FLUCLOXACILLIN

Flucloxacillin Capsules: Caramel and Black capsules containing 250 mg or 500 mg flucloxacillin as Flucloxacillin Sodium BP.

Flucloxacillin Vials for Injection: Each vial contains 250 mg, 500 mg or 1 g flucloxacillin.
Flucloxacillin Sodium BP as a powder for reconstitution.

Flucloxacillin Oral solution: Bottles containing powder for the preparation of solution.
When reconstituted each 5 ml contains 125 mg or 250 mg flucloxacillin, as Flucloxacillin sodium BP. Flucloxacillin Oral solution contain sodium benzoate and sucrose.

THERAPEUTIC INDICATIONS

Flucloxacillin is indicated for the treatment of infections due to Gram-positive organisms, including infections caused by b-lactamase-producing staphylococci. Typical indications include:

Skin and soft tissue infections:
Boils, abscesses, carbuncles, furunculosis, cellulitis; infected skin conditions, e.g. ulcer, eczema and acne; infected wounds, infected burns, otitis externa, protection for skin grafts, impetigo. 

Respiratory tract infections:
Pneumonia, lung abscess, empyema, sinusitis, pharyngitis, otitis media, tonsillitis, quinsy. 

Other infections caused by Flucloxacillin-sensitive organisms:
Osteomyelitis, enteritis, endocarditis, urinary tract infection, meningitis, septicaemia.

Flucloxacillin is also indicated for use as a prophylactic agent during major surgical procedures where appropriate: for example, cardiothoracic and orthopaedic surgery.

Flucloxacillin is a narrow-spectrum antibiotic of the group of isoxazolylpenicillins; it is not inactivated by staphylococcal beta-lactamases.

Flucloxacillin, by its action on the synthesis of the bacterial cell wall, exerts a bactericidal effect on streptococci (including S.pneumoniae, S. pyogenes and S.viridans, but excluding group D streptococci such as S.faecilis), staphylococci (including the b-lactamase-producing strains), Clostridia (including C.tetani and C.welchii) and Neisseria (including N.gonorrhoeae and N.meningitidis). It is not active against methicillin-resistant staphylococci.

POSOLOGY AND METHOD OF ADMINISTRATION

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

Dosage information is provided as the total daily dose which is administered in divided doses 3 or 4 times daily.

Parenteral treatment is indicated for severe infections, e.g. osteomyelitis, staphylococcal septicemia and endocarditis.

Adults: Mild-Moderate infections

Oral, intravenous or intramuscular route: Total daily dosage of 1 g to 3 g, administered in 3-4 divided doses.

Severe infections: Up to 8g per day in 4 rapid infusions (20-30 minutes). No single infusion should exceed 2g.

In the case of bacterial endocarditis, a total daily dose of 12 g may be used.

Surgical prophylaxis: 2 g intravenously (bolus or infusion) upon induction of anaesthesia, to be repeated every 6 hours for 24 hours in cases of vascular and orthopaedic surgery, and for 48 hours in cases of cardiac or coronary surgery.

Children

Mild-Moderate infections, Oral, intravenous or intramuscular route: 25-50 mg/kg/day administered in 3-4 divided doses. Severe infections: Up to 100 mg/kg/day parenterally. No single bolus injection should exceed 33mg/kg.

Elderly

No dosage adjustment is required, unless there is evidence of renal impairment (see below).

Renal impairment

The excretion of flucloxacillin is slowed in cases of renal failure. If creatinine clearance drops below 10 ml/min, then the recommended dosage is 1 g every 8 to 12 hours (in anuric patients, the maximum dosage is 1 g every 12 hours). Neither haemodialysis nor peritoneal dialysis lower the serum levels of flucloxacillin. Therefore, dialysis need not be accompanied by an additional
dose.

Administration

By the oral route (parenteral therapy is indicated if the oral route is considered impracticable or unsuitable, as in the case of severe diarrhoea or vomiting, and particularly for the urgent treatment of severe infection). It is recommended that at least 10 days treatment be given for any infection caused by beta-haemolytic streptococci.

Oral forms of Flucloxacillin are to be taken 1 hour before meals.

Flucloxacillin Vials for Injection should be reconstituted as follows:

• Intramuscular injection: Dissolve 250 mg, 500 mg or 1 g Flucloxacillin in 1 ml, 2 ml or 4 ml respectively of Water for Injection BP or in a 1% solution of lidocaine. Stability of the solution at room temperature: 30 minutes
• Intravenous injection: Dissolve 250 mg, 500 mg or 1 g Flucloxacillin in 5 ml, 10 ml or 20 ml respectively of Water for Injection BP or in Sodium Chloride Intravenous Injection BP (0.9% w/v). Stability of the solution at room temperature: 24 hours (72 hours at 5 °C).
• Intravenous infusion: Dissolve 250 mg, 500 mg or 1 g Flucloxacillin in 25 ml, 50 ml or 100 ml of a suitable solvent, e.g. Water for Injection; Sodium Chloride Intravenous Injection BP (0.9% w/v): 5% w/v glucose; 0.18% w/v sodium chloride with 4% w/v glucose; Hartmann's solution; sodium lactate M/6. Stability of the solution at room temperature: 24 hours (72 hours at 5°C. Flucloxacillin solutions containing lidocaine should not be used for intravenous administration. 

Incompatibilities

Flucloxacillin should not be mixed with blood products, other proteinaceous fluids such as protein hydrolysates or with intravenous lipid emulsions. Loss of activity or physical incompatibility in solution with numerous other drugs has been reported. Therefore, it is advisable not to combine Flucloxacillin with other drugs in solution for parenteral administration.

CONTRAINDICATIONS

• Flucloxacillin is a penicillin and should not be given to patients with a history of hypersensitivity to beta-lactam antibiotics (e.g. penicillins, cephalosporins).
• Flucloxacillin is contra-indicated in patients with a previous history of flucloxacillin-associated jaundice/hepatic dysfunction.
• Flucloxacillin should be used with caution in patients with evidence of hepatic dysfunction. Ocular administration.

SPECIAL WARNINGS AND SPECIAL PRECAUTIONS FOR USE

Before initiating therapy with Flucloxacillin, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactams. Cross-sensitivity between penicillins and
cephalosporins is well documented. Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) have been reported in patients receiving beta-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 history of beta-lactam hypersensitivity. If an allergic reaction occurs, Flucloxacillin should be discontinued and the therapy. These reactions are more likely to occur in individuals with a history of beta-lactam anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral emergency treatment with adrenaline. 

Oxygen, intravenous steroids, and airway management, including intubation, may also be required. Hepatitis, predominantly of a cholestatic type has appropriate therapy instituted. Serious anaphylactoid reactions may require immediate been reported and, very rarely, deaths have occurred, almost always in patients with serious prolonged treatment (See Undesirable Effects). Flucloxacillin should be used with caution in patients with evidence of hepatic dysfunction. Special caution is essential in the newborn because of the risk of hyperbilirubinemia. 

Studies have shown that, at high dose following parenteral therefore predispose to kernicterus in a jaundiced baby. In addition, special caution is essential in administration, flucloxacillin can displace bilirubin from plasma protein binding sites, and may 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. Prolonged use may occasionally result in overgrowth of non-susceptible organisms. Sodium content: The sodium salt of flucloxacillin contains 52.0 mg sodium per gram. 

This should be included in the daily allowance of patients on sodium restricted diets. This should be considered for patients with impaired renal function (creatinine clearance of less than 30 ml/min).

Flucloxacillin Oral Solution contain tartrazine, which can cause allergic-type reactions including asthma in susceptible people, especially people with a history of allergy to aspirin.

 Interaction with other medicaments.

Bacteriostatic drugs may interfere with the bactericidal action of Flucloxacillin.

PREGNANCY AND LACTATION 

Pregnancy: Penicillin is generally considered safe for use in pregnancy. Animal studies with Flucloxacillin have shown no teratogenic effects. Limited information is available concerning the results of the use of Flucloxacillin in human pregnancy. The decision to administer any drug during pregnancy should be taken with the utmost care. Therefore, Flucloxacillin should only be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment. Lactation:
Trace quantities of flucloxacillin are excreted in breast milk. The possibility of hypersensitivity reactions must be considered in breast feeding infants. Therefore, Flucloxacillin should only be administered to a breast-feeding mother when the potential benefits outweigh the potential risks associated with the treatment.

UNDESIRABLE EFFECTS

Hypersensitivity reactions: If any hypersensitivity reaction occurs, the treatment should be discontinued. Rash, urticaria, purpura, fever, eosinophilia; sometimes angioneurotic oedema, rarely anaphylactic shock (exceptional with oral administration). Certain reactions (fever, arthralgia, myalgia) sometimes develop more than 48 hours after the start of the treatment. Erythema multiforme has been reported rarely.

Gastrointestinal reactions: Minor gastrointestinal disturbances may occur during treatment. As with other antibiotics, pseudomembranous colitis has been reported rarely. If this condition develops, Flucloxacillin Minor gastrointestinal disturbances may occur during treatment. As with other antibiotics, treatment should be discontinued and appropriate therapy, e.g. oral vancomycin should be initiated.

Hepatic effects: Hepatitis and cholestatic jaundice have been reported (See Special Warnings and Special Precautions for Use). These may be delayed for up to two months post-treatment. In some cases, the course has been protracted and lasted for several months. Very rarely, deaths have been reported, almost always in patients with serious underlying disease. Changes in liver function test results may occur but are reversible when treatment is discontinued.

Renal effects: Interstitial nephritis may occur but is reversible when treatment is discontinued.
Neurological effects: In patients suffering from renal failure, neurological disorders with convulsions are possible with the intravenous injection of high doses.
Haematological effects: Neutropenia and thrombocytopenia may occur but are reversible when treatment is discontinued.

OVERDOSE 

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.

PHARMACEUTICAL PRECAUTIONS

Flucloxacillin Capsules: Do not store above 25°C.
Flucloxacillin Vials for Injection: Should be stored in a cool, dry place. Reconstituted solutions for intravenous or intramuscular injection should normally be administered within 30 minutes of preparation.

Flucloxacillin Oral solution: Store in a dry place below 25°C. keep the bottle tightly closed and used within 7 days Once reconstituted. After reconstitution store in refrigerator.

FURTHER INFORMATION

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 1 hour are as follows: approximately 8.8 mg/L (250 mg by oral route), 14.5 mg/L (500 mg by oral route) and 16.5 mg/L (500 mg by intramuscular route). The total quantity absorbed by the oral route represents approximately 79% of the quantity administered. Flucloxacillin diffuses well into most tissues, but only a small proportion enters the cerebrospinal fluid of subjects whose meninges are not inflamed. In normal subjects approximately 10% of the flucloxacillin administered is metabolised to penicilloic acid. The elimination half-life of flucloxacillin is of the order of 53 minutes. Excretion occurs mainly through the kidney. Between 65.5% (oral route) and 76.1% (parenteral route).

A small portion of the dose is excreted in the bile. The excretion of flucloxacillin is slowed in cases of renal failure. The serum protein-binding rate is 95%.

KEEP OUT OF THE REACH AND SIGHT OF CHILDREN

Not all presentations available in every country.
Pack Insert Leaflet text revised December 2014. Further Information available on request.

A Product of:
EXETER HEALTH LIMITED
Queensgate House, 48, Queen Street,
Exeter, Devon EX4 3SR, U.K.