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  • Title: The effect of co-trimoxazole on serum potassium concentration: safety evaluation of a randomized controlled trial.
    Author: Chan WY, Clark AB, Wilson AM, Loke YK, TIPAC investigatorsNorwich Medical School, University of East Anglia, Norwich, UK..
    Journal: Br J Clin Pharmacol; 2017 Aug; 83(8):1808-1814. PubMed ID: 28192629.
    Abstract:
    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.
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