the adult formulations of Augmentin. Children < 40 kg Children may be treated with Augmentin tablets, suspensions or paediatric sachets. Recommended dose: 40 mg/5 mg/kg/day to 80 mg/10 mg/kg/day (not exceeding 3000 mg/375 mg per day) given in three divided doses, depending on the severity of infection. There are no clinical data for the 8:1 formulation for patients under 1 month of age. Additional text for markets using millilitre graduated dosage measurements: 40 mg/5 mg/kg/ 80 mg/10 mg/kg/ 40 mg/5 mg/kg/ 80 mg/10 mg/kg/ Weight day dose (ml). day dose (ml). Weight day dose (ml). day dose (ml). (kg) Given three times Given three times (kg) Given three times Given three times daily. daily. daily. daily. 2.0 0.3 0.5 21.0 2.8 5.6 3.0 0.4 0.8 22.0 2.9 5.9 4.0 0.5 1.1 23.0 3.1 6.1 5.0 0.7 1.3 24.0 3.2 6.4 6.0 0.8 1.6 25.0 3.3 6.7 7.0 0.9 1.9 26.0 3.5 6.9 8.0 1.1 2.1 27.0 3.6 7.2 9.0 1.2 2.4 28.0 3.7 7.5 10.0 1.3 2.7 29.0 3.9 7.7 11.0 1.5 2.9 30.0 4.0 8.0 12.0 1.6 3.2 31.0 4.1 8.3 13.0 1.7 3.5 32.0 4.3 8.5 14.0 1.9 3.7 33.0 4.4 8.8 15.0 2.0 4.0 34.0 4.5 9.1 16.0 2.1 4.3 35.0 4.7 9.3 3 17.0 2.3 4.5 36.0 4.8 9.6 18.0 2.4 4.8 37.0 4.9 9.9 19.0 2.5 5.1 38.0 5.1 NR 20.0 2.7 5.3 39.0 5.2 NR NR – Not recommended. Children weighing more than 37.5 kg should not be treated at the higher dose of 80 mg/kg/day so as not to exceed the recommended maximum daily limit. Alternatively, the dose (ml) to be given to the patient three times daily can be calculated using the following formula below: * Dose (ml) given Recommended amoxicillin dose (mg/kg/day) x weight (kg) = three times daily Reconstituted amoxicillin* in suspension (mg/ml) x 3 (daily doses) * Only consideration of the amoxicillin component is required for this calculation. For example, a 6 kg child treated at 80 mg/10 mg/kg/day: Dose (ml) given 80 (mg/kg/day) x 6 (kg) = three times daily 100 (mg/ml) x 3 (daily doses) + Dose (ml) given 480 (mg) = three times daily 300 (mg/ml) Dose (ml) given = 1.6 ml three times daily + Must not exceed 3000 mg amoxicillin. Elderly No dose adjustment is considered necessary. Renal impairment No dose adjustment is required in patients with creatinine clearance (CrCl) greater than 30 ml/min. In patients with creatinine clearance less than 30 ml/min, the use of Augmentin presentations with an amoxicillin to clavulanic acid ratio of 8:1 is not recommended, as no recommendations for dose adjustments are available. Hepatic impairment Dose with caution and monitor hepatic function at regular intervals (see sections 4.3 and 4.4). Method of administration Augmentin is for oral use. 4 Augmentin should be administered with a meal to minimise potential gastrointestinal intolerance. Therapy can be started parenterally according to the SmPC of the IV formulation and continued with an oral preparation. Shake to loosen powder, add water as directed, invert and shake. Shake the bottle before each dose (see section 6.6). For instructions on reconstitution of the medicinal product before administration, see section 6.6. 4.3 Contraindications Hypersensitivity to the active substances, to any of the penicillins or to any of the excipients listed in section 6.1. History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam agent (e.g. a cephalosporin, carbapenem or monobactam). History of jaundice/hepatic impairment due to amoxicillin/clavulanic acid (see section 4.8). 4.4 Special warnings and precautions for use Before initiating therapy with amoxicillin/clavulanic acid, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam agents (see sections 4.3 and 4.8). Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions) have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in atopic individuals. If an allergic reaction occurs, amoxicillin/clavulanic acid therapy must be discontinued and appropriate alternative therapy instituted. In the case that an infection is proven to be due to an amoxicillin-susceptible organisms(s) then consideration should be given to switching from amoxicillin/clavulanic acid to amoxicillin in accordance with official guidance. This presentation of Augmentin may not be suitable for use when there is a high risk that the presumptive pathogens have reduced susceptibility or resistance to beta-lactam agents that is not mediated by beta-lactamases susceptible to inhibition by clavulanic acid. This presentation may not be suitable for treatment of penicillin-resistant S. pneumoniae. Convulsions may occur in patients with impaired renal function or in those receiving high doses (see section 4.8). Amoxicillin/clavulanic acid 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 amoxicillin. Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions. Prolonged use may occasionally result in overgrowth of non-susceptible organisms. 5 The occurrence at the treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthemous pustulosis (AGEP) (see section 4.8). This reaction requires Augmentin discontinuation and contraindicates any subsequent administration of amoxicillin. Amoxicillin/clavulanic acid should be used with caution in patients with evidence of hepatic impairment (see sections 4.2, 4.3 and 4.8). 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. In all populations, signs 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 circumstances, deaths have been reported. These have almost always occurred in patients with serious underlying disease or taking concomitant medications known to have the potential for hepatic effects (see section 4.8). Antibiotic-associated colitis has been reported with nearly all antibacterial agents including amoxicillin and may range in severity from mild to life threatening (see section 4.8).