AMOKLAVIN

Main information

  • Trade name:
  • AMOKLAVIN DUO 400/57 amoxicillin 400mg (as trihydrate) and clavulanic acid 57mg (as potassium clavulanate) powder for oral suspe
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • AMOKLAVIN DUO 400/57 amoxicillin 400mg (as trihydrate) and clavulanic acid 57mg (as potassium clavulanate) powder for oral suspe
    Australia
  • Language:
  • English

Other information

Status

  • Source:
  • Dept. of Health,Therapeutic Goods Administration - Australia
  • Authorization number:
  • 216347
  • Last update:
  • 09-10-2017

Public Assessment Report

Public Summary

Summary for ARTG Entry:

216347

AMOKLAVIN DUO 400/57 amoxicillin 400mg (as trihydrate) and clavulanic acid 57mg (as potassium

clavulanate) powder for oral suspension bottle

ARTG entry for

Medicine Registered

Sponsor

Deva Holdings Australia Ltd

Postal Address

PO Box 339,CURRUMBIN WATERS, QLD, 4223

Australia

ARTG Start Date

15/12/2014

Product category

Medicine

Status

Active

Approval area

Drug Safety Evaluation Branch

Conditions

Conditions applicable to all therapeutic goods as specified in the document "Standard Conditions Applying to Registered or Listed Therapeutic Goods

Under Section 28 of the Therapeutic Goods Act 1989" effective 1 July 1995.

Conditions applicable to the relevant category and class of therapeutic goods as specified in the document "Standard Conditions Applying to Registered

or Listed Therapeutic Goods Under Section 28 of the Therapeutic Goods Act 1989" effective 1 July 1995.

Products

1. AMOKLAVIN DUO 400/57 amoxicillin 400mg (as trihydrate) and clavulanic acid 57mg (as potassium

clavulanate) powder for oral suspension bottle

Product Type

Single Medicine Product

Effective date

15/12/2014

Warnings

See Product Information and Consumer Medicine Information for this product

Standard Indications

Specific Indications

AMOKLAVIN DUO 400/57 (amoxicillin and clavulanic acid) oral suspension is indicated in the short term treatment of the following bacterial infections

when caused by sensitive organisms (see Microbiology):,Skin and Skin Structure Infections,Urinary Tract Infections (complicated and

uncomplicated),Upper Respiratory Tract Infections including sinusitis and otitis media,Lower Respiratory Tract Infections including acute exacerbations

of chronic bronchitis and community acquired pneumonia,Appropriate culture and susceptibility studies should be performed to identify the causative

organism(s) and determine its (their) susceptibility to AMOKLAVIN DUO 400/57. However, when there is reason to believe an infection may involve any

of the beta-lactamase producing organisms listed above, therapy may be instituted prior to obtaining the results from bacteriological and susceptibility

studies. Once these results are known, therapy should be adjusted if appropriate.,The treatment of mixed infections caused by amoxicillin susceptible

organisms and beta-lactamase producing organisms susceptible to AMOKLAVIN DUO 400/57, should not require the addition of another antibiotic due to

the amoxicillin content of AMOKLAVIN DUO 400/57.

Additional Product information

Container information

Type

Material

Life Time

Temperature

Closure

Conditions

Bottle

Glass Type III

Coloured

18 Months

Store below 25

degrees Celsius

Child resistant closure

Reconstituted Solution

see label for shelf life

Pack Size/Poison information

Pack Size

Poison Schedule

60 mL

(S4) Prescription Only Medicine

Components

1. AMOKLAVIN DUO 400/57 amoxicillin 400mg (as trihydrate) and clavulanic acid 57mg (as potassium clavulanate) powder for oral

suspension bottle

Dosage Form

Suspension, powder for

Route of Administration

Oral

Visual Identification

White to cream coloured powder

Active Ingredients

amoxicillin trihydrate

91.823 mg/mL

potassium clavulanate

13.58 mg/mL

© Commonwealth of Australia.This work is copyright.You are not permitted to re-transmit, distribute or commercialise the material without obtaining prior

written approval from the Commonwealth.Further details can be found at http://www.tga.gov.au/about/website-copyright.htm.

Public Summary

Page 1 of

Produced at 26.11.2017 at 07:26:20 AEDT

This is not an ARTG Certificate document.

The onus is on the reader to verify the current accuracy of the information on the document subsequent to the date shown.

Visit www.tga.gov.au for contact information

Summary of Product characteristics

AMOKLAVIN DUO 400/57 SUSPENSION

PRODUCT INFORMATION

(Amoxicillin Trihydrate and Potassium Clavulanate)

NAME OF THE MEDICINE

AMOKLAVIN DUO 400/57 (amoxicillin and clavulanic acid) is a combination product containing

the semisynthetic antibiotic, amoxicillin (as the trihydrate) and the β-lactamase inhibitor, potassium

clavulanate (as the potassium salt of clavulanic acid). Chemically, amoxicillin is D-(-)-α-amino-p-

hydroxybenzylpenicillin. It is susceptible to hydrolysis by β-lactamases. Amoxicillin trihydrate may

be represented structurally as:

(Chemical formula: C

S, 3H

O; Molecular weight: 419.4; CAS – 61336-70-7)

Clavulanic acid is produced by the fermentation of

Streptomyces clavuligerus

. It is an irreversible

inhibitor of many β-lactamase enzymes except type 1 (Richmond). It is a β-lactam compound with

only weak antibacterial activity. Chemically potassium clavulanate is potassium

Z

R

R

)-3-(ß-

hydroxyethylidene) clavam-2-carboxylate, and may be represented structurally as:

(Chemical formula: C

; Molecular weight: 237.3; CAS – 61177-45-5)

DESCRIPTION

Amoxicillin trihydrate is a white or almost white, crystalline powder and is slightly soluble in water.

A 0.2% solution in water has a pH of 3.5 to 5.5.

Potassium clavulanate is supplied in diluted potassium clavulanate, a dry mixture of potassium

clavulanate and silicon dioxide. Potassium clavulanate is a white or almost white, hygroscopic,

crystalline powder and is freely soluble in water and has a pKa of 2.7 (clavulanic acid). Its

experimental partition coefficient is -1.5. A 1% solution in water has a pH of 4.8 to 8.0.

AMOKLAVIN

400/57

oral

suspension

also

contains

hypromellose,

silica-colloidal

anhydrous (Aerosil 200), saccharin sodium, silicon dioxide (Syloid AL-1 FP), xanthan gum, methyl

hydroxybenzoate, succinic acid, Golden Syrup Flavour 501118 AP0551 and Orange 51941

AP0551.

The powder in a bottle is diluted with 52 mL water to make up to 60 mL suspension. Each 5 mL of

suspension contains 400 mg amoxicillin and 57 mg clavulanic acid. It also contains 0.29 mmol of

potassium.

PHARMACOLOGY

Pharmacokinetics

Absorption

Amoxicillin is stable in the presence of gastric acid. The two components in oral suspension

(amoxicillin and clavulanic acid) are rapidly absorbed if administered before or with a meal, but if

given after meals, the serum levels of clavulanic acid are significantly reduced. To optimise

absorption of clavulanic acid, amoxicillin/clavulanic acid oral suspension should be administered

at the start of a meal. The pharmacokinetics of amoxicillin are not affected by food.

In children aged 2 - 12 years, oral administration of amoxicillin and clavulanic acid oral suspension

(7:1 ratio) every 12 hours (q12h) at a dose of 45mg/kg/day amoxicillin (6.4mg/kg/day clavulanic

acid) was compared to amoxicillin and clavulanic acid oral suspension (4:1 ratio) every 8 hours

(q8h) at a dose of 40mg/kg/day amoxicillin (10mg/kg/day clavulanic acid), either immediately prior

to the start of a meal or at least three hours after a meal.

In this study, the following mean pharmacokinetic parameters were observed for amoxicillin for

amoxicillin

clavulanic

acid

oral

suspension

(45mg/kg/day)

taken

every

hours

amoxicillin and clavulanic acid oral suspension (40mg/kg/day) taken every 8 hours respectively:

peak plasma concentration (C

) of 12.0 and 7.33μg/mL, area under the plasma concentration-time

curve between 0 and 24 hours after the first dose (AUC

(0-24 hours)

) of 35.2 and 18.6μg.h/mL, half life

(t½) of 1.22 and 1.02 hours, median time to peak plasma concentration (T

) of 1.0 and 2.1 hours

and the mean predicted time above the minimum inhibitory concentration (T

24 hours) of 12.3

hours and 14.0 hours.

The following pharmacokinetic parameters were observed for clavulanic acid for amoxicillin and

clavulanic acid oral suspension (45mg/kg/day) taken every 12 hours and amoxicillin and clavulanic

acid oral suspension (40mg/kg/day) taken every 8 hours respectively: C

of 5.49 and 2.66 μg /mL,

(0-24 hours)

of 13.3 and 5.51 μg.h/mL, t½ of 0.99 and 0.94 hours and median T

of 1.0 and 1.6

hours, and mean predicted T

24 hours of 9.80 hours and 9.81 hours.

The clinical efficacy of amoxicillin and clavulanic acid (7:1 ratio) and amoxicillin and clavulanic

acid (4:1 ratio) have been shown to be comparable in the approved indications, despite the

differences in some pharmacokinetic parameters.

Distribution

Following oral administration, both amoxicillin and clavulanic acid have been shown to diffuse in

significant concentrations into pus, bile, pleural, synovial and peritoneal fluids. Therapeutic

concentrations of both compounds have been detected in gall bladder, abdominal tissue, skin fat,

and muscle tissues. Both penetrate poorly into the CSF when the meninges are normal. Amoxicillin

penetrates into the CSF better through inflamed meninges but the maximum concentrations are still

much lower than the peak serum levels. There are no data at present on the CSF penetration of

clavulanic acid in patients with meningeal inflammation.

Neither amoxicillin nor clavulanic acid is highly protein bound. Clavulanic acid has been variously

reported to be bound to human serum in the range of 9 - 30% and amoxicillin approximately 20%

bound. From animal studies, there is no evidence to suggest either component accumulates in any

organ.

Elimination

As with other penicillins, renal excretion is the major route of amoxicillin clearance, while

clavulanate clearance is via both renal and non-renal mechanisms. Approximately seventy percent

of the dose of amoxicillin is excreted in urine as amoxicillin. For clavulanic acid, following the

administration of 125mg of radiolabelled potassium clavulanate orally to normal volunteers 68% of

the administered radioactivity was recovered in the urine in 24 hours. Of this, 34% (ie. 23% of the

administered dose) represented unchanged clavulanic acid. 2,5-Dihydro-4-(2-hydroxyethyl)-5-oxo-

1H-pyrrole-3-carboxylic

acid

(the

major

metabolite)

1-amino-4-hydroxy-butan-2-one

accounted for a further 23% and 12% (ie. 16% and 8% respectively of the administered dose). Small

amounts of other yet unidentified metabolites were also present. These metabolites were also

present in the urine of rat and dog. The extent of urinary excretion of clavulanic acid and its

metabolites is lower in rat urine than in dog and human urine.

Concurrent administration of probenecid delays amoxicillin excretion but does not notably delay

renal excretion of clavulanic acid.

Similar amoxicillin and clavulanic acid elimination pharmacokinetics occur in adults, children and

infants with mature renal function.

Clinical Trials

A randomised, single-blind study in 868 children aged 2 months to 12 years with acute otitis media

compared the efficacy of l amoxicillin and clavulanic acid oral suspension 45mg/kg/day amoxicillin

(6.4mg/kg/day clavulanic acid) administered q12h for 5 days (n= 293) or 10 days (n=287) with

amoxicillin and clavulanic acid 40mg/kg/day amoxicillin (10mg/kg/day clavulanic acid) given q8h

for 10 days (n=288). At the end of therapy (days 12 to 14) equivalent per protocol clinical success

rates of 78.8% (n=189) and 86.5% (n=178) respectively were demonstrated for the q8h and q12h

10 day treatment groups, compared with a 71.1% (n=197) success rate for the q12h 5 day treatment

group. At 32 to 38 days follow up, equivalent success rates were demonstrated for q8h and q12h 10

day regimens of 64.2% and 63.1% respectively, compared with a 57.8% success rate for the q12h

5 day treatment group.

Microbiology

Like other penicillins, amoxicillin has a bactericidal effect on sensitive organisms during the stage

of active multiplication. However, amoxicillin is susceptible to hydrolysis by β-lactamases and the

addition of clavulanic acid in amoxicillin and clavulanic acid oral suspension extends the

antimicrobial spectrum of amoxicillin to include organisms normally resistant to amoxicillin due to

beta lactamase production.

In vitro

studies have demonstrated the susceptibility of most strains of

the following organisms:

Table 1 – Acquired resistance data for amoxicillin/clavulanic acid in Australia according

to NCCLS guidelines (M100-S10) for amoxicillin/clavulanic acid

Percentage of Strains

Number of Pathogens (n)

Intermediate

Resistant

Streptococcus pneumoniae *

1020

Haemophilus influenzae #

*: - Data collected between March to November 1997.

#: - Data collected in 1999.

Table 2 – MIC Distribution for Sensitive/intermediate/resistant S. pneumoniae Isolates

MIC ≤2 mcg/ml

MIC =4 mcg/ml

MIC ≥ 8mcg/ml

99.6%

0.3%

0.1%

Table 3– Acquired resistance data for amoxicillin/clavulanic acid from other countries

Breakpoints

Number of

Pathogens (n)

Percentage acquired

resistance (%)

Sensitive aerobe gram positive

Enterococcus faecalis

Staphylococcus aureus

Staphylococcus aureus

(MSSA

)

2,458

Coagulase negative staphylococci

Streptococcus agalactiae

Streptococcus pneumoniae

Streptococcus pneumoniae

(Pen-S)

Streptococcus pyogenes

Streptococcus species

Sensitive aerobe gram negative

Escherichia coli

Haemophilus influenzae

Haemophilus influenzae

(BLN

)

Haemophilus influenzae

(BLP)

Klebsiella pneumoniae

Klebsiella oxytoca

1,540

Moraxella catarrhalis

Proteus sp.

Sensitive anaerobe

Clostridium species

Clostridium difficile

Peptostreptococcus species

Bacteroides fragilis

Bacteroides fragilis group

Fusobacterium species

Intermediate aerobe gram negative

Acinetobacter

Resistant aerobe gram positive

Staphylococcus aureus

(MRSA)

59.2

Resistant aerobe gram negative

Citrobacter

Enterobacter

Morganella

Providencia

Serratia

S. maltophilia

The percent acquired resistance data provided in the above table has been collected from the following countries during the time period

specified: US, 1996; Canada, 1993-1994; US/Canada, 1996-1997; France, 1994-1995; US, Arabia, 1994-1995; US, 1996-1997; US, 1991-

1993; Belgium, 1993-1994; UK, Netherlands, 1989-1995.

Note: Resistance can vary from region to region and information on local resistance should be taken into account.

The following

in vitro data

are available but their clinical significance is unknown.

Table 4- In Vitro Activity of amoxicillin/clavulanic acid

N

MIC 90 (μg/mL)

GRAM POSITIVE AEROBES:

Enterococcus faecalis

Staphylococcus aureus

Staphylococcus aureus

(MSSA)

Staphylococcus aureus

(MRSA)

Staphylococcus epidermidis

Staphylococcus saprophyticus

Coagulase negative staphylococci

Streptococcus agalactiae

0.06

Streptococcus pneumoniae

1,476

Streptococcus pyogenes

0.12

Streptococcus viridans

GRAM NEGATIVE AEROBES:

Escherichia coli

Haemophilus influenzae

2,268

Haemophilus influenzae

(BLN)

Haemophilus influenzae

(BLP)

Klebsiella pneumoniae

Klebsiella oxytoca

Moraxella catarrhalis

0.25

Neisseria gonorrheae

Neisseria meningitidis

0.06

Proteus mirabilis

Proteus vulgaris

GRAM POSITIVE ANAEROBES:

Clostridium species

Clostridium perfringens

0.06

Clostridium difficile

Peptostreptococcus species

Clostridium perfringens

0.06

Clostridium perfringens

0.12

Clostridium perfringens

0.25

Clostridium difficile

Clostridium difficile

Clostridium difficile

Propionibacterium sp.

0.06

Peptostreptococcus

Ruminococcus sp.

0.25

Peptostreptococci

0.25

Peptostreptococcus sp.

Peptostreptococcus sp.

GRAM NEGATIVE ANAEROBES

Bacteroides fragilis

Bacteroides fragilis group

Fusobacterium species

0.125

Bacteroides fragilis

Bacteroides fragilis

Bacteroides fragilis

Bacteroides fragilis

Bacteroides thetaiotamicron

Bacteroides vulgatus

Other Bacteroides sp. of

B. fragilis group

Bacteroides fragilis group

Non-B. fragilis

Prevotella sp

Prevotella, Porphyromonas and Bacteroides sp.

0.25

Fusobacterium sp.

0.125

Fusobacterium sp.

0.125

B. capillosus

P. bivia

P. disiens

0.25

* Methicillin resistant strains are resistant to amoxicillin/clavulanic acid.

Proteus vulgaris

and Klebsiella species may not be susceptible to amoxicillin/clavulanic acid at

concentrations

amoxicillin

clavulanic

acid

achieved

plasma.

However,

concentrations of amoxicillin and clavulanic acid achievable in the urine the majority of strains are

susceptible.

Susceptibility Testing

Dilution or diffusion techniques - either quantitative (MIC) or breakpoint - should be used following

a regularly updated, recognised and standardised method (eg. NCCLS). Standardised susceptibility

test procedures require the use of laboratory control micro-organisms to control the technical

aspects of the laboratory procedures.

A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial

compound in the blood reaches the concentrations usually achievable. A report of "Intermediate"

indicates that the result should be considered equivocal, and if the micro-organism is not fully

susceptible to alternative clinically feasible drugs, the test should be repeated. This category implies

possible clinical applicability in body sites where the drug is physiologically concentrated, or in

situations where high dosage of drug can be used. This category also provides a buffer zone, which

prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A

report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial

compound in the blood reaches the concentrations usually achievable; other therapy should be

selected.

INDICATIONS

AMOKLAVIN DUO 400/57 (amoxicillin and clavulanic acid) oral suspension is indicated in the

short term treatment of the following bacterial infections when caused by sensitive organisms (see

Microbiology):

Skin and Skin Structure Infections

Urinary Tract Infections (complicated and uncomplicated)

Upper Respiratory Tract Infections including sinusitis and otitis media

Lower Respiratory Tract Infections including acute exacerbations of chronic bronchitis and

community acquired pneumonia

Appropriate culture and susceptibility studies should be performed to identify the causative

organism(s) and determine its (their) susceptibility to AMOKLAVIN DUO 400/57. However, when

there is reason to believe an infection may involve any of the β-lactamase producing organisms

listed above, therapy may be instituted prior to obtaining the results from bacteriological and

susceptibility studies. Once these results are known, therapy should be adjusted if appropriate.

The treatment of mixed infections caused by amoxicillin susceptible organisms and β-lactamase

producing organisms susceptible to AMOKLAVIN DUO 400/57, should not require the addition

of another antibiotic due to the amoxicillin content of AMOKLAVIN DUO 400/57.

CONTRAINDICATIONS

A history of allergic reaction to β-lactams (eg. penicillins or cephalosporins) is a contraindication.

AMOKLAVIN DUO 400/57 is contraindicated in patients with a previous history of

amoxicillin/clavulanic acid -associated jaundice/hepatic dysfunction.

PRECAUTIONS

Before initiating therapy with amoxicillin-clavulanate, careful enquiry should be made concerning

previous hypersensitivity reactions to penicillins, cephalosporins or other allergens.

SERIOUS

OCCASIONALLY

FATAL

HYPERSENSITIVITY

(ANAPHYLACTOID)

REACTIONS

HAVE

BEEN

REPORTED

PATIENTS

PENICILLIN

THERAPY.

ALTHOUGH

ANAPHYLAXIS

MORE

FREQUENT

FOLLOWING

PARENTERAL

THERAPY,

OCCURRED

PATIENTS

ORAL

PENICILLINS.

THESE

REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A HISTORY OF

PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO MULTIPLE

ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF

PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS

WHEN TREATED WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY WITH ANY

PENICILLIN,

CAREFUL

INQUIRY

SHOULD

MADE

CONCERNING

PREVIOUS

HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS OR OTHER

ALLERGENS.

ALLERGIC

REACTION

OCCURS,

AMOKLAVIN

SHOULD

DISCONTINUED

APPROPRIATE

THERAPY

INSTITUTED.

SERIOUS

ANAPHYLACTOID

REACTIONS

REQUIRE

IMMEDIATE

EMERGENCY

TREATMENT

WITH

ADRENALINE.

OXYGEN,

INTRAVENOUS

STEROIDS,

AIRWAY

MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS

INDICATED.

Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including

amoxicillin. A toxin produced by

Clostridium difficile

appears to be the primary cause. The severity

of the colitis may range from mild to life-threatening. It is important to consider this diagnosis in

patients who develop diarrhoea or colitis in association with antibiotic use (this may occur up to

several

weeks

after

cessation

antibiotic

therapy).

Mild

cases

usually

respond

drug

discontinuation alone. However in moderate to severe cases appropriate therapy with a suitable oral

antibiotic agent effective against Clostridium difficile should be considered. Fluids, electrolytes and

protein replacement should be provided when indicated. Drugs which delay peristalsis, eg. opiates

and diphenoxylate with atropine (Lomotil) may prolong and/or worsen the condition and should not

be used.

As with any potent drug, periodic assessment of organ system functions, including renal, hepatic

and hematopoietic function is advisable during prolonged therapy.

Since AMOKLAVIN DUO 400/57 (amoxicillin and clavulanic acid) contains amoxicillin, an

aminopenicillin, it is not the treatment of choice in patients presenting with sore throat or pharyngitis

because of the possibility that the underlying cause is infectious mononucleosis, in the presence of

which there is a high incidence of rash if amoxicillin is used.

AMOKLAVIN DUO 400/57 (amoxicillin and clavulanic acid) should be given with caution to

patients with lymphatic leukemia since they are especially susceptible to amoxicillin induced skin

rashes.

AMOKLAVIN DUO 400/57 (amoxicillin and 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.

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

Abnormal prolongation of prothrombin time (increased INR) has been reported rarely in patients

receiving amoxicillin-clavulanate 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.

The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during

therapy. If superinfections occur (usually involving Aerobacter, Pseudomonas or Candida), the drug

should be discontinued and/or appropriate therapy instituted.

Cholestatic hepatitis, which may be severe but is usually reversible, has been reported rarely. Signs

and symptoms may not become apparent until several weeks after treatment has ceased. In most

cases resolution has occurred with time. However, in extremely rare circumstances, deaths have

been reported. These have almost always been cases associated with serious underlying disease or

concomitant medications. Hepatic events subsequent to amoxicillin/clavulanic acid have occurred

predominantly in males and elderly patients and may be associated with prolonged treatment. These

events have been very rarely reported in children. AMOKLAVIN DUO 400/57 (amoxicillin and

clavulanic acid) should be used with care in patients with evidence of hepatic dysfunction.

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 (see

OVERDOSAGE

In children with renal impairment, dosage should be adjusted according to degree of impairment

using the alternative amoxicillin and clavulanic acid (4:1 ratio) 125mg/31.25mg or 250mg/62.5mg

formulations (available from other brand/s).

AMOKLAVIN DUO 400/57 (amoxicillin and clavulanic acid 400/57 mg in 5 mL) formulation is

not recommended for use in children with renal impairment.

Carcinogenicity

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of

amoxicillin and clavulanic acid.

Genotoxicity

genotoxic

potential

amoxicillin

and clavulanic acid

investigated

assays

chromosomal damage (mouse micronuclucleus test and a dominant lethal test) and gene conversion.

All were negative.

Effects on Fertility

Amoxicillin and clavulanic acid at oral doses of up to 1200 mg/kg/day had no effect on fertility and

reproductive performance in rats dosed with a 2:1 ratio formulation of amoxicillin and clavulanate.

Use in Pregnancy

(Category B1).

Animal studies with orally and parenterally administered amoxicillin and clavulanic acid have

shown no teratogenic effects. There is limited experience of the use of amoxicillin and clavulanic

acid in human pregnancy. In women with preterm, premature rupture of the foetal membrane

(pPROM), prophylactic treatment with amoxicillin and clavulanic acid 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.

Use in Labor and Delivery

Oral ampicillin class antibiotics are generally poorly absorbed during labor. Studies in guinea pigs

have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of

contractions, height of contractions and duration of contractions. However, it is not known whether

the use of amoxicillin and clavulanic acid in humans during labor or delivery has immediate or

delayed adverse effects on the foetus, prolongs the duration of labor or increases the likelihood that

forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary.

Use in Lactation

Amoxicillin is excreted in milk. There are no data on the excretion of clavulanic acid in human or

animal

milk.

Therefore,

caution

should

exercised

when

amoxicillin/clavulanic

acid

administered to a nursing woman.

Effects on ability to drive and use machines

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

Effect on laboratory tests

Oral administration of amoxicillin and clavulanic acid will result in high urine concentrations of

amoxicillin. Since high urine concentrations of ampicillin may result in false positive reactions

when testing for the presence of glucose in urine using Clinitest, Benedict's Solution or Fehling's

Solution, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such

as Clinistix® or Testape®) be used.

Following

administration

ampicillin

pregnant

women

transient

decrease

plasma

concentration of total conjugated oestriol, oestriol-glucuronide, conjugated oestrone and oestradiol

has been noted. This effect may also occur with amoxicillin and therefore AMOKLAVIN DUO

400/57 (amoxicillin and clavulanic acid).

INTERACTIONS WITH OTHER MEDICINES

Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular

secretion of amoxicillin but does not notably affect clavulanic acid excretion. Concurrent use with

amoxicillin and clavulanic acid oral suspension may result in increased and prolonged blood levels

of amoxicillin but not of clavulanic acid.

The concurrent administration of allopurinol and ampicillin increases substantially the incidence of

rashes in patients receiving both drugs as compared to patients receiving ampicillin alone. It is not

known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia

present in these patients. There are no data with amoxicillin and clavulanic acid and allopurinol

administered concurrently.

In common with other antibiotics, amoxicillin and clavulanic acid 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 amoxicillin. If co-administration is

necessary, the prothrombin time or international normalised ratio should be carefully monitored

with the addition or withdrawal of amoxicillin.

ADVERSE EFFECTS

Amoxicillin and clavulanic acid oral suspension is generally well tolerated. The majority of events

were of a mild and transient nature.

Clinical Trials

The following adverse events reported in a pivotal clinical trial with amoxicillin and clavulanic

acid oral suspension (45/6.4mg/kg/day q12h for 10 days) and are compared to amoxicillin and

clavulanic acid oral suspension (40/10mg/kg/day q8h for 10 days).

The most frequently (≥1%) reported adverse experiences in decreasing order for the

BD 10 days regimen.

Total No. of Patients

TDS 10 days

BD 10 days

Preferred Term

Frequency %

Frequency %

Coughing

12.5

11.5

Vomiting

10.8

10.1

Rhinitis

Fever

Pharyngitis

Diarrhoea

Dermatitis, contact *

Rash

Therapeutic response increased **

Conjunctivitis

Infection, fungal

Abdominal pain

Respiratory disorder (Not specified)

Asthma

Tooth Ache

Insomnia

Moniliasis

Infection, viral

Hyperkinesia

Injury

Otitis Media

Headache

Constipation

Somnolence

Earache

Sinusitis

Allergy

Gastroenteritis

Ear disorder (not specified)

Lymphadenopathy, cervical

Herpes zoster

Nausea

* Diaper rash

** Accidental/intentional overdose

POST MARKETING

In addition, the following adverse reactions have been reported for ampicillin class antibiotics and

may occur with amoxicillin and clavulanic acid oral suspension:

very common ≥1/10

common ≥1/100 and <1/10

uncommon ≥1/1000 and <1/100

rare ≥1/10000 and <1/1000

very rare <1/10000

Infections and infestations:

common

: mucocutaneous candidiasis.

Gastro-intestinal disorders:

very common:

diarrhoea

common:

nausea, vomiting

uncommon:

indigestion

rare

: gastritis, stomatitis, glossitis, black "hairy" tongue, enterocolitis. Antibiotic-associated colitis

(including pseudomembranous colitis and haemorrhagic colitis), See

PRECAUTIONS

Hepatobiliary:

uncommon

: moderate rise in AST and/or ALT.

rare

: Hepatitis, cholestatic jaundice which may be severe but is usually reversible.

Nervous system disorders:

uncommon:

dizziness, headache

very rare

: reversible hyperactivity, convulsions. Convulsions may occur in patients with impaired

renal function or those receiving high doses.

Haematopoietic and lymphatic systems:

uncommon:

thrombocytosis

rare

: anaemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, reversible leukopenia

(including neutropenia or agranulocytosis) these are usually reversible on discontinuation of therapy

and are believed to be hypersensitivity phenomena, prolongation of bleeding time and prothrombin

time.

Hypersensitivity and skin:

common

: skin rashes, pruritis, urticaria

rare

: angioneurotic oedema, anaphylaxis, serum-sickness-like syndrome, erythema multiforme,

Stevens-Johnson

syndrome,

hypersensitivity,

vasculitis,

toxic

epidermal

necrolysis,

bullous

exfoliative dermatitis and acute generalised exanthematous putulosis (AGEP) have been reported

rarely. Whenever such reactions occur, amoxicillin/clavulanic acid oral suspension should be

discontinued, unless in the opinion of the physician no alternative treatment is available and

continued use of amoxicillin/clavulanic acid oral suspension is considered essential. Serious and

occasional fatal hypersensitivity (anaphylactic) reactions and angioneurotic oedema can occur with

oral penicillins (See

PRECAUTIONS

Renal and urinary disorders:

rare

: interstitial nephritis

very rare:

crystalluria (see Overdosage)

Miscellaneous:

rare:

superficial tooth discolouration which can usually be removed by brushing.

DOSAGE AND ADMINISTRATION

AMOKLAVIN DUO 400/57 (amoxicillin and clavulanic acid) should be taken immediately before

or with the first mouthful of food,

to minimise potential gastrointestinal intolerance and to optimise

absorption.

Children aged 2 months up to 12 years

For moderate to severe infections the dose should be 45 mg/kg/day, based on the amoxicillin

component, (or 6.4mg/kg/day clavulanic acid) in two divided doses every 12 hours.

The children's dosage is intended for individuals whose weight will not cause dosage to be

calculated greater than that recommended for adults. Children weighing 40 kg and more should be

dosed according to the adult recommendations for other amoxicillin/clavulanic acid preparations

(available from other brand/s).

There are no clinical data available for amoxicillin and clavulanic acid in infants with immature

renal function. The use of AMOKLAVIN DUO 400/57 (amoxicillin and clavulanic acid) in this

group cannot be recommended.

Use in Hepatic Impairment

Data is currently insufficient for a dosage recommendation. Dose with caution and monitor

hepatic function at regular intervals.

Use in Renal Impairment

AMOKLAVIN DUO 400/57 (amoxicillin and clavulanic acid) is not recommended for use in

children with renal impairment or in haemodialysis. In children with renal impairment, dosage

should be adjusted according to degree of impairment using the alternative amoxicillin and

clavulanic acid (4:1 ratio) 125mg/31.25mg or 250mg/62.5mg formulations (available from other

brand/s).

Direction for reconstituting the oral suspension

Prepare the oral suspension at time of dispensing as follows: Tap bottle until all the powder flows

freely. Add approximately 1/2 of the total amount of water for reconstitution (see table below) and

shake vigorously to suspend powder. Add remainder of the water and again shake vigorously.

AMOKLAVIN DUO 400/57

(amoxicillin and clavulanic acid)

400/57 mg in 5 mL oral suspension

Bottle size

Amount of water

required for

reconstitution

Final volume of

reconstituted

oral suspension

100 mL (glass)

52 mL

60 mL

Shake oral suspension well before using. Reconstituted syrup must be stored under refrigeration

(2 -8°C) and discarded after 7 days.

OVERDOSAGE

Problems of overdosage with amoxicillin and clavulanic acid are unlikely to occur. If encountered,

gastrointestinal symptoms and disturbance of the fluid and electrolyte balance may be evident. They

may be treated symptomatically, with attention to the water/electrolyte balance.

Amoxicillin

crystalluria,

some

cases

leading

renal

failure,

been

observed

see

Precautions)

Amoxicillin may be removed from the circulation by haemodialysis.

Contact the Poisons Information Centre (telephone 13 11 26) for advice on overdose management.

PRESENTATION AND STORAGE CONDITIONS

Store dry powder below 25°C. Under these conditions the shelf life is 18 months.

Store reconstituted suspension at 2-8°C in a refrigerator. Under these conditions the shelf life is 7

days.

AMOKLAVIN DUO 400/57 (amoxicillin and clavulanic acid) Oral Suspension: Each 5mL of

reconstituted

white

cream,

orange-golden

syrup

flavoured

suspension

contains

amoxicillin (as trihydrate) and 57 mg clavulanic acid (as the potassium salt). It is presented in 100

mL amber coloured glass bottles containing white to cream dry powder for reconstitution in water

to form 60 mL of an oral suspension with white, opaque child-resistant cap.

NAME AND ADDRESS OF THE SPONSOR:

Deva Holdings (Australia) Pty Ltd

30 Periwinkle Drive,

Cranbourne East, VIC 3977

Australia

POISON SCHEDULE OF THE MEDICINE:

DATE OF FIRST INCLUSION IN THE AUSTRALIAN REGISTER OF THERAPEUTIC

GOODS (THE ARTG): 15 December, 2014

DATE OF MOST RECENT AMENDMENT:

Version 1.0

9-11-2018

Sandoz Inc. Issues Voluntary Nationwide Recall of One Lot of Losartan Potassium and Hydrochlorothiazide Due to the Detection of Trace Amounts of NDEA (N-Nitrosodiethylamine) Impurity Found in the Active Pharmaceutical Ingredient (API)

Sandoz Inc. Issues Voluntary Nationwide Recall of One Lot of Losartan Potassium and Hydrochlorothiazide Due to the Detection of Trace Amounts of NDEA (N-Nitrosodiethylamine) Impurity Found in the Active Pharmaceutical Ingredient (API)

Sandoz Inc. is voluntarily recalling one lot of Losartan Potassium Hydrochlorothiazide Tablets, USP 100mg/25mg to the consumer level. This product is being recalled due to the trace amount of an impurity, N-nitrosodiethylamine (NDEA) contained in the API Losartan, USP manufactured by Zhejiang Huahai Pharmaceutical Co. Ltd. Sandoz Inc. Losartan Potassium Hydrochlorothiazide product is manufactured by Lek Pharmaceuticals dd, Ljubljana, Slovenia. This impurity, which is a substance that occurs naturally in ...

FDA - U.S. Food and Drug Administration

19-9-2018

Modification of the existing maximum residue levels for potassium phosphonates in certain berries and small fruits

Modification of the existing maximum residue levels for potassium phosphonates in certain berries and small fruits

Published on: Tue, 18 Sep 2018 00:00:00 +0200 In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant LTZ Augustenberg submitted a request to the competent national authority in Germany to modify the existing maximum residue levels (MRLs) for the active substance potassium phosphonates in raspberries, blackberries, currants, blueberries, gooseberries and elderberries. The data submitted in support of the request were found to be sufficient to derive MRL proposals for all crops under c...

Europe - EFSA - European Food Safety Authority Publications

7-9-2018

Camber Pharmaceuticals, Inc. Issues Voluntary Nationwide Recall of Montelukast Tablets USP, 10mg 30Ct. due to Product/Label Mix-Up

Camber Pharmaceuticals, Inc. Issues Voluntary Nationwide Recall of Montelukast Tablets USP, 10mg 30Ct. due to Product/Label Mix-Up

Camber Pharmaceuticals, Inc. is voluntarily recalling one single lot of Montelukast Sodium Tablets, USP 10mg, to the consumer level. This recall of one batch of Montelukast Sodium Tablets, USP 10mg, lot# MON17384 Exp. 12/31/2019, was prompted because a complaint of a sealed bottle labeled as Montelukast 10mg 30 ct found to contain 90 tablets of Losartan Potassium Tablets, USP 50mg

FDA - U.S. Food and Drug Administration

18-5-2018

Unauthorized prescription antibiotic drugs seized from Gigi's Market in Ottawa, ON, may pose serious health risks

Unauthorized prescription antibiotic drugs seized from Gigi's Market in Ottawa, ON, may pose serious health risks

Health Canada has seized four unauthorized drugs from Gigi’s Market, 23 Montreal Road, Ottawa, ON. The products (Ampicillin, Kamox, Medampi and Medomox) are labelled to contain antibiotic drugs (ampicillin or amoxicillin) that can only be dispensed by a healthcare professional to a patient with a valid prescription. The products listed below have not been evaluated by Health Canada for safety, effectiveness or quality and may pose serious health risks.

Health Canada

15-3-2018

Duro-K 600 mg potassium chloride tablets

Duro-K 600 mg potassium chloride tablets

Advisory – lead content may exceed regulatory guidelines

Therapeutic Goods Administration - Australia

There are no news related to this product.