Conivaptan

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Conivaptan Brand Name– Vaprisol

What is Conivaptan

Conivaptan (YM-087) is a non-peptide dual V1A and V2 vasopressin receptor antagonist. Intravenous conivaptan is indicated for the treatment of euvolemic or hypervolemic hyponatremia in hospitalized patients.

At recommended doses, IV conivaptan increases serum sodium concentrations and increases free water clearance.

Examples of euvolemic hyponatremia states include the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), hypothyroidism, adrenal insufficiency, and certain pulmonary disorders.

Examples of hypervolemic hyponatremic states include heart failure, cirrhosis, and nephrotic syndrome.

There are preliminary hemodynamic findings which suggest beneficial effects of conivaptan in heart failure; however, this use requires further investigation for efficacy and safety in this population.

Currently, conivaptan can be used in hyponatremic patients with underlying heart failure if the benefits of raising the serum sodium concentration outweigh any risks of adverse events.

Conivaptan has a different mechanism compared other drugs used to treat hyponatremia.

Conivaptan increases urine output and decreases reabsorption of free water by antagonizing V2 receptors in the kidneys.

Conivaptan has been proposed to enhance free water excretion with less effect on electrolyte balance compared to furosemide based on animal data and case reports; however, comparative studies of IV conivaptan and furosemide have not been conducted in humans.

The most prominent electrolyte disorder reported during conivaptan infusion is hypokalemia (9.8%). Injection site reactions occur frequently (52.5%), despite appropriate preparation and administration.

Although conivaptan has been preliminarily evaluated for the treatment of CHF, the drug is not currently indicated for this use.

A double blind, placebo-controlled, randomized trial (ADVANCE) has been designed to investigate conivaptan for use in heart failure patients.

This study will evaluate the change in exercise time to reach 70% of peak oxygen consumption following oral conivaptan doses of 10, 20, and 40 mg; the results of this study are pending.

Theoretically, blocking the vasoconstrictive effects of the V1A receptor can produce beneficial hemodynamic effects in CHF. Preliminary data suggests that conivaptan reduces pulmonary capillary wedge pressure without affecting systemic vascular resistance, heart rate, or cardiac output.

Several clinical trials are underway to further evaluate the safety, efficacy, and hemodynamics of conivaptan for the treatment of heart failure.

Conivaptan (Vaprisol®) was approved by the FDA for the treatment of euvolemic hyponatremia in hospitalized patients in December 2005 and for the treatment of hypervolemic hyponatremia in hospitalized patients in February 2007.

Indications

  1. hyponatremia
  2. increased intracranial pressure

For the treatment of hospitalized patients with euvolemic hyponatremia (e.g., syndrome of inappropriate secretion of antidiuretic hormone (SIADH), hypothyroidism, adrenal insufficiency, pulmonary disorders) or hypervolemic hyponatremia (e.g., cirrhosis, nephrotic syndrome)

NOTE: Conivaptan is not indicated for the treatment of heart failure and has not been shown to be effective for the treatment of the signs and symptoms of heart failure.

NOTE: Conivaptan should be administered only in settings where serum sodium concentrations, volume status, and blood pressure can be closely monitored.

NOTE: It has not been established that utilizing conivaptan to raise serum sodium concentrations provides a symptomatic benefit to patients.

Side Effects

  1. anemia
  2. atrial fibrillation
  3. confusion
  4. constipation
  5. diarrhea
  6. edema
  7. erythema
  8. fever
  9. headache
  10. heart failure
  11. hypernatremia
  12. hypertension
  13. hypokalemia
  14. hypomagnesemia
  15. hyponatremia
  16. hypotension
  17. infection
  18. injection site reaction
  19. insomnia
  20. nausea
  21. orthostatic hypotension
  22. osmotic demyelination syndrome
  23. peripheral edema
  24. phlebitis
  25. polydipsia
  26. pruritus
  27. vomiting

Monitoring Parameters

  • blood pressure
  • serum magnesium
  • serum potassium
  • serum sodium

Contraindications

  • alcoholism
  • anuria
  • breast-feeding
  • corn hypersensitivity
  • geriatric
  • heart failure
  • hepatic disease
  • hyponatremia
  • hypotension
  • hypovolemia
  • infertility
  • malnutrition
  • pregnancy
  • renal disease
  • renal failure
  • renal impairment
  • reproductive risk

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