Oral Tolvaptan Is Safe and Effective in Chronic Hyponatremia

Abstract

Vasopressin antagonists increase the serum sodium concentration in patients who have euvolemia and hypervolemia with hyponatremia in the short term (Յ30 days), but their safety and efficacy with longer term administration is unknown. SALTWATER was a multicenter, open-label extension of the Study of Ascending Levels of Tolvaptan in Hyponatremia (SALT-1 and SALT-2). In total, 111 patients with hyponatremia received oral tolvaptan for a mean follow-up of 701 days, providing 77,369 patient-days of exposure. All patients had hyponatremia at randomization in SALT-1 and SALT-2, and 85% continued to have hyponatremia at entry in SALTWATER. The most common adverse effects attributed to tolvaptan were pollakiuria, thirst, fatigue, dry mouth, polydipsia, and polyuria. Six drug-related adverse effects led to study discontinuation. The increase in serum sodium exceeded the desired 1 mmol/L per h at initiation in five patients. Hypernatremia (Ͼ145 mmol/L) led to discontinuation in one patient. Mean serum sodium increased from 130.8 mmol/L at baseline to Ͼ135 mmol/L throughout the observation period (P Ͻ 0.001 versus baseline at most points). Responses were comparable between patients with euvolemia and those with heart failure but more modest in patients with cirrhosis. In conclusion, prolonged administration of tolvaptan maintains an increased serum sodium with an acceptable margin of safety.

Tolvaptan Can Improve Clinical Course in Responders

“…Previous studies demonstrated that hyponatremia improved after the administration of TLV due to excretion of free water in urine, 4,6,15) but as we showed in this study, such an improvement was observed mostly in responders. Non-responders were associated with reduced concentrating and diluting ability of urine probably due to dysfunction of the collecting ducts, 11,12) and not surprisingly their serum sodium concentrations did not increase.…”

Case report of domiciliary treatment with Tolvaptan in patients with advanced heart failure and persistent hyponatremia

“…Therefore, Tolvaptan could be a good alternative added to chronic treatment of HF, especially loop diuretics, to maintain patient status, as reported in previous trials [7]. The only side Case Report effect linked to Tolvaptan was thirst, probably related to habitual water restriction in HF and other diuretics intake.…”

Successful treatment with tolvaptan to control blood volume and hyponatremia in a chronic kidney disease patient

“…The most frequently observed adverse effects of tolvaptan are thirst and dry mouth [4,15]. Myelinolysis, which is caused by the rapid correction of hyponatremia, is a serious side effect of tolvaptan [15].…”

“…Myelinolysis, which is caused by the rapid correction of hyponatremia, is a serious side effect of tolvaptan [15]. In addition, Irazabal et al [16] reported that tolvaptan significantly reduced the GFR during a one-week treatment, with an increase of uric acid in autosomal dominant polycystic kidney disease (ADPKD) patients.…”