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Samsca effective in difficult-to-treat cirrhotic ascites

Samsca, also known as tolvaptan, was safe when combined with conventional diuretics and presented promising results in treating patients with difficult-to-treat cirrhotic ascites, according to results of a recent prospective study. Blood urea nitrogen was a favorable marker for selecting patients most likely to respond to treatment.

“The main differences between tolvaptan and conventional diuretics are that tolvaptan does not stimulate the sodium channel and increases free water excretion without affecting urinary sodium and potassium excretion,” Hideto Kawaratani, MD, PhD, from the Nara Medical University, Japan, and colleagues wrote. “This mechanism seems to reduce the occurrence of diuretic-induced electrolyte abnormalities or renal failure.”

The researchers enrolled 50 patients with persistent ascites despite treatment with Lasix (furosemide, Sanofi Aventis) or Aldactone (spironolactone, Pfizer). Treatment consisted of 3.75 mg or 7.5 mg of Samsca (tolvaptan, Otsuka Pharmaceuticals) per day for 7 days combined with 20 mg to 120 mg per day of furosemide and/or 25 mg to 125 mg per day of spironolactone under dietary sodium restriction of less than 6 grams per day.

At the end of 7 days, the researchers observed a median body weight decrease of 1.2 kg, a median urine volume increase of 606 mL and a slight median increase in serum sodium levels from 133.1 mEq/L to 135.9 mEq/L compared with baseline. There were no significant changes in potassium level, serum creatinine, blood urea nitrogen, estimated glomerular filtration rate or vital signs.

Eighteen patients lost over 2 kg of body weight at the end of treatment and 26 had achieved an increase in urine volume on day 2 of over 300 mL, though there were no clear correlations between the two parameters.

Patients who lost less than 2 kg at the end of treatment had significantly higher basal blood urea nitrogen levels (24.1 vs. 17.1 mg/dL; P < .01), plasma renin activity (13.1 vs. 4.8 ng/mL/h; P < .01) and plasma aldosterone levels (367.8 vs. 142.8 ng/dL; P = .01), and lower serum sodium (131.7 vs. 135.6 mEq/L; P = .02) and urine sodium levels (44.3 vs. 69.8 mEq/L; P = .04) compared with those who responded well to treatment. Additionally, the poor responders received a significantly lower dose of tolvaptan (6.4 vs. 7.5 mg/d; P < .01) than those who responded well.

On multivariate analysis, blood urea nitrogen level was correlated with better response to treatment with Samsca (OR = 0.09; 95% CI, 0.01-0.67). The most appropriate cut-off value based on blood urea nitrogen was 26.9 mg/dL (area under the curve = 0.77).

During treatment, no patients had severe adverse events. Mild adverse events included thirst (n = 22) and mild renal dysfunction from dehydration (n = 5), which improved for four patients once the diuretics were decreased.

“Large doses of diuretics frequently lead to difficult-to-treat hyponatremia and renal disturbance, which disturbs the further use of diuretics. These become a rationale for early treatment with tolvaptan while patients are treated with conventional diuretics,” Kawaratani and colleagues wrote. “Measurement of [blood urea nitrogen], not creatinine, before commencement of tolvaptan is expected to be useful for patient selection and decision-making on the initiation of tolvaptan treatment.” – by Talitha Bennett

Disclosure: The researchers report no relevant financial disclosures.