Flucloxacillin 125mg/5ml Sugar-Free Powder for Oral Solution

Each 5ml reconstituted solution contains flucloxacillin sodium equivalent to 125mg flucloxacillin.

For full list of excipients, see section 6.1

Powder for oral solution

Free flowing white granular powder for oral solution.

Treatment of infections due to sensitive Gram-positive organisms, including infections caused by β-lactamase-producing Staphyloccoci.

Typical indications include:

Skin and soft tissue infections:

Infected skin conditions e.g. ulcers, eczema and acne.

Respiratory tract infections:

Other infections caused by Flucloxacillin sensitive organisms:

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.

Route of administration

Oral. To be administered ½ - 1 hour before meals.

Adults (including the elderly)

Oral: - 250mg every 6 hours.

In serious infections, the dosage may be doubled.

Children

2 - 10 years: 125mg every 6 hours.

Under 2 years: 62.5mg every 6 hours.

Depends on age, weight and renal function of the patient, as well as the severity of the infection.

In cases of severe renal impairment (creatinine clearance < 10ml/min) a reduction in dosage maybe necessary. 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.

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.

Flucloxacillin should not be given to patients with a history of hypersensitivity to β- lactam antibiotics (e.g. penicillins, cephalosporins) or excipients.

Flucloxacillin is contra-indicated in patients with a previous history of flucloxacillin-associated jaundice/hepatic dysfunction.

This medicinal product contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

This medicinal product contains 0.74 mmol (or 17.08 mg) sodium per 5ml dose. To be taken into consideration by patients on a controlled sodium diet.

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. 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 discontinued and the appropriate therapy instituted. In cases of serious anaphylactic reactions immediate emergency treatment may be required, as appropriate.

Flucloxacillin should be used with caution in patients with evidence of hepatic dysfunction (see section 4.8)

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.

Probenecid and sulfinpyrazone slows down the excretion of flucloxacillin

Other drugs, such as piperacillin, which are excreted via renal tubular secretion, may interfere with flucloxacillin elimination.

In common with other antibiotics, flucloxacillin may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of the combined oral contraceptive.

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

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.

Flucloxacillin is secreted into mother's milk and may occasionally cause sensitisation of the infant. Therefore flucloxacillin should only be administered to a breast-feeding mother when the potential benefits outweigh the potential risks associated with the treatment.

None known.

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).

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. Haemolytic anaemia.

Immune system disorders

Very rare: Anaphylactic shock (exceptional with oral administration) (see Section 4.4 Special warnings and special precautions for use), 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.

Hepato-biliary disorders

Very rare: Hepatitis and cholestatic jaundice. (See Section 4.4 Special Warnings and Special Precautions for Use). 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. 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. 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.

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).

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.

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.

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.

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.

Metabolism: 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.

Excretion: 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%.

No relevant information additional to that already contained elsewhere in the SPC.

As for penicillins. Incompatibilities with colistin polymyxin B sulphate. Loss of potency after mixing with streptomycin has also been reported.

Dry powder -

Bottle not placed in Aluminium pouch – 12 months

Bottle in Aluminium pouch – 24 months

Once reconstituted the mixture should be used within 7 days.

Powder: Do not store above 25°C.

Reconstituted solution: Store at 2°C-8°C in a refrigerator.

150ml high density polyethylene bottle with tamper evident cap.

Or

150ml high density polyethylene bottle with a tamper evident/child resistant 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 adaptor

Preparation of the 100 ml solution: Add 87ml 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.

Actavis Group PTC ehf

Reykjavíkurvegur 76-78,

IS-220 Hafnarfjörður,

Iceland

PL 30306/0259

16/11/2007 / 22^nd Oct 2009

05.03.2012