Flucloxacillin

CLINICAL USE

Antifungal agent

DOSE IN NORMAL RENAL FUNCTION

50–400 mg daily

PHARMACOKINETICS

Molecular weight :306.3

%Protein binding :11–12

%Excreted unchanged in urine : 80

Volume of distribution (L/kg) :0.65–0.7

half-life – normal/ESRD (hrs) :30/98

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 20 : Dose as in normal renal function

<10 : 50% of normal dose

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Dialysed. Dose as in GFR

<10 : mL/min

HD :Dialysed. 50% of normal dose daily, or 100% of normal dose 3 times a week after dialysis

HDF/high flux :Dialysed. 50% of normal dose daily, or 100% of normal dose 3 times a week after dialysis

CAV/VVHD :Dialysed. Dose as in normal renal functionCVVhd/HDFDialysed. 400–800 mg every 24 hours1

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Analgesics: increases concentration of celecoxib – halve celecoxib dose; increases concentration of parecoxib – reduce parecoxib dose; inhibits metabolism of alfentanil

Antibacterials: increases rifabutin levels – reduce dose; metabolism accelerated by rifampicin

Anticoagulants: potentiates effect of coumarins

Antidepressants: avoid concomitant use with reboxetineAntidiabetics: possibly enhances hypoglycaemic effect of nateglinide; increases concentration of sulphonylureas

Anti-epileptics: increases phenytoin levels; possibly increased carbamazepine concentration

Antimalarials: avoid concomitant administration with artemether/lumefantrine

Antipsychotics: increased risk of ventricular arrhythmias with pimozide and sertindole – avoid concomitant use; possibly increase quetiapine levels – reduce dose of quetiapine

Antivirals: increases nevirapine, ritonavir, tipranavir and zidovudine levels, and possibly saquinavirAnxiolytics and hypnotics: increases midazolam levelsBosentan: increased bosentan levels – avoid concomitant use

Calcium-channel blockers: avoid with nisoldipine

Ciclosporin: increases blood/serum ciclosporin levels

Diuretics: increased eplerenone levels – avoid concomitant use; concentration of fluconazole increased by hydrochlorothiazide

Ergot alkaloids: increased risk of ergotism – avoid concomitant useIvabradine: increased ivabradine levels – reduce initial doseLipid-lowering drugs: possibly increased risk of myopathy with atorvastatin or simvastatinSirolimus: may increase sirolimus concentration

Tacrolimus: increases blood/serum tacrolimus levelsTheophylline: possibly increases theophylline levels

ADMINISTRATION

Reconstition

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Route

Oral, IV

Rate of Administration

IV: 5–10 mL/minute peripherally

Comments

Oral ≡ IV dose. Very high bioavailability

OTHER INFORMATION

Oral bioavailability is 90% Approximately 50% is removed during a 3 hour haemodialysis sessionHas been used as adjunct to IV amphotericin and IP flucytosine in

CAPD : peritonitisNo dose adjustment is required for single dose therapyRecurrent yeast peritonitis: flucytosine 2000 mg orally stat, then 1000 mg daily in addition to fluconazole 150 mg IP or 200 mg orally on alternate days. Remove Tenckhoff after 4–7 days if no responseDose of 800 mg is appropriate as long as dialysate flow rate is 2 L/hour and treating a relatively resistant organism

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