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

Abstract

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.

• Authors: Andrés Cárdenas, Pere Ginès, Paul Marotta, Frank Czerwiec, John Oyuang, Mónica Guevara, Nezam H Afdhal
• Journal: Journal of hepatology (J Hepatol) Vol. 56 Issue 3 Pg. 571-8 (Mar 2012) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 22027579 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antidiuretic Hormone Receptor Antagonists
• Benzazepines
• Tolvaptan
• Sodium

Topics

• Administration, Oral
• Antidiuretic Hormone Receptor Antagonists
• Ascites (complications)
• Benzazepines (administration & dosage, adverse effects)
• Chronic Disease
• Female
• Health Surveys
• Humans
• Hyponatremia (blood, drug therapy, etiology)
• Liver Cirrhosis (complications)
• Male
• Middle Aged
• Prospective Studies
• Recurrence
• Sodium (blood)
• Tolvaptan
• Treatment Outcome