Vaprisol (conivaptan HCl/dextrose 5 % in water)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Conivaptan, a benzazepine derivative, is a nonpeptide antagonist of arginine vasopressin (antidiuretic hormone) V1A and V2 receptors.
Conivaptan, a benzazepine derivative, is a nonpeptide antagonist of arginine vasopressin (antidiuretic hormone) V1A and V2 receptors. Circulating concentrations of vasopressin, which usually are elevated in patients with euvolemic or hypervolemic hyponatremia, play an important role in the regulation of fluid and electrolyte balance. The activity of vasopressin at renal V2 receptors, which are functionally coupled to aquaporin channels in the apical membrane of the renal collecting ducts, helps maintain plasma osmolality within the normal range by increasing permeability of the renal collecting ducts to water.
Vasopressin also causes vasoconstriction through its actions on vascular V1A receptors. Conivaptan antagonizes the effects of vasopressin at V2 receptors, resulting in excretion of free water (or increased effective water clearance), which generally is accompanied by increased net fluid loss, increased urine output, and decreased urine osmolality. Blockade of vascular V1A receptors may cause splanchnic vasodilation, possibly resulting in hypotension or variceal bleeding in patients with cirrhosis (especially those with portal hypertension).
Conivaptan is extensively metabolized by cytochrome P-450 (CYP) isoenzyme 3A and also is a potent inhibitor of CYP3A. Following IV or oral administration, conivaptan exhibits nonlinear pharmacokinetics, probably secondary to the drug inhibiting its own metabolism. Several active metabolites have been identified, but their contribution to the drug's clinical effects probably is minimal since exposure to the metabolites combined is only about 7% that of the parent drug.
Following administration of an IV dose of 10 mg or an oral dose of 20 mg, about 83% of the dose was excreted in the feces and about 12% in the urine over several days. About 1% of the dose was excreted in urine as unchanged drug over the first 24 hours after IV administration.
Generic name: conivaptan HCl/dextrose 5 % in water
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
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Indications
The following indications are listed for Vaprisol:
- Hyponatremia
Also known as: Decreased Serum Na, Decreased Serum Sodium, Low Serum Sodium.
Dosing
The recommended adult dosage of conivaptan hydrochloride for the treatment of euvolemic or hypervolemic hyponatremia is a loading dose of 20 mg infused IV over 30 minutes followed by continuous IV infusion of 20 mg over 24 hours; following the first day of treatment, conivaptan hydrochloride therapy should be continued for an additional 1-3 days at a dosage of 20 mg daily by continuous IV infusion. Vital signs, fluid status, and serum sodium concentration must be monitored carefully, and administration of the drug should be discontinued if hypotension or hypovolemia occurs or if serum sodium concentration increases at too rapid a rate (see Overly Rapid Correction of Serum Sodium Concentration and also see Hypovolemia and Hypotension under Cautions: Warnings/Precautions). If serum sodium concentration is not increasing at the desired rate, the dosage of conivaptan hydrochloride may be increased to 40 mg daily (the maximum recommended daily dosage (after the loading dose)) as a continuous IV infusion. In clinical trials of the drug, a dosage of 80 mg daily was not substantially more effective than 40 mg daily and was associated with a higher incidence of infusion site reactions and adverse effects requiring drug discontinuance. The total duration of conivaptan therapy should not exceed 4 days.
Conivaptan hydrochloride is administered by IV infusion. The manufacturer states that the drug should be administered to hospitalized patients only.
Commercially available premixed conivaptan hydrochloride injection containing 0.2 mg/mL of conivaptan hydrochloride in 5% dextrose injection may be used without further dilution; the manufacturer's labeling should be consulted for proper methods of administration and other associated precautions for this preparation. The premixed conivaptan hydrochloride injection is available in single-use flexible containers; any unused portions should be discarded. Additives should not be introduced into the premixed injection. The premixed conivaptan hydrochloride injection in flexible plastic containers should not be used in series connections, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.
Conivaptan hydrochloride solutions should be inspected visually for particulate matter and/or discoloration prior to administration, and the solution should be discarded if it is cloudy or discolored or contains particulates.
The commercially available premixed conivaptan hydrochloride injection is compatible with 5% dextrose injection. In addition, the premixed conivaptan hydrochloride injection is compatible with 0.9% sodium chloride injection for up to 22 hours when the 2 solutions are administered simultaneously through a Y-site connection at flow rates of 4.2 mL/hour for conivaptan hydrochloride injection and 2.1 or 6.3 mL/hour for 0.9% sodium chloride injection. Conivaptan hydrochloride injection should not be administered with lactated Ringer's injection and should not be administered simultaneously through the same IV line with other drugs.
The IV loading dose of conivaptan hydrochloride should be infused over 30 minutes, followed by a continuous IV infusion of the drug over 24 hours. Conivaptan hydrochloride should be administered into a large vein, and the infusion site should be changed every 24 hours to minimize the risk of venous irritation (see Infusion Site Reactions under Cautions: Warnings/Precautions).
Although conivaptan has been administered orally in clinical trials, the drug is not being developed commercially for oral use because of the risk of serious cytochrome P-450 (CYP) isoenzyme 3A-mediated drug interactions with longer-term oral use (see Drug Interactions: Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes and see Description).
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Hypovolemic hyponatremia.
Concomitant use of potent inhibitors of cytochrome P-450 (CYP) isoenzyme 3A (e.g., clarithromycin, indinavir, itraconazole, ketoconazole, ritonavir). (See Inhibitors of Cytochrome P-450 3A Isoenzyme under Drug Interactions: Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes.)
Anuria. Anuric patients are not expected to obtain clinical benefit from conivaptan therapy.
The manufacturer states that solutions containing dextrose, including commercially available premixed conivaptan hydrochloride in 5% dextrose injection, are contraindicated in patients with known allergy to corn or corn products.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in about 5% or more of individuals receiving conivaptan and more frequently than in those receiving placebo include infusion site reactions (including erythema, pain, phlebitis), hypokalemia, headache, peripheral edema, vomiting, diarrhea, constipation, hypertension, orthostatic hypotension, hyponatremia, thirst, anemia, hypotension, pyrexia, nausea, and confusion.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy have not been established in children younger than 18 years of age.
Category C. (See Users Guide.)
Conivaptan is distributed into milk in rats; it is not known whether conivaptan is distributed into human milk. A decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
Adverse effect profile in geriatric patients is similar to that observed in younger adults.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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