Consumer medicine information

Flubiclox for Injection

Flucloxacillin

BRAND INFORMATION

Brand name

Flubiclox

Active ingredient

Flucloxacillin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Flubiclox for Injection.

What is in this leaflet

This leaflet answers some common questions about FLUBICLOX.

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.

Your doctor has weighed the risks of you taking FLUBICLOX against the benefits this medicine is expected to have for you.

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

Keep this leaflet in a safe place You may need to read it again.

What is FLUBICLOX used for

FLUBICLOX is an antibiotic that belongs to a group of medicines called penicillins. These antibiotics work by killing the bacteria that are causing your infection.

FLUBICLOX, like other antibiotics, will not work against infections caused by viruses such as colds or the flu.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is not addictive.

This medicine is available only with a doctor’s prescription.

Before you are given FLUBICLOX

When you must not be given it

Do not use FLUBICLOX if:

  1. You have had an allergic reaction to flucloxacillin or other penicillins. Symptoms of an allergic reaction may include skin rash, itching, difficulty breathing or swelling.
  2. You have had an allergic reaction to cephalosporin antibiotics.
    You may have an increased chance of being allergic to FLUBICLOX if you are allergic to cephalosporins.
  3. You have a previous history of inflammation of the liver or yellow skin caused by flucloxacillin.
  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.
    If you are not sure if you should be given FLUBICLOX, talk to your doctor

WARNING
Liver Toxicity. FLUBICLOX can cause severe inflammation of the liver and yellow skin, which may be long lasting. This reaction is more frequent in older patients and those who take the drug for long periods.

Before you are given it

Tell your doctor or pharmacist 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 FLUBICLOX 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, or have ever had, any other medical conditions including:
  • asthma, hayfever or hives
  • liver problems
  • kidney problems
  • glandular fever (infectious mononucleosis)
  1. You are pregnant or intend to become pregnant. Your doctor will discuss the possible risks and benefits of using FLUBICLOX during pregnancy.
  2. You are breast-feeding or plan to breast-feed. Your doctor will discuss the possible risks and benefits of using FLUBICLOX while breast-feeding.

If you have not told your doctor or pharmacist any of the above, tell them before you are given FLUBICLOX.

Taking other medications

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

Some medicines may be affected by FLUBICLOX, or they may affect how well it works.
These include:

  • probenecid, a medicine used to treat gout
  • aminoglycosides; a group of antibiotic medicines used to treat some infections.

You may need different amounts of your medicine, or you may need to take different medicines.

Your doctor will advise you.

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

How FLUBICLOX is given

FLUBICLOX is available in three strengths – 500mg, 1g and 2g.

FLUBICLOX 500mg and 1g injection is diluted and then given:

  • as an injection into a vein
  • as a deep injection into a large muscle
  • in fluids given into a vein
  • into the space around the lungs
  • within a joint

FLUBICLOX 2g injection is diluted and then given:

  • as an injection into a vein
  • in fluids given into a vein

FLUBICLOX must only be given by a doctor or nurse.

Your doctor will decide what dose and how long you will receive FLUBICLOX.

This depends on your infection and other factors, such as your weight. For most infections, FLUBICLOX is usually given in divided doses throughout the day.

If you receive too much (overdose)

As FLUBICLOX is given to you under the supervision of your doctor, it is very unlikely that you will receive too much.

However, if you experience severe side effects after being given this medicine, tell your doctor immediately.

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26 in Australia) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much FLUBICLOX. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of an overdose may include the side effects listed below in the ‘Side Effects’ section, but are usually of a more severe nature.

While you are being given FLUBICLOX

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 FLUBICLOX, 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 FLUBICLOX has been stopped.

Diarrhoea may mean that you have a serious condition affecting your bowel. You may need urgent medical care. Do not take any diarrhoea medicine without first checking with your doctor.

If you get a sore white mouth or tongue while being treated with or soon after stopping FLUBICLOX, tell your doctor.

Also tell your doctor if you get vaginal itching or discharge. This may mean you have a fungal infection called thrush.

Sometimes the use of FLUBICLOX allows fungi to grow and the above symptoms to occur.

FLUBICLOX does not work against fungi.

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

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

If you have to have any blood or urine tests, tell your doctor you are being given FLUBICLOX.

FLUBICLOX may affect the results of some blood or urine tests.

Tell all the doctors dentists and pharmacists who are treating you that you are being given FLUBICLOX.

Things to be careful of

Be careful driving or operating machinery until you know how flucloxacillin affects you.

This medicine does not generally cause any problems with your ability to drive a car or operate machinery. However, as with many other medicines, flucloxacillin may cause dizziness in some people.

If you experience dizziness, do not drive.

If you drink alcohol, dizziness may be worse.

Side effects

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

Like other medicines, FLUBICLOX 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.

If you are over 65 years of age you may have an increased chance of getting side effects.

You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

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

  • oral thrush - white, furry, sore tongue and mouth
  • vaginal thrush - sore and itchy vagina and/or discharge
  • nausea, stomach upsets
  • mild diarrhoea or constipation
  • dizziness or headaches
  • pain or an uncomfortable feeling in the stomach or belching after eating.

The above list includes side effects which are usually mild.

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

  • signs of an allergic reaction, such as shortness of breath wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body
  • red and/or itchy skin, rash or hives on the skin
  • difficulty breathing
  • swelling
  • yellowing of the skin and/or eyes (these may be symptoms of a type of liver disease called jaundice)
  • nausea, vomiting, loss of appetite, feeling generally unwell, fever, itching and dark coloured urine (these may be symptoms of a type of liver disease called hepatitis)

The above list includes very serious side effects. You may need urgent medical attention. Serious side effects are rare.

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

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 FLUBICLOX

Storage

FLUBICLOX should be stored in the pharmacy or in the ward. The powder for injection is kept in a cool dry place where the temperature stays below 25°C.

After you finish using it

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

  • 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.

Product description

What it looks like

White or almost white crystalline powder for injection contained in a vial.

500 mg: 5, 10’s
1 g: 5, 10’s
2 g: 1, 10

Ingredients

Active ingredient:

Flucloxacillin as sodium

FLUBICLOX does not contain any other ingredients.

FLUBICLOX does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Sponsor

Australian Sponsor:

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

FLUBICLOX is available in the following strengths:

This leaflet was prepared in: January 2020.

Published by MIMS April 2020

BRAND INFORMATION

Brand name

Flubiclox

Active ingredient

Flucloxacillin

Schedule

S4

 

1 Name of Medicine

The name of the medicine is Flubiclox and it contains the active ingredient flucloxacillin as the sodium salt.

6.7 Physicochemical Properties

Chemical structure.


Chemical name.

(2S, 5R, 6R)-6- [[[3-(2-chloro-6-fluorophenyl)-5-methylisoxazol-4- yl]carbonyl]amino] -3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate.

CAS number.

[1847-24-1].

Molecular formula.

C19H16ClFN3NaO5S.H2O.

Molecular weight.

493.9.

2 Qualitative and Quantitative Composition

Flubiclox is a white to off-white powder contained in a clear glass vial.
Each vial contains 95-105% of the stated amount of flucloxacillin.
Each gram of flucloxacillin sodium monohydrate contains approximately 2 mmol of sodium.
Each 2 g product vial contains 2 g flucloxacillin (as flucloxacillin sodium monohydrate) and approximately 4.52 mmol (104 mg) sodium.
This product contains no excipients.

3 Pharmaceutical Form

Flucloxacillin 500 mg powder for injection.
Flucloxacillin 1 gram powder for injection.
Flucloxacillin 2 gram powder for injection.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

See Microbiology, Susceptibility tests below.

Microbiology.

Flucloxacillin sodium is a narrow spectrum antibiotic belonging to the isoxazolyl group of semi-synthetic penicillins which characteristically combine resistance to penicillinase with gastric acid stability and activity against Gram-positive organisms. It is not active against Gram-negative bacilli, methicillin resistant staphylococcus, nor Streptococcus faecalis.

Susceptibility tests.

Dilution or diffusion techniques - either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardised method (e.g. NCCLS). Standardised susceptibility test procedures require the use of laboratory control microorganisms 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 microorganism 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.

Note.

The prevalence of resistance may vary geographically for selected species and local information on resistance is desirable, particularly when treating severe infections.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

The pharmacokinetics of flucloxacillin sodium follow a similar pattern for both oral and intramuscular (i.m.) administration, however, since oral absorption is incomplete, higher peak plasma concentrations are achieved after i.m. injection.

Distribution.

Peak plasma concentrations occur approximately 30 minutes after i.m. injection with therapeutic concentrations persisting for about four hours. Doubling the dose can double the plasma concentration.

Metabolism.

Flucloxacillin sodium is approximately 93% protein bound and has been reported to have a plasma half-life of about one hour. The half-life is prolonged in neonates. Metabolism occurs to a limited extent with the unchanged drug.

Excretion.

The metabolites are excreted in the urine. Up to 90% of an i.m. dose is excreted within 6 hours. Flucloxacillin sodium is not removed from the circulation by dialysis.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of confirmed or suspected staphylococcal infections and other Gram-positive coccal infections including pneumonia, skin and skin structure and wound infections, infected burns and cellulitis.

4.3 Contraindications

Hypersensitivity to penicillins, cephalosporins and multiple allergens. Flucloxacillin sodium should not be given by sub-conjunctival injection.
Patients with a previous history of flucloxacillin sodium associated jaundice or hepatic dysfunction.
Lignocaine should not be used as a diluent for intramuscular injections in patients who are hypersensitive to lignocaine.

4.4 Special Warnings and Precautions for Use

Warning.

Liver toxicity.

Flucloxacillin sodium can cause severe hepatitis and cholestatic jaundice, which may be protracted. This reaction is more frequent in older patients and those who take the drug for prolonged periods (see Section 4.8 Adverse Effects (Undesirable Effects)).
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has been reported in patients on oral penicillin therapy. Before therapy with any penicillin, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. If an allergic reaction occurs, the drug should be discontinued and appropriate therapy instituted (e.g. adrenaline or other pressor amines, oxygen, antihistamines or corticosteroids).

Identified precautions.

Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including flucloxacillin sodium. A toxin produced with 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, electrolytes 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.

Use in hepatic impairment.

Hepatitis predominantly of a cholestatic type, has been reported (see Section 4.8 Adverse Effects (Undesirable Effects)). Reports have been more frequent with increasing age or following prolonged treatment (more than 14 days). Jaundice may first appear several weeks after therapy: in several cases the course of the reactions has been protracted and lasted for several months. Resolution has occurred with time in most cases. In rare cases, deaths have been reported, nearly always in patients with serious underlying disease or receiving concomitant medication.
During prolonged treatment it is advisable to check periodically for hepatic dysfunction in patients with impaired hepatic function.
Animal studies show that high doses of flucloxacillin reduce albumin bound bilirubin to 50 to 70% of the base line concentration. The drug should therefore be used with extreme caution in jaundiced neonates or premature infants.

Use in renal impairment.

The dose or dose interval may need modification in patients with renal failure as the half life in patients with renal failure is increased. As renal function is not fully developed in the neonate the risk/benefit ratio should be considered before administration to such patients.
Caution should be exercised in the treatment of patients with an allergic diathesis.
It should be recognised that each 1 g of flucloxacillin sodium contains 2.0 mmol of sodium.

Use in the elderly.

No data available.

Paediatric use.

No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Probenecid decreases the renal tubular secretion of flucloxacillin. Concurrent use with flucloxacillin sodium for injection may result in increased and prolonged blood levels of flucloxacillin.
It is recommended that flucloxacillin sodium for injection and aminoglycosides not to be mixed together in the same solution for injection due to possible precipitation and the gradual inactivation of the aminoglycosides under these circumstances.
Flucloxacillin sodium for injections should not be mixed with blood products or other proteinases fluids (e.g. protein hydrolysates).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B1)
The safety of flucloxacillin sodium in pregnancy has not been established.
Australian Definition of Pregnancy Classification B: Category B1 drugs have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage.
Flucloxacillin sodium is excreted in breastmilk in trace amounts. An alternative feeding method is recommended to avoid any possible sensitisation of the newborn.

4.8 Adverse Effects (Undesirable Effects)

The following adverse reactions have been reported as associated with the use of flucloxacillin sodium for injection.

Hepatic.

Hepatitis and cholestatic jaundice (occasionally severe) have been reported with a frequency of about 1 in 15,000 exposure (see Section 4.4 Special Warnings and Precautions for Use).

Gastro-intestinal.

Nausea, vomiting, diarrhoea, dyspepsia, constipation, abdominal pain, heartburn, and loss of appetite. As with other antibiotics, pseudomembranous colitis has been reported rarely (see Section 4.4 Special Warnings and Precautions for Use).

Hypersensitivity reactions.

Erythematous maculopapular rashes, urticaria, purpura, eosinophilia, angioneurotic oedema, and erythema nodosum. Anaphylaxis and erythema multiforme have been reported rarely. Certain reactions (fever, arthralgia and myalgia) sometimes develop more than 48 hours after the start of treatment. Whenever such reactions occur, flucloxacillin sodium for injection should be discontinued. (Note: Urticaria, other skin rashes and serum sickness-like reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids).

Renal.

Isolated cases of nephritis, interstitial nephritis, frequency of micturition and haematuria have been reported.

Pulmonary.

Bronchospasm.

Haemic and lymphatic systems.

Reactions such as anaemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leucopoenia and agranulocytosis have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.

Other.

Malaise, bad taste, sore throat, sore tongue, pruritus vulvae, dizziness, depression and headache.

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.

4.2 Dose and Method of Administration

Usual adult dosage.

Intramuscular.

250 mg 6 hourly.

IV injection/infusion.

250 mg to 1 g 6 hourly.

Intrapleural.

250 mg once daily.

Intra-articular.

250 to 500 mg once daily.

Note.

Systemic doses may be doubled where necessary in severe infections.

Children's dosage.

2 to 10 years: half adult dose. Under 2 years: quarter adult dose.

Note.

In severe infections dosage may be increased.

Dosage in patients with impaired liver function.

Adjustment of dosage may not be necessary as flucloxacillin is not metabolised in the liver to any appreciable extent. However, during prolonged treatment it is advisable to check periodically for hepatic dysfunction.

Dosage in patients with impaired renal function.

As flucloxacillin is excreted to a large extent by the kidney, the dose or dose interval may need modification in patients with renal failure, as the half life in patients with renal failure is increased. However, dosage recommendations for various plasma creatinine levels for patients with impaired renal function are not available. Flucloxacillin is not significantly removed by haemodialysis.

Directions for use.

500 mg and 1 gram vials.

Intramuscular.

Dissolve the contents of the 500 mg and 1 g vials in, respectively, 2 and 2.5 mL of Water for Injections B.P.

Intravenous.

Dissolve the contents of the 500 mg and 1 g vials in, respectively, 10 and 20 mL of Water for Injections B.P., and administer by slow i.v. injection over 3 to 4 minutes. Flucloxacillin sodium may also be added to infusion fluids or injected, suitably diluted, into drip tube over a period of 3 to 4 minutes.

Intrapleural.

Dissolve 250 mg in 5 to 10 mL of Water for Injections B.P.

Intra-articular.

Dissolve 250 mg to 500 mg in up to 5 mL Water for Injections B.P., or in 0.5% lignocaine hydrochloride solution.

2 gram vial.

Intravenous.

Dissolve 2 g in 40 mL Water for Injections. Administer by slow intravenous injection. Flucloxacillin may also be added to infusion fluids or injected, suitably diluted, into the drip tube over a period of 20-30 minutes.
Flucloxacillin 2 g, Powder for Solution for Injection or Infusion has a displacement volume of approximately 1.5 mL when reconstituted as described above.
Flucloxacillin Injection may be added to the following infusion fluids: water for injections, sodium chloride 0.9%, glucose 5%, sodium chloride 0.18% with glucose 4%, compound sodium lactate intravenous infusion (Ringer-Lactate solution; Hartmann's Solution).

Stability in solution.

Solutions of flucloxacillin sodium in water for injections should be freshly prepared. The maximum period that solutions of flucloxacillin (500 mg) in intravenous fluids (500 mL) of normal saline, glucose saline or 5% glucose are stable when stored at 2°C - 8°C (under refrigeration) is 24 hours. However, to reduce microbiological hazards, the solution should be used as soon as practicable after preparation.
For intramuscular use, dissolve 500 mg vial content in 2.0 mL Water for Injections BP or 1 g vial content in 2.5 mL Water for Injections BP.
Flucloxacillin sodium should not be mixed with blood products or other proteinaceous fluids (e.g. protein hydrolysates).
Flucloxacillin sodium contains no antimicrobial preservative. Product is for single use in one patient only. Discard any residue.

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 its registration.

4.9 Overdose

Symptoms.

No information is available.

Treatment.

The drug should be withdrawn and general supportive measures of symptomatic treatment instituted.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

This product has no excipients.

6.2 Incompatibilities

Ciprofloxacin.

Flucloxacillin 1 g with ciprofloxacin 200 mg in 100 mL solvent, causes immediate precipitation.

Pefloxacin.

Flucloxacillin 1 g/100 mL with pefloxacin 400 mg/100 mL in sodium chloride 0.9%, causes immediate precipitation; flucloxacillin 1 g/100 mL with pefloxacin 400 mg/100 mL in dextrose 5% in water, causes immediate precipitation.

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 light. Protect from moisture.

6.5 Nature and Contents of Container

Type I transparent, clear, glass vials. The vials sealed with rubber stoppers and an aluminium sealing ring with a flip-off cap.

Pack size.

500 mg: 5*, 10's; 1 g: 5*, 10's; 2 g: 1, 10's.

6.6 Special Precautions for Disposal

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

Summary Table of Changes