title: The effect of co-trimoxazole on serum potassium concentration: safety evaluation of a randomized controlled trial.
abstract: Co-trimoxazole maintains a well-established role in the treatment of Pneumocystis jirovecii and Toxoplasma gondii, as well as urinary tract infections. Observational studies report hyperkalaemia to be associated with co-trimoxazole, which may stem from an amiloride-like potassium-sparing effect. The current study investigated changes in serum potassium in patients without acute infections, and the influence of concomitant antikaliuretic drugs on this effect.
  
  
  
  A post hoc analysis was carried out of a randomized controlled trial in patients with interstitial lung disease who were assigned to placebo or 960 mg co-trimoxazole twice daily. Serum potassium and creatinine were measured at baseline, 6 weeks, and 6, 9 and 12 months. The primary outcome was the difference in mean serum potassium concentrations between co-trimoxazole and placebo at 6 weeks.
  
  
  
  Mean serum potassium levels were similar at baseline: 4.24 (± 0.44) mmol l-1in the 87 co-trimoxazole group participants and 4.25 (± 0.39) mmol l-1in the 83 control participants. Co-trimoxazole significantly increased mean serum potassium levels at 6 weeks, with a difference between means compared with placebo of 0.21 mmol l-1[95% confidence interval (CI) 0.09, 0.34; P = 0.001). This significant increase in serum potassium was detectable even after exclusion of patients on antikaliuretic drugs, with a difference between means for co-trimoxazole compared with placebo of 0.23 mmol l-1(95% CI 0.09, 0.38; P = 0.002). There were 5/87 (5.7%) patients on co-trimoxazole whose serum potassium concentrations reached ≥5.5 mmol l-1during the study period.
  
  
  
  Co-trimoxazole significantly increases serum potassium concentration, even in participants not using antikaliuretic drugs. While the magnitude of increase was often minor, a small proportion in our outpatient cohort developed hyperkalaemia of clinical importance.
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: Wei Yee
authors.initials: WY
authors.lastname: Chan
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: Allan B
authors.initials: AB
authors.lastname: Clark
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Wilson
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: Yoon K
authors.initials: YK
authors.lastname: Loke
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, UK.
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D062865:Diuretics, Potassium Sparing / Q000494:pharmacology; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006947:Hyperkalemia / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy; D017563:Lung Diseases, Interstitial / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D019338:Polypharmacy; D011188:Potassium / Q000097:blood*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D062865:Diuretics, Potassium Sparing; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D011188:Potassium
keywords: adverse effect; co-trimoxazole; hyperkalaemia; serum potassium