Consumer medicine information

Amoxiclav Juno

Amoxicillin + Clavulanic acid

BRAND INFORMATION

Brand name

Amoxiclav Juno

Active ingredient

Amoxicillin + Clavulanic acid

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Amoxiclav Juno.

What is in this leaflet

This leaflet answers some common questions about Amoxiclav Juno injection.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. In deciding to give you. Amoxiclav Juno, your doctor has weighed the risks of you taking Amoxiclav Juno against the benefits it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with this medicine. You may need to read it again.

What Amoxiclav Juno is used for

This product contains two active ingredients. One of these is a penicillin called amoxicillin and the other is clavulanic acid.

Amoxiclav injection belongs to the penicillin group of antibiotics.

This product is used to treat a wide range of infections caused by bacteria. These infections may affect the respiratory tract (bronchitis, pneumonia, tonsillitis, sinusitis), genito-urinary tract (cystitis, urethritis, pyelonephritis, gonorrhoea), gastrointestinal tract, (peritonitis, intra-abdominal sepsis) the ears (otitis media) and the skin. This product can also be used to prevent infections in major surgical procedures.

Amoxicillin clavulanic acid injection works by killing the bacteria that cause these infections. This medicine will not work against infections caused by viruses such as colds or the flu.

Your doctor may have prescribed this medicine for another reason.

Ask your doctor or pharmacist if you have any questions about why this medicine has been prescribed for you.

Before you take it

When you must not use Amoxiclav Juno

  1. Do not use Amoxiclav Juno if you are allergic to penicillins and cephalosporins or clavulanic acid.
  2. Do not use Amoxiclav Juno if you have a previous history of amoxicillin / clavulanic acid associated jaundice / hepatic dysfunction.
  3. You have had an allergic reaction to cephalosporin antibiotics. You may have an increased chance of being allergic to Amoxiclav Juno if you are allergic to cephalosporins.
  4. The packaging is torn or shows signs of tampering.
  5. The expiry date (EXP) printed on the pack has passed. If you use this medicine after the expiry date has passed, it may not work as well.

Talk to your doctor if you are unsure whether you have any of the conditions listed above.

Do not use Amoxiclav Juno if the packaging is torn or shows signs of tampering.

Do not use it to treat any other complaint unless your doctor says it is safe. Do not give this medicine to anyone else.

Before you are given Amoxiclav Juno

You must tell your doctor if:

  1. You have any type of allergic reaction to penicillin, amoxicillin or cephalosporin antibiotics. You may have an increased chance of being allergic to Amoxiclav Juno if you are allergic to cephalosporins.
  2. You have any allergies to any other medicines or any other substances, such as foods, preservatives or dyes.
  3. You have any other medical conditions, including:
  • asthma, hayfever or hives
  • kidney problems
  • glandular fever (infectious mononucleosis)
  1. Tell your doctor if you are pregnant or intend to become pregnant. Your doctor will discuss the possible risks and benefits of using Amoxiclav Juno during pregnancy.
  2. You are breast-feeding or plan to breast-feed. Your doctor will discuss the possible risks and benefits of taking / using Amoxiclav Juno while breast-feeding.

Tell your doctor if you have or have had any medical conditions, especially either of the following:

  • Reduced kidney function
  • On controlled potassium intake

If you have not told your doctor about any of the above, tell them before you use this medicine.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food store.

Some medicines may interfere with Amoxiclav Juno. These include:

  • allopurinol and probenecid, drugs used to treat high levels of uric acid in the blood such as gout and stone formations
  • The contraceptive pill. As with other antibiotics, you may need to use extra birth control methods e.g. condoms.
  • Other antibiotics such as tetracyclines, erythromycin, chloramphenicol and gentamicin.
  • Anticoagulants (used to prevent blood clots) such as warfarin.
  • Due to risk of disulfiram (Antabuse) like reaction in some patients treated with beta-lactam antibiotics, the ingestion of alcohol should be avoided during and for several days after treatment with AMOXYCLAV JUNO.

These medicines may be affected by Amoxiclav Juno, or they may affect how well it works. You may need different medicines. Your doctor will advise you.

Your doctor may have more information on medicines to be careful with or to avoid while taking Amoxiclav Juno.

You need to tell your doctor if you are using any other medicines.

If you are unsure whether you are taking one of the drugs that may interact with Amoxiclav Juno, ask your doctor or pharmacist. Your doctor or pharmacist can tell you what to do if you are taking any of such medicines.

If you have not told your doctor about any of these things, tell them before you take Amoxiclav Juno.

How Amoxiclav Juno is given

How Amoxiclav Juno is given

It must only be given by a doctor or nurse. Your doctor will decide what dose and how long you will receive it. This depends on your infection and other factors, such as your weight.

Amoxicillin / clavulanic acid may be administered either by slow intravenous injection over a period of 3 to 4 min directly into a vein or via a drip tube or by infusion over 30 to 40 min. This medicine is not suitable for intramuscular administration.

Children aged less than 3 months should be administered Amoxicillin / clavulanic acid by infusion only.

Amoxiclav Juno injection should be reconstituted with water for injection before use.

Treatment with amoxicillin / clavulanic acid may be initiated by the use of an intravenous preparation and completed with an appropriate oral presentation as will be considered appropriate for you.

While you are using Amoxiclav Juno

Things you must do

If the symptoms of your infection do not improve within a few days, or if they become worse, tell your doctor.

If you develop itching with swelling or skin rash or difficulty breathing while you are receiving Amoxiclav Juno, do not have any more and tell your doctor immediately.

If you get severe diarrhoea, tell your doctor, pharmacist or nurse immediately. Do this even if it occurs several weeks after Amoxiclav Juno has been stopped.

If you become pregnant while you are receiving Amoxiclav Juno, tell your doctor.

If you are about to start taking any new medicine, tell your doctor and pharmacist that you are receiving Amoxiclav Juno.

If you have to have any blood or urine tests, tell your doctor you are being given Amoxiclav. It may affect the results of some blood and urine tests.

Tell all the doctors, dentists and pharmacists who are treating you that you are being treated with Amoxiclav.

Avoid alcohol during and for several days after treatment.

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while using Amoxiclav Juno.

All medicines can have side effects.

Check with your doctor as soon as possible if you have any problems while being treated with Amoxiclav Juno, even if you do not think the problems are connected with the medicine or are not listed in this leaflet.

Like other medicines, Amoxiclav Juno can cause some side effects. If they occur, most are likely to be minor and temporary. However, some may be serious and need medical attention.

Tell your doctor if you notice any of the following and they worry you:

  • Headache
  • Nausea
  • Vomiting
  • Diarrhoea
  • Indigestion
  • Dizziness
  • Soreness of the mouth or tongue
  • Overgrowth of yeast infections (thrush).

Tell your doctor immediately if you notice any of the following:

  • Wheezing, swelling of the lips/mouth, difficulty in breathing, hayfever, lumpy rash (hives) or fainting. These could be symptoms of an allergic reaction.
  • pain around the site of injection
  • unusual bleeding or bruising
  • yellowing of the skin or eyes
  • dark urine or pale stools
  • Difficulty or pain on passing urine.
  • Severe diarrhoea.

Some people may get other side effects while being treated with Amoxiclav Juno.

Ask your doctor or pharmacist if you don't understand anything in this list.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After using Amoxiclav Juno

Tell your doctor immediately if you notice any of the following side effects, particularly if they occur several weeks after stopping treatment with Amoxiclav Juno:

  • severe stomach cramps or abdominal cramps
  • watery and severe diarrhoea, which may also be bloody
  • fever, in combination with one or both of the above.

These are rare but serious side effects. You may have a rare but serious condition affecting your bowel which may need urgent medical attention.

Do not take any diarrhoea medicine without first checking with your doctor.

How is Amoxiclav Juno stored

Amoxiclav Juno should be stored below 25°C.

It should be used immediately after reconstitution.

If storage is required, it may be stored at 5°C.

  • 3 hours at 20-25°C: Ringers Solution, Hartmann’s Solution; Ringer-Lactate Solution, Potassium Chloride and Sodium Intravenous Infusion B.P
  • 4 hours at 20-25°C: Sodium Lactate Intravenous Infusion, Sodium Chloride Intravenous Infusion B.P. 0.9% (w/v), Water sterile for injection
  • 8 hours at 2-8°C: Water sterile for injection, Sodium Chloride Intravenous Infusion B.P. 0.9% (w/v)

Product description

What it looks like

Amoxiclav Juno 500/100 Powder for Injection: sterile white to off-white powder providing amoxicillin sodium equivalent to 500 mg amoxicillin and potassium clavulanate equivalent to 100 mg clavulanic acid.

Amoxiclav Juno 1000/200 Powder for Injection: sterile white to off-white powder providing amoxicillin sodium equivalent to 1 g amoxicillin and potassium clavulanate equivalent to 200 mg clavulanic acid.

Amoxiclav Juno 2000/200 Powder for Injection: sterile white to off-white powder providing amoxicillin sodium equivalent to 2 g amoxicillin and potassium clavulanate equivalent to 200 mg clavulanic acid.

Ingredients

Active Ingredient:

Amoxicillin sodium
Potassium clavulanate

Manufacturer

Amoxiclav Juno is supplied in Australia by:

Juno Pharmaceuticals Pty Ltd
42 Kelso Street,
Cremorne, VIC – 3121
Australia

This leaflet was prepared in September 2020.

AUST R 269158

AUST R 269159

AUST R 269162

Doc ID: 78.JU.M.1.2

Published by MIMS November 2020

BRAND INFORMATION

Brand name

Amoxiclav Juno

Active ingredient

Amoxicillin + Clavulanic acid

Schedule

S4

 

1 Name of Medicine

Amoxicillin sodium, potassium clavulanate.

2 Qualitative and Quantitative Composition

Amoxiclav Juno 500/100.

Amoxiclav Juno 500/100 Powder for Injection consists of vials of sterile white to off-white powder providing amoxicillin sodium equivalent to 500 mg amoxicillin and potassium clavulanate equivalent to 100 mg clavulanic acid. Each vial contains 0.5 mmoL (19.6 mg) of potassium and 1.4 mmoL (31.4 mg) of sodium.

Amoxiclav Juno 1000/200.

Amoxiclav Juno 1000/200 Powder for Injection consists of vials of sterile white to off-white powder providing amoxicillin sodium equivalent to 1 g amoxicillin and potassium clavulanate equivalent to 200 mg clavulanic acid. Each vial contains 1.0 mmoL (39.3 mg) of potassium and 2.7 mmoL (62.9 mg) of sodium.

Amoxiclav Juno 2000/200.

Amoxiclav Juno 2000/200 Powder for Injection consists of vials of sterile white to off-white powder providing amoxicillin sodium equivalent to 2 g amoxicillin and potassium clavulanate equivalent to 200 mg clavulanic acid. Each vial contains 1.0 mmoL (39.3 mg) of potassium and 5.5 mmoL (125.9 mg) of sodium.
Amoxiclav Juno contains no other excipients.

3 Pharmaceutical Form

Amoxiclav Juno Powder for Injection consists of vials of sterile white to off-white powder.

4 Clinical Particulars

4.1 Therapeutic Indications

Amoxiclav Juno is an antibiotic alternative to narrow spectrum and broad-spectrum antibiotics for the treatment of polymicrobial infections; especially in mixed Gram negative and Gram positive infections, and situations where microbial confirmation has not yet been obtained.
Infections caused by amoxicillin susceptible organisms are amenable to Amoxiclav Juno treatment due to its amoxicillin content. Infections caused by β-lactamase producing amoxicillin resistant organisms are also amenable to Amoxiclav Juno due to its clavulanic acid content.
Susceptibility to Amoxiclav Juno will vary with geography and time. Local susceptibility data should be consulted where available, and microbiological sampling and susceptibility testing performed where necessary. Amoxicillin/clavulanic acid should be used in accordance with local official antibiotic-prescribing guidelines and local susceptibility data.
Amoxiclav Juno is indicated for the short term treatment of serious bacterial infections such as:
Upper respiratory tract infections (including ENT): e.g. mastoiditis, tonsillitis, otitis media, epiglotitis and sinusitis when accompanied by severe signs and symptoms.
Lower respiratory tract infections: e.g. acute exacerbations of chronic bronchitis, lobar, broncho-pneumonia and community acquired pneumonia.
Genito-urinary tract infections: e.g. cystitis, urethritis, pyelonephritis, female genital infections.
Gastrointestinal infections: e.g. intra-abdominal sepsis, peritonitis.
Skin and skin structure infections, in particular cellulitis, animal bites, diabetic foot infections, vascular surgery infection/ischaemic soft tissue infection, severe dental abscess.
Other infections: e.g. septic abortion, puerperal sepsis, post-surgical infections.
Amoxiclav Juno is indicated for prophylaxis against infection in major surgical procedures that may be associated with higher risk of infectious complications e.g. gastrointestinal surgery.

4.2 Dose and Method of Administration

Dosage.

Doses are expressed throughout in terms of amoxicillin/clavulanic acid content (i.e. each 1.2 g dose provides 200 mg clavulanic acid with 1 g amoxicillin).
The dose that is selected to treat individual infections should take into account:
The expected pathogens and their likely susceptibility to antibacterial agents.
The severity and the site of the infection.
The age, weight and renal function of the patient as shown below.
The duration of therapy should be determined by the response of the patient. Some infections (e.g. osteomyelitis) require longer periods of treatment. Treatment should not be extended beyond 14 days without review.
Amoxiclav Juno powder for injection is for administration by IV or IVI route after reconstitution. Amoxiclav Juno powder for Injection is not for intramuscular administration.
Consideration should be given to local therapeutic guidelines on appropriate dosing frequencies for amoxicillin/clavulanic acid.

Adults and children 40 kg and over.

Usually 1.2 g eight hourly. In more serious infections, increase the frequency to six-hourly intervals.
If higher doses are required, the dosage can be increased to 2.2 g eight hourly. In more serious infections, increase the frequency to six hourly.

Children 3 months-12 years.

Usually 30 mg/kg 8 hourly. In more serious infections, increase frequency to 6 hourly intervals.

Children 0-3 months.

30 mg/kg every 12 hours in infants < 4 kg and 30 mg/kg every 8 hours in infants > 4 kg.

Elderly.

No dose adjustment is considered necessary, unless there is evidence of renal impairment.

Dosage for surgical prophylaxis.

Adults.

Surgical prophylaxis with amoxicillin/clavulanic acid should aim to protect the patient for the period of risk of infection.
The recommended dose is 1.2 g or 2.2 g of Amoxiclav Juno given at induction of anaesthesia with a further 1.2 g or 2.2 g of Amoxiclav Juno given after 2 hours if necessary.
Clear clinical signs of infection at operation will require a normal course of IV or oral therapy post-operatively.

Dosage in renal impairment.

Adults and children 40 kg and over.

Each 600mg vial contains 0.5 mmoL (19.6 mg) of potassium and 1.4 mmoL (31.4 mg) of sodium (approx.).
Each 1.2 g vial contains 1.0 mmoL (39.3 mg) of potassium and 2.7 mmoL (62.9 mg) of sodium (approx.).
Each 2.2 g vial contains 1.0 mmoL (39.3 mg) of potassium and 5.5 mmoL (125.9 mg) of sodium (approx.).
Dosing adjustments are based on the maximum recommended level of amoxicillin. See Table 1.

Children under 40 kg.

(See Table 2).

Dosage in hepatic impairment.

Dose with caution; monitor hepatic function at regular intervals for both adults and children.
There are as yet insufficient data on which to base a dosage recommendation.

Dosage in elderly.

No adjustment needed, dose as for adults. If there is evidence of renal impairment, dose should be adjusted as for renally impaired adults (see Tables 1 and 2).

Method of administration.

Reconstituted amoxicillin/clavulanic acid solutions are stable for 20 minutes when stored at room temperature with the diluent sterile water for injections.
Amoxicillin/clavulanic acid may be administered either by slow intravenous injection over a period of 3 to 4 min directly into a vein or via a drip tube or by infusion over 30 to 40 min. This medicine is not suitable for intramuscular administration.
Children aged less than 3 months should be administered amoxicillin/clavulanic acid by infusion only.
Treatment with amoxicillin/clavulanic acid may be initiated by the use of an intravenous preparation and completed with an appropriate oral presentation as considered appropriate for the individual patient.

Reconstitution of powder.

600 mg vial: to reconstitute dissolve in 10 mL of Water for Injections B.P. (final volume 10.5 mL).
1.2 g vial: to reconstitute dissolve in 20 mL of Water for Injections B.P. (final volume 20.9 mL).
2.2 g vial: to reconstitute dissolve in 20 mL of Water for Injections B.P. (final volume 20.9 mL).

Preparation of infusion.

Add without delay the 600 mg reconstituted solution to 50 mL infusion fluid or the 1.2 g and 2.2 g reconstituted solutions to 100 mL infusion fluids (e.g. using a mini-bag or in-line burette).
Satisfactory antibiotic concentrations are retained at 5°C and at room temperature (25°C) in the recommended volumes of the following infusion fluids. If reconstituted and maintained at room temperature, infusions should be completed within the time stated (See Table 3).
For storage at 5°C, the reconstituted solution should be added to pre-refrigerated infusion bags which may be stored for up to 8 hours. Thereafter, the infusion should be administered immediately after reaching room temperature.
Amoxicillin/clavulanic acid is less stable in infusions containing glucose, dextran or bicarbonate. Reconstituted solution should therefore not be added to such infusions but may be injected into the drip tubing over a period of 3-4 minutes.
Amoxicillin/clavulanic acid Intravenous should not be mixed with blood products, other proteinaceous fluids such as protein hydrolysates or with intravenous lipid emulsions.
Amoxiclav Juno vials are not suitable for multi-dose use. Product is for single use in one patient only. Discard any residue.

4.3 Contraindications

In patients with a history of hypersensitivity to beta-lactams, e.g. penicillins and cephalosporins.
In patients with a previous history of amoxicillin/clavulanic acid associated jaundice/hepatic dysfunction.

4.4 Special Warnings and Precautions for Use

Serious, and occasionally fatal, hypersensitivity reactions (anaphylaxis) have been reported in patients receiving beta-lactam antibiotics, e.g. penicillins. Before commencing therapy with any beta-lactam antibiotic, careful enquires should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. If a hypersensitivity reaction occurs, appropriate therapy should be instituted and amoxicillin/clavulanic acid therapy discontinued.
Serious anaphylactic reactions require emergency treatment with adrenaline. Oxygen, intravenous steroids and 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 of antibiotic therapy). Mild cases usually respond to drug discontinuation alone. However in moderate to severe cases, appropriate therapy with a suitable oral antibacterial agent effective against Clostridium difficile should be considered. Fluids, electrolyte and protein replacement should be provided when indicated. Drugs which delay peristalsis, e.g. opiates and diphenoxylate with atropine (Lomotil) may prolong and/or worsen the condition and should not be used.
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.
Amoxicillin is not the treatment of choice in patients presenting with sore throat or pharyngitis. This is because of the possibility that the underlying cause may be infectious mononucleosis, in the presence of which there is a high incidence of rash if amoxicillin is used. Patients with lymphatic leukaemia also appear to have a higher incidence of skin rashes when treated with amoxicillin.
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.
In general amoxicillin/clavulanic acid is well tolerated and possesses the characteristic low toxicity of the penicillin group of antibiotics. However, as with any potent drug, periodic assessment of renal, hepatic and haematopoietic function should be made during prolonged therapy. The possibility of super-infections with mycotic or bacterial pathogens should be kept in mind during therapy. If super-infections occur (usually involving Enterobacter, Pseudomonas or Candida), the drug should be discontinued and/or appropriate therapy instituted.

Sodium and potassium content.

The 500 mg/100 mg powder for solution for injection or infusion contains 31.4 mg (1.4 mmol) of sodium per vial. This should be taken into consideration by patients on a controlled sodium diet. It also contains 19.6 mg (0.5 mmol) of potassium per vial. This should be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet.
The 1000 mg/200 mg powder for solution for injection or infusion contains 62.9 mg (2.7 mmol) of sodium per vial. This should be taken into consideration by patients on a controlled sodium diet. It also contains 39.3 mg (1.0 mmol) of potassium per vial. This should be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet.

Use in hepatic impairment.

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.
Amoxicillin/clavulanic acid should be used with caution in patients with evidence of hepatic dysfunction.

Use in renal impairment.

Amoxicillin has been found to cause dose-related renal toxicity in laboratory animals when administered daily as a bolus injection at dose levels of 100 mg/kg/day and above. As the metabolic pattern of amoxicillin in humans appears to be similar to that in animals, the possibility of nephrotoxic effect from amoxicillin should be borne in mind, as must the possibility of venous irritation.
During treatment with high doses of amoxicillin, particularly by bolus injection, an adequate fluid intake and urinary output must be maintained. Also indwelling catheters should be checked regularly for patency since, due to high urinary concentrations, amoxicillin may, at room temperature, precipitate out of solution. The risk of crystalluria should be avoided by maintaining a high urinary output. Dosage should be adjusted in severe and moderate renal impairment (see Section 4.2 Dose and Method of Administration).

Use in the elderly.

No data available.

Paediatric use.

No data available.

Effects on laboratory tests.

As administration of amoxicillin will result in high amoxicillin concentrations in the urine, false positive reactions may be elicited when testing the urine for glucose with Clinitest, Benedict's solution or Fehling's solution. Tests based on enzymatic glucose oxidase reactions such as Testape or Clinistix should be used instead.
The presence of clavulanic acid in Amoxiclav Juno may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test.

4.5 Interactions with Other Medicines and Other Forms of Interactions

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.

Allopurinol.

The concurrent administration of allopurinol and amoxicillin increases substantially the incidence of rashes in patients receiving both drugs as compared to patients receiving amoxicillin alone. It is not known whether this potentiation of amoxicillin rashes is due to allopurinol or the hyperuricemia present in these patients. There are no data with amoxicillin/clavulanic acid and allopurinol administered concurrently.

Oral contraceptives.

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

Oral anticoagulants.

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 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.

Tetracyclines and other bacteriostatic drugs.

Tetracyclines and other bacteriostatic drugs may interfere with the bactericidal effects of amoxicillin.

Alcohol.

No information is available about the concurrent use of IV amoxicillin-clavulanic acid and alcohol. However, the ingestion of alcohol whilst being treated with the beta-lactam antibiotics has precipitated a disulfiram (Antabuse) like reaction in some patients. Therefore the ingestion of alcohol should be avoided during and for several days after treatment with Amoxiclav Juno.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Amoxicillin/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.
(Category B1)
Reproduction studies in animals (mice and rats at doses up to 10 times the human dose) with orally and parentally administered amoxicillin/clavulanic acid 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 amoxicillin/clavulanic acid may be associated with an increased risk of necrotising enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy, unless considered essential by the physician.
 Amoxicillin is excreted in the milk. Therefore, caution should be exercised when amoxicillin/clavulanic acid is administered to a nursing woman.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of this registration.

4.8 Adverse Effects (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 amoxicillin/clavulanic acid, sorted by MedDRA System Organ Class are listed below.
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. Not known: overgrowth of non-susceptible organisms.

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. Not known: meningitis.

Vascular disorders.

Rare: thrombophlebitis at the site of injection.

Gastrointestinal disorders following intravenous administration.

Common: diarrhoea. Uncommon: nausea, vomiting, indigestion. Very rare: antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis) (see Section 4.4 Special Warnings and Precautions for Use) are less likely to occur after parenteral administration.

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 (see Section 4.4 Special Warnings and Precautions for Use).

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

Renal and urinary disorders.

Very rare: interstitial nephritis, crystalluria (see Section 4.9 Overdose).

General disorders and administration site conditions.

Uncommon: Fever.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. They may be treated symptomatically, with attention to the water/electrolyte balance.
Amoxicillin crystalluria, in some cases leading to renal failure, has been observed.
Amoxicillin has been reported to precipitate in bladder catheters after intravenous administration of large doses. A regular check of patency should be maintained.
Amoxicillin/clavulanic acid can be removed from the circulation by haemodialysis.
A prospective study of 51 paediatric patients at a poison control centre suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms and do not require gastric emptying.
Convulsions may occur in patients with impaired renal function or in those receiving high doses.

Drug abuse and dependence.

Drug dependency, addiction and recreational abuse have not been reported as a problem with this compound.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Microbiology.

Amoxicillin is a semi synthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBP's) 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. Beta-lactamase related resistance can be constitutive or acquired (plasmid mediated beta-lactamases).
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 microorganisms resistant to penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid mediated betalactamases frequently responsible for transferable drug resistance. It is generally less effective against chromosomally-mediated type 1 beta-lactamases, such as found in Enterobacter, Serratia and Citrobacter species.
The presence of clavulanic acid in Amoxiclav Juno formulations protects amoxicillin from degradation by beta-lactamase enzymes and effectively extends the antibacterial spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other penicillins and cephalosporins.
In Table 4, organisms are categorised according to their in vitro susceptibility to amoxicillin-clavulanate.

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.
Non-susceptibility and resistance rates to amoxicillin/clavulanic acid for the top six ranked species tested is presented in Table 5 (extracted from the Australian Group on Antimicrobial Resistance Enterobacteriaceae Sepsis Outcome Programme (ENSOP) 2013 Antimicrobial Susceptibility Report). Testing was performed by two commercial semi-automated methods.
Acquired resistance data for amoxicillin/clavulanic acid in Australia (extracted from the Australian Group on Antimicrobial Resistance Enterobacteriaceae Sepsis Outcome Programme (ENSOP) 2013 Antimicrobial Susceptibility Report) is presented in Table 6. This data is presented for both CLSI and EUCAST criteria respectably.
*For EUCAST interpretation, the clavulanate is fixed at 2 mg/L, rather than a 2:1 ratio used in CLSI guidelines. As all cards used have a 2:1 ratio of clavulanate no EUCAST category has been applied.

Comments.

Intermediate susceptibility or resistance to amoxicillin-clavulanate is intrinsic in Enterobacter spp., due to natural β-lactamases, and hence resistance rates not reported here. Some strains may test as susceptible in vitro, but are generally reported as resistant. Intermediate susceptibility is common in E. coli due to hyperproduction of acquired narrow-spectrum β-lactamases, and in Klebsiella spp. due to higher levels of natural β-lactamases.
The CLSI M100-A241 and EUCAST v4.02 breakpoints from January 2014 have been employed in the analysis.

Susceptibility testing.

Dilution or diffusion techniques.

Either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardised method (e.g. CLSI, EUCAST). Standardised susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures.
CLSI and EUCAST disc diffusion, CDS and dilution tests are internationally acceptable and should be employed to determine susceptibility.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Following intravenous injection of amoxicillin over a 3 to 4 minute period the serum half-life measured as unchanged (active) antibiotic in the excretory phase, is approximately 1 hour in the presence of normal renal function, rising to about 7 hours with a creatinine clearance of 13 mL/minute without dialysis. The elimination half-life does not appear to change until creatinine clearance reaches approximately 30 mL/minute. In patients with a creatinine clearance of 10 mL/minute, elimination half-life has been shown to vary between 7.5 and 21 hours after a 2 g intravenous dose.
After 30 min intravenous infusion (100 mg) peak serum concentrations of clavulanic acid were attained immediately after completion of infusion. The mean peak serum level for clavulanic acid was 8 microgram/mL. The corresponding area under the serum concentration curve for clavulanic acid was 8.2 microgram/mL.hr. The mean serum half-life of clavulanic acid in healthy volunteers is 64 minutes.

Distribution.

Amoxicillin and clavulanic acid are not highly bound to human serum protein. The degree of binding of amoxicillin is 17%, whereas clavulanic acid has been variously reported to be bound to human serum in the range of 9 to 30%.
Penetration of amoxicillin into the CSF is poor in the absence of inflammation. Some penetration occurs though inflamed meninges but maximum CSF levels are very much lower than peak serum levels. Bile levels vary with the functional integrity of secretory mechanisms, being absent in the presence of biliary tract obstruction.

Excretion.

The major route of excretion for amoxicillin is renal (by glomerular filtration and tubular secretory mechanisms). The secretory mechanisms may be inhibited by the concurrent administration of probenecid, leading to prolonged and some elevation of serum levels. If renal function is normal, approximately 70% of a dose administered by intramuscular or rapid intravenous injection will be excreted unchanged within six hours, and approximately 20% will be excreted as the penicilloic acid derivative in the same time. In patients with renal failure, renal excretion falls in relation to the glomerular filtration rate but therapeutic levels are still maintained in the urine. Results of studies in man, employing thin layer chromatography and bioautography, show that amoxicillin is not changed in vivo into substances with antibacterial activity. There appears to be only one metabolic breakdown product, namely, penicilloic acid.
Approximately 35 to 45% of clavulanic acid is excreted unchanged in urine during the first 6 hours after administration to normal volunteers with normal renal function. During the first two hours after intravenous injection, concentrations of clavulanic acid in urine exceeds 40 microgram/mL following administration of 100 mg. By 4 to 6 hours after injection, the urine concentration of clavulanic acid declines to approximately 2 microgram/mL.

5.3 Preclinical Safety Data

Genotoxicity.

The genotoxic potential of amoxicillin/clavulanic acid was investigated in assays for chromosomal damage (mouse micronucleus test and a dominant lethal test) and gene conversion. All were negative.

Carcinogenicity.

Carcinogenicity studies have not been conducted with amoxicillin/clavulanic acid or its components.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from moisture. Protect from light.

6.5 Nature and Contents of Container

Amoxiclav Juno 600 mg, 1.2 g and 2.2 g Powder for Injection is presented in type III transparent, clear glass vials with a nominal capacity of 20 mL closed with chlorobutylic rubber stopper and aluminium seal.
(Not all pack sizes may be marketed).

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Amoxicillin sodium is a white or almost white, crystalline powder, very hygroscopic, very soluble in water. pH of the aqueous solution is 8.0 to 10.0.
Potassium clavulanate is a white or almost white, hygroscopic, crystalline powder and is freely soluble in water. A 1% solution in water has a pH of 5.5 to 8.0.
Amoxiclav Juno Powder for Injection is a combination product containing the semisynthetic antibiotic, amoxicillin sodium and the β-lactamase inhibitor, potassium clavulanate (as the potassium salt of clavulanic acid).

Amoxicillin sodium.

Chemical name.

(2S,5R,6R)-6- [[(2R)-2-amino-2- (4-hydroxyphenyl)acetyl] amino]-3,3- dimethyl-7-oxo- 4-thia-1-azabicyclo [3.2.0]heptane-2-carboxylate.

Chemical structure.


CAS number.

34642-77-8.

Molecular weight.

387.4.

Molecular formula.

C16H18N3NaO5S.

Potassium clavulanate.

Chemical name.

Z-(2R,5R)-3-(2- hydroxyethylidene) 7-oxo-4- oxa-1-azabicyclo[3.2.0] heptane-2-carboxylate.

Chemical structure.


CAS number.

61177-45-5.

Molecular weight.

237.25.

Molecular formula.

C8H8KNO5.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription only Medicine.

Summary Table of Changes