Original GlobalRPh source
- Product / population
- Preserved GlobalRPh source, not a freshly verified product label
- Renal measure
- Use the method specified in the original source
Historical source: not automatically current. Review current official labeling and separately attributed additions before use.
The historical sodium-rise warning is preserved as a warning, not promoted as a safe correction target.
Mechanism and indication
Conivaptan hydrochloride is a dual arginine vasopressin antagonist with nanomolar affinity for human V1A and V2 receptors in vitro. Circulating AVP regulates water/electrolyte balance and is usually elevated in euvolemic and hypervolemic hyponatremia. V2 receptors coupled to collecting-duct aquaporin channels help maintain plasma osmolality. Predominant activity in hyponatremia is V2 antagonism causing aquaresis (free-water excretion).
VAPRISOL is indicated to raise serum sodium in hospitalized patients with euvolemic or hypervolemic hyponatremia. It is not approved for heart failure and has not been shown to treat its signs or symptoms. Symptomatic benefit from raising sodium has not been established.
Usual Dosing (Adults)
IV use only, hospitalized patients only. Use large veins and change infusion site every 24 hours to minimize vascular irritation.
Load with 20 mg IV over 30 minutes, then 20 mg continuously over 24 hours. After day 1, continue 20 mg/day for 1 to 3 more days; may increase to 40 mg/day continuous infusion if sodium is not rising at the desired rate. After the loading dose, maximum duration 4 days and maximum dose 40 mg/day.
Frequently monitor sodium and volume status. The source warns that a rise >12 mEq/L in 24 hours can cause serious neurologic sequelae. Stop therapy for an undesirably rapid rise; monitor sodium and neurologic status. Do not resume if sodium continues rising. If hyponatremia persists/recurs without neurologic sequelae, a reduced dose may be resumed, as described in the referenced package-insert warning.
For hypovolemia or hypotension, discontinue and monitor volume/vital signs frequently. Once euvolemic and no longer hypotensive, reduced-dose therapy may be resumed if hyponatremia remains.
Renal Dosing
After oral administration, exposure increases of 1.7-fold at CrCl 30 to 60 mL/min and 1.9-fold at 10 to 29 were observed. Adjust VAPRISOL accordingly. Severe impairment (CrCl <30) is not recommended because of infusion-site phlebitis, potential loss of vascular access and unlikely benefit.
The effect of renal impairment on elimination after IV administration has not been evaluated. With oral dosing, AUC was 70% and 85% higher after a single dose, and 58% and 69% higher after repeated doses, for CrCl 30 to 60 and 10 to 29 respectively.
Moderate impairment (CrCl 30 to 60): 10 mg loading dose, then 10 mg continuously over 24 hours for 2 to a maximum of 4 days; may increase to 20 mg per 24 hours if needed. CrCl >60: no adjustment. CrCl <30: not recommended.
Hemodialysis
Not recommended in severe renal impairment (CrCl <30 mL/min).