Flucloxacillin Capsule 250mg
: Yellow body, Black Cap, Size 2, contains a white powder. Each capsule contains 250mg flucloxacillin (as the sodium salt).
Flucloxacillin Capsule 500mg:
Yellow body, Black Cap, Size 0, contains a white powder. Each capsule contains 500mg flucloxacillin (as the sodium salt).
Flucloxacillin is an isoxazolyl penicillin of the beta-lactam group of antibiotics, which exerts a bactericidal effect upon many Gram positive organisms including streptococci and beta-lactamase producing staphylococci.
Properties:
Flucloxacillin is a narrow-spectrum antibiotic of the group of isoxazolylpenicillins; it is not inactivated by staphylococcal beta-lactamases.
Activity:
Flucloxacillin, by its action on the synthesis of the bacterial wall, exerts a bactericidal effect on streptococci, staphylococci, including the beta-lactamase-producing strains, clostridia and neisseria. It is not active against methicillin-resistant staphylococci. Strains of the following organisms are generally sensitive to the bactericidal action of flucloxacillin in vitro. (The minimal inhibitory concentrations (MIC) of flucloxacillin are quoted below.)
| Micro-organisms | MIC (mg/L) |
| Staphylococcus aureus | 0.1 - 0.25 |
| Staphylococcus aureus (beta- lactamase +) | 0.25 - 0.5 |
| Streptococcus pneumoniae | 0.25 |
| Streptococcus pyogenes (Group A beta-haemolytic) * | 0.1 |
| Streptococcus viridans group | 0.5 |
| Clostridium tetani | 0.25 |
| Clostridium welchii | 0.25 |
| Neisseria meningitidis | 0.1 |
| Neisseria gonorrhoeae | 0.1 |
| Neisseria gonorrhoeae (beta-lactamase +) | 2.5 |
* The Group A beta-haemolytic streptococci are less sensitive to the isoxazolyl penicillins than to penicillin G or penicillin V.
Absorption:
Flucloxacillin is stable in acid media and can therefore be administered by the oral route. The peak serum levels of flucloxacillin reached after one hour are as follows.
After 250mg by the oral route (in fasting subjects): approximately 8.8 mg/L.
After 500mg by the oral route (in fasting subjects): approximately 14.5 mg/L.
The total quantity absorbed by the oral route represents approximately 79% of the quantity administered.
Distribution:
Flucloxacillin diffuses well into most tissues. 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 metabolized to penicilloic acid. The elimination half-life of flucloxacillin is of 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.
Flucloxacillin is indicated for the treatment of infections due to Gram-positive organisms, including infections caused by -lactamase producing staphylococci. Typical indications include:
Skin and Soft Tissue Infections:
Boils, abscesses, carbuncles, furunculosis, cellulitis, infected wounds, infected burns, protection of skin grafts, and impetigo.
Infected Skin Conditions:
e.g. ulcer, eczema and acne.
Respiratory Tract Infections:
Pneumonia, lung abscess, empyema, sinusitis, pharyngitis, tonsillitis, quinsy, otitis media and externa. Other infections caused by flucloxacillin-sensitive organisms such as osteomyelitis, enteritis, endocarditis, urinary tract infection, meningitis, septicaemia. Oral preparations of the -lactamase-resistant penicillins (or flucloxacillin) should not be used as initial therapy in serious, life threatening infections. Oral therapy with flucloxacillin may be used to follow-up the previous use of parenteral flucloxacillin as soon as the clinical condition warrants.
Adults (including elderly patients):
500mg initially and then either 500mg or 250mg 8-hourly depending on severity of infection. Oral doses should be administered 1 hour before meals.
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 < 10mL/min) a reduction in dose or 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.
Flucloxacillin should not be given to patients with a history of hypersensitivity to beta-lactam antibiotics (e.g. penicillins, cephalosporins) or any of the excipients (see Pharmaceutical Particulars). Flucloxacillin is contraindicated in patients with a previous history of flucloxacillin-associated jaundice/hepatic dysfunction.
Before initiating therapy with flucloxacillin, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactams. 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 a history of beta-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, intravenous crystalloids, hydrocortisone, antihistamine and nebulised bronchodilators, may also be required. 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 (see Dosage and Administration) 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 (see Adverse Effects). Special caution is essential in the newborn because of the risk of hyperbilirubinemia. 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. Prolonged use may occasionally result in overgrowth of non-susceptible organisms.
Sodium content:
Each 1 gram of flucloxacillin sodium contains 2.2 mmol of sodium. This should be included in the daily allowance of patients on sodium restricted diets.
Magnesium content:
Each 1 gram of flucloxacillin magnesium contains approximately 1 mmol of magnesium. This should be considered for patients with impaired renal function (creatinine clearance of less than 30mL/min). Dosage should be adjusted in renal impairment.
Pregnancy:
Animal studies with flucloxacillin have shown no teratogenic effects. The product has been in clinical use since 1970 and the limited number of reported cases of use in human pregnancy have shown no evidence of untoward effects. 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 can be detected 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 treatment.
Effects on Ability to Drive and Use Machines:
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.
Blood and lymphatic system disorders:
Very rare:Neutropenia (including agranulocytosis) and thrombocytopenia. These are reversible when treatment is discontinued. Haemolytic anaemia.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.
Immune system disorders:
Very rare:anaphylactic shock (exceptional with oral administration) (see Warnings and Precautions), angioneurotic oedema. If any hypersensitivity reactions occur, flucloxacillin should be discontinued. (See also Skin and subcutaneous tissue disorders).
Hepato-biliary disorders:
Very rare:Hepatitis and cholestatic jaundice (See Warnings and Precautions). 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 death 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. *The incidence of these AEs was derived from clinical studies involving a total of approximately 929 adult and paediatric patients taking flucloxacillin.
Probenecid decreases the renal tubular secretion of flucloxacillin. Concurrent administration of probenecid delays the excretion of flucloxacillin. In common with other antibiotics, flucloxacillin may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.
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.
List of Excipients
Capsule Contents:
Talc, povidone, microcrystalline cellulose, magnesium stearate and sodium starch glycollate.
Capsule Shells Also Contain:
Gelatin, FD&C Blue 1, red iron oxide, yellow iron oxide and titanium dioxide. Staphlex capsules do not contain gluten or lactose.
Storage Precautions
Capsules: Store below 25C.
Prescription Medicine.
STAPHLEX 250 mg capsules: Bottles of 100's, 500's and 250's. STAPHLEX 500 mg capsules: Bottles of 50's, 250's and 500's. Not all pack sizes may be marketed.
Nil.
Mylan New Zealand Limited PO Box 11-183 Ellerslie AUCKLAND Telephone: 09-579-2792
24 January 2013