Description
Trimethoprim impairs renal potassium excretion and may inhibit tubular secretion of tacrolimus, collectively increasing the risk of hyperkalemia and tacrolimus nephrotoxicity.
Mechanism
Trimethoprim blocks the epithelial sodium channel (ENaC) in the distal nephron, reducing potassium secretion; tacrolimus independently reduces GFR and promotes hyperkalemia. Trimethoprim may also mildly inhibit P-gp-mediated tacrolimus renal elimination.
Clinical Significance
Case reports and retrospective analyses in transplant patients show clinically significant hyperkalemia (K⁺ >6.0 mEq/L) and acute kidney injury when trimethoprim or TMP-SMX is added to tacrolimus.
Management
Monitor serum potassium and creatinine within 3–5 days of starting trimethoprim; consider alternative antibiotics (e.g., azithromycin, doxycycline for susceptible organisms) when feasible in tacrolimus-treated transplant recipients.