AUGMENTIN 375MG TABLETS

Active substance: POTASSIUM CLAVULANATE

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1.

NAME OF THE MEDICINAL PRODUCT
‘Augmentin’ 375 mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains amoxicillin trihydrate equivalent to 250 mg amoxicillin and
potassium clavulanate equivalent to 125 mg of clavulanic acid.
For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Film-coated tablet.
White to off-white, oval shaped tablets debossed with “Augmentin” on one side.

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).
Acute bacterial sinusitis (adequately diagnosed)
Cystitis
Pyelonephritis
Cellulitis
Animal bites
Severe dental abscess with spreading cellulitis.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2

Posology and Method of Administration
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).

For adults and children ≥ 40 kg, this formulation of Augmentin provides a total daily dose of 750 mg
amoxicillin/375 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).
Treatment should not be extended beyond 14 days without review.
Adults and children ≥ 40 kg
One 250 mg/125 mg tablet taken three times a day.
Children < 40 kg
Augmentin 250 mg/125 mg film-coated tablets are not recommended in children < 40 kg.
Elderly
No dose adjustment is considered necessary.
Renal impairment
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
ml/min.
Adults and children ≥ 40 kg
CrCl: 1030 ml/min
CrCl < 10 ml
/min
Haemodialysis

250 mg/125 mg twice daily
250 mg/125 mg once daily
Two doses of 250 mg/125 mg every 24 hours, plus two doses
of 250 mg/125 mg during dialysis, to be repeated at the end of
dialysis (as serum concentrations of both amoxicillin and
clavulanic acid are decreased)

Children < 40 kg
In children < 40 kg with creatinine clearance less than 30 ml/min, the use of Augmentin
presentations with an amoxicillin to clavulanic acid ratio of 2:1 is not recommended, as no dose
adjustments are available. In such patients, Augmentin formulations with an amoxicillin to
clavulanic acid ratio of 4:1 are recommended.
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 oral use.
Administer at the start of a meal to minimise potential gastrointestinal intolerance and optimise
absorption of amoxicillin/clavulanic acid.

4.3

Contra-indications
Hypersensitivity to the active substances, to any of the penicillins or to any of the excipients.
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 Special 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.
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 guidance.
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 (e.g. penicillin-insusceptible 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 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. Antiperistaltic medicinal products 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 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 nonenzymatic 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.

4.5

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 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 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.

4.6

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.
Lactation
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
organisms

Not known

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
Reversible hyperactivity
Convulsions2
Aseptic meningitis

Uncommon
Uncommon
Not known
Not known
Not known

Gastrointestinal disorders
Diarrhoea
Nausea3
Vomiting
Indigestion
Antibiotic-associated colitis4
Black hairy tongue

Very common
Common
Common
Uncommon
Not known
Not known

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

Uncommon
Not known
Not known

Skin and subcutaneous tissue disorders 7
Skin rash
Uncommon
Pruritus
Uncommon
Urticaria
Uncommon
Erythema multiforme
Rare
Stevens-Johnson syndrome
Not known
Toxic epidermal necrolysis
Not known
Bullous exfoliative-dermatitis
Not known
Acute generalised exanthemous
Not known
9
pustulosis (AGEP)
Renal and urinary disorders

Interstitial nephritis
Not known
8
Crystalluria
Not known
1
See section 4.4
2
See section 4.4.
3
Nausea is more often associated with higher oral doses. If gastrointestinal
reactions are evident, they may be reduced by taking amoxicillin/clavulanic
acid at the start of a meal.
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

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.

Mode 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.
PK/PD 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).
Susceptibility Breakpoints (μg/ml)
Susceptible
Intermediate
Resistant



2




>1

1
2

-

>1
>2

0.25

> 0.25

4
0.25

8
-

>8
> 0.25

0.5

1-2

>2

4

8

>8
>8

4

8

>8






Coagulase-negative
staphylococci 2
Enterococcus1
Streptococcus A, B, C,
G5
Streptococcus
pneumoniae3
Enterobacteriaceae1,4
Gram-negative
Anaerobes1
Gram-positive

-



Haemophilus
influenzae1
Moraxella catarrhalis1
Staphylococcus aureus

1




Organism

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
Staphylococcus aureus (methicillin-susceptible)£
Streptococcus agalactiae
Streptococcus pneumoniae1
Streptococcus pyogenes and other beta-hemolytic streptococci
Streptococcus viridans group
Aerobic Gram-negative micro-organisms
Capnocytophaga spp.
Eikenella corrodens
Haemophilus influenzae2
Moraxella catarrhalis
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.
Morganella morganii
Providencia spp.
Pseudomonas sp.
Serratia sp.

Stenotrophomonas maltophilia
$ 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 is fully susceptible to penicillin may be
treated with this presentation of amoxicillin/clavulanic acid. Organisms that
show any degree of reduced susceptibility to penicillin should not be treated
with this presentation (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
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. Absorption of
amoxicillin/clavulanic acid is optimised when taken at the start of a meal. 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 (250 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
Active
substance(s)
administered

AUC (0-24h)
((μg.h/ml)

T 1/2
(h)

Amoxicillin
3.3
1.5
(1.0-2.0)
± 1.12

26.7±4.56

1.36
± 0.56

Clavulanic acid
1.5
1.2
(1.0-2.0)
± 0.70

AMX/CA
250 mg/125
mg

Dose
(mg)

Cmax
(μg/ml)

250

12.6
± 3.25

1.01
± 0.11

AMX/CA
125
250 mg/125
mg
AMX – amoxicillin, CA – clavulanic acid
* Median (range)

Tmax *
(h)

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 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 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.

5.3

Preclinical Safety Data
Nonclinical 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.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Tablet core:
Magnesium stearate
Sodium starch glycolate, Type A
Colloidal silica anhydrous
Microcrystalline cellulose
Tablet film coat:
Titanium dioxide (E171)
Hypromellose
Macrogol (4000, 6000)
Dimeticone

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
2 years
Tablets in desiccated pouch packs should be used within 30 days of opening.

6.4

Special precautions for storage
Store in the original package in order to protect from moisture.
Do not store above 25°C.

6.5

Nature and contents of container

Aluminium PVC/PVdC blister enclosed within an aluminium laminate pouch containing a desiccant
sachet, referred to as a desiccated pouch pack (DPP) containing 21 tablets.
6.6.
Instructions for Use, Handling and Disposal
None

7.

MARKETING AUTHORISATION HOLDER
Beecham Group plc
980 Great West Road,
Brentford,
Middlesex
TW8 9GS

Trading as
GlaxoSmithKline UK, Stockley Park West, Uxbridge, Middlesex, UB11 1BT
Or
Beecham Research, Mundells, Welwyn Garden City, Hertfordshire, AL7 1EY

8.

MARKETING AUTHORISATION NUMBER(S)
PL 0038/0270

9.

DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION
6 August 1996

10

DATE OF REVISION OF THE TEXT
09/10/2013

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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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