New drug approved to treat hyponatremia

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Symptoms typically do not occur until plasma sodium drops below 120 mEq/L. Even then, symptoms tend to be nonspecific. However, as sodium concentrations decrease, symptoms of hyponatremia can include confusion, vomiting, and seizures.

Heart failure, hepatic cirrhosis, and renal disease are the most common causes of hypervolemic hyponatremia, while the syndrome of inappropriate antidiuretic hormone secretion is the most common cause of euvolemic hyponatremia. Several physiologic conditions and drugs may trigger increased production of antidiuretic hormone (i.e., arginine vasopressin), including pituitary tumors, small cell lung cancer, head trauma, and pulmonary diseases. Additionally, adrenal insufficiency, hypothyroidism, and even use of selective serotonin reuptake inhibitors can cause euvolemic hyponatremia.

On the other hand, slow correction of serum sodium can increase the risk of brain swelling and seizures. Demeclocycline, a tetracycline derivative, though not approved for this use, has also been used to correct hyponatremia but has been limited by azotemia, renal damage, thyroid dysfunction, and central nervous system adverse effects.

Conivaptan restores proper fluid balance by antagonizing arginine vasopressin receptors. The blocking of those receptors results in aquaresis, or loss of water without loss of sodium or potassium. This differs, of course, from diuretics, which stimulate loss of both water and electrolytes.

Michael Cawley, Pharm.D., associate professor of clinical pharmacy at the University of the Sciences in Philadelphia and a critical care clinical pharmacy specialist at Crozer-Chester Medical Center in Upland, Pa., has served on Astellas' Health System Advisory Board panel. According to Cawley, "Conivaptan has great potential in patients who specifically need to lose fluid." However, he cautioned, the drug may not make it onto hospital formularies if it is priced too high.

In a clinical study of 56 patients, intravenous administration of conivaptan 40 mg/day for four days corrected sodium and water balance in hospitalized patients with mild to moderate euvolemic hyponatremia, with significant improvements seen within the first day of treatment.

Frequent monitoring of serum sodium and volume status is needed as an overly rapid rise in serum sodium (>12 mEq/day) may result in serious sequelae. Data from clinical studies indicated that ~9% of patients met criteria for overly rapid correction of serum sodium, but none had permanent neurological damage.

THE AUTHOR is a medical writer based in Pennsylvania.