Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Wockhardt UK Ltd, Ash Road North, Wrexham, LL13 9UF, UK
Pharmacotherapeutic group: Beta-lactamase resistant penicillins
ATC code: J01CF05
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.
Flucloxacillin is bactericidal with a similar mode of action to benzylpenicillin. It is resistant to staphylococcal penicillinase and therefore active against penicillinase-producing and non-penicillinase-producing staphylococci. It has minimum inhibitory concentrations in the range of 0.25 to 0.5µg per ml.
Its activity against streptococci such as Streptococcus pneumoniae and Str. pyogenes is less than that of benzylpenicillin but sufficient to be useful when these organisms are present with penicillin-resistant staphylococci. It is virtually ineffective against Enterococcus faecalis.
After the intramuscular administration of a single 250 or 500mg dose of flucloxacillin to volunteers, mean peak concentrations of the drug in serum were approximately 10.5 and 16mg.l-1 respectively. Mean urinary excretion of flucloxacillin following its intramuscular use is 61% of the administered dose.
Flucloxacillin may also be administered by intravenous bolus injection or by slow intravenous infusion. High serum levels of the drug are achieved by these modes of administration: 30 minutes and 2 hours after a single 500mg intravenous bolus injection of flucloxacillin the mean serum concentration of the drug was 38 and 7.5mg.l-1, respectively; 30 minutes and 3 hours after a single 1g intravenous bolus injection of flucloxacillin, the mean serum concentrations were 60 and 4mg.l-1 respectively. The administration of 2g flucloxacillin by intravenous infusion over 20 minutes resulted in mean serum concentrations of 244 and 27.7mg.l-1 15 minutes and 120 minutes respectively after the end of the infusion.
The percentage of a dose of intravenous flucloxacillin recovered in urine in an 8 hour collection period varies from 60 to 76%.
About 95% of flucloxacillin in the circulation is bound to plasma proteins. Flucloxacillin has been reported to have a plasma half-life of approximately one hour. The half-life is prolonged in neonates.
The serum half-life of flucloxacillin in patients with severe kidney disease has been reported as 135 to 173 minutes. No significant difference in the half-life was found between patients on or off haemodialysis. Flucloxacillin is not removed by haemodialysis.
Flucloxacillin is metabolised to a limited extent and the unchanged drug and metabolites are excreted in the urine by glomerular filtration and renal tubular secretion. Up to 90% of an intramuscular dose is excreted in the urine within six hours. Only small amounts are excreted in the bile.
Flucloxacillin is unlikely to be excreted in breast milk to any significant extent. Similarly, placental transfer is unlikely to occur to any appreciable extent.
There are no pre-clinical data of relevance to the prescriber which are additional to those included in other sections.
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