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AUGMENTIN 125/31 SF SUSPENSION
Active substance(s): AMOXICILLIN / CLAVULANIC ACID
NAME OF THE MEDICINAL PRODUCT
Augmentin 125/31 SF Suspension
QUALITATIVE AND QUANTITATIVE COMPOSITION
When reconstituted, every ml of oral suspension contains amoxicillin
trihydrate equivalent to 25 mg amoxicillin and potassium clavulanate
equivalent to 6.25 mg of clavulanic acid.
Excipients with known effect:
Contains 2.5 mg of aspartame (E951) per ml.
Contains maltodextrin (glucose).
For the full list of excipients, see section 6.1.
Powder for oral suspension.
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
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
Posology and method of administration
Doses are expressed throughout in terms of amoxicillin/clavulanic acid content except when doses
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
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
and/or different ratios of amoxicillin to clavulanic acid) should be considered as necessary (see
For adults and children ≥ 40 kg, this formulation of Augmentin provides a total daily dose of
1500 mg amoxicillin/375 mg clavulanic acid, when administered as recommended below. For
children < 40 kg, this formulation of Augmentin provides a maximum daily dose of 2400 mg
amoxicillin/600 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
without review (see section 4.4 regarding prolonged therapy).
Adults and children ≥ 40 kg
One 500 mg/125 mg dose taken three times a day.
Children < 40 kg
20 mg/5 mg/kg/day to 60 mg/15 mg/kg/day given in three divided doses.
Children may be treated with Augmentin tablets, suspensions or paediatric sachets. Children aged
and below should preferably be treated with Augmentin suspension or paediatric sachets.
No clinical data are available on doses of Augmentin 4:1 formulations higher than
40 mg/10 mg/kg per day
in children under 2 years.
No dose adjustment is considered necessary.
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
Adults and children ≥ 40 kg
CrCl: 10500 mg/125 mg twice daily
CrCl < 10 ml
500 mg/125 mg once daily
Children < 40 kg
CrCl: 1030 ml/min
CrCl < 10 ml
500 mg/125 mg every 24 hours, plus 500 mg/125 mg during
dialysis, to be repeated at the end of dialysis (as serum
concentrations of both amoxicillin and clavulanic acid are
15 mg/3.75 mg/kg twice daily (maximum 500 mg/125 mg twice
15 mg/3.75 mg/kg as a single daily dose (maximum
500 mg/125 mg).
15 mg/3.75 mg/kg per day once daily.
Prior to haemodialysis 15 mg/3.75 mg/kg. In order to restore
circulating drug levels, 15 mg/3.75 mg per kg should be
administered after haemodialysis.
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.
Therapy can be started parenterally according 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
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
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 (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 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
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. This presentation should not be used to treat
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
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/clavulanic acid should be used with caution in patients with
evidence of hepatic impairment (see section 4.2).
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 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 section 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
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.
Augmentin 125 mg/31.25 mg/5 ml powder for oral suspension contains 2.5
mg of aspartame (E951) per ml, a source of phenylalanine. This medicine
should be used with caution in patients with phenylketonuria.
This medicinal product contains maltodextrin (glucose). Patients with rare
glucose-galactose malabsorption should not take this medicine.
Interaction with other medicinal products and other forms of interaction
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 section 4.4 and 4.8).
Penicillins may reduce the excretion of methotrexate causing a potential
increase in toxicity.
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
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
Fertility, pregnancy and lactation
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.
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 breast-feeding after benefit/risk assessment by the
physician in charge.
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).
The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and
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
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)
Infections and infestations
Overgrowth of non-susceptible
Blood and lymphatic system disorders
Reversible leucopenia (including
Prolongation of bleeding time and
Immune system disorders10
Serum sickness-like syndrome
Nervous system disorders
Black hairy tongue
Rises in AST and/or ALT5
Skin and subcutaneous tissue disorders7
Toxic epidermal necrolysis
Acute generalised exanthemous
Renal and urinary disorders
See section 4.4
See section 4.4
Nausea is more often associated with higher oral doses. If gastrointestinal
reactions are evident, they may be reduced by taking amoxicillin/clavulanic acid
with a meal.
Including pseudomembranous colitis and haemorrhagic colitis (see section 4.4)
A moderate rise in AST and/or ALT has been noted in patients treated with betalactam class antibiotics, but the significance of these findings is unknown.
These events have been noted with other penicillins and cephalosporins (see
If any hypersensitivity dermatitis reaction occurs, treatment should be
discontinued (see section 4.4).
See section 4.9
See section 4.4
See sections 4.3 and 4.4
Superficial tooth discolouration has been reported very rarely in children. Good
oral hygiene may help to prevent tooth discolouration as it can usually be removed
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:
Symptoms and signs of overdose
Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may
be evident. Amoxicillin crystalluria, in some cases leading to renal failure, has been
observed (see section 4.4).
Convulsions may occur in patients with impaired renal function or in those receiving
Amoxicillin has been reported to precipitate in bladder catheters, predominantly after
intravenous administration of large doses. A regular check of patency should be
maintained (see section 4.4).
Treatment of intoxication
Gastrointestinal symptoms may be treated symptomatically, with attention to the
Amoxicillin/clavulanic acid can be removed from the circulation by haemodialysis.
Pharmacotherapeutic group: Combinations of penicillins, incl. beta-lactamase
inhibitors; ATC code: J01CR02.
Mechanism of action
Amoxicillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits
one or more enzymes (often referred to as penicillin-binding proteins, PBPs)
in the biosynthetic pathway of bacterial peptidoglycan, which is an integral
structural component of the bacterial cell wall. Inhibition of peptidoglycan
synthesis leads to weakening of the cell wall, which is usually followed by
cell lysis and death.
Amoxicillin is susceptible to degradation by beta-lactamases produced by
resistant bacteria and therefore the spectrum of activity of amoxicillin alone
does not include organisms which produce these enzymes.
Clavulanic acid is a beta-lactam structurally related to penicillins. It
inactivates some beta-lactamase enzymes thereby preventing inactivation of
amoxicillin. Clavulanic acid alone does not exert a clinically useful
The time above the minimum inhibitory concentration (T>MIC) is considered
to be the major determinant of efficacy for amoxicillin.
Mechanisms of resistance
The two main mechanisms of resistance to amoxicillin/clavulanic acid are:
• Inactivation by those bacterial beta-lactamases that are not themselves
inhibited by clavulanic acid, including class B, C and D.
• Alteration of PBPs, which reduce the affinity of the antibacterial agent for
Impermeability of bacteria or efflux pump mechanisms may cause or
contribute to bacterial resistance, particularly in Gram-negative bacteria.
MIC breakpoints for amoxicillin/clavulanic acid are those of the European
Committee on Antimicrobial Susceptibility Testing (EUCAST)
Susceptibility Breakpoints (μg/ml)
Streptococcus A, B,
The reported values are for Amoxicillin concentrations. For
susceptibility testing purposes, the concentration of clavulanic acid is fixed
at 2 mg/l.
The reported values are oxacillin concentrations.
Breakpoint values in the table are based on ampicillin breakpoints.
The resistant breakpoint of R>8 mg/l ensures that all isolates with
resistance mechanisms are reported resistant.
Breakpoint values in the table are based on benzylpenicillin breakpoints.
The prevalence of resistance may vary geographically and with time for
selected species, and local information on resistance is desirable, particularly
when treating severe infections. As necessary, expert advice should be sought
when the local prevalence of resistance is such that the utility of the agent in at
least some types of infections is questionable.
Commonly susceptible species
Aerobic Gram-positive micro-organisms
Staphylococcus aureus (methicillin-susceptible)£
Coagulase-negative staphylococci (methicillin-susceptible)
Streptococcus pyogenes and other beta-haemolytic streptococci
Streptococcus viridans group
Aerobic Gram-negative micro-organisms
Species for which acquired resistance may be a problem
Aerobic Gram-positive micro-organisms
Enterococcus faecium $
Aerobic Gram-negative micro-organisms
Inherently resistant organisms
Aerobic Gram-negative micro-organisms
$ Natural intermediate susceptibility in the absence of acquired mechanism
£All methicillin-resistant staphylococci are resistant to
Streptococcus pneumoniae that are resistant to penicillin should not be
treated with this presentation of amoxicillin/clavulanic acid (see sections
4.2 and 4.4).
Strains with decreased susceptibility have been reported in some
countries in the EU with a frequency higher than 10%.
Amoxicillin and clavulanic acid, are fully dissociated in aqueous solution at physiological pH.
Both components are rapidly and well absorbed by the oral route of administration.
Following oral administration, amoxicillin and clavulanic acid are approximately 70%
bioavailable. The plasma profiles of both components are similar and the time to peak plasma
concentration (Tmax) in each case is approximately one hour.
The pharmacokinetic results for a study, in which amoxicillin/clavulanic acid
(500 mg/125 mg tablets three times daily) was administered in the fasting state to groups of
healthy volunteers are presented below.
Mean (± SD) pharmacokinetic parameters
500 mg/125 m
AMX – amoxicillin, CA – clavulanic acid
* Median (range)
Amoxicillin and clavulanic acid serum concentrations achieved with amoxicillin/clavulanic
acid are similar to those produced by the oral administration of equivalent doses of
amoxicillin or clavulanic acid alone.
About 25% of total plasma clavulanic acid and 18% of total plasma amoxicillin is bound to
protein. The apparent volume of distribution is around 0.3-0.4 l/kg for amoxicillin and around
0.2 l/kg for clavulanic acid.
Following intravenous administration, both amoxicillin and clavulanic acid have been found
in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids, bile
and pus. Amoxicillin does not adequately distribute into the cerebrospinal fluid.
From animal studies there is no evidence for significant tissue retention of drug-derived
material for either component. Amoxicillin, like most penicillins, can be detected in breast
milk. Trace quantities of clavulanic acid can also be detected in breast milk (see section 4.6).
Both amoxicillin and clavulanic acid have been shown to cross the placental barrier (see
Amoxicillin is partly excreted in the urine as the inactive penicilloic acid in quantities
equivalent to up to 10 to 25% of the initial dose. Clavulanic acid is extensively metabolized
in man and eliminated in urine and faeces and as carbon dioxide in expired air.
The major route of elimination for amoxicillin is via the kidney, whereas for clavulanic acid it
is by both renal and non-renal mechanisms.
Amoxicillin/clavulanic acid has a mean elimination half-life of approximately one hour and a
mean total clearance of approximately 25 l/h in healthy subjects. Approximately 60 to 70%
of the amoxicillin and approximately 40 to 65% of the clavulanic acid are excreted unchanged
in urine during the first 6 h after administration of single Augmentin 250 mg/125 mg or
500 mg/125 mg tablets. Various studies have found the urinary excretion to be 50-85% for
amoxicillin and between 27-60% for clavulanic acid over a 24 hour period. In the case of
clavulanic acid, the largest amount of drug is excreted during the first 2 hours after
Concomitant use of probenecid delays amoxicillin excretion but does not delay renal
excretion of clavulanic acid (see section 4.5).
The elimination half-life of amoxicillin is similar for children aged around 3 months to 2
years and older children and adults. For very young children (including preterm newborns) in
the first week of life the interval of administration should not exceed twice daily
administration due to immaturity of the renal pathway of elimination. Because elderly
patients are more likely to have decreased renal function, care should be taken in dose
selection, and it may be useful to monitor renal function.
Following oral administration of amoxicillin/clavulanic acid to healthy males and female
subjects, gender has no significant impact on the pharmacokinetics of either amoxicillin or
The total serum clearance of amoxicillin/clavulanic acid decreases proportionately with
decreasing renal function. The reduction in drug clearance is more pronounced for
amoxicillin than for clavulanic acid, as a higher proportion of amoxicillin is excreted via the
renal route. Doses in renal impairment must therefore prevent undue accumulation of
amoxicillin while maintaining adequate levels of clavulanic acid (see section 4.2).
Hepatically impaired patients should be dosed with caution and hepatic function monitored at
Preclinical safety data
Non-clinical data reveal no special hazard for humans based on studies of
safety pharmacology, genotoxicity and toxicity to reproduction.
Repeat dose toxicity studies performed in dogs with amoxicillin/clavulanic
acid demonstrate gastric irritancy and vomiting, and discoloured tongue.
Carcinogenicity studies have not been conducted with Augmentin or its
List of excipients
Colloidal anhydrous silica
Orange dry flavour 1 (including maltodextrin)
Orange dry flavour 2 (including maltodextrin)
Raspberry dry flavour (including maltodextrin)
Golden syrup dry flavour (including maltodextrin)
Dry powder: 2 years
Reconstituted suspension: 7 days
Reconstituted suspensions should be stored at 2°C - 8°C (but not frozen) for
up to 7 days.
Special precautions for storage
Store the dry powder in the original container. Do not store above 25°C. For
storage conditions of the reconstituted medicinal product, see section 6.3.
Nature and contents of container
Clear glass bottles containing powder for reconstitution to 100 ml. This may
be supplied with a measuring spoon or cup.
Special precautions for disposal
Check cap seal is intact before using. Shake bottle to loosen powder. Add
volume of water (as indicated below). Invert and shake well.
Alternatively, shake the bottle to loosen powder then fill the bottle with water
to just below the line on the bottle or label. Invert and shake well, then top up
with water exactly to the line. Invert and again shake well.
Volume of water to be
added at reconstitution
Final volume of
Shake the bottle well before each dose.
Any unused medicinal product or waste material should be disposed of in
accordance with local requirements.
MARKETING AUTHORISATION HOLDER
Beecham Group plc
980 Great West Road
Middlesex TW8 9GS
Stockley Park West
Middlesex UB11 1BT
MARKETING AUTHORISATION NUMBER(S)
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
Date of first authorisation: 11 October 1982
Date of latest renewal: 19 October 2014
DATE OF REVISION OF THE TEXT
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