FDA approves new treatment for euvolemic hyponatremia

Susan Jeffrey

January 05, 2006

Jan 5, 2006

Deerfield, IL - Astellas Pharma announced that the US Food and Drug Administration (FDA) has approved conivaptan hydrochloride injection (Vaprisol), an arginine vasopressin antagonist, for the treatment of euvolemic hyponatremia in hospitalized patients [ 1 ]. The drug is the first specifically indicated for the treatment of this condition, a press release from the company notes.

The FDA also issued an approvable letter for the same drug for another indication, hypervolemic hyponatremia. The company "plans on working closely with the FDA" to obtain approval for this indication, the release notes.

Hyponatremia affects an estimated 4% of hospitalized patients each year in the US, the company writes; although many have no symptoms, severe cases can result in brain swelling, respiratory arrest, or death. Hyponatremia often results from elevated levels of the hormone arginine vasopressin (AVP), which regulates the balance of water and salt in the body, the release said.

Common causes of hyponatremia include syndrome of inappropriate antidiuretic hormone, advanced kidney failure, hypothyroidism, cancer, and chronic hypertension. Dilutional hyponatremia, which includes both euvolemic and hypervolemic hyponatremia, is the most common form and occurs when retained water dilutes serum sodium, they write.


Aquaresis

This new drug blocks the activity of AVP, increasing urine output without the loss of electrolytes such as sodium and potassium, the company notes, an effect known as aquaresis.

In a randomized, double-blind, placebo-controlled trial, intravenous conivaptan, at a dose of 40¿mg/day for four days, corrected sodium and water balance in hospitalized patients with mild to moderate euvolemic hyponatremia, the company release said. Common adverse reactions to the drug were infusion-site reactions, hypokalemia, headache, thirst, and vomiting, they note, but "the majority of the reactions were mild and did not lead to discontinuation of the drug."

Therapy should begin with an IV loading dose of 20¿mg, followed by 20¿mg given as a continuous infusion over 24 hours; after the first day, the drug is given for an additional one to three days as a continuous infusion of 20 mg/day. If serum sodium does not rise at the desired rate, the dose can be titrated to 40 mg/day as a continuous infusion, the release said.

The drug is contraindicated for patients with hypovolemic hyponatremia and those with hypersensitivity to any of its components, the company notes, as is the coadministration of CYP3A4 inhibitors, including ketoconazole, itraconazole, clarithromycin, ritonavir, and indinavir. Use of the drug in patients with hepatic impairment?including ascites, cirrhosis, or portal hypertension?has not been systematically evaluated, they add, and it is not indicated for use in congestive heart failure.

"Currently available treatment options for hyponatremia, such as fluid restriction, diuretics, and saline solution, are inconsistent in their effects," Dr¿ Joseph Verbalis (Georgetown University Medical Center, Washington, DC) is quoted as saying in the Astellas release. "Vaprisol will allow us to effectively correct the sodium-water balance in patients with euvolemic hyponatremia and will help us to better manage this common and potentially very serious condition."


Source

  1. Astellas Pharma. FDA approves Astellas' Vaprisol for the treatment of euvolemic hyponatremia [press release]. December 30, 2005. Available at: http://www.astellas.com/global/about/news/2006/pdf/060104_eg.pdf.

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