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

AUGMENTIN DDS

Amoxycillin and Potassium Clavulanate Oral Suspension IP

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 5 ml of the reconstituted suspension contains:

Amoxycillin Trihydrate IP equivalent to Amoxycillin 400 mg

Potassium Clavulanate Diluted IP equivalent to Clavulanic Acid 57 mg

PHARMACEUTICAL FORM

Dry powder for reconstitution in water, at time of dispensing, to form an oral sugar free
suspension.

CLINICAL PARTICULARS

Therapeutic Indications

AUGMENTIN should be used in accordance with local official antibiotic-prescribing

guidelines and local susceptibility data.

AUGMENTIN DDS Suspension (457mg/5 ml), for twice daily (b.i.d) oral dosing, is
indicated for short term treatment of bacterial infections at the following sites when
amoxycillin resistant beta-lactamase producing strains are suspected as the cause. In other
situations, amoxycillin alone should be considered.

Upper Respiratory Tract Infections (including ENT) e.g. Recurrent tonsilitis, sinusitis,
otitis media.

Lower Respiratory Tract Infections e.g. acute exacerbation of chronic bronchitis, lobar
and bronchopneumonia.

Urinary Tract Infections e.g. cystitis, urethritis, pyelonephritis.

Skin and Soft Tissue Infections e.g. cellulitis, animal bites.

Dental infections e.g. severe dental abscess with spreading cellulitis.

Susceptibility to AUGMENTIN will vary with geography and time (see Pharmacological
Properties, Pharmacodynamic Properties for further information). Local susceptibility

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data should be consulted where available, and microbiological sampling and susceptibility
testing performed where necessary.

Mixed infections caused by amoxycillin-susceptible organisms in conjunction with

AUGMENTIN susceptible beta-lactamase-producing organisms may be treated with
AUGMENTIN DDS Suspension 457 mg/5 ml. These infections should not require the
addition of another antibiotic resistant to beta-lactamases.

Posology and Method of Administration

The usual recommended daily dosage is:

• 25/3.6 mg/kg/day in mild to moderate infections (upper respiratory tract infections e.g.
recurrent tonsillitis, lower respiratory infections and skin and soft tissue infections)

• 45/6.4 mg/kg/day for the treatment of more serious infections (upper respiratory tract
infections e.g. otitis media and sinusitis, lower respiratory tract infections e.g.
bronchopneumonia and urinary tract infections)

The tables below give guidance for children.

Children over 2 years

25/3.6 mg/kg/day 2 - 6 years 2.5 ml AUGMENTIN DDS Suspension

(13 - 21 kg) 457 mg/5 ml twice daily
7 - 12 years 5.0 ml AUGMENTIN DDS Suspension
(22 - 40 kg) 457 mg/5 ml twice daily
45/6.4 mg/kg/day 2 - 6 years 5.0 ml AUGMENTIN DDS Suspension
(13 - 21 kg) 457 mg/5 ml twice daily
7 - 12 years 10.0 ml AUGMENTIN DDS
Suspension 457 mg/5 ml twice daily

Children aged 2 months to 2 years

Children under 2 years should be dosed according to body weight.

AUGMENTIN DDS Suspension 457 mg/5 ml

Weight (kg) 25/3.6 mg/kg/day 45/6.4 mg/kg/day
(ml/twice daily) (ml/twice daily)
2 0.3 0.6
3 0.5 0.8
4 0.6 1.1
5 0.8 1.4
6 0.9 1.7
7 1.1 2.0
8 1.3 2.3

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 9 1.4 2.5
10 1.6 2.8
11 1.7 3.1
12 1.9 3.4
13 2.0 3.7
14 2.2 3.9
15 2.3 4.2

There is insufficient experience with AUGMENTIN DDS Suspension 457 mg/5 ml to make
dosage recommendations for children under 2 months old.

Renal Impairment

For children with a GFR of >30 ml/min no adjustment in dosage is required. For children
with a GFR of <30 ml/min AUGMENTIN DDS Suspension 457 mg/5 ml is not
recommended.

Infants with immature kidney function

For infants with immature renal function AUGMENTIN DDS Suspension 457 mg/5 ml are
not recommended.

Hepatic Impairment

Dose with caution; monitor hepatic function at regular intervals. There is, as yet,
insufficient evidence on which to base a dosage recommendation.

Oral Administration

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

absorption of AUGMENTIN is optimised when taken at the start of a meal. Duration of
therapy should be appropriate to the indication and should not exceed 14 days without
review. Therapy can be started parenterally and continued with an oral preparation.

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.

Special Warnings and Special Precautions for Use

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

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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 Contraindications). If an allergic reaction occurs, AUGMENTIN
therapy must 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 but 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 Overdose).

AUGMENTIN DDS Suspension 457 mg/5ml contain 12.5 mg aspartame per 5 ml dose and
therefore care should be taken in patients with phenylketonuria.

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Interaction with Other Medicaments and Other Forms of Interaction

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 clavulanate.

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 amoxicillin plus clavulanic acid. The change in pre-dose level may
not accurately represent changes in overall MPA exposure.

Pregnancy and Lactation

Reproduction studies in animals (mice and rats) 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 detrimental effects for the infant.

Effects on Ability to Drive and Use Machines

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

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.

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

Very common ≥ 1/10

Common ≥ 1/100 and < 1/10
Uncommon ≥ 1/1000 and < 1/100
Rare ≥ 1/10,000 and < 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 and convulsions. Convulsions may occur

in patients with impaired renal function or in those receiving high
doses.

Gastrointestinal disorders:

Adults:

Very common Diarrhoea

Common Nausea, vomiting

Children:

Common Diarrhoea, nausea, vomiting

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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 Special Warning and Special
Precautions for Use).

Black hairy tongue

Superficial tooth discolouration has been reported very rarely in

children. Good oral hygiene may help to prevent tooth
discolouration as it can usually be removed by brushing.

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)

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

Renal and urinary disorders

Very rare Interstitial nephritis, crystalluria (see Overdose)

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
Special Warnings and Special Precautions for Use).

AUGMENTIN can be removed from the circulation by haemodialysis.

PHARMACOLOGICAL PROPERTIES

Pharmacodynamic Properties

Resistance to many antibiotics is caused by bacterial enzymes which destroy the antibiotic
before it can act on the pathogen. The clavulanate in AUGMENTIN suspension anticipates
this defence mechanism by blocking the β-lactamase enzymes, thus rendering the
organisms sensitive 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

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Listeria monocytogenes
Nocardia asteroides
Streptococcus pyogenes*†
Streptococcus agalactiae*†
Streptococcus spp. (other β-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

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 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.

Infections caused by amoxycillin-susceptible organisms are amenable to AUGMENTIN

treatment due to its amoxycillin content. Mixed infections caused by amoxycillin -
susceptible organisms in conjunction with AUGMENTIN-susceptible β-lactamase
producing organisms may therefore be treated with AUGMENTIN.

Pharmacokinetic Properties

Absorption:

The two components of AUGMENTIN DDS Suspension 457 mg/5 ml, amoxycillin and
clavulanate, are each fully dissociated in aqueous solution at physiological pH. Both

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components are rapidly and well absorbed by the oral route of administration. Absorption
of AUGMENTIN is optimised when taken at the start of a meal.

Distribution:

The pharmacokinetics of the two components of AUGMENTIN are closely matched. Both
clavulanate and amoxycillin have low levels of serum binding; about 70% remains free in
the serum.

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

Preclinical Safety Data

No further information of relevance.

PHARMACEUTICAL PARTICULARS

List of Excipients

Xanthan gum, hydroxypropylmethylcellulose, colloidal anhydrous silica, succinic acid,

silicon dioxide, raspberry, orange “1”, orange “2”, golden syrup dry flavours, aspartame.

Incompatibilities

No incompatibilities have been identified.

Shelf Life

The expiry date is indicated on the label and packaging.

Special Precautions for Storage

Unopened container: Store in a well closed container at a temperature not exceeding 25°C,
protected from moisture.

Reconstituted suspensions: should be stored in a refrigerator (2°-8°C) and used within

seven days.

Keep out of reach of children.

Nature and Specifications of Container

Bottle in a carton.

When reconstituted, an off-white suspension is formed.

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Instructions for Use/Handling

At time of dispensing, the dry powder should be reconstituted to form an oral suspension.

Direction for Preparation:

To make upto 30 ml shake the bottle to loosen powder. Add boiled and cooled water to 3/4
th of fill-mark on bottle. Replace the cap and shake the bottle until all of the powder is
suspended. Add more water until the level of the fill line is attained and shake again.
When first reconstituted, allow to stand for 5 minutes to ensure full dispersion.

After reconstitution keep in a refrigerator when not in use.

Use reconstituted suspension within 7 days.

Do not use if powder / reconstituted solution turns pale yellow to brown colour.

Do not use the product if seal is missing or not intact.

For paediatric use.

For further information please contact:

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

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

Version: AUG-DDS/PI/IN/2017/02 dated 12-Dec-2017.

Adapted from Augmentin Oral GDS 23 and Augmentin Paediatric Syrup IPI 12 dated 15
August 2017.

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