Thirst tolvaptan

In two multicenter, randomized, double-blind, placebo-controlled studies of tolvaptan in 448 patients with euvolemic or hypervolemic hyponatremia, tolvaptan 15-60 mg/day increased serum sodium concentrations significantly compared with placebo (6). The main adverse effects associated with tolvaptan included increased thirst, dry mouth, and increased urination. 

In a multicenter randomized, double-blind, placebo-controlled study in 4133 patients with heart failure, tolvaptan 30 mg/day for a minimum of 60 days in addition to standard therapy significantly improved dyspnea, body weight, and edema in patients with hyponatremia, serum sodium concentrations increased significantly (7). The main adverse effects were increased thirst and a dry mouth. 

In two double-blind, randomized, placebo-controlled studies in 17 subjects in all, the main adverse effects of tolvaptan 60-240-mg/day were excess thirst, frequent urination, and a dry mouth (8). 

Observational studies The use of tolvaptan in short- and long-term studies in heart failure and hyponatremia has been reviewed [82 ]. In an open extension study in 4133 patients with heart failure who were followed for a mean of 10 months, 111 patients with hyponatremia took oral tolvaptan for a mean of 701 days dry mouth, thirst, and hypernatremia were more common in those who took tolvaptan the incidences of hypotension and renal failure were comparable in the two groups [83 ]. The most common adverse events that were assessed by the investigator as being potentially related to the use of tolvaptan were pollakiuria ( = 11) thirst (n = 10) fatigue (n = 6) and dry mouth, polydipsia, polyuria, hypotension, hypernatremia, dizziness, headache, peripheral edema, and acute renal failure (four patients each) [84 ]. 

In two randomized placebo-controlled trials of tolvaptan 15-60 mg in patients with either euvolemic or hypervolemic hyponatremia, adverse events were similar to those with placebo [43 ]. The most common adverse reactions were thirst (14% versus 5%) and dry mouth (13% versus 4%). Death rates were similar 14 of 223 patients who took tolvaptan compared with 13 of 220 patients who took placebo. Four patients who took tolvaptan had an increased serum sodium concentration to over 146 mmol/1, and in four patients the rate of increase of sodium was more rapid than clinically appropriate. Close moiutor-ing of serum sodium concentrations and plasma volume status is essential. Fluid restriction is not required. Polyuria is common. 

A randomised, placebo-controlled trial of oral tolvaptan in healthy Korean men (N = 46) found that the most common treatment-emergent adverse event was thirst (occurring in 40% of the treatment group vs 0% of the placebo group) due to the aquaretic actions of tolvaptan [83 ]. 

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