» Vaprisol (conivaptan hydrochloride injection), the only arginine vasopressin receptor antagonist currently on the market, is now available as a single-use, premixed formulation from Astellas Pharma US Inc.

Originally approved by the FDA for use in an ampule, conivaptan is now also approved for use as a sterile premixed solution. "Premixed formulations are always ideal, especially for medications utilized in critical-care patients, such as [conivaptan]. When patients take a turn for the worse in the ICU, every minute counts in preparing the medication and getting it up to the floor," said Nermin Boles-Attia, pharmacy coordinator at The University Hospital in Newark, N.J.

The new 100 mL formulation of conivaptan comes in an Intravia container, a product of Baxter Healthcare Corporation, containing 20 mg of conivaptan hydrochloride in a 5 percent dextrose solution. It has an expiration date of 24 months. The sterile solution in ampules is also still available.

Conivaptan blocks the activity of AVP, resulting in increased urine output without the loss of electrolytes such as sodium and potassium. This effect (aquaresis) helps to increase serum sodium levels in patients with hyponatremia.

Conivaptan is contraindicated in patients with hypovolemic hyponatremia, which occurs following decreases in both total body water and total body sodium stores. Conivaptan is not indicated for the treatment of congestive heart failure. It should be used only for the treatment of hyponatremia in patients with underlying heart failure when the expected benefit of raising serum sodium outweighs the increased risk of adverse events.

Conivaptan therapy should begin with a loading dose of 20 mg IV administered over 30 minutes, followed by 20 mg administered as a continuous intravenous infusion over 24 hours. Conivaptan can be given for an additional one to three days as a continuous infusion of 20 mg/day. It can be titrated upward to a maximum dose of 40 mg daily in a continuous infusion. Conivaptan should not be administered for more than four days.

Serum sodium, volume, and neurological status must be monitored frequently to prevent an overly rapid correction of sodium. A rise in serum sodium greater than 12 mEq/L over a 24-hour period may result in serious neurologic sequelae. The most common adverse reactions associated with conivaptan therapy include infusion-site reactions, headaches, hypokalemia, orthostatic hypotension, and pyrexia.

Conivaptan is known to affect the pharmacokinetics of midazolam, simvastatin, digoxin, and amlodipine. Concomitant use of conivaptan with drugs that are primarily metabolized by CYP3A4 should be closely monitored, or the combination should be avoided. In addition, coadministration of conivaptan with potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, clarithromycin, ritonavir, and indinavir, is contraindicated. The use of conivaptan in patients with hepatic impairment (including ascites, cirrhosis, or portal hypertension) or renal impairment has not been evaluated, and caution is advised when administering conivaptan to these patients.

Mona Nashed, PharmD, BCPS, is a hospital pharmacist in New Jersey.