AUGMENTIN 375 MG TABLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Augmentin 375 mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains amoxicillin trihydrate equivalent to 250 mg amoxicillin and potassium clavulanate equivalent to 125 mg of clavulanic acid.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Film-coated tablet.

White to off-white, oval shaped tablets debossed with “Augmentin” on one side.

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)

Cystitis

Pyelonephritis

Cellulitis

Animal bites

Severe dental abscess with spreading cellulitis.

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)

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 adults and children > 40 kg, this formulation of Augmentin provides a total daily dose of 750 mg amoxicillin/375 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).

Treatment should not be extended beyond 14 days without review.

Adults and children > 40 kg

One tablet taken three times a day.

Children < 40 kg

Augmentin 250 mg/125 mg film-coated tablets are not recommended in children < 40 kg.

Elderly

No dose adjustment is considered necessary.

Renal impairment

Dose adjustments are based on the maximum recommended level of amoxicillin.

No adjustment in dose is required in patients with creatinine clearance (CrCl) greater than 30 ml/min.

Adults and children > 40 kg

Children < 40 kg

In children < 40 kg with creatinine clearance less than 30 ml/min, the use of Augmentin presentations with an amoxicillin to clavulanic acid ratio of 2:1 is not recommended, as no dose adjustments are available. In such patients, Augmentin formulations with an amoxicillin to clavulanic acid ratio of 4:1 are recommended.

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.

Augmentin should be administered with a meal to minimise potential gastrointestinal intolerance.

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 is not 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 (e.g. penicillin-insusceptible 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.

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 contra-indicates 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). Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of any antibiotics. Should antibiotic-associated colitis occur, amoxicillin/cla­vulanic acid should immediately be discontinued, a physician be consulted and an appropriate therapy initiated. Anti-peristaltic medicinal products are contraindicated in this situation.

Periodic assessment 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 amoxicillin/cla­vulanic acid. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation (see sections 4.5 and 4.8).

In patients with renal impairment, the dose 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. In patients with bladder catheters, a regular check of patency should be maintained (see section 4.9).

During treatment with amoxicillin, enzymatic glucose oxidase methods should be used whenever testing for the presence of glucose in urine because false positive results may occur with non-enzymatic methods.

The presence of clavulanic acid in Augmentin may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test.

There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus EIA test in patients receiving amoxicillin/cla­vulanic acid who were subsequently found to be free of Aspergillus infection. Crossreactions with non-Aspergillus polysaccharides and polyfuranoses with BioRad Laboratories Platelia Aspergillus EIA test have been reported. Therefore, positive test results in patients receiving amoxicillin/cla­vulanic acid should be interpreted cautiously and confirmed by other diagnostic methods.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

Oral anticoagulants

Oral anticoagulants and penicillin antibiotics have been widely used in practice without reports of interaction. However, in the literature there are cases of increased international normalised ratio in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxicillin. If coadministration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of amoxicillin. Moreover, adjustments in the dose of oral anticoagulants may be necessary (see sections 4.4 and 4.8).

Methotrexate

Penicillins may reduce the excretion of methotrexate causing a potential increase in toxicity.

Probenecid

Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use of probenecid may result in increased and prolonged blood levels of amoxicillin but not of clavulanic acid.

Mycophenolate mofetil

In patients receiving mycophenolate mofetil, reduction in pre-dose concentration of the active metabolite mycophenolic acid (MPA) of approximately 50% has been reported following commencement of oral amoxicillin plus clavulanic acid. The change in pre-dose level may not accurately represent changes in overall MPA exposure. Therefore, a change in the dose of mycophenolate mofetil should not normally be necessary in the absence of clinical evidence of graft dysfunction. However, close clinical monitoring should be performed during the combination and shortly after antibiotic treatment.

4.6 Fertility, pregnancy and lactation

Pregnancy

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). Limited data on the use of amoxicillin/cla­vulanic acid during pregnancy in humans do not indicate an increased risk of congenital malformations. In a single study in women with preterm, premature rupture of the foetal membrane it was reported that prophylactic treatment with amoxicillin/cla­vulanic acid may be associated with an increased risk of necrotising enterocolitis in neonates. Use should be avoided during pregnancy, unless considered essential by the physician.

Breastfeeding

Both substances are excreted into breast milk (nothing is known of the effects of clavulanic acid on the breast-fed infant). Consequently, diarrhoea and fungus infection of the mucous membranes are possible in the breast-fed infant, so that breast-feeding might have to be discontinued. The possibility of sensitisation should be taken into account. Amoxicillin/cla­vulanic acid should only be used during breastfeeding after benefit/risk assessment by the physician in charge.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. However, undesirable effects may occur (e.g. allergic reactions, dizziness, convulsions), which may influence the ability to drive and use machines (see section 4.8).

4.8 Undesirable effects

The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and vomiting.

The ADRs derived from clinical studies and post-marketing surveillance with Augmentin, sorted by MedDRA System Organ Class are listed below.

The following terminologies have been used in order to classify the occurrence of undesirable effects.

Very common (>1/10)

Common (>1/100 to <1/10)

Uncommon (>1/1,000 to <1/100)

Rare (>1/10,000 to <1/1,000)

Very rare (<1/10,000)

Not known (cannot be estimated from the available data)

unknown.

6 These events have been noted with other penicillins and cephalosporins (see section 4.4).

7 If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued (see section 4.4).

8 See section 4.9

9 See section 4.4

10 See sections 4.3 and 4.4

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or by searching for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

5.1   Pharmacodynamic properties

5.2 Pharmacokinetic properties

6   PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core:

Magnesium stearate

Sodium starch glycolate, Type A

Colloidal silica anhydrous

Microcrystalline cellulose

Tablet film coat:

Titanium dioxide (E171)

Hypromellose

Macrogol (4000, 6000)

Dimeticone

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years.

Tablets in desiccated pouch packs should be used within 30 days of opening.

6.4 Special precautions for storage

Store in the original package to protect from moisture.

Do not store above 25°C.

6.5 Nature and contents of container

Aluminium PVC/PVdC blister enclosed within an aluminium laminate pouch containing a desiccant sachet, referred to as a desiccated pouch pack (DPP) containing 21 tablets.

6.6 Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Beecham Group plc

980 Great West Road, Brentford, Middlesex TW8 9GS Trading as GlaxoSmithKline UK,

8 MARKETING AUTHORISATION NUMBER(S)

PL 00038/0270

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

Date of first authorisation: 03 April 1981

Date of latest renewal: 06 January 2012

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