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KIMBERLY A. WALTER, PHARM.D., BCPS, AQ, is Medical Science Liaison, Scientific Affairs, Bayer HealthCare Pharmaceuticals, St. Petersburg, FL; at the time of writing she was Clinical Specialist, Cardiology and Drug Utilization, Yale-New Haven Hospital, New Haven, CT.

Address correspondence to Mary Ellen Bonk, Pharm.D., University HealthSystem Consortium, 2001 Spring Road, Suite 700, Oak Brook, IL 60523-1890 (bonk{at}uhc.edu).

Purpose. The pharmacology, bioavailability and pharmacokinetics, clinical efficacy, adverse effects and toxicities, drug interactions, dosage and administration, and safety issues related to the use of conivaptan are discussed. Summary. Conivaptan hydrochloride is a nonpeptide, V1A and V2 vasopressin-receptor antagonist. It is available as an i.v. formulation in 4-mL ampules containing 20 mg of conivaptan hydrochloride. The drug is active both orally and i.v. Conivaptan injection is approved for the treatment of euvolemic hyponatremia in hospitalized patients. Three double-blind, placebo-controlled, randomized, multicenter studies have been conducted in the United States and internationally. The studies used various dosing regimens for conivaptan but maintained the same efficacy endpoints. Each study showed conivaptan to be effective in increasing serum sodium and in water clearance. Conivaptan is being evaluated in the treatment of acute decompensated heart failure and chronic heart failure, but the safety of this drug has not been fully established. The drug has been generally well tolerated in clinical trials with both oral and i.v. administration. The approved dosing regimen consists of a 20-mg i.v. loading dose administered over 30 minutes, followed by a continuous infusion of 20 mg administered over 24 hours. Clinical studies evaluating conivaptan have been short term; longer-term effects of hemodynamic parameters are unknown. Conclusion. Conivaptan, the first vasopressin antagonist approved for the treatment of euvolemic hyponatremia, has a unique mechanism of action that results in free-water excretion and offers a new option for the treatment of resistant hyponatremia in the acute setting when patients have not responded to standard management. Index terms: Conivaptan hydrochloride; Dosage; Drug administration routes; Drug administration; Drug interactions; Drugs, availability; Heart failure; Hyponatremia; Mechanism of action; Pharmacokinetics; Toxicity; Vasopressin antagonists