Dosing and uses of Vaprisol (conivaptan)
Adult dosage forms and strengths
premixed injectable solution
- 5mg/mL (20mg/100mL D5W)
Hyponatremia
Indicated to raise serum sodium in hospitalized patients with euvolemic and hypervolemic hyponatremia
Load: 20 mg IV infusion over 30 minutes; and THEn
20 mg IV as continuous infusion over 24-hour period for 2-4 days
After initial day of treatment, may increase to 40 mg/day if necessary
Monitor serum sodium and volume status frequently; a significant increase in serum sodium (>12 mEq/L/24 hours) may result in serious neurologic effects
Renal Impairment
CrCl > 60 mL/minute: No dosage adjustment required
CrCl 30-60 mL/minute: 10 mg infused over 30 minutes; follow by continuous infusion of 10 mg over 24 hr; may increase to maximum 20 mg over 24 hr if sodium levels do not increase as necessary; duration of therapy not to exceed 4 days
Severe (CrCl <30 mL/min): Not recommended
Hepatic Impairment
Moderate: Initiate with loading dose of 10 mg IV infused over 30 minutes, followed by 10 mg/day as a continuous infusion (ie, over 24 hr) for 2-4 days; may titrate up to 20 mg/day if serum sodium is not rising at desired rate
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
Hyponatremia
Indicated to raise serum sodium in hospitalized patients with euvolemic and hypervolemic hyponatremia
Load: 20 mg IV infusion over 30 minutes; and THEn
20 mg IV as continuous infusion over 24-hour period for 2-4 days
After initial day of treatment, may increase to 40 mg/day if necessary
Monitor serum sodium and volume status frequently; a significant increase in serum sodium (>12 mEq/L/24 hours) may result in serious neurologic effects
Vaprisol (conivaptan) adverse (side) effects
>10%
Headache (12%)
Infusion site phlebitis (15.8%)
Infusion site reactions (20.2%)
1-10%
Anemia
Atrial fibrillation
Hypertension
Hypotension
Confusion
Insomnia
Dehydration
Dry mouth
Thirst
Constipation
Diarrhea
Nausea
Vomiting
Erythema
Hematuria
Pollakiuria
Polyuria
UTI
Hyperglycemia
Hypoglycemia hypokalemia
Hypomagnesemia
Hyponatremia
Oral candidiasis
Pain
Peripheral edema
Phlebitis
Pneumonia
Pyrexia
Warnings
Contraindications
Hypersensitivity
Hypovolemic hyponatremia
Anuria; no benefit can be expected in patients unable to make urine
Cautions
Has not been shown to be effective for the treatment of the signs and symptoms of heart failure and is not approved for this indication
Safety data with hypervolemic hyponatremia associated with heart failure is limited; restrict use to raise serum sodium in such patients only after consideration of other treatment options
Infusion site reactions are common and can include serious reactions, even with proper infusion rates; administer via large veins, and rotate infusion site q24hr
Discontinue if undesirably rapid rise in serum Na (>12 mEq/L/day)
Osmotic demyelination syndrome: Associated with overly rapid correction of hyponatremia (ie, > 12 mEq/L/day) and results in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, or death; susceptible patients include those with severe malnutrition, alcoholism, or advanced liver disease, use slower rates of correction
Hepatic/renal impairment
Conivaptan inhibits CYP3A4; rhabdomyolysis occurred in patients who were also receiving a CYP3A-metabolized HMG-CoA reductase inhibitor; avoid concomitant use with drugs eliminated primarily by CYP3A-mediated metabolism; subsequent treatment with CYP3A substrate drugs may be initiated no sooner than 1 week after conivaptan infusion completed
Coadministration of digoxin with oral conivaptan resulted in a 1.8- and 1.4-fold increase in digoxin Cmax and AUC, respectively; monitor digoxin levels
Pregnancy and lactation
Pregnancy: There are no available data in pregnant women to inform a drug-associated risk for major birth defects and miscarriage
Lactation: No information regarding conivaptan or metabolites in human milk, effects of conivaptan on breastfed infant, or effects of conivaptan on milk production; because of potential for serious adverse reactions, including electrolyte abnormalities (e.g., hypernatremia), hypotension, and volume depletion in breastfed infants, advise a woman not to breastfeed during treatment with conivaptan
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Vaprisol (conivaptan)
Mechanism of action
Arginine vasopressin receptor antagonist; antidiuretic action is mediated through antagonism of vasopressin at the V2 receptor, which regulates water and electrolyte balance at the collecting ducts in the kidney. Antagonism of the V2 receptor generates the excretion of free water (without electrolytes). This results in increased urine output and subsequent restoration of normal serum sodium concentrations
Pharmacokinetics
Protein Bound: 99%
Metabolized through CYP3A4; produces four metabolites with limited activity
Half-Life elimination: 5-8 hr
Excretion: 83% feces; 12% urine
Administration
IV Incompatibilities
Solution: LR, Ns
Do not infuse with any other drug
IV Compatibilities
Solution: Dextrose 5% (D5W)
Y-site: Physically and chemically compatible with 0.9% NaCl (NS) for up to 48 hr when coadministered at a flow rate of 4.2 mL/hr for conivaptan and either 2.1 mL/hr or 6.3 mL/hr for Ns
IV Administration
Loading dose: Over 30 min
Continuous infusion: Over 24 hr
Storage
Store premixed injectable solution at room temperature
