conivaptan


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conivaptan

(con-i-vap-tan) ,

Vaprisol

(trade name)

Classification

Therapeutic: electrolyte modifiers
Pharmacologic: vasopressin antagonists
Pregnancy Category: C

Indications

To increase serum sodium in hospitalized patients with euvolemic or hypervolemic hyponatremia.

Action

Antagonizes vasopressin at V2 receptor sites in renal collecting ducts, resulting in excretion of free water.

Therapeutic effects

Increased serum sodium concentrations.
Improved fluid status.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Protein Binding: 99% protein bound.
Metabolism and Excretion: Metabolized solely by the CYP3A4 enzyme system. 83% excreted in feces as metabolites, 12% in urine (as metabolites).
Half-life: 5 hr.

Time/action profile

ROUTEONSETPEAKDURATION
IVunknown12 hrend of infusion

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Hypovolemic hyponatremia;Concurrent use of ketonconazole, itraconazole, clarithromycin, ritonavir, or indinavir.
Use Cautiously in: Moderate hepatic impairment (↓ dose recommended)Severe renal impairment (not recommended if CCr <30 mL/min); Obstetric / Lactation: Safety not established; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • headache (most frequent)
  • confusion
  • insomnia

Cardiovascular

  • hypertension
  • hypotension

Gastrointestinal

  • diarrhea

Genitourinary

  • polyuria

Fluid and Electrolyte

  • dehydration
  • hypokalemia
  • hypomagnesemia
  • hyponatremia

Local

  • infusion reactions (most frequent)

Miscellaneous

  • fever
  • thirst

Interactions

Drug-Drug interaction

Blood levels and effects are ↑ by ketoconazole, itraconazole, clarithromycin, ritonavir, or indinavir ; concurrent use is contraindicated.↑ blood levels and may ↑ effects of midazolam, simvastatin, lovastatin, amlodipine, and other drugs metabolized by CYP3A4 ; careful monitoring recommended.May ↑ digoxin levels.

Route/Dosage

Intravenous (Adults) 20 mg loading dose initially, followed by 20 mg/day as a continuous infusion for 2–4 days. May titrate conivaptan up to 40 mg/day as a continuous infusion if serum sodium is not rising at desired rate. Total duration of therapy should not exceed 4 days.

Hepatic Impairment

(Adults) Moderate hepatic impairment—10 mg loading dose initially, followed by 10 mg/day as a continuous infusion for 2–4 days; may titrate up to 20 mg/day as a continuous infusion if serum sodium is not rising at desired rate.

Availability

Premixed infusion: 20 mg/100 mL D5W

Nursing implications

Nursing assessment

  • Monitor injection site during administration. Frequently causes erythema, pain, swelling and phlebitis. May require discontinuation of therapy.
  • Monitor vital signs frequently during therapy. Discontinue therapy if patient becomes hypovolemic and hypotensive. Therapy may be resumed at a reduced dose once patient is euvolemic and no longer hypotensive, if patient remains hyponatremic.
  • Assess neurologic status during administration. Overly rapid rise in serum sodium may cause neurologic sequelae.
  • Lab Test Considerations: Monitor serum sodium concentration frequently during therapy. If serum sodium rises at an undesirably rapid rate (>12 mEq/L/24 hr), discontinue administration of conivaptan. If serum sodium continues to rise, do not resume therapy. If hyponatremia persists or recurs (after discontinuation for rapid rise of serum sodium) and patient has no evidence of neurologic sequelae from rapid increase, conivaptan may be resumed at a reduced dose.
    • May cause hyperglycemia, hypoglycemia, hypokalemia, hypomagnesemia, and hyponatremia.

Potential Nursing Diagnoses

Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • Intravenous Administration
  • Administer IV through large veins and rotate infusion site every 24 hr to minimize risk if vascular irritation.
  • Loading Dose
  • Intermittent Infusion: Diluent: Premixed containers require no further dilution.Concentration: 0.2 mg/mL.
  • Rate: Administer over 30 min.
  • Continuous Infusion
  • Continuous Infusion: Diluent: Premixed containers require no further dilution.Concentration: 0.2 mg/mL.
  • Rate: Administer continuous infusion at a rate of 20 mg/24 hr. If patient requires 40 mg/24 hr continuous infusion, infuse 20 mg over 12 hr, followed by 20 mg over 12 hr.
  • Additive Incompatibility: Do not admix with LR, furosemide, or combine with any other product in the same IV line or bag.

Patient/Family Teaching

  • Explain purpose of medication to patient.
  • Instruct patient to notify health care professional if pain or redness occurs at infusion site.

Evaluation/Desired Outcomes

  • Restoration of normal fluid and electrolyte balance.

conivaptan

a vasopressin receptor antagonist.
indications This drug is used to treat euvolemia hyponatremia in those hospitalized.
contraindications Hypovolemia and known hypersensitivity to this drug prohibit its use.
adverse effects Adverse effects of this drug include headache, confusion, insomnia, hypotension, hypertension, orthostatic hypotension, phlebitis, nausea, vomiting, constipation, dry mouth, hematuria, polyuria, urinary tract infection, pollaklura, anemia, erythema, injection site reaction, dehydration, hyperglycemia, hypoglycemia, hypokalemia, hypomagnesia, hyponatremia, oral candidiasis, pain, peripheral edema, and pneumonia. Atrial fibrillation is a life-threatening side effect.
References in periodicals archive ?
Some examples of strong CYP3A4 inhibitors are ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelflnavir, indinavir, boceprevir, telaprevir, telithromycin, and conivaptan.
These strong inhibitors include: ketoconazole, itraconazole, conivaptan,HIV protease inhibitors, and clarithromycin.
DRUGS IN PHASE IIB AND BEYOND Drug Indication conivaptan hyponatremia, acute decompensated heart failure aps 1585 chronic kidney disease ym443 dyspepsia DRUGS COMING OFF PATENT Drug Indication Vaprisol hyponatremia (2010) TOP SELLING DRUGS Drug Indication $ (+/-%) Prograf transplantation $2,010 13% Harnal BPH $1,166 8% Lipitor cholesterol $953 11% Vesicare bladder $714 35% Micardis hypertension $644 17% Gaster acid reflux $530 -1% Account for 62% of total pharma sales, same as in 2007.
SAN FRANCISCO -- Satavaptan and conivaptan appear to be effective in the treatment of dilutional hyponatremia, a frequent consequence of heart failure and of renal failure.
SAN FRANCISCO -- Satavaptan and conivaptan seem effective in treating dilutional hyponatremia, a frequent consequence of heart failure and of renal failure.
While familiarity with new agents in development including Sanofi's satavaptan, Cardiokine's lixivaptan, and Astellas's oral conivaptan is low, nephrologists report a preference for non-peptide selective vasopressin V2 receptor antagonists over V1A/V2 receptor antagonists.
Other investigators assessed conivaptan (Vaprisol, Astellas) and supported its use for euvolemic hyponatremia because the drug increased urine output of mostly free water with little electrolyte loss (J.
Effects of conivaptan, a combined vasopressin V(1a) and V(2) receptor antagonist, on vasopressin-induced cardiac and haemodynamic changes in anaesthetized dogs.
Two vasopressin antagonists, or "vaptans," have been tested in clinical trials: conivaptan and tolvaptan.
NEW ORLEANS -- Conivaptan was safe and effective for treating hyponatremia in three phase III studies that together involved about 200 evaluable patients.
NEW ORLEANS -- Conivaptan was safe and effective for treating hyponatremia in three phase III clinical trials that together involved about 200 evaluable patients.
TORONTO -- The investigational agent conivaptan significantly increases serum sodium concentrations in patients with hyponatremia, according to phase III results presented at the annual meeting of the Heart Failure Society of America.