Floxapen

FLOXAPEN® Capsules 250mg

Floxapen Capsules (Flucloxacillin Capsules BP) containing 250 mg flucloxacillin as Flucloxacillin Sodium BP.

Capsule, hard

Caramel coloured hard gelatin capsules printed with ' 250', fitted with black caps

Floxapen is indicated for the treatment of infections due to sensitive Gram-positive organisms, including β-lactamase-producing staphylococci and streptococci. Typical indications include:

Skin and soft tissue infections:

Respiratory tract infections:

Other infections caused by Floxapen-sensitive organisms:

Floxapen is also indicated for use as a prophylactic agent during major surgical procedures when appropriate; for example cardiothoracic and orthopaedic surgery.

Parenteral usage is indicated where oral dosage is inappropriate.

Premature infants, neonates, sucklings and infants

Other pharmaceutical forms/strengths may be more appropriate for administration to this population.

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

Usual adult dosage (including elderly patients)

Oral - 250 mg four times a day.

Osteomyelitis, endocarditis - Up to 8 g daily, in divided doses six to eight hourly.

Surgical prophylaxis - 1 to 2 g IV at induction of anaesthesia followed by 500 mg six hourly IV, IM or orally for up to 72 hours.

Usual children's dosage

2-10 years: half adult dose.

Under 2 years: quarter adult dose.

Abnormal renal function: In common with other penicillins, Floxapen usage in patients with renal impairment does not usually require dosage reduction. However, in the presence of severe renal failure (creatinine clearance < 10 ml/min) a reduction in dose or an extension of dose interval should be considered. Floxapen 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. The maximum recommended dose in adults is 1 g every 8 to 12 hours.

Hepatic impairment¹

Dose reduction in patients with reduced hepatic function is not necessary.

Administration

Oral: Oral doses should be administered half to one hour before meals.

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.

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 parenteral 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. 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.

Flucloxacillin should be used with caution in patients with evidence of hepatic dysfunction, patients > 50 years and those with serious underlying disease. In these patients, hepatic events may be severe, and in very rare circumstances, deaths have been reported.

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.

During prolonged treatments (e.g. osteomyelitis, endocarditis), regular monitoring of hepatic and renal functions is recommended.

Prolonged use may occasionally result in overgrowth of non-susceptible organisms.

Floxapen capsules contain approximately 51 mg sodium per g. This should be included in the daily allowance of patients on sodium restricted diets.

Adverse effects on the ability to drive or operate machinery have not been observed.

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, <1/1000), 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.

*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; website: www.mhra.gov.uk/yellowcard

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.

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) staphylococci. It is not active against methicillin-resistant staphylococci.

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

Absorption: Flucloxacillin is stable in acid media and can therefore be administered either by the oral or parenteral route. The peak serum levels of flucloxacillin reached after one hour are as follows.

- After 250 mg by the oral route (in fasting subjects): Approximately 8.8 mg/l.

- After 500 mg by the oral route (in fasting subjects): Approximately 14.5mg/l.

- After 500 mg by the IM route: Approximately 16.5 mg/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: 11.6 mg/l (compact bone) and 15.6 mg/l (spongy bone), with a mean serum level of 8.9 mg/l.

Crossing the meningeal barrier: Flucloxacillin diffuses in only small proportion into 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% (parenteral 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 further information of relevance to add.

Capsule content:

Magnesium stearate

Capsule shell:

Titanium dioxide (E171)

Black iron oxide (E172)

Yellow iron oxide (E172)

Red iron oxide (E172)

Printing ink:

Shellac (E904)

Propylene glycol (E1520)

Sodium hydroxide (E524)

Povidone

Titanium dioxide (E171)

None known.

Tray foil blister: 24 months

Fibreboard drums: 36 months

Floxapen Capsules in Original Packs should be stored in a dry place. Floxapen Capsules in reclosable containers should be stored in a cool, dry place. Fibreboard drums should be kept tightly closed in a cool, dry place.

Floxapen Capsules 250 mg: Aluminium canister - 20, 50, 100 and 500; Glass bottle with screwcap - 20, 50, 100 and 500; Polypropylene tube with polyethylene closure - 20, 50, 100 and 500; Aluminium foil - 12; Aluminium/PVC Blister with an aluminium overseal (tray foil blister pack) - 28; Fibreboard drum with metal or HDPE lid - 50,000

None stated.

Actavis Group PTC ehf

Reykjavíkurvegi 76-78

220 Hafnarfjordur

Iceland.

PL 30306/0015

11^th October 2007

03/08/2015