Co trimoxazole.JPG

Co trimoxazole

CLINICAL USE

Antibacterial agent:Treatment and prophylaxis of Pneumocystis jiroveci pneumonia (PCP)Acute exacerbations of chronic bronchitis Urinary tract infections, on microbiological advice

DOSE IN NORMAL RENAL FUNCTION

PCP: 120 mg/kg/day in 2–4 divided doses Oral prophylaxis: 480–960 mg daily or 960 mg on alternate daysAcute exacerbations of chronic bronchitis and urinary tract infections on microbiological advice:IV: 960 mg – 1.44 g of co-trimoxazole twice a dayOral: 960 mg of co-trimoxazole twice a day

PHARMACOKINETICS

  • Molecular weight                           :Sulfamethoxazole: 253.3; trimethoprim: 290.3
  • %Protein binding                           :Sulfamethoxazole: 70; trimethoprim: 45
  • %Excreted unchanged in urine     : Sulfamethoxazole: 15–30; trimethoprim: 40–60
  • Volume of distribution (L/kg)       :Sulfamethoxazole: 0.28–0.38; trimethoprim: 1–2.2
  • half-life – normal/ESRD (hrs)      :Sulfamethoxazole: 6–12/
  • 20 to 50
  • ; trimethoprim: 8–10/20–49

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

    30–50 Dose as in normal renal function 15–30 50% of dose; PCP: 60 mg/kg twice daily for 3 days then 30 mg/kg twice daily<15 50% of dose; PCP: 30 mg/kg twice daily. (This should only be given if haemodialysis facilities are available)

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Not dialysed. Dose as in GFR<15 mL/min
  • HD                     :Dialysed. Dose as in GFR<15 mL/min
  • HDF/high flux   :Dialysed. Dose as in GFR<15 mL/min
  • CAV/VVHD      :Dialysed. Dose as in GFR=15–30 mL/min

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugsAnti-arrhythmics: increased risk of ventricular arrhythmias with amiodarone – avoid concomitant use; concentration of procainamide increasedAntibacterials: increased risk of crystalluria with methenamineAnticoagulants: effect of coumarins enhancedAnti-epileptics: antifolate effect and concentration of phenytoin increasedAntimalarials: increased risk of antifolate effect with pyrimethamineAntipsychotics: avoid concomitant use with clozapine, increased risk of agranulocytosisCiclosporin: increased risk of nephrotoxicity; possibly reduced ciclosporin levelsCytotoxics: increased risk of haematological toxicity with azathioprine and mercaptopurine. Antifolate effect of methotrexate increased

    ADMINISTRATION

    Reconstition

    Route

    IV, oral

    Rate of Administration

    Over 60–90 minutes Alternatively: 2–3 hours for high doses as undiluted solution via central line (unlicensed).Co-TriMoXAZoLE (TriMEThoPriM + sULFAMEThoXAZoLE) 191

    Comments

    For an

    IV infusion

    dilute each 5 mL co- trimoxazole strong solution with 125 mL sodium chloride 0.9% or glucose 5%Glaxo Smith Kline: dilute 5 mL to 75 mL glucose 5% and administer over 1 hour if fluid restricted

    OTHER INFORMATION

    Alternative dosing (for acute exacerbations of chronic bronchitis and urinary tract infections) on microbiological advice only; not PCPAfter 2–3 days, plasma samples collected 12 hours post dose should have levels of sulfamethoxazole not higher than 150 micrograms/mL. If higher, stop treatment until levels fall below 120 micrograms/mL. Plasma levels of trimethoprim should be 5 micrograms/mL or higher, for optimum efficacy for PCPFolic acid supplementation may be necessary during chronic therapy. Monthly blood counts advisable