Tolvaptan

Tolvaptan is a selective oral antagonist of the vasopressin V2 receptor. By blocking V2 receptors in the renal collecting ducts, it promotes free water excretion (aquaresis) with minimal electrolyte loss. This mechanism raises serum sodium in hyponatremia and increases urine output in fluid-overload states without acting as a conventional diuretic.

In adults, tolvaptan is approved for the treatment of clinically significant hyponatremia (euvolemic or hypervolemic) and, under a risk-management program, to slow the progression of autosomal dominant polycystic kidney disease (ADPKD).

Administration is oral, with dosing guided by indication. Starting doses for hyponatremia are commonly low and titrated while monitoring electrolyte correction; dosing for ADPKD follows label-specific regimens under regulatory oversight. Clinicians determine duration and adjustments based on response and tolerability.

Safety considerations center on the risk of serious liver injury. Tolvaptan is subject to a risk-management program in some jurisdictions. Baseline and periodic liver function tests are recommended, particularly during the first 18 months of therapy. Serum sodium and overall fluid status should be monitored to avoid overly rapid correction, and patients should be cautioned about thirst and potential dehydration.

Pharmacokinetics and interactions: tolvaptan is metabolized mainly by CYP3A. Strong CYP3A inhibitors can increase exposure, while inducers can reduce it, necessitating dose adjustments and monitoring. Common adverse effects include thirst, polyuria, nocturia, dry mouth, and, in some cases, hypernatremia. The drug is prescription-only and regulated to ensure safe use, especially when treating ADPKD.