Summary of Product Characteristics (SmPC) - Flucloxacillin 250 mg / 5 ml sugar-free powder for oral solution
1 NAME OF THE MEDICINAL PRODUCT
Flucloxacillin 250mg/5ml Sugar-Free Powder for Oral Solution
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 5ml reconstituted solution contains flucloxacillin sodium equivalent to 250mg flucloxacillin.
Excipients with known effect: Sodium 49.41 mg / 5ml
Sorbitol 1000.34 mg / 5ml
For a full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Powder for oral solution
Free flowing white granular powder for oral solution.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Treatment of infections due to sensitive Gram-positive organisms, including infections caused by β
-lactamase-producing Staphyloccoci and Streptococci
Typical indications include:
Skin and soft tissue infections:
Boils Impetigo
Abscesses Infected wounds
Carbuncles Infected burns Furunculosis Protection for skin grafts
Cellulitis
Infected skin conditions e.g. ulcers, eczema and acne.
Respiratory tract infections:
Pneumonia Pharyngitis
Lung abscess Tonsillitis
Empyema Quinsy
Sinusitis
Otitis media and externa
Other infections caused by Flucloxacillin sensitive organisms:
Osteomyelitis Septicaemia
Enteritis Meningitis
Endocarditis Urinary-tract infection
Flucloxacillin is also indicated for use as a prophylactic during major surgical procedures such as cardiothoracic and orthopaedic surgery. Parenteral usage is indicated where oral dosage is inappropriate.
Consideration should be given to official local guidance (e.g. national recommendations) on the appropriate use of antibacterial agents.
Susceptibility of the causative organism to the treatment should be tested (if possible), although therapy may be initiated before the results are available.
4.2 Posology and method of administration
Posology
The dosage depends on age, weight and renal function of the patient, as well as the severity of the infection.
Adults (including the elderly)
Oral: - 250mg every 6 hours.
In serious infections, the dosage may be doubled.
Paediatric population
2 - 10 years: 125mg every 6 hours.
Under 2 years: 62.5mg every 6 hours.
Premature infants, neonates, sucklings and infants
Other pharmaceutical forms/strengths may be more appropriate for administration to this population
Abnormal renal function
In patients with renal insufficiency, excretion of flucloxacillin is slowed but dosage does not normally require dosage reduction. However, in the presence of severe renal insufficiency (creatinine clearance < 10ml/min) a reduction in dosage or an extension of dose interval should be considered. The maximum recommended dose in adults is 1g every 8 to 12 hours. Flucloxacillin is not significantly removed by dialysis and hence no supplementary dosages need to be administered either during, or at the end of the dialysis period.
Hepatic impairment
Dose reduction in patients with reduced hepatic function is not necessary.
Endocarditis or osteomyelitis
Up to 8g daily in divided doses six to eight hourly.
Surgical prophylaxis
1 to 2g IV at induction of anaesthesia followed by 500mg six hourly IV, IM or orally for up to 72 hours.
Method of administration
Oral. To be administered ½ - 1 hour before meals.
4.3 Contraindications
Hypersensitivity to the active substance, to any of the excipients listed in section 6.1.
Flucloxacillin should not be given to patients with a history of hypersensitivity to b-lactam antibiotics (e.g. penicillins, cephalosporins).
Flucloxacillin is contra-indicated in patients with a previous history of flucloxacillin- associated jaundice/hepatic dysfunction.
4.4 Special warnings and precautions for use
The use of Flucloxacillin (like other penicillins) in patients with renal impairment does not usually require dosage reduction. In the presence of severe renal failure (creatinine clearance less than 10ml/min), however, a reduction in dose or an extension of dose interval should be considered because of the risk of neurotoxicity.
Flucloxacillin is not significantly removed by dialysis and so no supplementary dosages need to be administered either during or at the end of the dialysis period.
Hepatitis and cholestatic jaundice have been reported. These reactions are related neither to the dose nor to the route of administration. Flucloxacillin should be used with caution in patients with evidence of hepatic dysfunction, patients >50 years or patients with underlying
disease all of whom are at increased risk of hepatic reactions. The onset of these hepatic 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 (see section 4.8).
As for other penicillins contact with the skin should be avoided as sensitisation may occur.
Patients with a known history of allergy are more likely to develop a hypersensitivity reaction.
Prolonged use of an anti-Infective agent may occasionally result in overgrowth of non- susceptible organisms.
Before initiating therapy with flucloxacillin, careful enquiry should be made concerning previous hypersensitivity reactions to β-lactams. Cross-sensitivity between penicillins and cephalosporins is well documented.
Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) have been reported in patients receiving β-lactam antibiotics. Although anaphylaxis is more frequent following parental therapy, it has occurred in patients on oral therapy. These reactions are more likely to occur in individuals with a history of β-lactam hypersensitivity. If anaphylaxis occurs, flucloxacillin should be discounted and the appropriate therapy instituted.
Serious anaphylactic reactions may require immediate emergency treatment with adrenaline (epinephrine). Ensure adequate airway and ventilation and give 100% oxygen. IV crystalloids, hydrocortisone, antihistamine and nebulised bronchodilators may also be required.
Special caution is essential in the newborn because of the risk of hyperbilirubinaemia. Studies have shown that, at high dose following parenteral administration, flucloxacillin can displace bilirubin from plasma protein binding sites, and may therefore predispose to kernicterus in a jaundiced baby. In addition, special caution is essential in the newborn because of the potential for high serum levels of flucloxacillin due to a reduced rate of renal excretion.
During prolonged treatments (e.g. osteomyelitis, endocarditis), regular monitoring of hepatic and renal functions is recommended.
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, a close monitoring is recommended in order to detect the appearance of acid–base disorders, namely HAGMA, including the search 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).
Hypokalaemia (potentially life threatening) can occur with the use of flucloxacillin, especially in high doses. Hypokalaemia caused by flucloxacillin can be resistant to potassium supplementation. Regular measurements of potassium levels are recommended during the therapy with higher doses of flucloxacillin. Attention for this risk is warranted also when combining flucloxacillin with hypokalemia-inducing diuretics or when other risk factors for the development of hypokalemia are present (e.g. malnutrition, renal tubule disfunction).
The occurrence at the treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthematous pustulosis (AGEP) (see section 4.8). In case of AGEP diagnosis, flucloxacillin should be discontinued and any subsequent administration of flucloxacillin contra-indicated.
This medicinal product contains 49.41mg sodium per 5ml dose, equivalent to 2.47% of the WHO recommended maximum daily intake of 2 g sodium for an adult. To be taken into consideration by patients on a controlled sodium diet
This medicinal product contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.
4.5 Interaction with other medicinal products and other forms of
interaction
Probenecid and sulfinpyrazone slow down the excretion of flucloxacillin by decreasing tubular secretion. Concurrent administration of probenecid delays the renal excretion of flucloxacillin.
Other drugs, such as piperacillin, which are excreted via renal tubular secretion, may interfere with flucloxacillin elimination.
Oral typhoid vaccine may be inactivated by flucloxacillin
Flucloxacillin reduces the excretion of methotrexate which can cause methotrexate toxicity
Flucloxacillin may reduce the response to sugammadex.
Bacteriostatic drugs may interfere with the bactericidal action of flucloxacillin.
There are rare cases of altered international normalised ratio (INR) in patients taking warfarin and prescribed a course of flucloxacillin. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored during addition or withdrawal of flucloxacillin.
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.)
Flucloxacillin (CYP450 inducer) has been reported to significantly decrease plasma voriconazole concentrations. If concomitant administration of flucloxacillin with voriconazole cannot be avoided, monitor for potential loss of voriconazole effectiveness (e.g. by therapeutic drug monitoring); increasing the dose of voriconazole may be needed.
4.6 Fertility, pregnancy and lactation
Pregnancy
Animal studies with Flucloxacillin have shown no teratogenic effects. Flucloxacillin preparations have been in 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 should only be used in pregnancy when the potential benefits outweigh the risks associated with treatment.
Breastfeeding
Flucloxacillin is secreted into mother’s milk and may occasionally cause sensitisation of the infant. The possibility of hypersensitivity reactions must be considered in breastfeeding infants. Therefore, flucloxacillin should only be administered to a breast-feeding mother when the potential benefits outweigh the potential risks associated with the treatment.
4.7 Effects on ability to drive and use machines
Flucloxacillin has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
The following convention has been utilised for the classification of undesirable effects: Very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000,
<1/100), rare (>1/10,000, <1/1,000), very rare ( <1/10,000), not known (cannot be estimated from the available data).
Unless otherwise stated, the frequency of the adverse events has been derived from more than 30 years of post-marketing reports.
Blood and lymphatic system disorders
Very rare: Neutropenia (including agranulocytosis) and thrombocytopenia. These are reversible when treatment is discontinued. Eosinophilia, haemolytic anaemia.
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.) Frequency not known (cannot be estimated from the available data): Hypokalaemia
Immune system disorders
Very rare: Anaphylactic shock (exceptional with oral administration) (see Section 4.4 ), angioneurotic oedema. If any hypersensitivity reaction occurs, the treatment should be discontinued. (See also Skin and subcutaneous tissue disorders).
Gastrointestinal disorders
*Common: Minor gastrointestinal disturbances.
Very rare: Pseudomembranous colitis.
If pseudomembranous colitis develops, flucloxacillin treatment should be discontinued and appropriate therapy, e.g. oral vancomycin should be initiated.
Frequency not known (cannot be estimated from the available data): Oesophageal pain and related events such as oesophagitis, burn oesophageal, throat irritation, oropharyngeal pain or oral pain
Hepatobiliary disorders
Very rare: Hepatitis and cholestatic jaundice. (See Section 4.4). Changes in liver function laboratory test results (reversible when treatment is discontinued). These reactions are related neither to the dose nor to the route of administration.
Hepatitis and cholestatic jaundice 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. Hepatic events may be severe and in very rare circumstances a fatal outcome has been reported. Most reports of deaths have been in patients ≥50 years and 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
*Uncommon: Rash, urticaria and purpura.
Very rare: Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.
(See also Immune system disorders).
Not known: AGEP - acute generalized exanthematous pustulosis (see section 4.4)
Musculoskeletal and connective tissue disorders
Very rare: Arthralgia and myalgia sometimes develop more than 48 hours after the start of the treatment.
Renal and urinary
disorders Very rare:
Interstitial nephritis.
This is reversible when treatment is discontinued.
General disorders and administration site conditions Very rare: Fever sometimes develops more than 48 hours after the start of the treatment.
*The incidence of these AEs was derived from clinical studies involving a total of approximately 929 adult and paediatric patients taking flucloxacillin.
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 Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
With high doses (mainly parenteral) neurotoxicity may develop.
Gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and should be treated symptomatically.
Flucloxacillin is not removed from the circulation by haemodialysis.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
ATC Code – J01CF05
Group – Beta-lactamase resistant penicillins
Properties: Flucloxacillin is a narrow-spectrum antibiotic of the group of isoxazolyl penicillins; it is not inactivated by staphylococcal β-lactamases.
Activity: Flucloxacillin, by its action on the synthesis of the bacterial wall, exerts a bactericidal effect on streptococci, except those of group D (Enterococcus faecalis), and staphylococci. It is not active against methicillin-resistant staphylococci.
Risk of hepatic injury: 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.
Susceptibility testing breakpoints
MIC (minimum inhibitory concentration) interpretive criteria for susceptibility testing have been established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for flucloxacillin and are listed here: https://www.ema.europa.eu/documents/other/minimum-inhibitory- concentration-mic-breakpoints_en.xlsx.
5.2 Pharmacokinetic properties
Absorption: Flucloxacillin is stable in acid media and can therefore be administered either by the oral or parental route. The peak serum levels of flucloxacillin reached after one hour are as follows.
- After 250mg by the oral route (in fasting subjects): Approximately 8.8mg/l.
- After 500mg by the oral route (in fasting subjects): Approximately 14.5mg/l.
- After 500mg by the IM route: Approximately 16.5mg/l.
The total quantity absorbed by the oral route represents approximately 79% of the quantity administered.
Distribution: Flucloxacillin diffuses well into most tissue. Specifically, active concentrations of flucloxacillin have been recovered in bones: 11.6mg/l (compact bone) and 15.6mg/l (spongy bone), with a mean serum level of 8.9mg/l.
Crossing the meningeal barrier: Flucloxacillin diffuses in only small proportion in to the cerebrospinal fluid of subjects whose meninges are not inflamed.
Crossing into mother’s milk: Flucloxacillin is excreted in small quantities in mother’s milk.
Biotransformation: In normal subjects approximately 10% of the flucloxacillin administered is metabolised to penicilloic acid. The elimination half-life of flucloxacillin is in the order of 53 minutes.
Elimination: Excretion occurs mainly through the kidney. Between 65.5% (oral route) and 76.1% (parental route) of the dose administered is recovered in unaltered active form in the urine within 8 hours. A small portion of the dose administered is excreted in the bile. The excretion of flucloxacillin is slowed in cases of renal failure.
Protein binding: The serum protein-binding rate is 95%.
5.3 Preclinical safety data
No relevant information additional to that already contained elsewhere in the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium Citrate Anhydrous
Disodium Edetate
Sodium Benzoate
Citric Acid Monohydrate
Xanthan Gum
Saccharin Sodium
Silica, Collodial Anhydrous
Menthol Flavour
Lemon Flavour
Strawberry Flavour
Sorbitol (E420)
6.2 Incompatibilities
As for penicillins, incompatibilities with Colistin Polymyxin B sulfate. Loss of potency after mixing with streptomycin has also been reported.
6.3 Shelf life
Dry powder -
Bottle not placed in Aluminium pouch – 12months
Bottle in Aluminium pouch – 2years
Once reconstituted the mixture should be used within 7 days.
6.4 Special precautions for storage
Powder: Do not store above 25oC.
Reconstituted solution: Store at 2oC-8oC in a refrigerator.
6.5 Nature and contents of container
150ml natural high density polyethylene (HDPE) bottle with tamper evident cap or
150ml natural high density polyethylene (HDPE) bottle with tamper evident/child resistant (CRC) cap.
Contents of the bottle after reconstitution: 100ml
Optional - Bottle placed in Aluminium pouch.
Hugo Meding – polypropylene spoon - Article number – 7229
5ml MediSpoon
Or
A dosing syringe with a bottle neck adapto
6.6 Special precautions for disposal
Preparation of the 100 ml solution: Add 79ml of potable water and shake until all contents are dissolved. The resulting solution should be an opaque off white coloured solution with a lemon smell and flavour.
7 MARKETING AUTHORISATION HOLDER
Kent Pharmaceuticals Limited,
2nd Floor,
Connect 38,
1 Dover Place,
Ashford,
Kent,
England,
TN23 1FB.
8 MARKETING AUTHORISATION NUMBER(S)
PL 08215/0122
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
16/01/2025
10 DATE OF REVISION OF THE TEXT
06/02/2026