Introduction
Co-trimoxazole, a broad-spectrum antibiotic comprising trimethoprim and sulfamethoxazole, is widely used for the treatment and prophylaxis of Gram-positive, Gram-negative bacteria, and other parasitic infections1. Co-trimoxazole use has been associated with hyperkalemia, a severe and potentially fatal adverse drug reaction (ADR)2,3. Co-trimoxazole-induced hyperkalemia mechanism is mediated through the blockage of amiloride-sensitive sodium channels in the distal tubule, due the structural similarity of trimethoprim with potassium-sparing diuretics, leading to the impairment of renal potassium excretion 2. Age and co-administered medications have been recognized as risk factors for co-trimoxazole-induced hyperkalemia 3. Evidence suggests that concurrent administration of drugs such as angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin-II receptor blockers (ARBs), β-blockers, and spironolactone can increase serum potassium concentration, leading to increased incidence of severe hyperkalemia, hospitalization, and mortality 3. ACE-Is, ARBs, and spironolactone have an additional mechanism of inducing hyperkalemia by decreasing the serum concentration of aldosterone, resulting in reabsorbing potassium at the distal renal tubule 4. Several studies have also identified age as a factor potentially increasing the risk of hyperkalemia and mortality3. When potassium serum concentration reaches 6 mEq/L or more, treatment interruption and close monitoring are warranted to avoid cardiac toxicity 2. Limiting potassium intake and avoiding other medications that might contribute to hyperkalemia are approaches to consider when the potassium level is controlled below 6 mEq/L 2. Despite the clinical significance of co-trimoxazole-induced hyperkalemia, this ADR has been neglected by many clinicians, and no clear guidelines are available to monitor patients.