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.

SUMMARY CMI

FLUBICLOX Injection

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

WARNING: Important safety information is provided in a boxed warning in the full CMI. Read before using this medicine.

1. Why am I being given FLUBICLOX?

FLUBICLOX contains the active ingredient flucloxacillin sodium monohydrate. FLUBICLOX is an antibiotic used to treat some infections in different parts of the body caused by bacteria.

For more information, see Section 1. Why am I being given FLUBICLOX? in the full CMI.

2. What should I know before I am given FLUBICLOX?

Do not use if you have ever had an allergic reaction to FLUBICLOX, other penicillins or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I am given FLUBICLOX? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with FLUBICLOX and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How am I given FLUBICLOX?

FLUBICLOX will be given to you by a doctor or nurse. Your doctor will decide what the dose is 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.

More instructions can be found in Section 4. How am I given FLUBICLOX? in the full CMI.

5. What should I know after receiving FLUBICLOX?

Things you should 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 after you have been given FLUBICLOX, contact your doctor immediately.
  • If you develop yellow eyes and/or skin (jaundice) while, or soon after receiving FLUBICLOX, contact your doctor immediately.
  • If you get severe diarrhoea, tell your doctor or pharmacist immediately. Do this even if it occurs up to several weeks after FLUBICLOX has been stopped.
  • If you get a sore white mouth or tongue after you have been given FLUBICLOX, tell your doctor. Also tell your doctor if you get a vaginal itching or discharge.
  • If you become pregnant while you are receiving FLUBICLOX, tell your doctor.
  • If you have to have any tests tell your doctor you have been given FLUBICLOX.
  • Remind any doctor, dentist or pharmacist you visit that you are being treated with FLUBICLOX.
Things you should not do
  • Do not take any diarrhoea medicine without first checking with your doctor.
Driving or using machines
  • Be careful driving or operating machinery until you know how FLUBICLOX affects you.

For more information, see Section 5. What should I know after receiving FLUBICLOX? in the full CMI.

6. Are there any side effects?

Side effects include pain or redness at the site of injection, mild rash, oral thrush, vaginal thrush, nausea, stomach upsets, mild diarrhoea, constipation, dizziness or headaches.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

WARNING
Flucloxacillin (FLUBICLOX) can cause jaundice (yellowing of skin and/or eyes) and severe liver disease which may last for a long time. This reaction is more frequent in older patients (particularly those over 55 years of age) and those who receive the drug for more than 14 days.



FULL CMI

FLUBICLOX Injection

Active ingredient(s): flucloxacillin (as sodium)

Consumer Medicine Information (CMI)

This leaflet provides important information about using FLUBICLOX. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using FLUBICLOX.

Where to find information in this leaflet:

1. Why am I being given FLUBICLOX?
2. What should I know before I am given FLUBICLOX?
3. What if I am taking other medicines?
4. How am I given FLUBICLOX?
5. What should I know after receiving FLUBICLOX?
6. Are there any side effects?
7. Product details

1. Why am I being given FLUBICLOX?

FLUBICLOX contains the active ingredient flucloxacillin (as flucloxacillin sodium). 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 is an antibiotic used to treat some infections in different parts of the body caused by bacteria.

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

Your doctor may have prescribed FLUBICLOX for another reason.

There is no evidence that FLUBICLOX is addictive.

2. What should I know before I am given FLUBICLOX?

Warnings

Do not use FLUBICLOX if:

  • your skin and/or eyes have turned yellow (Jaundice) while, or soon after receiving flucloxacillin (FLUBICLOX).
  • you are allergic to flucloxacillin, other penicillins or any of the ingredients listed at the end of this leaflet. Some of the symptoms of an allergic reaction may include skin rash, itching, difficult breathing or swelling.
  • 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.
  • the packaging is torn or shows signs of tampering.
  • 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.

Check with your doctor if 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.
  • have any allergies to any other medicines or any other substances, such as foods, preservatives or dyes. This may include medicines that you buy without a prescription from your pharmacy, supermarket or health food shop.
  • Have or have ever had any other medical conditions including:
    - asthma, hayfever or hives
    - liver problems
    - kidney problems
    - glandular fever (infectious mononucleosis)
  • your skin and/or eyes have turned yellow (Jaundice) while, or soon after, receiving any antibiotics.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or breastfeeding, intend to become pregnant or breastfeed. Your doctor will discuss with you whether you can be given FLUBICLOX.

3. What if I am taking other medicines?

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

Some medicines may interfere with FLUBICLOX and affect how it works. These include:

  • probenecid (Benemid)
  • paracetamol
  • aminoglycosides.

Some antibiotics may decrease the effectiveness of some birth control pills. Talk to your doctor about the need for an additional method of contraception whilst receiving FLUBICLOX.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect FLUBICLOX.

4. How am I given FLUBICLOX?

How much is given

  • your doctor will decide what the dose is and for 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. Sometimes only a single dose of FLUBICLOX is required for the treatment and prevention of certain infections.

How FLUBICLOX is given

FLUBICLOX may be given in two ways:

  • as a slow injection into vein
  • as a deep injection into a large muscle, a joint or the sac surrounding the lung.

FLUBICLOX must only be given by a doctor or nurse.

If you use too much FLUBICLOX

As FLUBICLOX injection 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

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

5. What should I know after receiving FLUBICLOX?

Things you should do

Call your doctor straight away if:

  • the symptoms of your infection do not improve within a few days, or if they become worse.
  • you develop itching with swelling or skin rash or difficulty breathing after you have been given FLUBICLOX.
  • you develop yellow eyes and/or skin (jaundice) while, or soon after receiving FLUBICLOX.
  • you get severe diarrhoea. Do this even if it occurs up to 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.
  • you get a sore white mouth or tongue after you have been given FLUBICLOX. Also tell your doctor if you get a 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 have to have any tests, tell your doctor you have been given FLUBICLOX. FLUBICLOX may affect the results of some tests.

If you are about to start taking any new medicine, tell your doctor and pharmacist that you are receiving FLUBICLOX Remind any doctor, dentist or pharmacist you visit that you are being treated FLUBICLOX.

Things you should not do

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

Driving or using machines

Be careful before you drive or use any machines or tools until you know how FLUBICLOX affects you.

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

If you experience dizziness, do not drive.

If you drink alcohol, dizziness may be worse.

Looking after your medicine

FLUBICLOX injection is usually stored in the pharmacy or on the ward. Your doctor, pharmacist or nurse is responsible for storing FLUBICLOX and disposing of any unused product correctly.

Store it in a cool dry place where the temperature stays below 25°C.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

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

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

You may not experience any of them.

Less serious side effects

Less serious side effectsWhat to do
  • Pain or redness at the site of injection
  • oral thrush - white, furry, sore tongue and mouth
  • vaginal thrush - sore and itchy vagina and/or discharge
  • nausea or vomiting
  • upset stomach or belching after eating
  • mild diarrhoea or constipation
  • dizziness or headache
  • a mild rash.
  • Pain in the joints.
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • signs of allergic reaction, e.g. shortness of breath, wheezing, difficulty breathing, swelling of face, lips, tongue or other parts of the body
  • red and/or itchy skin, severe rash or hive on the skin
  • irregular heart beat
  • yellow skin and/or eyes
  • nausea, vomiting, loss of appetite, feeling generally unwell, fever, itching and dark coloured urine (this may be symptoms of hepatitis).
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Other side effects not listed here may occur in some people.

An illness consisting of a rash, swollen glands, joint pains and fever may occur about a week after treatment.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What FLUBICLOX contains

Active ingredient
(main ingredient)		Flucloxacillin sodium
Other ingredients
(inactive ingredients)		None

FLUBICLOX Powder for Injection contains no antiseptics or buffering agents nor are there any excipients.

Do not take this medicine if you are allergic to any of these ingredients.

What FLUBICLOX looks like

FLUBICLOX Injection is a white or almost white crystalline powder for injection contained in a clear glass vial. FLUBICLOX Injection is available in

500 mg (AUST R: 92841); Pack size: 5, 10's

1 g (AUST R 92842); Pack size: 5, 10's

2 g: (AUST R 302381) Pack size: 1, 10's

Who distributes FLUBICLOX

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

www.junopharm.com.au

This leaflet was prepared in September 2023.

Published by MIMS October 2023

BRAND INFORMATION

Brand name

Flubiclox

Active ingredient

Flucloxacillin

Schedule

S4

 

1 Name of Medicine

Flucloxacillin (as flucloxacillin sodium).

2 Qualitative and Quantitative Composition

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

Flubiclox is a white to off-white powder contained in a clear glass vial.

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.

4.2 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.

4.3 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.
Use in the eye.

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).
Serious anaphylactoid reactions require emergency treatment with adrenaline. Oxygen, intravenous steroids and airway management including intubation, should also be administered as indicated.

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.

High anion gap metabolic acidosis.

Caution is advised when flucloxacillin is administered concomitantly with paracetamol due to the increased risk of high anion gap metabolic acidosis (HAGMA). Patients at high risk for HAGMA are in particular those with severe renal impairment, sepsis or malnutrition especially if the maximum daily doses of paracetamol are used.
After co-administration of flucloxacillin and paracetamol, close monitoring is recommended in order to detect the appearance of acid-base disorders, namely HAGMA, including the testing of urinary 5-oxoproline.
If flucloxacillin is continued after cessation of paracetamol it is advisable to ensure that there are no signals of HAGMA, as there is a possibility of flucloxacillin maintaining the clinical picture of HAGMA (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in patients taking beta-lactam antibiotics. When SCAR is suspected, flucloxacillin should be discontinued immediately and an alternative treatment should be considered.
The occurrence at the treatment initiation of a feverish generalised erythema associated with pustule may be a symptom of acute generalised exanthematous pustulosis (AGEP). In case of AGEP diagnosis, flucloxacillin should be discontinued and any subsequent administration of flucloxacillin contraindicated.

Use in hepatic impairment.

Flucloxacillin should be used with caution in patients with evidence of hepatic dysfunction even though the latter is not a recognised predisposing factor to hepatic reactions to the drug.

Hepatitis.

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 (particularly over 55 years of age) or following prolonged treatment (more than 14 days). Jaundice may first appear several weeks after therapy: in some 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.

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.
Very high doses of flucloxacillin can cause hypokalaemia and sometimes hypernatraemia. In patients undergoing high-dose treatment for more than 5 days, electrolyte balance, blood counts, and renal function should be monitored. Additionally, use of a potassium-sparing diuretic may be helpful.

Use in the elderly.

See Hepatitis.

Paediatric use.

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.

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.
In common with other antibiotics, patients should be warned that flucloxacillin sodium may reduce the effectiveness of oral contraceptives.
Caution should be taken when flucloxacillin is used concomitantly with paracetamol as concurrent intake has been associated with high anion gap metabolic acidosis, especially in patients with risk factors. (See Section 4.4 Special Warnings and Precautions for Use).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B1)
The safety of flucloxacillin in the first trimester of pregnancy has not yet been established. Animal studies with flucloxacillin have shown no teratogenic effects. The product has been in clinical use since 1970 and the limited number of reported cases of use in human pregnancy have shown no evidence of untoward effect. The use of flucloxacillin in pregnancy should be reserved for cases considered essential by the clinician.
 Flucloxacillin sodium is excreted in breastmilk in trace amounts. An alternative feeding method is recommended to avoid any possible sensitisation of the newborn.

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.

4.8 Adverse Effects (Undesirable Effects)

As with all penicillins, the possibility of hypersensitivity reactions should always be considered. Reactions are more likely to occur in those with an allergic diathesis. Anaphylactic shock is most likely to occur with injected penicillins (see Section 4.4 Special Warnings and Precautions for Use).
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 exposures (see Section 4.4 Special Warnings and Precautions for Use).

Gastro-intestinal disorders.

Nausea, vomiting, diarrhoea and 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).

Immune system disorders, hypersensitivity reactions.

Erythematous maculopapular rashes, urticaria, purpura, eosinophilia and 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 and urinary disorders.

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

Pulmonary.

Bronchospasm.

Blood and lymphatic systems.

Haemolytic anaemia has been reported during therapy with flucloxacillin. 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.

Nervous system disorders.

Adverse effects have been reported rarely. They include dizziness and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses. As the blood brain barrier becomes more permeable in meningitis, toxic symptoms may be precipitated by lower levels of flucloxacillin in patients with meningitis.

Skin and subcutaneous tissue disorders.

A red, scaly rash with bumps under the skin and blisters - AGEP - acute generalized exanthematous pustulosis.
Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in beta-lactam antibiotics.

Metabolism and nutrition disorders.

Post marketing experience: very rare cases of high anion gap metabolic acidosis, when flucloxacillin is used concomitantly with paracetamol, generally in the presence of risk factors (see Section 4.4 Special Warnings and Precautions for Use).

Infections and infestations.

Vaginal or oral moniliasis may occur following the use of antibiotics.

General disorders and administration site conditions.

Pain may be experienced at the site of intramuscular injection and phlebitis at the site of intravenous injection.
Amongst the adverse events spontaneously reported to the Therapeutic Goods Administration (TGA), 61% were dermatological effects, 17% were jaundice, 16% were gastrointestinal reactions and 2.5% were CNS related.

Other.

Malaise, bad taste, sore throat, sore tongue, pruritus vulvae, arthralgia, 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.

4.9 Overdose

Symptoms.

No information is available, but it could be anticipated that overdosage with flucloxacillin would cause gastrointestinal and CNS symptoms (see Section 4.8 Adverse Effects (Undesirable Effects)). As the blood brain barrier becomes more permeable in meningitis, toxic symptoms may be precipitated by lower levels of flucloxacillin in patients with meningitis.
Flucloxacillin is not significantly removed from the circulation by haemodialysis. General supportive measures should be instituted.

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).

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.

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.
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).
Flucloxacillin sodium for injection is incompatible with aminoglycosides, amiodarone, atropine, buprenorphine, calcium gluconate, chlorpromazine, ciprofloxacin, diazepam, dobutamine, erythromycin lactobionate, metoclopramide, morphine sulphate, pefloxacin, pethidine, prochlorperazine edisylate and verapamil.

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.

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.

7 Medicine Schedule (Poisons Standard)

Schedule 4 (Prescription Only Medicine).

Summary Table of Changes