conivaptan (Rx)

>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

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

Discontinue in patients who develop hypovolemia or hypotension, and monitor volume status and vital signs; once the patient is again euvolemic and is no longer hypotensive, resume therapy at a reduced dose if patient remains hyponatremic

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: 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.

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

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