Colistin.JPG

Colistin

CLINICAL USE

Antibacterial agent

DOSE IN NORMAL RENAL FUNCTION

Oral for bowel sterilisation or gram negative GI infections: 1.5–3 million units every 8 hoursIV: <60 kg: 50,000–75,000 units/kg in 3 divided doses>60 kg 1–2 million units every 8 hours Nebulised solution: 1–2 million units every 12 hours

PHARMACOKINETICS

  • Molecular weight                           :Approximately 1748 (as colistimethate sodium)
  • %Protein binding                           :551
  • %Excreted unchanged in urine     : 80
  • Volume of distribution (L/kg)       :0.09–0.341
  • half-life – normal/ESRD (hrs)      :1.5–8/13–20 (IV), 6.8–14 (Nebulised)

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : IV: 1–2 million units every 8 hours. Oral: Dose as in normal renal function; use with caution
  • 10 to 20     : IV: 1 million units every 12–18 hours or 50% of dose. Oral: Dose as in normal renal function; use with caution
  • <10           : IV: 1 million units every 18–24 hours or 30% of dose. Oral: Dose as in normal renal function; use with caution

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Dialysed. Dose as in GFR
  • <10           : mL/min
  • HD                     :Not dialysed. Dose as in GFR <10 mL/min
  • HDF/high flux   :Dialysed. Dose as in GFR
  • <10           : mL/min
  • CAV/VVHD      :Not dialysed. 2 million units every 48 hours1

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugsAntibacterials: increased risk of nephrotoxicity with aminoglycosides and capreomycin; increased risk of nephrotoxicity and ototoxicity with teicoplanin and vancomycinCiclosporin: increased risk of nephrotoxicityCytotoxics: increased risk of nephrotoxicity and possibly ototoxicity with platinum agentsDiuretics: increased risk of ototoxicity with loop diureticsMuscle relaxants: polymyxins enhance the effect of non-depolarising muscle relaxants and suxamethoniumParasympathomimetics: polymyxins antagonise the effect of neostigmine and pyridostigmine

    ADMINISTRATION

    Reconstition

    Sodium chloride 0.9% or water for injection

    Route

    Oral, IV, Nebulised, Topical

    Rate of Administration

    Infusion: over 30 minutes Bolus: over 5 minutes (only if patient has a totally implantable venous access device, TIVAD)

    Comments

    IV: Give in 10–50 mL sodium chloride 0.9% or water for injectionInhalation: Dissolve in 2–4 mL sodium chloride 0.9% or water for injection

    OTHER INFORMATION

    Less than 0.5 mmol/L sodium per 0.5–2 million unit vial (before reconstitution)Pharmacokinetic data: Lee CS, Marbury TC. Drug therapy in patients undergoing haemodialysis: clinical pharmacokinetic considerations. Clin Pharmacokinet. 1984; 9: 42–66.Can cause renal failure, muscle weakness and apnoea in overdose. Risk factors are usually the IV route, high doses, concomitant use with other nephrotoxic agents, and if the dose is not reduced appropriately in renal failureNo systemic absorption from oral administration in adults.188 CoLisTinIn renal impairment, neonates, and cystic fibrosis patients, plasma concentrations of 10–15 mg/L (125–200 units/mL) are usually adequateDosage schedules in renal impairment vary according to which preparation is being used. Doses in the following table are from Dollery (1999) and Colomycin SPCPromixin SPC (IV): GFR: 40–75 mL/min: 1–1.5 MIU twice daily25–40 mL/: 0.8–2 MIU once or twice daily<25 mL/min: 1–1.5 MIU every 36 hoursPromixin SPC (nebulised): GFR: 40–75 mL/min: 1–1.5 MIU twice daily25–40 mL/min: 1 MIU once or twice daily<25 mL/min: 1–1.5 MIU every 36 hoursreferences:1. Trotman RL, Williamson JC, Shoemaker DM, et al. Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy.