AUGMENTIN

AUGMENTIN 

AUGMENTINTM1 GM TABLETS
Amoxicillin trihydrate - Potassium clavulanate
QUALITATIVE AND QUANTITATIVE COMPOSITION
AUGMENTIN 1 g tablets" Each tablet contains 875 mg amoxicillin (as amoxicillin trii-iydrate)
and 125 mg clavulanic acid (as potassium clavulanate)-
PHARMACEUTICAL FORM
AUGMENTIN 1 g tablets: A white to off-white oval-shaped film-coated dsbosssd tablet, with
a score line on one side and plain on the other side.
CLINICAL PARTICULARS
Indications
AUGMENTIN is an antibiotic agent with a notably broad spectrum of activity against the
commonly occurring bacterial pathogens in general practice and hospital. The [3-lactamase
inhibitory action of clavulanate extends the spectrum of amoxicillin to embrace a wider range
of organisms, including many resistant to other B-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 fincluding 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
Susceptibility to AUGMENTIN will vary with geography and time (see Pharmacological
Properties, Pharrnacodynamlcs for further information). Local susceptibility data should be
consulted where available, and microbiological sampling and susceptibility testing
performed where necessary.
Infections caused by amoxicillin -susceptible organisms are amenable to
Augmentin-treatment due to its amoxicillin content. Mixed infections caused by amoxicillin
susceptible organisms in conjunction with augmentin -susceptible [Hactamase producing
organisms may therefore be treated with Augmentin.
Dosage and Administration
Usual dosages for the treatment of infection
Adults and children over 12 years‘
Severe infections One AUGMENTIN 1 g tablet twice daily
Therapy can be started parenterally and continued with an oral preparation.
‘ AUGMENTIN 1 g tablets are not recommended in children of 12 years and under
Dosage in renal impairment
Adults:
The AUGMENT IN 1g tablet should only be used in patients with a glomerular filtration rate of
>30 mVmin.
Mild impairment (Creatinine Moderate impairment (Creatinine Severe impairment (Creatinine
clearance >30 ml/min) clearance 10-30 ml/min) clearance <10 ml/min)
No change in dosage The 1 g tablet should not be Not more than one 625 mg tablet
1 g tablet twice daily administered. every 24 hours.
Dosage in hepatic impairment
Dose with caution; monitor hepatic function at regular intervals.
Administration
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.
AUGMENT IN is also available as AUGMENTlN intravenous for the short~term treatment of
bacterial infections and for prophylaxis against infection which may be associated with major
surgical procedures. AUGMENHN 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.
Contraindications
AUGMENT IN is contra-indicated in patients with a history of hyp9i5°"$i*iViiY to beta-lactams.
e.g. penicillins and cephalosporins.
AUGMENTIN is contra-indicated in patients with a previous histol'Y °fAUGME/VTIN-flSSOCiited
jaundice/hepatic dY5‘""°ii°"-
Wamings and Precautiom
Before initiating therapy with AUGMENTIN careful enquiry should be made conceming previous
hypersensitivity reactions to penicillins, cephalosporins, or other allergens.
Serious and occasionally iflilii hypersensitivity (anaphylactoid) reactions have been rebbfied in
patients on penicillin theralJy- These reactions are more likely to occur in individuals with a
history of penicillin hvpersansilivity (see Contra-indications).
AUGMENTIN should be avoided if infectious mononucleosis is suspected since the occurrence
of a morbillifomi rash has been associated with this condition fcllowin9 "19 l-I59 of 3rnOXicillin.
Prolonged use may also occasionally result in overgrowth of non-suscebiibie Organisms
Pseudomembranous colitis has been reported with the use of antibiotics and may range in
sevei'iTY i'°"l mild to life-threatening. Therefore, It is important to consider its diagnosis in
patients who develop diarrhoea during or after antibiotic use. lf prolonged or significant
dianhoea occurs or the patient experiences abdominal cramps. irefltmenl Siiuuld be
discontinued immediately and the patient investigated further.
- Abnblmai Prolongation of prothrombin time (inoroB$9d INR) n55 been reported rarely in
patients receiving AUGMENTIN and oral anticoagulfln\5- Abbrbbnaie ""°"it°"il'lQ 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 Paiienis receiving AUGMEMTN.
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 ieualiy 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 impaimlent AUGMENTIN dosage 5b°"id 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 the
possibility of amoxicillin crystalluria (see Overdose).
Interactions
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.
ln the literature there are rare cases of increased intemational normalised ratio in patients
maintained on acenocoumarol or warfarln and prescribed a course of amoxicillin. lf
co-administration is necessary, the prothrombin time or international normalised 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 clavulanlc acid. The change in ore-dose level may
not accurately represent changes in overall MPA exposure.
Pregnancy and Lactation
Reproduction studies in animals (mice and rats) with orally and parenteially 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 prophylactic
treatment with AUGMENTIN may be associated with an increased risk of necrotising
enterooolitis 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 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.
Adverse Reactions
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
Commgn Mucocutaneous candidiasis
Blood and lymphatic system disorders
Rare Reversible leucopenia (including neutropenia) and thrombocytopenia ‘
Very i-are Reversible agranulocytosis and haemolytic anaemia. Prolongation of bleeding
time and prothrombin time.
Immune system disorders
Very rare Angioneurotic oedema, anaphylaxis, semm 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.
Gastrointestinal disorders
Adults:
Very common Diarrhoea
Common Nausea, vomiting
Children: _
Common Diarrhoea, nausea, vomiting
All populations: _ ‘
Nausea is more often aSSOCli’:lted with higher om d°sages_ if gastrointestinal reactions are
evident, they may be reduced by taking AUGMENTTN at the start of a rnear
Uncommon Indigestion
Very rare Antibiotic-associated colitis fincluding pseudomembranous colitis and
haemonrhagic colitis - see Wamings and Precautions).
Black hairy I0ngu9
Hepatobiliary disorders
Uncommon A moderate rise in AST and/or ALT has been noted in patients treated with
beta-laclflm 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 cephalosporlns.
Hepfliiv events have been Febbned predominantly in males and elderly patients and may be
associated with prolonged treatment. These events have been very rarely reported in
children.
Signs and $Yl'nPi°in$ "Wally 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 l'9b°l‘i°d- 111958 have almost always occuned 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)
Overdose
Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be
evident. Gastrointestinal symptoms may be treated symptomatically with attention to the
water electrolyte balance.
Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see
Wamings and Precautions).
AUGMENT IN can be removed from the circulation by haemodialysis.
PHARMACOLOGICAL PROPERTIES
Pharmacodynamics
Resistance to many antibiotics is caused by bacterial enzymes which destroy the antibiotic
before it can act on the pathogen. The clavulanate in AUGMEN‘l7N anticipates this defence
mechanism by blocking the l3~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 amoxicillin
asAUGMENTIN it pmd n antibiotic agent of broad spectrum with wide application in
hospital and general p '. .
-Augmentin is a bactericidalto a wide range of organisms.
Phan-nacoklnetics
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
PHARMACEUTICAL PARTICULARS
List of Excipients
AUGMENTIN 1 g tablets contain the following inactive ingredients; colloidal silicon dioxide.
sodium starch glycolate, magnesium stearate, microcrystalline cellulose, titanium dioxide,
hydroxypropyl methylcellulose 5 CPS, hydroxypropyl methylcellulose 15 CPS. bniYeii‘lYi9"°
glycol 4000, 6000, silicone oil.
special Precautions for storage
AUGMENTIN tablets should be stored in un-opened, original packs in a dril Place 5’
temperature not exceeding 30°C.
Keep out of the reach of children.
Nature and Contents of Container
Carton box containing 2 strips each of 7 film coated tablets and inner leaflet-
Version number: GDS21lIP|09
Date of issue: 18 January 2013
AUGMENTIN is a trademark or the Glax0SmithKline group of COmpanleS
Q‘i66/07/88
@GlaxoSmithKline P‘.