AUGMENTINTM BD TABLETS
Amoxicillin trihydrate – Potassium clavulanate
QUALITATIVE AND QUANTITATIVE COMPOSITION
AUGMENTIN 625 mg tablets: Each tablet contains 500 mg amoxicillin (as amoxicillin trihydrate) and 125 mg clavulanic acid (as potassium clavulanate).
AUGMENTIN 1 g tablets: Each tablet contains 875 mg amoxicillin (as amoxicillin trihydrate) and 125 mg clavulanic acid (as potassium clavulanate).
AUGMENTIN 625 mg tablets: A white to off-white oval shaped film- coated debossed tablet, with a score line on one side and plain on the other side.
AUGMENTIN 1 g tablets: A white to off-white oval-shaped film-coated debossed tablet, with a score line on one side and plain on the other side.
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 amoxicillin to embrace a wider range of organisms, including many resistant to other β-lactam antibiotics.
AUGMENTIN should be used in accordance with local official antibiotic-prescribing guidelines and local susceptibility data.
AUGMENTIN oral presentations for twice daily dosing, 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 exacerbation of 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.
Susceptibility to AUGMENTIN will vary with geography and time (see Pharmacological Properties, Pharmacodynamics for further information). Local susceptibility data should be consulted where available, and microbiological sampling and susceptibility testing performed where necessary.
Dosage and Administration
Usual dosages for the treatment of infection
Adults and children over 12 years+
Mild – Moderate infections One AUGMENTIN 625 mg tablet twice daily
Severe infections One AUGMENTIN 1 g tablet twice daily.
Therapy can be started parenterally and continued with an oral preparation.
Dosage in dental infections (e.g. dentoalveolar abscess)
Adults and children over 12 years: One AUGMENTIN 625 mg tablet 2 times a day for five days + AUGMENTIN 625 mg and 1 g tablets are not recommended in children of 12 years and under
Dosage in renal impairment
The AUGMENTIN 1g tablet should only be used in patients with a glomerular filtration rate of >30 mI/mm.
|Mild impairment (Creatinine clearance 10-30 ml/mm)||Moderate impairment (Creatinine clearance >30 ml/mm)||Severe impairment (Creatinine clearance <10 ml/mm)|
|No change in dosage
(i.e. either one 625 mg tablet twice daily or one 1 g tablet twice daily)
|One 625 mg tablet twice daily. The 1 g tablet should not be administered.||Not more than one 625 mg tablet every 24 hours.|
Dosage in hepatic impairment
Dose with caution; monitor hepatic function at regular intervals.
Tablets should be swallowed whole without chewing. If required, tablets may be broken in half and swallowed without chewing.
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.
AUGMENTIN is also available as AUGMENTIN intravenous for the short-term treatment of bacterial infections and for prophylaxis against infections which may be associated with major surgical procedures.
AUGMENTIN intravenous is described in a separate Pack Insert.
AUGMENTIN is also available as a suspension for three times daily dosing for administration to children under the age of 12 years for the treatment of bacterial infections. AUGMENTIN suspension three times daily is described in a separate Pack Insert.
AUGMENTIN is contra-indicated in patients with a history hypersensitivity to beta-lactams, e.g. penicillins and cephalosporins.
AUGMENTIN is contra-indicated in patients with a previous history of AUGMENTIN-associated jaundice/hepatic dysfunction.
Warnings and Precautions
Before initiating therapy with AUGMENTIN careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephaIosporins, or other allergens.
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).
AUGMENTIN 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.
Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.
Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild to life-threatening. Therefore, it is import to consider its diagnosis in patients who develop diarrhoea during or after antibiotic use. If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further. Abnormal prolongation of prothrombin time (increabed INR) has been reported rarely in patients receiving AUGMENTIN and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.
Changes in liver function tests have been observed in some patients receiving AUGMENTIN. The clinical significance of these changes is uncertain. 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 renal impairment AUGMENTIN dosage should be adjusted as recommended in the Dosage and Administration section.
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 possibility of amoxicillin crystalluria (see Overdose).
Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use with AUGMENTIN may result in increased and prolonged blood levels of amoxicillin but not of clavulanate.
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.
In common with other antibiotics, AUGMENTIN may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.
In the literature there are rare cases of increased international normalised ratio in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxicillin. If co-administration is necessary, the prothrombin time or international normaIised ratio should be carefully monitored with the addition or withdrawal of AUGMENTIN.
In patients receiving mycophenolate mofetil, reduction in pre-dose concentration of the active metabolite mycophenolic acid 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.
Pregnancy and Lactation
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 pre-term, premature rupture of the foetal membrane (pPROM), it was reported that prophylatic 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 Iactation. 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.
Effects on Ability to Drive and Use Machines
Adverse effects on the ability to drive or operate machinery have not been observed.
Data from large clinical trials were used to determine the frequency of very common to rare undesirable effects. The frequencies assigned to all other undesirable effects (i.e., those occurring at <1/10,000) were mainly determined using post-marketing data and refer to a reporting rate rather than a true frequency. The following convention has been used for the classification of frequency:-
very common >1/10
common >1/100 and <1/10
uncommon >1/1000 and <1/100
rare >1/10,000 and <1/1000
very rare <1/10,000.
Infections and infestations
Common: Mucocutaneous candidiasis, Blood and lymphatic system disorders
Rare: Reversible leucopenia (including neutropenia) and thrombocytopenia
Very rare: Reversible agranulocytosis and haemolytic anaemia. Prolongation of bleeding time and prothrombin time.
Immune system disorders
Very rare: Angioneurotic oedema, anaphylaxis, serum sickness-like syndrome, hypersensitivity vasculitis
Nervous system disorders
Uncommon: Dizziness, headache
Very rare: Reversible hyperactivity and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses.
Very common: Diarrhoea
Common: Nausea, vomiting
Common: Diarrhoea, nausea, vomiting
Nausea is more often associated with higher oral dosages. If gastrointestinal reactions are evident, they may be reduced by taking AUGMENTIN at the start of a meal.
Very rare: Antibiotic-associated colitis (incIuding pseudomembranous colitis and haemorrhagic colitis) – see Warnings and Precautions. Black hairy tongue
Uncommon: A moderate rise in AST and/or ALT has been noted in patients treated with beta-lactam class antibiotics, but the significance of these findings is unknown.
Very rare: Hepatitis and cholestatic jaundice. These events have been noted with other penicillins and cephalosporins.
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.
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.
Skin and subcutaneous tissue disorders
Uncommon: Skin rash, pruritus, urticaria
Rare: Erythema multiforme
Very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative-dermatitis, acute generalised exanthemous pustulosis (AGEP)
If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued.
Renal and urinary disorders
Very rare: Interstitial nephritis, crystalluria (see Overdose)
Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Gastrointestinal symptoms may be treated symptomically with attention to the water electrolyte balance. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see Warnings and Precautions).
AUGMENTIN can be removed from the circulation by haemodialysis.
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 β-lactamase enzymes, thus rendering the organisms susceptible to amoxicillin’s rapid bactericidal effect at concentrations readily attainable in the body. Clavulanate by itself has little antibacterial activity; however, in association with amoxicilIin as AUGMENTIN it produces an antibiotic agent of broad spectrum with wide application in hospital and general practice.
In the list below, organisms are categorised acccording to their in vitro susceptibility to AUGMENTIN.
In vitro susceptibility of micro-organisms to AUGMENTIN
Where clinical efficacy of AUGMENTIN has been demonstrated in clinical trials this is indicated with an asterisk (*).
Organisms that do not produce beta-lactama are identified (with Ɨ). If an isolate is susceptible to amoxicillin, it can be considered susceptible AUGMENTIN.
Commonly susceptible species
Streptococcus pyogenes* Ɨ
Streptococcus agalactiae* Ɨ
Streptococcus spp. (other β-hemolytic)* Ɨ
Staphylococcus aureus (methicillin susceptible)* Ɨ
Staphylococcus saprophyticus (methicillin susceptible)
Coagulase negative staphylococcus (methicillin susceptible)
Helicobacter pylon 1
Gram positive anaerobes:
Species for which acquired resistance may be a problem
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.
Doubling the dosage of AUGMENTIN approximately doubles the serum levels achieved.
Both clavulanate and amoxicillin have low levels of serum binding; about 70% remains free in the serum.
Pre-clinical Safety Data
No further information of relevance.
List of Excipients
AUGMENTIN 625 mg and 1 g tablets contain the following inactive ingredients: colloidal silicon dioxide, sodium starch glycolate, magnesium stearate (E572), microcrystalline cellulose, titanium dioxide (E171), hydroxypropyl methylcellulose, polyethylene glycol, dimethicone (silicon oil).
The expiry date is indicated on the packaging.
Special Precautions for Storage
AUGMENTIN tablets should be stored in un-opened, original packs in a dry place at below 25°C.
Not all presentations are available in every country.
Version number: GDS21/IPI09
Date of Issue: 18 January 2013
AUGMENTIN trademark of the GlaxoSmithKline group of companies