For the use only of Registered Medical Practitioners or a Hospital or a Laboratory

AUGMENTIN 625 / 1g DUO

1. GENERIC NAME

Amoxycillin and Potassium Clavulanate Tablets IP

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

AUGMENTIN 625 DUO:

Each film-coated tablet contains:
Amoxycillin Trihydrate IP equivalent to Amoxycillin 500 mg
Potassium Clavulanate Diluted IP equivalent to Clavulanic Acid 125 mg
Colour: Titanium Dioxide IP

AUGMENTIN 1g DUO:
Each film coated tablet contains:
Amoxycillin Trihydrate IP equivalent to Amoxycillin 875 mg
Potassium Clavulanate Diluted IP equivalent to Clavulanic Acid 125 mg
Colour: Titanium Dioxide IP

3. DOSAGE FORM AND STRENGTH

AUGMENTIN 625 DUO: Film-coated tablets

AUGMENTIN 1g DUO: Film-coated tablets

4. CLINICAL PARTICULARS

4.1. Therapeutic Indications

AUGMENTIN is an antibiotic agent with a notably broad spectrum of activity against the commonly
occurring bacterial pathogens in general practice and hospital. The beta-lactamase inhibitory action of
clavulanate extends the spectrum of amoxycillin to embrace a wider range of organisms, including many
resistant to other beta-lactam antibiotics.

AUGMENTIN should be used in accordance with local official antibiotic-prescribing guidelines and local
susceptibility data.

AUGMENTIN 625 /1g DUO, are indicated for short-term treatment of bacterial infections at the following
sites:

Upper respiratory tract infections (including ENT) e.g. recurrent tonsillitis, sinusitis, otitis media

Lower respiratory tract infections e.g. acute exacerbation of chronic obstructive pulmonary disease
(AECOPD)/acute exacerbation of chronic bronchitis (AECB), lobar and bronchopneumonia

Genito-urinary tract infections e.g. cystitis, urethritis, pyelonephritis

Skin and soft tissue infections e.g. boils, abscesses, cellulitis, wound infections
Bone and joint infections e.g. osteomyelitis

Dental infections e.g. dentoalveolar abscess

Other infections e.g. septic abortion, puerperal sepsis, intra-abdominal sepsis

Susceptibility to AUGMENTIN will vary with geography and time (see 5 Pharmacological Properties, 5.2
Pharmacodynamic Properties for further information). Local susceptibility data should be consulted where
available, and microbiological sampling and susceptibility testing performed where necessary.

4.2. Posology and Method of Administration

Dosage depends on the age and renal function of the patient and the severity of the infection.

To minimize potential gastrointestinal intolerance, administer at the start of a meal.

The absorption of AUGMENTIN is optimized when taken at the start of a meal.

Tablets to be consumed in whole, not to be broken.

Treatment should not be extended beyond 14 days without review.

Therapy can be started parenterally and continued with an oral preparation.

AUGMENTIN 625 /1g DUO are not recommended in children of 12 years and under.

Adults and Children over 12 years

The usual recommended daily dosage is:

Mild - Moderate infections One AUGMENTIN 625 mg tablet every 12 hours.

Severe infections One AUGMENTIN 1 g tablet every 12 hours or One AUGMENTIN 625
mg tablet every 8 hours

Renal Impairment

No adjustment in dose is required in patients with creatinine clearance (CrCl) greater than 30 mL/min. The
AUGMENTIN 1g tablet should only be used in patients with a creatinine clearance (CrCl) rate of more than
30 mL/min.

CrCl 10-30 mL/min One AUGMENTIN 625 mg tablet every 12 hours.

CrCl < 10 mL/min One AUGMENTIN 625 mg tablet every 24 hours.
Haemodialysis One AUGMENTIN 625 mg tablet every 24 hours, plus a further one
tablet during dialysis, to be repeated at the end of dialysis (as serum
concentrations of both amoxycillin and clavulanic acid are decreased.)

Hepatic Impairment

Dose with caution; monitor hepatic function at regular intervals.

4.3. Contraindications

AUGMENTIN is contraindicated in patients with a history of hypersensitivity to beta-lactams, e.g.

penicillins and cephalosporins

AUGMENTIN is contraindicated in patients with a previous history of AUGMENTIN-associated

jaundice/hepatic dysfunction.

4.4. Special Warnings and Precautions for Use

Before initiating therapy with AUGMENTIN careful enquiry should be made concerning previous
hypersensitivity reactions to penicillins, cephalosporins, or other allergens.

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 (see 4.3 Contraindications).
Hypersensitivity reactions can also progress to Kounis syndrome, a serious allergic reaction that can result
in myocardial infarction. Presenting symptoms of such reactions can include chest pain occurring in
association with an allergic reaction to AUGMENTIN (see 4.8 Undesirable effects). If an allergic reaction
occurs, AUGMENTIN therapy should be discontinued and appropriate alternative therapy instituted. Serious
anaphylactic reactions require immediate emergency treatment with adrenaline. Oxygen, intravenous (i.v.)
steroids and airway management (including intubation) may also be required.

AUGMENTIN 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 amoxycillin.

Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.

Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild
to life-threatening. Therefore, it is important to consider its diagnosis in patients who develop diarrhoea
during or after antibiotic use. If prolonged or significant diarrhoea occurs or the patient experiences
abdominal cramps, treatment should be discontinued immediately and the patient investigated further.

Abnormal prolongation of prothrombin time [increased International Normalized Ratio (INR)] has been
reported rarely in patients receiving AUGMENTIN and oral anticoagulants. Appropriate monitoring should
be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral
anticoagulants may be necessary to maintain the desired level of anticoagulation.

Changes in liver function tests have been observed in some patients receiving AUGMENTIN. The clinical
significance of these changes is uncertain. AUGMENTIN should be used with caution in patients with
evidence of hepatic dysfunction.

Cholestatic jaundice, which may be severe, but is usually reversible, has been reported rarely. Signs and
symptoms may not become apparent for up to six weeks after treatment has ceased.

In patients with renal impairment AUGMENTIN dosage should be adjusted as recommended in the Posology
and Method of Administration section.

In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with
parenteral therapy. During the administration of high doses of amoxycillin, it is advisable to maintain
adequate fluid intake and urinary output in order to reduce the possibility of amoxycillin crystalluria (see 4.9
Overdose).
4.5. Drug Interactions

Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of
amoxycillin. Concomitant use with AUGMENTIN may result in increased and prolonged blood levels of
amoxycillin but not of clavulanic acid.

Concomitant use of allopurinol during treatment with amoxycillin can increase the likelihood of allergic
skin reactions. There are no data on the concomitant use of AUGMENTIN and allopurinol.

In common with other antibiotics, AUGMENTIN may affect the gut flora, leading to lower oestrogen
reabsorption and reduced efficacy of combined oral contraceptives.

In the literature there are rare cases of increased international normalised ratio in patients maintained on
acenocoumarol or warfarin and prescribed a course of amoxycillin. If co-administration is necessary, the
prothrombin time or international normalised ratio should be carefully monitored with the addition or
withdrawal of AUGMENTIN.

In patients receiving mycophenolate mofetil, reduction in pre-dose concentration of the active metabolite
mycophenolic acid of approximately 50% has been reported following commencement of oral amoxycillin
plus clavulanic acid. The change in pre-dose level may not accurately represent changes in overall MPA
exposure.

4.6. Use in Special Populations

Pregnancy and Lactation

Reproduction studies in animals (mice and rats at doses up to 10 times the human dose) with orally and
parenterally administered AUGMENTIN have shown no teratogenic effects. In a single study in women
with preterm, premature rupture of the foetal membrane (pPROM), it was reported that prophylactic
treatment with AUGMENTIN may be associated with an increased risk of necrotising enterocolitis in
neonates. As with all medicines, use should be avoided in pregnancy, especially during the first trimester,
unless considered essential by the physician.

AUGMENTIN may be administered during the period of lactation. With the exception of the risk of
sensitisation, associated with the excretion of trace quantities in breast milk, there are no known detrimental
effects for the breast-fed infant.

Renal Impairment

No adjustment in dose is required in patients with creatinine clearance (CrCl) greater than 30 mL/min. The
AUGMENTIN 1g tablet should only be used in patients with a creatinine clearance (CrCl) rate of more than
30 mL/min.

CrCl 10-30 mL/min One AUGMENTIN 625 mg tablet every 12 hours.

CrCl < 10 mL/min One AUGMENTIN 625 mg tablet every 24 hours.
Haemodialysis One AUGMENTIN 625 mg tablet every 24 hours, plus a further one
tablet during dialysis, to be repeated at the end of dialysis (as serum
concentrations of both amoxycillin and clavulanic acid are decreased.)

Hepatic Impairment
Dose with caution; monitor hepatic function at regular intervals.

4.7. Effects on Ability to Drive and Use Machines

Adverse effects on the ability to drive or operate machinery have not been observed.

4.8. Undesirable Effects

Data from large clinical trials were used to determine the frequency of very common to rare undesirable
effects. The frequencies assigned to all other undesirable effects (i.e., those occurring at <1/10,000) were
mainly determined using post-marketing data and refer to a reporting rate rather than a true frequency.

The following convention has been used for the classification of frequency:

Very common ≥ 1/10

Common ≥ 1/100 to < 1/10
Uncommon ≥ 1/1000 to < 1/100
Rare ≥ 1/10,000 to < 1/1000
Very rare < 1/10,000

Infections and infestations:

Common Mucocutaneous candidiasis

Blood and lymphatic system disorders:

Rare Reversible leucopenia (including neutropenia) and thrombocytopenia

Very rare Reversible agranulocytosis and haemolytic anaemia. Prolongation of bleeding time and
prothrombin time

Immune system disorders:

Very rare Angioneurotic oedema, anaphylaxis, serum sickness-like syndrome, hypersensitivity

vasculitis

Nervous system disorders:

Uncommon Dizziness, headache

Very rare Reversible hyperactivity, aseptic meningitis, convulsions. Convulsions may occur in patients
with impaired renal function or in those receiving high doses.

Cardiac disorders

Very rare Kounis syndrome (see 4.4 Special Warnings and Precautions for use).

Gastrointestinal disorders:
 Adults:

Very common Diarrhoea

Common Nausea, vomiting

Children:

Common Diarrhoea, nausea, vomiting

All populations:

Nausea is more often associated with higher oral dosages. If gastrointestinal reactions are evident, they
may be reduced by taking AUGMENTIN at the start of a meal.

Uncommon Indigestion

Very rare Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic

colitis) (See 4.4 Special Warnings and Precautions for use.)

Black hairy tongue

Hepatobiliary disorders

Uncommon 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.

Very rare Hepatitis and cholestatic jaundice. These events have been noted with other penicillins
and cephalosporins.

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.

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.

Skin and subcutaneous tissue disorders

Uncommon Skin rash, pruritus, urticaria

Rare Erythema multiforme

Very rare Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative-dermatitis,

acute generalised exanthemous pustulosis (AGEP), and drug reaction with eosinophilia
and systemic symptoms (DRESS)

If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued.

 Renal and urinary disorders

Very rare Interstitial nephritis, crystalluria (see 4.9 Overdose)

4.9. Overdose

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident.
Gastrointestinal symptoms may be treated symptomatically, with attention to the water/electrolyte balance.

Amoxycillin crystalluria, in some cases leading to renal failure, has been observed (see 4.4 Special
Warnings and Precautions for Use).

AUGMENTIN can be removed from the circulation by haemodialysis.

5. PHARMACOLOGICAL PROPERTIES

5.1. Mechanism of Action

Amoxycillin is a semisynthetic antibiotic with a broad spectrum of antibacterial activity against many gram-
positive and gram-negative micro-organisms. Amoxycillin is, however, susceptible to degradation by beta-
lactamases and therefore the spectrum of activity of amoxycillin alone does not include organisms which
produce these enzymes.

Clavulanic acid is a beta-lactam, structurally related to the penicillins, which possesses the ability to
inactivate a wide range of beta-lactamase enzymes commonly found in micro-organisms resistant to
penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid
mediated beta-lactamases frequently responsible for transferred drug resistance. It is generally less effective
against chromosomally-mediated type 1 beta-lactamases.

The presence of clavulanic acid in amoxycillin-clavulanate formulations protects amoxycillin from

degradation by beta-lactamase enzymes and effectively extends the antibacterial spectrum of amoxycillin to
include many bacteria normally resistant to amoxycillin and other penicillins and cephalosporins. Thus
amoxycillin-clavulanate possesses the distinctive properties of a broad spectrum antibiotic and a beta-
lactamase inhibitor.

5.2. Pharmacodynamic Properties

ATC code: J01CR02.

Pharmacotherapeutic group: Combinations of penicillins, incl. beta-lactamase inhibitors.

Resistance to many antibiotics is caused by bacterial enzymes which destroy the antibiotic before it can act
on the pathogen. The clavulanate in AUGMENTIN anticipates this defence mechanism by blocking the beta-
lactamase enzymes, thus rendering the organisms susceptible to amoxycillin’s rapid bactericidal effect at
concentrations readily attainable in the body. Clavulanate by itself has little antibacterial activity; however,
in association with amoxycillin as AUGMENTIN it produces an antibiotic agent of broad spectrum with
wide application in hospital and general practice.

In the list below, organisms are categorised according to their in vitro susceptibility to AUGMENTIN.
In vitro susceptibility of micro-organisms to AUGMENTIN

Where clinical efficacy of AUGMENTIN has been demonstrated in clinical trials this is
indicated with an asterisk (*).

Organisms that do not produce beta-lactamase are identified (with †). If an isolate is
susceptible to amoxycillin, it can be considered susceptible to AUGMENTIN.
Commonly susceptible species
Gram-positive aerobes:
Bacillius anthracis
Enterococcus faecalis
Listeria monocytogenes
Nocardia asteroides
Streptococcus pyogenes*†
Streptococcus agalactiae*†
Streptococcus spp. (other beta-hemolytic)*†
Staphylococcus aureus (methicillin susceptible)*
Staphylococcus saprophyticus (methicillin susceptible)
Coagulase negative staphylococcus (methicillin susceptible)
Gram-negative aerobes:
Bordetella pertussis
Haemophilus influenzae*
Haemophilus parainfluenzae
Helicobacter pylori
Moraxella catarrhalis*
Neisseria gonorrhoeae
Pasteurella multocida
Vibrio cholerae
Other:
Borrelia burgdorferi
Leptospira ictterohaemorrhagiae
Treponema pallidum
Gram positive anaerobes:
Clostridium spp.
Peptococcus niger
Peptostreptococcus magnus
Peptostreptococcus micros
Peptostreptococcus spp.
Gram-negative anaerobes:
Bacteroides fragilis
Bacteroides spp.
Capnocytophaga spp.
Eikenella corrodens
Fusobacterium nucleatum
Fusobacterium spp.
Porphyromonas spp.
Prevotella spp.
Species for which acquired resistance may be a problem
 Gram-negative aerobes:
Escherichia coli*
Klebsiella oxytoca
Klebsiella pneumoniae*
Klebsiella spp.
Proteus mirabilis
Proteus vulgaris
Proteus spp.
Salmonella spp.
Shigella spp.
Gram-positive aerobes:
Corynebacterium spp.
Enterococcus faecium
Streptococcus pneumoniae*†
Viridans group streptococcus
Inherently resistant organisms
Gram-negative aerobes:
Acinetobacter spp.
Citrobacter freundii
Enterobacter spp.
Hafnia alvei
Legionella pneumophila
Morganella morganii
Providencia spp.
Pseudomonas spp.
Serratia spp.
Stenotrophomas maltophilia
Yersinia enterolitica
Others:
Chlamydia pneumoniae
Chlamydia psittaci
Chlamydia spp.
Coxiella burnetti
Mycoplasma spp.

5.3. Pharmacokinetic Properties

The pharmacokinetics of the two components of AUGMENTIN are closely matched. Peak serum levels of
both occur about 1 hour after oral administration. Absorption of AUGMENTIN is optimised at the start of a
meal.

Doubling the dosage of AUGMENTIN approximately doubles the serum levels achieved.

Both clavulanate and amoxycillin have low levels of serum binding; about 70% remains free in the serum.

6. NONCLINICAL PROPERTIES

6.1. Animal Toxicology and Pharmacology

No further information of relevance.

7. DESCRIPTION

General Description

AUGMENTIN (beta-lactam antibacterial penicillin coformulated with a beta- lactamase inhibitor) is an

antibiotic agent with a notably broad spectrum of activity against the commonly occurring bacterial
pathogens in general practice and hospital. The beta-lactamase inhibitory action of clavulanate extends the
spectrum of amoxycillin to embrace a wider range of organisms, including many resistant to other beta-
lactam antibiotics.

Chemical Structure

AUGMENTIN is a coformulation of amoxycillin trihydrate and potassium clavulanate.

Amoxycillin trihydrate

Chemical name (2S,5R,6R)-6-[(R)-(-)-2-amino-2-(p-hydroxyphenyl) acetamido]-3,3-dimethyl-

7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate.
Structural formula

Molecular formula C16H19N3O5 S·3H2O

Relative molecular mass 365.4 (anhydrous)
419.4 (trihydrate form)

Potassium clavulanate

Chemical name Potassium (Z)-(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-

oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate.
Structural formula

Molecular formula C8H8NO5K

Relative molecular mass 237.3 (as the potassium salt)
199.2 (as the free acid)

Excipients:

AUGMENTIN 625 DUO: Magnesium stearate, colloidal anhydrous silica, sodium starch glycollate,
microcrystalline cellulose, Opaspray KI-7000/ Titanium Dioxide suspension, ethylcellulose, propylene
glycol, hydroxypropyl methyl cellulose, methylene chloride, methanol and activated dimethicone.
 AUGMENTIN 1g DUO: Magnesium stearate, colloidal silicon dioxide, sodium starch glycollate,
microcrystalline cellulose, Opaspray KI-7000/Titanium Dioxide suspension, ethylcellulose, propylene
glycol, hydroxypropyl methyl cellulose, methylene chloride, methanol and activated dimethicone.

8. PHARMACEUTICAL PARTICULARS

8.1. Incompatibilities

There are no relevant data available.

8.2. Shelf Life

The expiry date is indicated on the label and packaging.

8.3. Packaging Information

Aluminium strips

8.4. Storage and Handling Information

Store protected from moisture at a temperature not exceeding 25°C.

Keep out of reach of children.

There are no special requirements for use and handling of this product

9. PATIENT COUNSELLING INFORMATION

Registered Medical Practitioners may counsel their patients (and/or patient’s caregiver as applicable) about
the special warnings and precautions for use, drug interactions, undesirable effects, and any relevant contra-
indications of AUGMENTIN 625 / 1g DUO. Patients (and/or patient’s caregiver) may also be informed
about posology, method of administration and storage/handling information as applicable.

10. DETAILS OF MANUFACTURER

The Manufacturing Site details are mentioned on the label and packaging.

For further information, please contact:

GlaxoSmithKline Pharmaceuticals Limited.
Registered Office:
Dr. Annie Besant Road, Worli,
Mumbai 400 030, India.

11. DETAILS OF PERMISSION OR LICENSE NUMBER WITH DATE

Manufacturing License number is indicated on the label and packaging.

12. DATE OF REVISION

20-MAY-2022

Trade marks are owned by or licensed to the GSK group of companies.

Version: AUG-TAB/PI/IN/2022/01

Adapted from Amoxicillin-clavulanate (Oral) GDS, Amoxicillin trihydrate - Potassium clavulanate BD

Tablets IPI 14 and Amoxicillin trihydrate - Potassium clavulanate TID Tablets and Suspension IPI 17 dated
10 Feb 2022