What it is and what it is used for

for Flucloxacillin belongs to a group of medicines called penicillins, which are antibiotics. These medicines work by killing bacteria that cause infections. Flucloxacillin Injection is used for the treatment of a range of bacterial infections including bone infections (osteomyelitis) and infections within the lining of the heart (endocarditis). It is also used to prevent infections that can occur during major surgical operations such as heart and lung operations (cardiothoracic surgery) and bone, joint and muscle operations (orthopaedic surgery).

What you need to know before you take it

e Flucloxacillin Injection

Customer

Wockhardt UK Limited

Description

Flucloxacillin Inj Vial Common Labesfal

Item Code

108771/1

Profile

as per uploaded pdf

Size

600 x 210mm

Min.Point Size

9pt (Leaflet)

Market

UK

DATE

Warning! We cannot accept responsibility for any errors in this proof after approval. Whilst we take extreme care at all times to ensure accuracy to our client's brief, the final responsibility must be taken by our client. IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING FULL APPROVAL OF DESIGN AND TEXT.

Language

English

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Pharma Height

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SBL

Proof No.

3

Date

25.04.2024

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Your doctor or nurse will prepare your injection by mixing the Flucloxacillin Injection powder with a liquid such as water for injections, either in the vial or in another container. The mixture is usually injected into a muscle, or into a vein when it will be given slowly over three to four minutes using a syringe or drip (infusion). In certain circumstances Flucloxacillin Injection can be injected directly into an infected joint or the chest wall, or breathed in as a mist. Flucloxacillin is usually given as an intramuscular injection, slow intravenous injection and intravenous infusion. It may also be given by articular or intrapleural injection or inhaled. Flucloxacillin should not be given into the eye or the spine. Adults The recommended dose by intramuscular injection or infusion is 250mg every six hours. The recommended adult dose by intravenous injection is 250mg to 1g every six hours. These doses may be doubled in severe infections. Doses of up to 8g a day may be required for osteomyelitis or endocarditis. To prevent surgical infections you will be given 1 to 2g with your anaesthetic followed by 500mg every six hours. Use in children The recommended dose for children aged two to ten years is half the adult dose. The recommended dose for children under two years old is a quarter of the adult dose. Special care should be taken in newborn babies to prevent the risk of overdosing. Injections into joints or the chest, or inhalation of Flucloxacillin Injection The usual doses are:

• into infected joint – 250 to 500mg once a day
• into chest – 250mg once daily
• by inhaler – 125 to 250mg every six hours. Severe kidney disease If you have severe kidney failure you may be given a lower dose or you may receive your doses less frequently. Your doctor will decide the dose that is best for you. If you do not understand, or are in any doubt, ask your doctor or nurse. If you are given more Flucloxacillin Injection than you should A doctor or nurse will give you this medicine. If you think you may have received too much Flucloxacillin Injection, please tell your doctor or nurse immediately. Symptoms of an overdose may include fits, behaviour disorders, fever, weakness, breathlessness, bleeding more easily and longer than usual, or changes to the salt levels in the blood. If you think you have missed a dose of Flucloxacillin Injection A doctor or a nurse will give you this medicine. If you think you have missed a dose, please tell your doctor or nurse. If you have any further questions on the use of this medicine, ask your doctor or nurse.

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16 East Park Road | Leicester | LE5 4QA | UK

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How to take it

Flucloxacillin Injection

Actual Min Point Size 9pt

4. Possible side effects Like all medicines, this medicine can cause side effects, although not everybody gets them. Tell your doctor immediately if you notice any of the following side effects as they may be a sign of an allergic or sensitivity reaction:

• rash
• itching
• redness and blistering of the skin
• fever
• aching joints
• swelling of the face, throat or hands
• difficulty breathing
• anaemia
• kidney problems
• blood problems (causing a sore throat, mouth ulcers, repeated infections or a tendency to bleed easily)
• fits (convulsions) and other problems affecting the nervous system
• serious skin reactions
• a red, scaly rash with bumps under the skin and blisters (exanthematous pustulosis). Also tell your doctor immediately if you develop any of the following:
• tenderness of the upper abdomen which may indicate inflammation of the liver or jaundice (yellow skin and whites of eyes)
• severe diarrhoea. Treatment with Flucloxacillin can affect the normal bacteria in the gut, causing a new infection (pseudomembranous colitis). Hepatitis (inflammation of the liver) and jaundice may be long lasting. They are more likely in the elderly or patients who have been given flucloxacillin for more than two weeks. You should tell your doctor if you develop any of the symptoms above, even if they occur some weeks after you have stopped having the injections. Other side effects include:
• shortness of breath
• difficulty in breathing or wheezing
• tender red lumps under the skin
• blistering of the skin
• red or purple skin discolouration
• inflammation of blood vessels, often with skin rash
• severe attacks of porphyria (an inherited blood disorder)
• hallucinations
• feeling sick
• being sick
• thrush in the mouth
• coma
• high salt levels in the blood
• redness and pain around the area of infusion. Very rare (may affect up to 1 in 10,000 people): Very rare cases of blood and fluid abnormality (high anion gap metabolic acidosis) which occurs when there is an increase in plasma acidity, when flucloxacillin is used concomitantly with paracetamol, generally in the presence of risk factors (see section 2). Not known (cannot be estimated from the available data):
• Low potassium levels in the blood (hypokalaemia), which can cause muscle weakness, twitching or abnormal heart rhythm.

If you have syphilis Patients who have syphilis or leptospirosis (Weil's disease) have occasionally suffered from a type of reaction (Jarisch-Herxheimer reaction) shortly after their injection, with fever, chills, headache and sometimes heart or eye problems. If you receive high doses or a long course of treatment Your doctor may take blood tests during your treatment to check your liver, kidneys and blood, particularly if you receive high doses or a long course of treatment. Reporting of side effects If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report

Possible side effects

directly via the Yellow Card Scheme www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store By reporting side effects you can help provide more information on the safety of this medicine.

How to store it

Flucloxacillin Injection

Please be ready to give the following information Product name

Reference number

Flucloxacillin 250mg Powder for Solution for Injection or Infusion

PL 29831/0091

Flucloxacillin 500mg Powder for Solution for Injection or Infusion

PL 29831/0092

Flucloxacillin 1g Powder for Solution for Injection or Infusion

PL 29831/0093

This is a service provided by the Royal National Institute of Blind People. Marketing Authorisation Holder and Manufacturer Marketing Authorisation Holder: Wockhardt UK Ltd, Ash Road North, Wrexham, LL13 9UF, UK Manufacturer: CP Pharmaceuticals Ltd, Ash Road North, Wrexham, LL13 9UF, UK This leaflet was last revised in 04/2024

Keep this medicine out of the sight and reach of children.

• Flucloxacillin Injection should not be used after the expiry date given on the vial. The expiry date refers to the last day of that month
• Your doctor, nurse or pharmacist will be responsible for storing and preparing Flucloxacillin Injection before use and for checking that the vials have not passed their expiry date
• The medicine should not be used if it shows any signs of deterioration such as going cloudy
• Do not store above 25oC
• Once the solution has been diluted the product should be used immediately. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

Contents of the pack and other information

What Flucloxacillin Injection contains The active substance is flucloxacillin as flucloxacillin sodium monohydrate. There are no other ingredients. What Flucloxacillin Injection looks like and contents of the pack Flucloxacillin Injection is a white or almost white powder for solution for injection/infusion. Flucloxacillin Injection is supplied in glass vials fitted with a grey bromobutyl rubber stopper and sealed with an aluminium crimped flip-off cap. Flucloxacillin Injection is available in packs of 10 vials. Other formats To listen to or request a copy of this leaflet in Braille, large print or audio please call, free of charge: 0800 198 5000 (UK Only)

108771/1

Anaphylaxis occasionally occurs and has sometimes been fatal. Late sensitivity reactions may include serum sickness-like reactions (featuring symptoms such as arthralgia, rash, urticaria, fever, angioedema, lymphadenopathy), haemolytic anaemia, nephropathy and acute interstitial nephritis, which is reversible when treatment is discontinued. Some patients with spirochaete infections such as syphilis or leptospirosis may experience a Jarisch-Herxheimer reaction shortly after treatment with a penicillin is started. Symptoms include fever, chills, headache and reaction at the site of lesions. The reaction can be dangerous in cardiovascular syphilis or where there is a serious risk of increased local damage such as with optic atrophy. Metabolism and nutrition disorders: Electrolyte disturbances, such as hypokalaemia, due to administration of large amounts of sodium (see Section 4.4), are generally associated with large intravenous doses of flucloxacillin or impaired renal function. 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.) Psychiatric disorders: Hallucinations. Nervous system disorders: Convulsions and other signs of central nervous system toxicity are generally associated with large intravenous doses of flucloxacillin or impaired renal function. Encephalopathy has been reported following intrathecal administration and can be fatal. Coma may develop with high doses of flucloxacillin. Respiratory, thoracic and mediastinal disorders: Acute, severe dyspnoea; bronchospasm. Gastrointestinal disorders: Diarrhoea, nausea and vomiting, reported with flucloxacillin, commonly occur after oral or parenteral administration. Pseudomembranous colitis has been reported with most antibiotics. Prolonged use of penicillins may lead to the development of oral candidiasis. Hepatobiliary disorders: Changes in liver function test results may occur, but are reversible when treatment is discontinued. Hepatitis and cholestatic jaundice have been reported. These reactions are related neither to the dose nor to the route of administration; administration for more than two weeks and increasing age are risk factors. The onset of these effects may be delayed for up to two months post-treatment; in several cases the course of the reactions has been protracted and lasted for some months. In very rare cases, a fatal outcome has been reported, almost always in patients with serious underlying disease. There is evidence that the risk of flucloxacillin induced liver injury is increased in subjects carrying the HLA-B*5701 allele. Despite this strong association, only 1 in 500-1000 carriers will develop liver injury. Consequently, the positive predictive value of testing the HLA-B*5701 allele for liver injury is very low (0.12%) and routine screening for this allele is not recommended. Skin and subcutaneous tissue disorders: Erythema multiforme; Stevens-Johnson syndrome; toxic epidermal necrolysis (Lyell's syndrome); erythema nodosum; pemphigoid reactions; non-thrombocytopenic purpura; vasculitis. Frequency not known: AGEP – acute generalized exanthematous pustulosis (see section 4.4). Congenital, familial and genetic disorders: Acute attacks of porphyria (refer to section 4.4). General disorders and administration site conditions: Phlebitis has followed intravenous infusion. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation 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 via the national reporting system: United Kingdom Yellow Card Scheme www.mhra.gov.uk/yellowcard 4.9 Overdose Symptoms

With high parenteral doses of penicillins, neurotoxicity (e.g. convulsions, encephalopathy), blood disorders (e.g. neutropenia, haemolytic anaemia, prolongation of bleeding time, defective platelet function) or electrolyte disturbances may occur. Treatment Treatment is symptomatic. Flucloxacillin is not removed from the circulation by haemodialysis. 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Beta-lactamase resistant penicillins, ATC code: J01CF05. There is evidence that the risk of flucloxacillin induced liver injury is increased in subjects carrying the HLA-B*5701 allele. Despite this strong association, only 1 in 500-1000 carriers will develop liver injury. Consequently, the positive predictive value of testing the HLA-B*5701 allele for liver injury is very low (0.12%) and routine screening for this allele is not recommended. Mechanism of action Flucloxacillin is bactericidal with a similar mode of action to benzylpenicillin. It is resistant to staphylococcal penicillinase and therefore active against penicillinase-producing and non-penicillinase-producing staphylococci. It has minimum inhibitory concentrations in the range of 0.25 to 0.5μg per ml. Pharmacodynamic effects Its activity against streptococci such as Streptococcus pneumoniae and Str. pyogenes is less than that of benzylpenicillin but sufficient to be useful when these organisms are present with penicillin-resistant staphylococci. It is virtually ineffective against Enterococcus faecalis. 5.2 Pharmacokinetic properties Absorption After the intramuscular administration of a single 250 or 500mg dose of flucloxacillin to volunteers, mean peak concentrations of the drug in serum were approximately 10.5 and 16mg.l-1 respectively. Mean urinary excretion of flucloxacillin following its intramuscular use is 61% of the administered dose. Flucloxacillin may also be administered by intravenous bolus injection or by slow intravenous infusion. High serum levels of the drug are achieved by these modes of administration: 30 minutes and 2 hours after a single 500mg intravenous bolus injection of flucloxacillin the mean serum concentration of the drug was 38 and 7.5mg.l-1, respectively; 30 minutes and 3 hours after a single 1g intravenous bolus injection of flucloxacillin, the mean serum concentrations were 60 and 4mg.l-1 respectively. The administration of 2g flucloxacillin by intravenous infusion over 20 minutes resulted in mean serum concentrations of 244 and 27.7mg.l-1 15 minutes and 120 minutes respectively after the end of the infusion. Elimination The percentage of a dose of intravenous flucloxacillin recovered in urine in an 8 hour collection period varies from 60 to 76%. About 95% of flucloxacillin in the circulation is bound to plasma proteins. Flucloxacillin has been reported to have a plasma half-life of approximately one hour. The half-life is prolonged in neonates. The serum half-life of flucloxacillin in patients with severe kidney disease has been reported as 135 to 173 minutes. No significant difference in the half-life was found between patients on or off haemodialysis. Flucloxacillin is not removed by haemodialysis. Flucloxacillin is metabolised to a limited extent and the unchanged drug and metabolites are excreted in the urine by glomerular filtration and renal tubular secretion. Up to 90% of an intramuscular dose is excreted in the urine within six hours. Only small amounts are excreted in the bile. Flucloxacillin is unlikely to be excreted in breast milk to any significant extent. Similarly, placental transfer is unlikely to occur to any appreciable extent. 5.3 Preclinical safety data There are no pre-clinical data of relevance to the prescriber which are additional to those included in other sections.

Customer

Wockhardt UK Limited

Description

Flucloxacillin Inj Vial Common Labesfal

Item Code

108771/1

Profile

as per uploaded pdf

Size

600 x 210mm

DATE

Warning! We cannot accept responsibility for any errors in this proof after approval. Whilst we take extreme care at all times to ensure accuracy to our client's brief, the final responsibility must be taken by our client. IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING FULL APPROVAL OF DESIGN AND TEXT.

Min.Point Size

9pt (Leaflet)

Market

UK

Language

English

FPO

Pharma Height

7mm Minimum

Barcode Proof By

SBL

Proof No.

3

Date

25.04.2024

Body Text Fonts: Helvetica Neue LT W1G

108771/1

PRINTING COLOURS

16 East Park Road | Leicester | LE5 4QA | UK

APPROVAL SIGNATURE

PHARMACEUTICAL PARTICULARS 6.1 List of excipients None 6.2 Incompatibilities Flucloxacillin may be administered in combination with other antibiotics including ampicillin to produce a wider spectrum of antibacterial activity. If used concurrently with an aminoglycoside the two antibiotics should not be mixed in the syringe, container or giving set as precipitation may occur. Flucloxacillin should not be mixed with blood products or other proteinaceous fluids (e.g. protein hydrolysates) or with intravenous lipid emulsions. The following drugs are incompatible with flucloxacillin: amiodarone, atropine sulphate, buprenorphine, calcium gluconate, chlorpromazine hydrochloride, ciprofloxacin, clarithromycin, diazepam, dobutamine hydrochloride, erythromycin lactobionate, gentamicin sulphate, metoclopramide hydrochloride, morphine sulphate, netilmicin sulphate, ofloxacin, papaveretum, pethidine hydrochloride, prochlorperazine edisylate, promethazine hydrochloride, tobramycin and verapamil hydrochloride. 6.3 Shelf life 3 years The unreconstituted dry powder is stable for 3 years. For the reconstituted solution, chemical and physical in-use stability has been demonstrated for 24 hours at 2-8°C. From a microbiological point of view, once opened, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C, unless reconstitution has taken place in controlled and validated aseptic conditions. 6.4 Special precautions for storage Do not store above 25°C 6.5 Nature and contents of container Flucloxacillin for Injection is supplied in Type II clear glass vials containing 250mg, 500mg or 1g of flucloxacillin equivalent. The vials are closed with a grey bromobutyl rubber stopper and sealed with an aluminium crimped flip-off cap. The vials are packed in cartons of 10 vials. 6.6 Special precautions for disposal. None. 7. MARKETING AUTHORISATION HOLDER Wockhardt UK Ltd, Ash Road North, Wrexham, LL13 9UF, UK 8. MARKETING AUTHORISATION NUMBER(S) Flucloxacillin for Injection 250mg

• PL 29831/0091 Flucloxacillin for Injection 500mg
• PL 29831/0092 Flucloxacillin for Injection 1g
• PL 29831/0093 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 3 March 2008 (UK) 10. DATE OF REVISION OF THE TEXT April 2024

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