Article date: August 2017
By: Wei Yee Chan, Allan B. Clark, Andrew M. Wilson, Yoon K. Loke, on behalf of the TIPAC investigators, on behalf of the TIPAC investigators in Volume 83, Issue 8, pages 1808-1814
Aims
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.
Methods
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.
Results
Mean serum potassium levels were similar at baseline: 4.24 (± 0.44) mmol l–1 in the 87 co‐trimoxazole group participants and 4.25 (± 0.39) mmol l–1 in 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–1 during the study period.
Conclusions
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.
DOI: 10.1111/bcp.13263
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