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AUGMENTIN INTRAVENOUS 600MG AND AUGMENTIN INTRAVENOUS 1.2 G

Active substance(s): AMOXICILLIN / CLAVULANIC ACID

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Augmentin Intravenous

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each vial contains sodium amoxicillin equivalent to 500mg amoxicillin and
potassium clavulanate equivalent to 100 mg of clavulanic acid.
Excipients with known effect:
Sodium 31.4 mg (1.4 mmol) per vial.
Potassium 19.6 mg (0.5 mmol) per vial.
Each vial or bottle contains sodium amoxicillin equivalent to 1000 mg
amoxicillin and potassium clavulanate equivalent to 200mg of clavulanic acid.
Excipients with known effect:
Sodium 62.9 mg (2.7 mmol) per vial.
Potassium 39.3 mg (1.0 mmol) per vial.
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
500 mg/100 mg powder for solution for injection or infusion
Powder for solution for injection or infusion.
Vials containing a white to off-white sterile powder.
1000 mg/200 mg powder for solution for injection or infusion
Powder for solution for injection or infusion.
Vials or bottles containing a white to off-white sterile 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):












Severe infections of the ear, nose and throat (such as mastoiditis, peritonsillar
infections, epiglottitis, and sinusitis when accompanied by severe systemic signs
and symptoms)
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
Intra-abdominal infections
Female genital infections.

Prophylaxis against infections associated with major surgical procedures in adults,
such as those involving the:
• Gastrointestinal tract
• Pelvic cavity
• Head and neck
• Biliary tract surgery.
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).
This Augmentin powder for solution for injection or infusion provides a total
daily dose of 3000 mg amoxicillin and 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 an alternative
intravenous formulation of Augmentin is selected in order to avoid
administration of unnecessarily high daily doses of clavulanic acid.

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).
Consideration should be given to local guidelines on appropriate dosing
frequencies for amoxicillin/clavulanic acid.
Adults and children ≥ 40 kg
For treatment of infections as indicated in section 4.1: 1000 mg/ 200 mg every
8 hours
For surgical prophylaxis

For procedures less than 1 hour in
duration, the recommended dose of
Augmentin is 1000 mg/200 mg to
2000 mg/200 mg given at induction of
anaesthesia (Doses of 2000 mg/200 mg
can be achieved by using an alternative
intravenous formulation of Augmentin).
For procedures greater than 1 hour in
duration, the recommended dose of
Augmentin is 1000 mg/200 mg to
2000 mg/200 mg given at induction of
anaesthesia, with up to 3 doses of
1000 mg/200 mg in 24 hours.
Clear clinical signs of infection at
operation will require a normal course of
intravenous or oral therapy postoperatively.

Children < 40 kg
Recommended doses:
• Children aged 3 months and over: 25 mg/5 mg per kg every 8 hours
• Children aged less than 3 months or weighing less than 4 kg: 25 mg/5 mg
per kg every 12 hours.
Elderly
No dose adjustment is considered necessary.
Renal impairment

Dose adjustments are based on the maximum recommended level of
amoxicillin.
No dose adjustment is required in patients with creatinine clearance (CrCl)
greater than 30 ml/min.
Adults and children ≥ 40 kg
CrCl: 1030 ml/min
CrCl < 10 ml
/min
Haemodialysis

Initial dose of 1000 mg/200 mg and then 500 mg/100 mg
given twice daily
Initial dose of 1000 mg/200 mg and then 500 mg/100 mg
given every 24 hours
Initial dose of 1000 mg/200 mg and then followed by
500 mg/100 mg every 24 hours, plus a dose of
500 mg/100 mg at the end of dialysis (as serum
concentrations of both amoxicillin and clavulanic acid are
decreased)

Children < 40 kg
CrCl: 10 to
30 ml/min
CrCl < 10 ml
/min
Haemodialysi
s

25 mg/5 mg per kg given every 12 hours
25 mg/5 mg per kg given every 24 hours
25 mg/5 mg per kg given every 24 hours, plus a dose of
12.5 mg/2.5 mg per kg at the end of dialysis (as serum
concentrations of both amoxicillin and clavulanic acid are
decreased).

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 intravenous use.
Augmentin may be administered either by slow intravenous injection over a
period of 3 to 4 min directly into a vein or via a drip tube or by infusion over
30 to 40 min. Augmentin is not suitable for intramuscular administration.
Children aged less than 3 months should be administered Augmentin by
infusion only.
Treatment with Augmentin may be initiated by the use of an intravenous
preparation and completed with an appropriate oral presentation as considered
appropriate for the individual patient.

4.3

For instructions on reconstitution and dilution of the medicinal product before
administration, see section 6.6.
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 section 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 should 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 resistance to beta-lactam agents that is not
mediated by beta-lactamases susceptible to inhibition by clavulanic acid. As no
specific data for T>MIC are available and the data for comparable oral presentations
are borderline, this presentation (without additional amoxicillin) may not be suitable
for the 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.
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, Augmentin should immediately be
discontinued, a physician be consulted and an appropriate therapy initiated. Antiperistaltic drugs are contra-indicated 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 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. Cross-reactions with
non-Aspergillus polysaccharides and polyfuranoses with Bio-Rad 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.
500 mg/100 mg powder for solution for injection or infusion



This medicinal product contains 31.4 mg (1.4 mmol) of sodium per vial. To be
taken into consideration by patients on a controlled sodium diet.



This medicinal product contains 19.6 mg (0.5 mmol) of potassium per vial. To be
taken into consideration by patients with reduced kidney function or patients on a
controlled potassium diet.

1000 mg/200 mg powder for solution for injection or infusion
• This medicinal product contains 62.9 mg (2.7 mmol) of sodium per vial. To be
taken into consideration by patients on a controlled sodium diet.


4.5

This medicinal product contains 39.3 mg (1.0 mmol) of potassium per vial. To be
taken into consideration by patients with reduced kidney function or patients on a
controlled potassium diet.

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 section 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 breast-feeding 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)

Infections and infestations
Mucocutaneous candidosis

Common

Overgrowth of non-susceptible
Not known
organisms
Blood and lymphatic system disorders
Reversible leucopenia (including Rare
neutropenia)
Thrombocytopenia
Rare
Reversible agranulocytosis
Not known
Haemolytic anaemia
Not known
Prolongation of bleeding time
Not known
and
prothrombin time1
Immune system disorders10
Angioneurotic oedema
Anaphylaxis
Serum sickness-like syndrome
Hypersensitivity vasculitis

Not known
Not known
Not known
Not known

Nervous system disorders
Dizziness
Headache
Convulsions2
Aseptic meningitis

Uncommon
Uncommon
Not known
Not known

Vascular disorders
Thrombophlebitis3

Rare

Gastrointestinal disorders
Diarrhoea
Nausea
Vomiting
Indigestion
Antibiotic-associated colitis4

Common
Uncommon
Uncommon
Uncommon
Not known

Hepatobiliary disorders
Rises in AST and/or ALT5
Hepatitis6
Cholestatic jaundice6

Uncommon
Not known
Not known

Skin and subcutaneous tissue disorders7
Skin rash
Uncommon
Pruritus
Uncommon
Urticaria
Uncommon
Erythema multiforme
Rare
Stevens-Johnson syndrome
Not known
Toxic epidermal necrolysis
Not known

Bullous exfoliative-dermatitis
Acute generalised exanthemous
pustulosis (AGEP)9

Not known
Not known

Renal and urinary disorders
Interstitial nephritis
Not known
8
Crystalluria
Not known
1
See section 4.4
2
See section 4.4
3
At the site of injection
4
Including pseudomembranous colitis and haemorrhagic colitis (see section
4.4)
5
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.
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
4.9

Overdose
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
high doses.
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
water/electrolyte balance.

Amoxicillin/clavulanic acid can be removed from the circulation by haemodialysis.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Combinations of penicillins, incl. beta-lactamase
inhibitors; ATC code: J01CR02.
Mechansim 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 antibacterial effect.
Pharmacokinetic/pharmacodynamic relationship
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
the target.
Impermeability of bacteria or efflux pump mechanisms may cause or
contribute to bacterial resistance, particularly in Gram-negative bacteria.
Breakpoints
MIC breakpoints for amoxicillin/clavulanic acid are those of the European
Committee on Antimicrobial Susceptibility Testing (EUCAST)

Organism

Susceptibility Breakpoints (μg/ml)
Susceptible
Intermediate
Resistant

Haemophilus
≤1
>1
1
influenzae
Moraxella
≤1
>1
1
catarrhalis
Staphylococcus
≤2
>2
2
aureus
Coagulase-negative
≤ 0.25
> 0.25
2
staphylococci
Enterococcus1
≤4
8
>8
Streptococcus A, B,
≤ 0.25
> 0.25
C, G5
Streptococcus
≤ 0.5
1-2
>2
pneumoniae3
Enterobacteriaceae1,4
>8
Gram-negative
≤4
8
>8
Anaerobes1
Gram-positive
≤4
8
>8
Anaerobes1
Non-species related
≤2
4-8
>8
breakpoints1
1
The reported values are for Amoxicillin concentrations. For susceptibility
testing purposes, the concentration of Clavulanic acid is fixed at 2 mg/l.
2
The reported values are Oxacillin concentrations.
3
Breakpoint values in the table are based on Ampicillin breakpoints.
4
The resistant breakpoint of R>8 mg/l ensures that all isolates with
resistance mechanisms are reported resistant.
5
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
Enterococcus faecalis
Gardnerella vaginalis
Staphylococcus aureus (methicillin-susceptible)£
Coagulase-negative staphylococci (methicillin-susceptible)
Streptococcus agalactiae
Streptococcus pneumoniae1
Streptococcus pyogenes and other beta-haemolytic streptococci
Streptococcus viridans group
Aerobic Gram-negative micro-organisms
Actinobacillus actinomycetemcomitans
Capnocytophaga spp.
Eikenella corrodens
Haemophilus influenzae2
Moraxella catarrhalis
Neisseria gonorrhoeae§
Pasteurella multocida
Anaerobic micro-organisms
Bacteroides fragilis
Fusobacterium nucleatum
Prevotella spp.
Species for which acquired resistance may be a problem
Aerobic Gram-positive micro-organisms
Enterococcus faecium $
Aerobic Gram-negative micro-organisms
Escherichia coli
Klebsiella oxytoca
Klebsiella pneumoniae
Proteus mirabilis
Proteus vulgaris
Inherently resistant organisms
Aerobic Gram-negative micro-organisms
Acinetobacter sp.
Citrobacter freundii
Enterobacter sp.
Legionella pneumophila
Morganella morganii
Providencia spp.
Pseudomonas sp.
Serratia sp.
Stenotrophomonas maltophilia
Other micro-organisms
Chlamydia trachomatis

Chlamydophila pneumoniae
Chlamydophila psittaci
Coxiella burnetti
Mycoplasma pneumoniae
$ Natural intermediate susceptibility in the absence of acquired mechanism
of resistance.
£ All methicillin-resistant staphylococci are resistant to
amoxicillin/clavulanic acid.
§ All strains with resistance to amoxicillin that is not mediated by betalactamases are resistant to amoxicillin/clavulanic acid.
1
This presentation of amoxicillin/clavulanic acid may not be suitable for
treatment of Streptococcus pneumoniae that are resistant to penicillin (see
sections 4.2 and 4.4).
2
Strains with decreased susceptibility have been reported in some countries
in the EU with a frequency higher than 10%.

5.2

Pharmacokinetic Properties
Absorption
The pharmacokinetic results for studies in which amoxicillin/clavulanic acid was
administered to groups of healthy volunteers as either 500 mg/100 mg or
1000 mg/200 mg given as a bolus intravenous injection are presented below.
Mean (±SD) pharmacokinetic parameters
Bolus intravenous injection
Dose
administered
Dose
Mean peak
serum conc
(μg/ml)
AMX/CA
500 mg/100
mg
AMX/CA
1000 mg/200
mg
AMX/CA
500 mg/100
mg
AMX/CA
1000 mg/200
mg

Amoxicillin
T 1/2 (h)

500
mg

32.2

1.07

25.5

Urinary
recovery
(%, 0 to
6h)
66.5

1000
mg

105.4

0.9

76.3

77.4

100
mg

10.5

9.2

46.0

200
mg

28.5

27.9

63.8

Clavulanic acid
1.12

AMX – amoxicillin, CA – clavulanic acid

0.9

AUC
(h.mg/l)

Distribution
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 drugderived 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).
Biotransformation
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.
Elimination
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 a single 500/100 mg or a single 1000/200 mg bolus intravenous
injection. 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 administration.
Concomitant use of probenecid delays amoxicillin excretion but does not delay renal
excretion of clavulanic acid (see section 4.5).
Age
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.
Renal impairment
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).
Hepatic impairment
Hepatically impaired patients should be dosed with caution and hepatic function
monitored at regular intervals.

5.3

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
components.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
None.

6.2

Incompatibilities
This medicinal product must not be mixed with other medicinal products
except those mentioned in section 6.6.
Augmentin Intravenous should not be mixed with blood products, other
proteinaceous fluids such as protein hydrolysates or with intravenous lipid
emulsions.
If prescribed concomitantly with an aminoglycoside, the antibiotics should not
be mixed in the syringe, intravenous fluid container or giving set because loss
of activity of the aminoglycoside can occur under these conditions.
Augmentin solutions should not be mixed with infusions containing glucose,
dextran or bicarbonate.

6.3

Shelf life
Powder in vials
2 years
Reconstituted vials (for intravenous injection or before dilution for infusion)

500 mg/100 mg powder for solution for injection or infusion
The reconstituted solution (1 vial with 10 ml of Water for Injections Ph.Eur.)
should be used or diluted immediately, within 20 minutes.
1000 mg/200 mg powder for solution for injection or infusion
The reconstituted solution (1 vial with 20 ml of Water for Injections Ph.Eur.)
should be used or diluted immediately, within 20 minutes.
Diluted for intravenous infusion
500 mg/100 mg powder for solution for injection or infusion
Chemical and physical in-use stability has been demonstrated for 2-3 hours at
25°C, or 8 hours at 5°C. From a microbiological point of view, the
reconstituted and diluted solution (1 reconstituted vial in a minimum volume
of 50 ml of infusion fluid) should be used immediately.
1000 mg/200 mg powder for solution for injection or infusion
Chemical and physical in-use stability has been demonstrated for 2-3 hours at
25°C, or 8 hours at 5°C. From a microbiological point of view, the
reconstituted and diluted solution (1 reconstituted vial in a minimum volume
of 100 ml of infusion fluid) should be used immediately.
Intravenous infusions of amoxicillin/clavulanic acid may be given in a range
of different intravenous fluids. Satisfactory antibiotic concentrations are
retained at 5 °C and at room temperature (25°C) in the recommended volumes
of the following infusion fluids. If reconstituted and maintained at room
temperature (25°C), infusions should be completed within the times stated in
the table below.
Intravenous infusion

Stability period at 25°C

Water for Injection Ph.Eur.
0.9% w/v Sodium Chloride intravenous infusion (9 mg/ml)
Compound Sodium Chloride Injection 1959 (Ringer's)
Compound Sodium Lactate Intravenous Infusion (RingerLactate:Hartmann's)
0.3% w/v Potassium Chloride and 0.9% w/v Sodium
Chloride Intravenous Infusion (3 mg/ml and 9 mg/ml)

3 hours
3 hours
2 hours
2 hours
2 hours

For storage at 5°C, reconstituted solutions of Augmentin IV may be added to
pre-refrigerated infusion bags containing either Water for Injection Ph. Eur. or
sodium chloride BP (0.9% w/v), which may be stored for up to 8 hours.
Thereafter, the infusion should be administered immediately after reaching
room temperature.
The stability of Augmentin IV solutions is concentration dependent. In the
event that the use of more concentrated solutions is required, the stability
period should be adjusted accordingly.

Augmentin IV is less stable in infusions containing glucose, dextran or
bicarbonate. Reconstituted solutions of amoxicillin/clavulanic acid may be
injected into the drip tubing over a period of 3 to 4 min.
Any residual antibiotic solution should be discarded.
6.4

Special precautions for storage
Do not store above 25°C.
Store in the original package in order to protect from moisture.
For storage conditions after reconstitution of the medicinal product, see
section 6.3.

6.5

Nature and contents of container
500 mg/100 mg powder for solution for injection or infusion
Clear glass 10 ml or 25 ml vials (Type I or Type III glass) with chlorobutyl
rubber stopper and sealing ring
Packs of 1, 5 or 10 vials
Not all pack sizes may be marketed.
1000 mg/200 mg powder for solution for injection or infusion
Clear glass 25 ml vials or 50 ml bottles (Type I or Type III glass) with
chlorobutyl rubber stopper and sealing ring
Packs of 1, 5, 10, 25 or 100 vials
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
For single use only. Discard any unused solution.
The reconstitution/dilution is to be made under aseptic conditions. The
solution is to be inspected visually for particulate matter and discoloration
prior to administration. The solution should only be used if the solution is
clear and free from particles.
Any unused medicinal product or waste material should be disposed of in
accordance with local requirements.
Preparation of solutions for intravenous injection
500 mg/100 mg powder for solution for injection or infusion
Water for Injection Ph.Eur. is the normal solvent. Augmentin 500/100 mg
should be dissolved in 10 ml of solvent. This yields approximately 10.5 ml of
solution for single-dose use. A transient pink colouration may or may not
develop during reconstitution. Reconstituted solutions are normally colourless
to yellow in colour.
Augmentin should be administered within 20 min of reconstitution.
1000 mg/200 mg powder for solution for injection or infusion

Water for Injection Ph.Eur. is the normal solvent. Augmentin
1000 mg/200 mg should be dissolved in 20 ml of solvent. This yields
approximately 20.9 ml of solution for single-dose use. A transient pink
colouration may or may not develop during reconstitution. Reconstituted
solutions are normally colourless to yellow in colour.
Augmentin should be administered within 20 min of reconstitution.
Preparation of solutions for intravenous infusion
Augmentin vials are not suitable for multi-dose use.
500 mg/100 mg powder for solution for injection or infusion
Augmentin should be reconstituted as described above for injection. Without
delay the reconstituted solution should be added to 50 ml of infusion fluid
using a minibag or in-line burette.
1000 mg/200 mg powder for solution for injection or infusion
Augmentin should be reconstituted as described above for injection. Without
delay the reconstituted solution should be added to 100 ml of infusion fluid
using a minibag or in-line burette.

7

MARKETING AUTHORISATION HOLDER
Beecham Group Ltd
980 Great West Road
Brentford
Middlesex TW8 9GS
Trading as:
GlaxoSmithKline UK
Stockley Park West
Uxbridge
Middlesex UB11 1BT

8.

MARKETING AUTHORISATION NUMBER(S)
PL 0038/0320

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
Date of first authorisation: 23 September 1985
Date of latest renewal: 19 October 2014

10

DATE OF REVISION OF THE TEXT
03/10/2016

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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