Summary of Product Characteristics (SmPC) - Flucloxacillin 125 mg / 5 ml powder for oral solution
1. NAME OF THE MEDICINAL PRODUCT
Flucloxacillin 125mg/5ml powder for oral solution
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Flucloxacillin sodium 136 mg equivalent to Flucloxacillin 125mg.
Excipient(s) with known effect:
Sodium Benzoate: 5 mg /5 ml
Sucrose: 3.161 g / 5 ml)
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Powder for oral solution
Pinkish colour, free-flowing granular powder with characteristics odour
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Flucloxacillin Sodium is used for the treatment of infections due to staphylococci resistant to benzylpenicillin. It is also used for mixed streptococcal and staphylococcal, infections when the staphylococci are penicillin-resistant.
Typical indications include: skin and soft tissue infections (boils, abscesses, carbuncles, furunculosis, cellulitis, infected wounds, infected burns, protection for skin grafts, otitis media and externa), respiratory tract infections (pneumonia, lung abscess, empyema, sinusitis, pharyngitis, tonsilitis, quinsy). Other infections include: osteomyelitis, enteritis, endocarditis, urinary tract infections, meningitis and septicaemia.
4.2 Posology and method of administration
Posology
Dosage for all indications except osteomyelitis, endocarditis and surgical prophylaxis:
Adults (including the elderly): Oral – 10ml four times daily.
Osteomyelitis, endocarditis: Up to 320ml (8g) daily in divided doses 6-8 hourly.
Surgical prophylaxis: Following IV administration of the injectable form of flucloxacillin, oral administration of 20ml flucloxacillin elixir (containing 500mg flucloxacillin) should be administered six hourly for up to 72 hours postoperatively.
Paediatric population:
Children: 2-10 years: 5ml four times daily.
Under 2 years: 2.5ml four times daily.
In serious infections, dosages may be doubled. Treatment for over 2 weeks should be considered with caution, due to the risk of cholestatic jaundice after prolonged treatment.
Method of administration
Oral:
Flucloxacillin 125mg/5ml powder for oral solution should be taken at least 1 hour before or 2 hours after meals.
A full glass of water (250 ml) should be taken afterwards, to reduce the risk of oesophageal pain (see section 4.8). Patients should not lay down immediately after Flucloxacillin 125mg/5ml powder for oral solution intake.
4.3 Contraindications
Hypersensitivity to the active substance or penicillins or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
Flucloxacillin should be given with caution to patients with a history of allergy. Preparations should be made to deal with anaphylactic shock before the first dose is given. Care is necessary where large doses of sodium salts are given to patients with impaired renal function or congestive heart failure.
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.
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. 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.
Contact with penicillins should be avoided since skin sensitisation may occur.
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).
This medicine contains less than 1mmol sodium (23mg) per 5 m1 that is to say essentially 'sodium free'.
This medicine contains 5 mg Sodium Benzoate in each 5 ml which is equivalent to 5 mg/5ml. Sodium Benzoate may increase jaundice (yellowing of the skin and eyes) in newborn babies (up to 4 weeks old).
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Serum concentrations of Flucloxacillin are enhanced if Probenecid is given concomitantly.
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 Pregnancy and lactation
Flucloxacillin diffuses across the placenta into the foetal circulation and is excreted in the milk of nursing mothers. The use of Flucloxacillin in pregnancy should be reserved for cases considered essential by the clinician.
4.7 Effects on ability to drive and use machines
Flucloxacillin 125mg/5ml powder for oral solution is not expected to affect the ability to drive or operate machinery.
4.8 Undesirable effects
When Flucloxacillin Sodium is administered to a hypersensitive patient, anaphylactic shock with collapse and sometimes death may occur within minutes. A generalised sensitivity reaction can occur within 1-3 weeks with urticaria, fever, eosinophilia, joint pains, angioneurotic oedema, erythema multiforme, and exfoliative dermatitis, although an accelerated urticarial reaction can develop within hours.
Convulsions and other signs of toxicity to the central nervous system may occur with very high doses of Flucloxacillin particularly when administered to infants and the elderly, and to patients with renal failure. Administration of Flucloxacillin by mouth is liable to produce transient diarrhoea and sometimes nausea, heartburn and pruritis ani. Skin rashes may occur. If a rash occurs, treatment should be discontinued.
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.) Not known: Hypokalaemia
Gastrointestinal disorders
Not known: Oesophageal pain and related events *
* oesophagitis, burn oesophageal, throat irritation, oropharyngeal pain or oral pain
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
Treatment should be symptomatic. Patient should be kept under observation with high doses (mainly parenteral), neurotoxicity may develop.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Beta-lactamase resistant penicillins;
ATC Code: J01CF05
Flucloxacillin Sodium, like other isoxazolyl penicillins, is a potent inhibitor of the growth of most penicillinase-producing staphylococci. This agent, in general, is less effective against microorganisms susceptible to penicillin G and are not as useful against gram-negative bacteria.
Flucloxacillin Sodium is bactericidal. It is considered to act by inhibiting transpeptidase, the enzyme responsible for cross-linking of peptidoglycan during the final stages of synthesis of the bacterial cell wall and so exerts its effects against dividing bacteria. It is active against most gram-positive organisms and neisseria spp.
A minimum inhibitory concentration against penicillin-resistant staphylococci of 0.25-0.5*g/ml has been reported. It’s activity against both penicillin-resistant and penicillin-sensitive staphylococci is 4 to 8 times that of methicillin sodium, but against penicillin-sensitive staphylococci, its activity is only about one quarter that of benzylpenicillin or phenoxymethyl-penicillin. Its activity against streptococci is less than that of benzylpenicillin but sufficient to be useful when these organisms are present with penicillin-resistant staphylococci.
Resistance to Flucloxacillin has developed in both penicillinase and non-penicillinase producing staphylococci with cross resistance to other penicillins, including the penicillinase-resistant penicillins such as cloxacillin, nafcillin and oxacillin; to the cephalosporins and to other antibiotics including chloramphenicol, erythromycin, tetracycline, kanamycin, streptomycin, and lincomycin.
This resistance is intrinsic and unrelated to penicillin production.
5.2 Pharmacokinetic properties
Flucloxacillin Sodium is better absorbed from the gastrointestinal tract than cloxacillin sodium but absorption is also reduced by food in the stomach or small intestine. After an oral dose of 250mg to 500mg, in fasting subjects, peak serum concentrations in about 1 hour may range from 3 to 27μg per ml with mean peak concentrations of about 11 to 15μg per ml. A therapeutic concentration persists for about 4 hours. Doubling the dose can double the plasma concentration. Some 50% of a dose by mouth is excreted in the urine within 6 hours, serum concentrations are enhanced if probenecid is given concomitantly.
About 90-95% of Flucloxacillin in the circulation is bound to plasma albumin to a greater extent, none is removed from the circulation to a significant degree by haemodialysis.
The isoxazolyl penicillins, like Flucloxacillin, are rapidly excreted by the kidney. There is also significant hepatic elimination of these agents in the bile. The plasma half life of Flucloxacillin is 60 minutes in healthy subjects.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium Benzoate (E211)
Disodium Edetate
Saccharin Sodium
Mono-Ammonium-Glycyrrhizinate
Sodium Citrate (dried) (E331)
Flavour Pineapple
Flavour Menthol
Erythrosine (E127)
Sucrose
6.2 Incompatibilities
As for Penicillin. Incompatible with Colistin Polymixin B Sulphate. Loss of potency after mixing with Streptomycin has also been reported.
6.3 Shelf life
Unopened: 3 years
After reconstitution or when the container is opened for the first time: 7 days.
6.4. Special Precautions for Storage
Unopened bottle: Do not store above 25°C. Store in the original container. Keep the container tightly closed.
Reconstituted solution: Store at 2-8°C.
6.5 Nature and contents of container
Nature: 150ml amber glass Beatson Clark container with polypropylene screw cap or 150ml high density polyethylene bottle with tamper evident cap: 100ml
6.6 Special precautions for disposal and other handling
To reconstitute, tap the bottle to loosen the powder, add 58 ml of water slowly into the bottle. Shake gently till the powder get dissolved.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. Marketing Authorisation Holder
Medreich Plc
Warwick House
Plane Tree Crescent
Feltham
TW13 7HF
8 MARKETING AUTHORISATION NUMBER(S)
PL 21880/0063
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
01/11/2024
10 DATE OF REVISION OF THE TEXT
01/11/2024