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.