Flucloxacillin Syrup 125mg/5ml
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Flucloxacillin Syrup 125mg/5ml
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 5ml dose contains 125mg Flucloxacillin (as Sodium)
For Excipients see section 6.1.
3. PHARMACEUTICAL FORM
Powder for Oral Syrup
White free flowing powder with odour of orange.
4. CLINICAL PARTICULARS
4.1. Therapeutic indications
Flucloxacillin is presented as a powder for reconstitution with water to produce a syrup which is suitable for oral use in the treatment of infections due to Staphylcoccus resistant to benzylpenicillin. Flucloxacillin is indicated for the treatment of infections due to gram-positive organisms including those caused by P-Lactamase - producing staphylococci associated, for example with:
Skin and Soft Tissue Infections: Boils, abscesses, carbuncles, infected skin conditions, e.g. ulcer, eczema and acne, furunculosis, cellulitis, infected wounds, infected burns, protection for skin grafts and impetigo.
Respiratory Tract Infections: Pneumonia, lung abscess, empyema, sinusitis, pharyngitis, tonsillitis, quinsy and otitis media and externa.
Flucloxacillin should be reserved for those infections caused by penicillinase-producing staphylococci shown to be sensitive.
Consideration should be given to official local guidance (eg. 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
Oral administration.
Adults and Elderly: 250mg four times daily, six hourly, at least 30 minutes before food, doubled in severe infections if needed.
Children: Up to 2 years of age may be given one-quarter the adult dose and those aged 2 to 10 years, one-half the adult dose.
Note: Abnormal Renal Function
In common with other penicillins, flucloxacillin usage in patients with renal impairment does not usually require dosage reduction. However, in the presence of severe renal failure (creatinine clearance < 10 ml/minute) a reduction in dose or an extension of dose interval should be considered.
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.
4.3. Contraindications
Flucloxacillin is contraindicated in patients with hypersensitivity to B-lactam antibiotics (e.g. penicillins, cephalosporins); ocular administration.
Flucloxacillin is contraindicated in patients with a previous history of flucloxacillin-associated jaundice/hepatic dysfunction.
4.4. Special warnings and precautions for use
Careful enquiry should be made concerning previous hypersensitivity reactions to P-lactam antibiotics before initiating therapy with flucloxacillin syrup. Cross sensitivity with other B-lactam antibiotics has been reported.
Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) have been reported in patients receiving P-lactam antibiotics. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral therapy. These reactions are more likely to occur in individuals with a history of P-lactam hypersensitivity.
Flucloxacillin syrup should be used with caution in patients with evidence of hepatic dysfunction (see section 4.8).
Special caution is essential in the new-born because of the risk of hyperbilirubinaemia. Studies with parenteral administration of high doses have shown that, 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 new-born because of the potential for high serum levels of flucloxacillin due to a reduced rate of renal excretion.
During prolonged use (e.g. in osteomyelitis, endocarditis), monitoring of hepatic and renal functions regularly is recommended.
Prolonged use may occasionally result in overgrowth of non-susceptible organisms.
4.5. Interactions with other Medicaments and other forms of Interaction
Oral courses of broad spectrum antibacterials affect the hypoprothrombinaemic response to oral anticoagulants. Pseudomembranous colitis has been reported rarely and has usually been associated with use of flucloxacillin in combination with other antibiotics.
Methotrexate excretion is reduced by penicillins. Patients should be monitored carefully for signs of methotrexate toxicity.
Probenecid decreases the renal excretion of penicillins. Plasma concentrations are enhanced if probenecid is given concomitantly.
4.6. Pregnancy and lactation
Animal studies with flucloxacillin have shown no teratogenic effects. Flucloxacillin should only be used in pregnancy when the potential benefit outweighs the potential risks associated with treatment. The use of flucloxacillin should be reserved for cases considered essential by the clinician. Sensitivity reactions may occur in infants receiving breast milk from their mothers who are being treated with flucloxacillin.
Breast feeding is not contraindicated with flucloxacillin. Trace quantities of penicillins can be detected in breast milk. While adverse effects are apparently rare, three potential problems exist for the nursing infant: modification of bowel flora
direct effects on the infant such as allergy/sensitisation
interference with interpretation of culture results when pyrexia of unknown
origin occurs.
4.7. Effects on ability to drive and use machines
Adverse effects on the ability to drive or operate machinery have not been observed.
4.8. Undesirable effects
The most commonly reported adverse drug reactions are gastro-intestinal and skin reactions (> 1% but < 10%)
The following undesirable effects have been observed:
Blood and the lymphatic system disorders Uncommon (> 0.1% but < 1.0%)
• Eosinophilia
Rare (> 0.01 but < 0.1%)
• Agranulocytosis, Neutropenia, Leukopenia, Thrombocytopenia.
Immune System Disorder Common (> 1% but < 10%)
■ Exanthema
Uncommon (> 0.1% but < 1.0%)
• Angioedema, Fever, Myalgia, Urticaria, Arthralgia Rare (> 0.01 but < 0.1%)
Anaphylactic Reaction, Interstitial Nephritis, Nephropathy.
Nervous System Disorders Common (> 1% but < 10%)
■ Headache
Gastrointestinal Disorders Common (> 1% but < 10%)
■ Diarrhoea and Nausea
Rare (> 0.01 but < 0.1%)
• Pseudomembranous colitis
Hepato-Biliary Disorders Rare (> 0.01 but < 0.1%)
• Hepatitis and cholestatic jaundice.
4.9. Overdose
Problems of overdosage are unlikely to be encountered but include gastrointestinal effects such as nausea, vomiting and diarrhoea. If encountered they may be treated symptomatically. More specific measures may be necessary in patients with impaired renal function. flucloxacillin is not significantly removed by dialysis.
PHARMACOLOGICAL PROPERTIES
5.
5.1. Pharmacodynamic properties
ATC Code: Beta - Lactamase resistant penicillin J01C F05.
Mechanism of action
Flucloxacillin is a semi-synthetic penicillin of the isoxazolyl group which is stable to staphylococcal B-lactamase. During cell wall synthesis, it inhibits membrane-bound transpeptidase enzymes involved in the cross linking of peptidoglycan chains necessary for cell wall rigidity which is essential to the bacterial cell. Also, cell division and growth are inhibited and lysis and elongation of susceptible bacteria frequency occur. Rapidly dividing bacteria are more susceptible to the actions of penicillins.
Breakpoints
The following MIC breakpoints separating susceptible from intermediately susceptible organisms and intermediately susceptible from resistant organisms are used:
Table 1: Bacterial Breakpoints
|
Bacterial breakpoints |
Organism |
|
NCCLS Breakpoints S: < 2 pg/ml I:- R: > 4 pg/ml S: < 0.25 pg/ml I:- R: > 0.5 pg/ml |
Staphylococcus aureus Coagulase-negative staphylococci |
|
DIN Breakpoints S: 1 pg/ml I:- R: 2 pg/ml |
NCCLS: National Committee for Clinical Laboratory Standards, DIN: Deutsches Institut fur Norung, S: Susceptible, I: Intermediate, R: Resistant.
The prevalence of resistance may vary geographically and with time for selected species and local information is desirable, particularly when treating severe infections. This information gives only an approximate guidance on probabilities whether organisms will be susceptible to flucloxacillin or not.
|
SUSCEPTIBLE ORGANISMS |
European range of acquired resistance (%) |
|
Gram positive aerobes: | |
|
Staphylococcus aureus |
2-58% |
|
Staphylococci (coagulase-negative) |
33-94% |
|
Streptococcus agalactiae |
3% |
|
Streptococcus intermedius group |
0-33% |
|
Streptococcus pyogenes |
0% |
|
Streptococcus pneumoniae |
1.4-31% |
|
Viridans streptococci |
<50% |
|
Gram negative aerobes: Neisseria species | |
|
RESISTANT ORGANISMS | |
|
Gram negative aerobes: Enterobacteri aceae | |
|
Enterococcus species Haemophilus influenza Moraxella catarrhalis | |
|
Pseudomonas species Anaerobes: Bacteroides species Clostridium species Others: Chlamydia |
Mechanism of resistance
Resistance in staphylococci to flucloxacillin involves target by-pass by novel penicillin-binding protein PBP-2’ encoded on the mec A gene observed in MRSA and methicillin-resistant coagulase-negative staphylococci. Staphylococci that are resistant to flucloxacillin by this mechanism are crossresistant in-vivo to all other B-lactam antibiotics.
5.2. Pharmacokinetic properties
Flucloxacillin is rapidly but incompletely absorbed after oral administration from the gastro-intestinal tract but absorption is also reduced by food in the stomach or small intestine. After an oral dose of 250 to 500mg, in fasting subjects, peak serum concentrations in about 12 hours may range from 3 to 27pg per ml, with mean peak concentrations of about 11 to 15pg per ml; A therapeutic concentrations persists for about 4 hours. A similar pattern follows the intramuscular injection of flucloxacillin but peak concentrations are achieved in about 30 minutes. Doubling the dose can double the plasma concentration. About 95% of flucloxacillin in the circulation is bound to plasma proteins. Some 50% of a dose by mouth and up to 90% of an intramuscular dose is excreted in the urine within 6 hours. Serum concentrations are enhanced if probenecid is given concomitantly.
Flucloxacillin has been reported to have a plasma half-life of approximately 1 hour in healthy subjects. The half-life is prolonged in neonates.
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. About 50% of a dose by mouth and up to 90% of an intramuscular dose is excreted in the urine within 6 hours. Only small amounts are excreted in the bile.
5.3. Preclinical safety data
There is no preclinical safety data of relevance to the prescriber which are additional to those already included in other sections of the SPC.
6. PHARMACEUTICAL PARTICULARS
6.1. List of excipients
The powder contains Saccharin Sodium, Di-Sodium Edetate, Sodium Benzoate, Sodium Citrate Dihydrate, Licosoft, Flavour Fruit Punch, Flavour Creme de Menthe, Flavour Orange, Sunset Yellow (E110) and Sucrose.
6.2. Incompatibilities
None known.
6.3. Shelf life
The unconstituted product has a registered shelf life of 24 months. Once reconstituted it should be used within 14 days.
6.4. Special precautions for storage
Store reconstituted syrup at a temperature below 6oC and use the syrup within 14 days of reconstitution and to discard any remaining syrup after that time.
6.5
Nature and contents of container
6.6 Special precautions for disposal
Not applicable
7 MARKETING AUTHORISATION HOLDER
Generics [UK] Limited T/A Mylan Station Close Potters Bar Hertfordshire EN6 1TL
8. MARKETING AUTHORISATION NUMBER
PL: 04569/0193.
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Licence: 31st July 1987
Last Renewal: 11th February 1999.
10 DATE OF REVISION OF THE TEXT
26/05/2016