Also, as patients with cirrhosis may be at risk for more side effects, slower rates of increase are recommended by the FDA. Patients with cirrhosis tolerate hyponatremia with minimal neurologic sequelae and therefore use of tolvaptan should be

limited to those with serum sodiums of <125 mmol/L. Daily or every other day serum sodium Selleckchem JNK inhibitor levels should be determined while patients are receiving tolvaptan. Also, tolvaptan causes a diuresis, which if excessive, could lead to renal insufficiency. The use of diuretics in combination with tolvaptan has not been studied, but when diuretics were used with satavaptan, there was better control of the ascites without a significant decrease in renal dysfunction.13 Monitoring of renal function should be performed when patients receive tolvaptan,

especially in concert with Selleck ICG-001 diuretics, until more experience is gained with the use of this drug in patients with cirrhosis. The one side effect of major concern is the increased risk of variceal bleeding, and perhaps gastro-intestinal tract bleeding in general. There is no way to monitor for this risk but patients with known high risk varices or a past history of variceal or gastrointestinal tract bleeding probably should not receive tolvaptan. Tolvaptan has been used in fewer than 100 patients with cirrhosis and hyponatremia, and most of the safety data the FDA relied upon is from patients with congestive heart failure.12 Therefore, it remains unclear how safe this drug is in patients with cirrhosis. In addition, a similar drug when used for up to a year in patients with cirrhosis, ascites

and hyponatremia was associated with an increased risk of dying. A similar association has not been seen with tolvaptan but the drug was only given for 30 days so the long term risks and benefits with tolvaptan are unknown. We also lack information on how tolvaptan works when given in concert with diuretics. As these V2 receptor antagonists cause a diuresis it is possible that patients may develop renal insufficiency when the drug is given with diuretics. Lastly, patients with Child-Pugh scores of greater than 10 were excluded in the tolvaptan trials. The more severe forms of hyponatremia (Na <125 mmol/L) are seen in patients with more advanced liver disease, and hence the safety and efficacy of tolvaptan in this group of patients with cirrhosis is medchemexpress unknown as well. About 30% of patients in the satavaptan trial had Child-Pugh scores of >10.13 As this study showed an increased risk of mortality, the concern about giving V2 receptor antagonists to patients with advanced liver disease appears warranted. Clearly we need more studies of tolvaptan in patients with cirrhosis in order to better define how to use this drug. The use of tolvaptan should be limited to the inpatient setting to correct severe (Na <125 mmol/L) hyponatremia in the patient with cirrhosis. The current recommendation for initial use of tolvaptan is to increase the dose gradually from 15mg a day to 60 mg a day.