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| 009P London, UK Pharmacology 2016 |
The effect of co-trimoxazole on serum potassium concentration: safety evaluation of a randomised controlled trial
Introduction 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 associated with co-trimoxazole which may stem from an amiloride-like potassium sparing effect. Our placebo-controlled study reports on changes in serum potassium at 6 weeks on patients without acute infections, as well as the relevance of concomitant anti-kaliuretic drugs on this effect.
Method This is a post-hoc analysis of a randomised controlled trial investigating patients with interstitial lung disease. Patients were randomised to placebo or 960 mg twice daily co-trimoxazole. Blood samples including serum potassium and creatinine were scheduled at baseline, six weeks, 6, 9 and 12 months. The primary outcome is difference in mean serum potassium concentrations between co-trimoxazole and placebo at six weeks.
Results There were 87 participants in the co-trimoxazole intervention group and 83 control participants. Pre-randomisation baseline mean serum potassium concentration was 4.24 (± 0.44) mmol/L and 4.25 (± 0.39) mmol/L respectively. At 6 weeks, mean serum potassium was 4.46 (±0.41) mmol/L in the treatment group and 4.25 (±0.40) mmol/L in the control group, with a difference between means of (+0.21 mmol/L (95% Confidence Intervals [CI] 0.09-0.34) p=0.001). After exclusion of all patients on angiotensin converting enzyme inhibitors (ACE I), angiotensin receptor blockers (ARB) or potassium sparing diuretics, difference between means for co-trimoxazole vs. control was +0.23 mmol/L (95% CI 0.09-0.38, p=0.002). 15/87 (17%) patients on co-trimoxazole experienced a change of ≥ +1mmol/L serum potassium at any point in the study compared to 3/83 (3.6%) in the placebo arm. Relative risk for a rise of ≥ +1mmol/L serum potassium with co-trimoxazole is 4.77 (95% CI 1.43 - 15.88) compared to placebo. 25/87 (29%) of patients in the treatment group had a peak serum potassium ≥5.0 mmol/L at any point of follow up, compared to 15/83 (18%) patients in the placebo arm. The relative risk of serum potassium ≥5.0 mmol/L at any point in the trial was 1.59 (95% CI 0.90 - 2.80) with co-trimoxazole compared to placebo. There were 5/87 (5.7%) patients on co-trimoxazole whose serum potassium reached concentrations ≥5.5 mmol/L at any point during the study period.
Conclusions Co-trimoxazole significantly increases serum potassium concentration, even in participants who are not using ACE I, ARB or potassium sparing diuretics. Whilst the magnitude of increase is often minor, a small proportion in our outpatient cohort did develop hyperkalaemia of clinical importance.