Tolvaptan effective for hyponatremia for patients with heart failure — trials

MANILA, Philippines - Tolvaptan, a new vasopressin V2-receptor antagonist and the first and only oral drug in its class, has been shown in clinical trials to be an effective treatment for hypervolemic and euvolemic hyponatremia, especially for patients with heart failure, cirrhosis, and Syndrome of Inappropriate Antidiuretic Hormone (SIADH).

It prevents vasopressin-induced reabsorption of water, promoting aquaresis or electrolyte-free removal of water leading to an increase in urine volume with minimal change in the concentration of electrolytes.

Hyponatremia is the most common electrolyte disorder among hospitalized patients and has been shown to lengthen hospital stay, increase re-hospitalization rate and increase mortality.

It is a metabolic condition where the body lacks sodium in the body fluids outside the cells. Without enough sodium levels in the cells, they begin to absorb more water, causing them to swell. This eventually results in more serious conditions such as brain damage or even death.

One of the most common underlying conditions for hyponatremia is heart failure (HF). In HF, there is an increased production of vasopressin, a hormone that strongly influences water retention and functions as an antidiuretic.

The elevated levels of vasopressin causes water to be retained, causing an increase in total body water with relatively smaller increase in the total amount of sodium which is effectively “diluted,” causing hyponatremia.

Otsuka Philippines presented the most recent data for the efficacy of tolvaptan at the Makati Shangri-La last month.

According to Dr. Jun Chiong, associate professor of medicine, pharmacy and outcomes science at the Loma Linda University, the cost spent on treating hyponatremia in the United States ranges from $1.6 billion to $3.6 billion annually.

Also, hyponatremia patients spend $19,215 per year when compared to patients with normal serum sodium levels ($9,257).

In the SALT study conducted by Schrier et al, patients with HF, cirrhosis and SIADH with hyponatremia were randomly assigned to receive 15 mg of tolvaptan (225 patients) or placebo (223 patients) daily.

The dosage was increased to 30 mg daily then to 60 mg daily, depending on the basis of serum sodium concentrations.

Results indicate that serum sodium concentrations increased in the tolvaptan arm as compared to the placebo arm in the first four days (P<0.001) until the 30 full days of therapy (P<0.001).

The benefits of tolvaptan can be sustained for up to one year as demonstrated in the extension study SALTWATER.

Based on the EVEREST outcome and clinical status trial, tolvaptan initiated for the treatment of patients hospitalized for worsening HF significantly improved symptoms compared to standard treatment, was safe and did not worsen clinical outcomes after two years of follow-up.

Post-hoc analysis showed that the subgroup of heart failure patients with hyponatremia had more mortality benefits from tolvaptan compared to the general patient population.

Medical practitioners however should note that tolvaptan should not be given to patients requiring intervention to raise serum sodium urgently to prevent or to treat serious neurological symptoms, said Chiong.

Tolvaptan is the generic name for Samsca, a product of research developed by Otsuka Pharmaceutical.