Flucloxacillin

CLINICAL USE


Antifungal agent

DOSE IN NORMAL RENAL FUNCTION

50–400 mg daily

PHARMACOKINETICS

  • Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :306.3
  • %Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :11–12
  • %Excreted unchanged in urine &nbsp &nbsp : 80

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

  • half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :30/98

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50 &nbsp &nbsp : Dose as in normal renal function
  • 10 to 20 &nbsp &nbsp : Dose as in normal renal function
  • <10 &nbsp &nbsp &nbsp &nbsp &nbsp : 50% of normal dose

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Dialysed. Dose as in GFR
  • <10 &nbsp &nbsp &nbsp &nbsp &nbsp : mL/min

  • HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Dialysed. 50% of normal dose daily, or 100% of normal dose 3 times a week after dialysis
  • HDF/high flux &nbsp :Dialysed. 50% of normal dose daily, or 100% of normal dose 3 times a week after dialysis
  • CAV/VVHD &nbsp &nbsp &nbsp: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

    –

    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 &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp: 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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