Document: spc-doc_PL 25821-0020 change

• spc-doc_PL 04569-0040
• spc-doc_PL 06809-0057
• spc-doc_PL 25821-0020
• spc-doc_PL 36722-0011

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Flucloxacillin Capsules BP 500mg

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Flucloxacillin Sodium BP 500mg equivalent to 500mg Flucloxacillin.

3    PHARMACEUTICAL FORM

Capsules.

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, tonsillitis, quinsy). Other infections include: osteomyelitis, enteritis, endocarditis, urinary tract infections, meningitis and septicaemia.

4.2    Posology and method of administration

Dosage should be taken half to one hour before food.

Adults:

(Dosage for all indications except osteomyelitis, endocarditis, and surgical prophylaxis).

The equivalent of 250mg (1 x 250mg capsule) of flucloxacillin by mouth 4 times a day. However dose may be doubled in severe infections (1 x 500mg capsules 4 times a day).

Osteomyelitis, endocarditis: Up to 8g daily in divided doses 6-8 hourly. Children:

2-10 years: One half the adult dose administered in syrup form. For children under 2 years, capsules are not suitable.

Elderly patients:

As for adults, except where there is severe renal impairment. In these cases dosage may have to be reduced.

Route of administration: Oral.

4.3    Contraindications

Flucloxacillin Sodium is contraindicated in patients known to be hypersensitive to penicillins and should be given with caution to patients with a known history of allergy.

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. Contact with penicillins should be avoided since skin sensitisation may occur.

4.5    Interaction with other medicinal products and other forms of interaction

When concomitantly administered with oral contraceptives, the contraceptives have a reduced effect. Serum concentrations are enhanced if Probenecid is given concomitantly.

4.6    Fertility, Pregnancy and lactation

Flucloxacillin diffuses across the placenta into the foetal circulation and is excreted in the milk of nursing mothers. It may provoke allergic reactions in infants that are allergic to penicillins. Flucloxacillin can be used in pregnant mothers, if necessary.

4.7    Effects on ability to drive and use machines

Not applicable.

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.

Hepatitis and cholestatic jaundice have been reported occasionally with flucloxacillin and may be delayed in onset. Older patients and those receiving flucloxacillin for more than two weeks are at greater risk.

4.9 Overdose

Serious symptoms are unlikely. Treatment should be symptomatic. Patient should be kept under observation.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

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 micro-organisms 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.

On the basis of minimum inhibitory concentrations, its 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.

A minimum inhibitory concentration against penicillin-resistant staphylococci of 0.25-0.5p,g/ml has been reported. 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 nonpenicillinase 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 27p,g per ml with mean peak concentrations of about 11 to 15p,g 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 half life of Flucloxacillin is between 30-60 minutes.

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

Magnesium Stearate Colloidal Anhydrous Silica Capsule Shell Components:

Body:

Red Iron Oxide E172 Yellow Iron Oxide E172 Methyl Paraben E218 Propyl Paraben E216 Titanium Dioxide E171 Gelatin

Cap:

Black Iron Oxide E172 Titanium Dioxide E171 Methyl Paraben E218 Propyl Paraben E216 Gelatin

Ink components:

Titanium Dioxide Shellac

Isopropyl Alcohol Alcohol

Industrial Methylated Spirits Purified Water

30/06/2016