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Conivaptan (Vaprisol) for the Treatment of Hyponatremia



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Am Fam Physician. 2008 Oct 15;78(8):984-989.

Conivaptan (Vaprisol) is an antagonist of arginine vasopressin receptors V1A and V2 (10-fold higher affinity to V2 than V1A) that produces a water diuresis, with electrolyte-sparing effects on the kidney.1 It is labeled for the treatment of euvolemic and hypervolemic hyponatremia in hospitalized patients.1,2 Treatment may be required for rapid correction of sodium levels in symptomatic patients presenting with serum sodium levels less than 120 mEq per L (120 mmol per L).3

Name Starting dosage Dose form Approximate cost*

Conivaptan (Vaprisol)

20 mg intravenously over 30 minutes, followed by 20 mg over 24 hours (maximal dose of 40 mg per day; maximal course of therapy of four days)

20 mg per 4-mL ampule

$450 for one day oftherapy (20 mg)


*— Average wholesale cost, based on Red Book, Montvale, N.J.: Medical Economics Data, 2007.

Name Starting dosage Dose form Approximate cost*

Conivaptan (Vaprisol)

20 mg intravenously over 30 minutes, followed by 20 mg over 24 hours (maximal dose of 40 mg per day; maximal course of therapy of four days)

20 mg per 4-mL ampule

$450 for one day oftherapy (20 mg)


*— Average wholesale cost, based on Red Book, Montvale, N.J.: Medical Economics Data, 2007.

SAFETY

Conivaptan causes few serious problems when used in appropriate patients. It is contraindicated in patients with hypovolemic hyponatremia because it will cause an increase in free water excretion and may exacerbate the patient's existing hypovolemic condition.1 In addition, the safety of conivaptan in patients with heart failure has not been established; it should not be used in patients with heart failure or other edematous conditions.1,3 Conivaptan is classified as U.S. Food and Drug Administration pregnancy category C.

TOLERABILITY

Some of the most commonly reported adverse reactions are infusion related (22 percent), including erythema, phlebitis, and pain at the site of injection; however, few patients will need to discontinue treatment because of these adverse effects.1 Additionally, transient minor hypotension is common with conivaptan infusion. This adverse reaction is tolerable and is likely the result of water loss.4 No other significant hemodynamic effects have been reported. Some patients (9 percent) will develop overly rapid correction of serum sodium levels.1 There are no reported cases of neurologic sequelae.1

EFFECTIVENESS

Low serum sodium levels may occur in conjunction with a reduction in total body water and a greater loss of total body sodium (hypotonic hyponatremia); increased total body water relative to an increase in total body sodium (hypertonic hyponatremia); and normal total body sodium, but increased total body water (euvolemic hyponatremia). Conivaptan has been compared with placebo in patients with euvolemic and hypervolemic hyponatremia.1,2,4 Typically, conivaptan 40 mg per day will increase serum sodium levels after 24 hours by 6.4 mEq per L (6.4 mmol per L) more than that achieved with placebo. After 72 hours, this rise in sodium increases to a total of 6.9 mEq per L (6.9 mmol per L).2,4,5 Additional benefits are not seen with higher doses, and results are similar in patients with euvolemic and hypervolemic hyponatremia.4 Conivaptan has not been compared with hypertonic saline infusion. The effect of conivaptan on seizure risk, weakness, or mental status has not been evaluated.

PRICE

The estimated cost of the 20-mg maintenance dose of conivaptan is $450 per day. The cost of the 40-mg maintenance dose is $900 per day.

SIMPLICITY

The initial dose of conivaptan is 20 mg given over 30 minutes, followed by up to 20 mg administered over the next 24 hours. The dose can be increased to 40 mg per day. Administration of conivaptan can be continued for one to three days after the initial day of treatment for a maximum of four days total. Serum sodium levels, blood pressure, and volume status should be closely monitored throughout the infusion.

Bottom Line

In most cases, patients with hyponatremia can be adequately managed with fluid restriction alone. However, acutely symptomatic patients may require treatment, such as hypertonic saline. In these situations, conivaptan is an expensive alternative. The safety and effectiveness of conivaptan has not been compared directly with hypertonic saline. It would be ideal to have comparative data before conivaptan is considered a standard treatment for hyponatremia.

Address correspondence to Kristine Willett, BS, PharmD, at Kristine. willett@mcphs.edu. Reprints are not available from the author.

Author disclosure: Nothing to disclose.

REFERENCES

1. Vaprisol (conivaptan hydrochloride injection) [product information]. Deerfield, Ill.: Astellas Pharma US, Inc.; February 2007. http://www.astellas.us/docs/vaprisol.pdf. Accessed June 26, 2008.

2. Zeltser D, Rosansky S, van Rensburg H, Verbalis JG, Smith N, for the Conivaptan Study Group. Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia. Am J Nephrol. 2007;27(5):447–457.

3. Cawley MJ. Hyponatremia: current treatment strategies and the role of vasopressin antagonists. Ann Pharmacother. 2007;41(5):840–850.

4. Verbalis JG, Zeltser D, Smith N, Barve A, Andoh M. Assessment of the efficacy and safety of intravenous conivaptan in patients with euvolemic hyponatremia: subgroup analysis of a randomized, controlled study. Clin Endocrinol (Oxf). 2008;69(1):159–168.

5. Ali F, Guglin M, Vaitkevicius P, Ghali JK. Therapeutic potential of vasopressin receptor antagonists. Drugs. 2007;67(6):847–858.

STEPS new drug reviews cover Safety, Tolerability, Effectiveness, Price, and Simplicity. Each independent review is provided by authors who have no financial association with the drug manufacturer.

The series coordinator for AFP is Allen F. Shaughnessy, PharmD, Tufts University Family Medicine Residency Program at Cambridge Health Alliance, Malden, Mass.


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