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

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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