Tolvaptan, an oral vasopressin antagonist, in the treatment of hyponatremia in cirrhosis.

BACKGROUND & AIMS: Tolvaptan is a vasopressin V2-receptor antagonist that improves serum sodium concentration by increasing renal solute-free water excretion. Specific data on the safety and efficacy of tolvaptan in patients with cirrhosis and hyponatremia has not been exclusively evaluated.

METHODS: This sub-analysis of the Study of Ascending Levels of Tolvaptan trials examined cirrhotic patients with hyponatremia who received 15 mg oral tolvaptan (n=63; increased to 30 or 60 mg if needed) or placebo (n=57) once-daily for 30 days. At baseline, 44% had mild hyponatremia (serum sodium 130-134 mmol/L), 56% had marked hyponatremia (serum sodium <130 mmol/L), 85% had cirrhosis due to alcohol and/or hepatitis B/C, and 80% were Child-Pugh class B/C.

RESULTS: Tolvaptan was effective in raising serum sodium. Average daily area under the curve for serum sodium was significantly greater in the tolvaptan group from baseline to day 4 (p<0.0001) and day 30 (p<0.0001). This superiority was maintained after stratification by baseline hyponatremia (mild and marked), estimated glomerular filtration rate (≤ 60 ml/min and >60 ml/min), or serum creatinine levels (<1.5mg/dl and ≥ 1.5mg/dl). Hyponatremia recurred 7 days after discontinuation of tolvaptan. Mean mental component summary scores of the SF-12 health survey improved from baseline to day 30 in the tolvaptan group but not the placebo group (4.68 vs. 0.08, p=0.02). Major side effects due to tolvaptan were dry mouth and thirst. Gastrointestinal bleeding occurred in 10% and 2% of patients in the tolvaptan and placebo group, respectively (p=0.11). Adverse event rates, withdrawals, and deaths were similar in both groups.

CONCLUSIONS: One month of tolvaptan therapy improved serum sodium levels and patient-reported health status in cirrhotic patients with hyponatremia. Hyponatremia recurred in tolvaptan-treated patients after discontinuation.