CoAmox 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
• 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.
Consideration should be given to official guidance on the appropriate use of antibacterial
agents.

 

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 CoAmox 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 CoAmox (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 CoAmox provides a total daily dose of
1750 mg amoxicillin/ 250 mg clavulanic acid with twice daily dosing and 2625 mg
amoxicillin/375 mg clavulanic acid with three times daily dosing, when administered as
recommended below. For children < 40 kg, this formulation of CoAmox provides a
maximum daily dose of 1000-2800 mg amoxicillin/143-400 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 CoAmox 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 days without review (see section 4.4 regarding prolonged therapy).
Adults and children ≥ 40 kg
Recommended doses:
• standard dose (for all indications): 875 mg/125 mg two times a day;
• higher dose (particularly for infections such as otitis media, sinusitis, lower respiratory tract
infections and urinary tract infections): 875 mg/125 mg three times a day.
Children < 40 kg
Children may be treated with CoAmox tablets, suspensions or paediatric sachets.
Recommended doses:
• 25 mg/3.6 mg/kg/day to 45 mg/6.4 mg/kg/day given as two divided doses;
• up to 70 mg/10 mg/kg/day given as two divided doses may be considered for some
infections (such as otitis media, sinusitis and lower respiratory tract infections).
As the tablets cannot be divided children weighing less than 25 kg must not be treated with
CoAmox tablets.
The table below presents the received dose (mg/kg body weight) in children weighing 25 kg
to 40 kg upon administering a single 875 mg/125 mg tablet.

Children weighing less than 25 kg should preferably be treated with CoAmox suspension or
paediatric sachets.
No clinical data are available for CoAmox 7:1 formulations regarding doses higher than 45
mg/6.4 mg per kg per day in children under 2 years
There are no clinical data for CoAmox 7:1 formulations for patients under 2 months of age.
Dosing recommendations in this population therefore cannot be made.
No dose adjustment is considered necessary.
Elderly
No dose adjustment is required in patients with creatinine clearance (CrCl) greater than 30
ml/min.
Renal impairment
In patients with creatinine clearance less than 30 ml/min, the use of CoAmox presentations
with an amoxicillin to clavulanic acid ratio of 7:1 is not recommended, as no
recommendations for dose adjustments are available.
Dose with caution and monitor hepatic function at regular intervals (see sections 4.3 and 4.4).
Hepatic impairment
CoAmox is for oral use.
Method of administration
CoAmox should be administered with a meal to minimise potential gastrointestinal
intolerance.
Therapy can be started parenterally according to the SmPC of the IV formulation and
continued with an oral preparation.

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 betalactam agent (e.g. a cephalosporin, carbapenem or monobactam). History of jaundice/hepatic impairment due to amoxicillin/clavulanic acid (see section 4.8).

Before initiating therapy with amoxicillin/clavulanic acid, careful enquiry should be made
concerning previous hypersensitivity reactions to penicillins, cephalosporins or other betalactam
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 CoAmox is not suitable for use when there is a high risk that the
presumptive pathogens have resistance to beta-lactam agents that is not mediated by betalactamases
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 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 CoAmox discontinuation and contraindicates 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 CoAmox 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.

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 co-administration 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.

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.

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
vomiting.
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)

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.

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 betalactamase
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)

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 pneumoniae
Streptococcus pyogenes and other beta-haemolytic streptococci
1
Streptococcus viridans group
Aerobic Gram-negative micro-organisms
Capnocytophaga spp.
Eikenella corrodens
Haemophilus influenzae
Moraxella catarrhalis
2
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
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
1 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).
2 Strains with decreased susceptibility have been reported in some countries in the EU
with a frequency higher than 10%.

Absorption
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 (875 mg/125
mg tablets given twice daily) was administered in the fasting state to groups of healthy
volunteers.

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.
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 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
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 single CoAmox 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
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.
Gender
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
clavulanic acid.
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.

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 amoxicillin/clavulanic acid or its
components.

Tablet core
Colloidal silicon dioxide
Crospovidone, dried,
Crosslinked carboxymethylcellulose sodium dried
Magnesium stearate
Microcrystalline Cellulose, dried.
Film-coat
Hydropropoxycellulose
Ethylcellulose
Polysorbate
Triethylcitrate
Titanium dioxide
Talc

Not applicable

24 Months

Do not store above 30 °C.
Keep this medicine out of the sight & reach of children.

Tablets are packaged in Alu/Alu blister packs, enclosed in a carton. Each pack contains 12
tablets.

No special requirements.