Drug-induced hyponatremia associated with sodium-glucose cotransporter 2 inhibitors, immune checkpoint inhibitors, and targeted anticancer agents

Hyponatremia is the most common electrolyte disorder and a frequent trigger for urgent assessment in internal medicine. Beyond classic culprits, such as thiazide diuretics and antidepressants, clinicians increasingly face hyponatremia in the setting of modern metabolic and oncologic therapies. Sodium‑glucose cotransporter 2 inhibitors (notably empagliflozin and dapagliflozin) promote glucosuria‑driven osmotic diuresis and electrolyte‑free water clearance, and (based on emerging evidence) may mitigate dilutional hyponatremia in selected patients with the syndrome of inappropriate antidiuresis. At the same time, glucosuria can confound urine indices, and the diuretic effect may unmask occult hypovolemia. Immune checkpoint inhibitors (eg, nivolumab, pembrolizumab, ipilimumab) may cause hyponatremia through immune‑related endocrinopathies (secondary or primary adrenal insufficiency, thyroid dysfunction) and through nonendocrine toxicities leading to salt and water losses. In a large real‑world cohort of patients receiving immune checkpoint inhibitors, hyponatremia occurred in roughly two‑thirds, and severe hyponatremia (serum sodium <124 mmol/l) in 6%; endocrine causes accounted for a small but pivotal fraction. Targeted anticancer agents (eg, vascular endothelial growth factor receptor-directed multikinase tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors) add further complexity, often via gastrointestinal toxicity, renal tubular dysfunction, or inappropriate antidiuresis. We provide a bedside diagnostic algorithm and pragmatic monitoring recommendations aimed at preventing neurological harm from overly rapid correction. This narrative review summarizes contemporary mechanisms of drug‑related hyponatremia, highlights therapy‑specific diagnostic pitfalls, and proposes a practical framework for prevention, monitoring, and treatment that prioritizes neurological safety and avoidance of overcorrection.