CLINICAL USE

Antibacterial agent

DOSE IN NORMAL RENAL FUNCTION

IV: 1 g every 12 hours Oral: 125 mg or 500 mg 4 times daily (Higher dose for resistant cases of Clostridium difficile)

PHARMACOKINETICS

  • Molecular weight                           : 1449.3; (1485.7 as hydrochloride)
  • %Protein binding                           : 10–50 (19 CKD 5)
  • %Excreted unchanged in urine     : 80–90
  • Volume of distribution (L/kg)       : 0.47–1.1 (0.88 CKD 5)
  • half-life – normal/ESRD (hrs)      : 6/120–216

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : IV: 0.5–1 g every 12–24 hours Oral: dose as in normal renal function
  • 10 to 20     : IV: 0.5–1 g every 24–48 hours Oral: dose as in normal renal function
  • <10           : IV: 0.5–1 g every 48–96 hours Oral: dose as in normal renal function

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                : Not dialysed. Dose as in GFR <10 mL/min
  • HD                     : Not dialysed. Dose as in GFR <10 mL/min
  • HDF/high flux   : Dialysed. See ‘Other Information’ CAV/ VVh/
  • HD Dialysed. 1 g every 48 hours1 CVVhd/ HDF Dialysed. 1 g daily and see ‘Other Information’.1

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs

  • Ciclosporin: variable response; increased risk of nephrotoxicity
  • Diuretics: increased risk of ototoxicity with loop diuretics Muscle relaxants: enhanced effects of suxamethonium
  • Tacrolimus: possible increased risk of nephrotoxicity

    ADMINISTRATION

    Reconstition

    10 mL water for injection per 500 mg vial, then dilute 1 g to 250 mL with sodium chloride 0.9% (50 mL if giving centrally)

    Route

    IV, oral

    Rate of Administration

    Not faster than 10 mg/minute

    Comments

    Usual dilution is

  • 10 to 20     : mg/mL. (UK Critical Care Group, Minimum Infusion Volumes for fluid restricted critically ill patients, 3rd Edition, 2006.) USE IN
  • CAPD                : PERITONITIS: 12.5–25 mg/L per bag (see local protocol.) Various other regimens used in PD ranging from IV dosing to high dose stat IP use Some units use the following: Patient weight >60 kg: stat dose of 2 g — IP on days 1, 7 and 14 in with a 6 hour dwell Patient weight <60 kg: 1.5 g IP on days — 1, 7 and 14

    OTHER INFORMATION

    Second line to metronidazole in treatment of pseudomembranous colitis Not absorbed via oral route at low doses but monitor plasma levels at higher doses Injection solution may be given orally; however, oral capsules available Alternative Dosage Adjustment In Moderate And Severe Renal Impairment: Give 1 g loading dose and monitor — serum levels at 24 hour intervals. When level

  • <10           : mg/L give another 1 g dose. Peak levels, 2 hours after dose, should be in range 18–26 mg/L. Some units use a 500 mg loading dose Anephric/dialysis patients usually need 1 g once or twice weekly . In HDF higher doses are required; possible doses are 1 g initially followed by 500 mg every dialysis for 3 dialysis sessions. *
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