Trade Names:Vaprisol- Injection, liquid 5 mg/mL
Trade Names:Vaprisol- Premixed in Dextrose, injection, solution 0.2 mg/mL
Dual antagonist of arginine vasopressin (AVP) V 1A and V 2 receptors. V 2 receptors, which are functionally coupled to aquaporin channels in the apical membrane of the collecting ducts of the kidney, help maintain plasma osmolality in the normal range. The predominant effect of conivaptan in the treatment of hyponatremia is V 2 antagonism of AVP, which results in aquaresis (excretion of free water).
C max is 619 ng/mL and occurs at the end of loading dose. Minimum plasma concentrations occur approximately 12 h after start of loading dose and increase to a mean concentration of 188 ng/mL at the end of infusion.
Plasma protein binding is 99%.
Metabolism is via CYP3A4, and 4 metabolites have been identified.
Mean terminal elimination half-life is 5 h and mean Cl is 15.2 L/h. Approximately 83% is excreted in feces and 12% in urine over a period of several days.
Has not been evaluated. AUC for oral administration was up to 80% higher in patients with renal function impairment.Hepatic Function Impairment
Has not been evaluated; increased systemic exposure occurs after oral administration to patients with stable cirrhosis and moderate hepatic function impairment.Elderly
Drug exposure in elderly patients increased nearly 2-fold with the 60 mg dose compared with younger men.
Treatment of euvolemic and hypervolemic hyponatremia (eg, SIADH) in hospitalized patients.
Hypovolemic hyponatremia; coadministration with potent CYP3A4 inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, ritonavir); hypersensitivity to corn or corn products (premixed solution); or any component of the product.
IV Loading dose of 20 mg over 30 min followed by 20 mg via continuous infusion over 24 h. Following initial day of treatment, administer for additional 1 to 3 days in a continuous infusion of 20 mg/day. If serum sodium is not rising at desired rate, may titrate dose upward to 40 mg/day. Total infusion duration should not exceed 4 days.
Store at controlled room temperature (59° to 86°F) in cardboard container and protect from light. Do not store below 59°F.Premixed
Store at 77°F. Avoid excessive heat. Protect from freezing. Protect from light until ready to use.
Conivaptan plasma levels may be elevated; coadministration is contraindicated.Digoxin
Plasma levels may be elevated, increasing the risk of toxicity.Drugs primarily metabolized by CYP3A4 (eg, amlodipine, midazolam, simvastatin)
Conivaptan may elevate plasma levels of the agents, increasing the risk of adverse reactions.
None well documented.
Adverse cardiac failure events (32%); hypertension, orthostatic hypotension (6%); atrial dysrhythmias, ECG ST segment depression, hypotension (5%); atrial fibrillation (2%).
Headache (10%); thirst (6%); confusional state (5%); insomnia (4%).
Pharyngolaryngeal pain (1%).
Diarrhea, vomiting (7%); constipation (6%); nausea (5%).
Infusion-site phlebitis (32%); infusion-site reaction (19%); infusion-site erythema (6%); infusion-site pain (5%).
Hypokalemia (10%); hyponatremia (6%); hypomagnesemia (2%).
Peripheral edema, sepsis (8%); pyrexia (5%).
Frequently monitor serum sodium, vital signs, volume status, and neurologic status during conivaptan administration. Frequently assess administration site for reactions.
Category C .
Safety and efficacy not established.
Adverse reactions profile in elderly patients is similar to that seen in general population.
Use with caution.
Use with caution.
Safety in hyponatremic patients with underlying CHF not established.
Discontinue infusion if patient develops hypovolemia or hypotension. May resume conivaptan at a reduced dose once patient is euvolemic and no longer hypotensive.
May cause significant injection-site reactions. Administer conivaptan only via large veins following proper dilution. Rotate injection sites every 24 h.
Overly rapid increase in serum sodium (more than 12 mEq/L per 24 h) may result in serious sequelae (eg, osmotic demyelination syndrome). Discontinue conivaptan if patient develops an overly rapid rate of rise of serum sodium or neurologic changes. Do not resume conivaptan if serum sodium continues to rise. May resume conivaptan at a reduced dose if hyponatremia persists or recurs after initial discontinuation of conivaptan and patient has had no evidence of neurologic sequelae.
No data available; however, hypotension and thirst occur more frequently at high doses.
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