Short-term treatment of euvolemic or hypervolemic hyponatremia in hospitalized adults.
Not indicated for the treatment of hypovolemic hyponatremia.
Use for treatment of hyponatremia in patients with underlying heart failureonly when expected clinical benefit outweighs increased risk of adverse effects; safety in this patient population has not been established. (See CHF under Cautions.)
Not indicated for the treatment of CHF; safety and efficacy are not established for this indication.
Dosage and Administration
Administration
Administer by IV infusion; administer to hospitalized patients only. (See Administration Risks under Dosage and Administration.)
IV Administration
For solution and drug compatibility information, see Compatibility under Stability.
Ampuls are for single use only; concentrate for injection must be diluted before IV administration.
Do not mix with or administer simultaneously through the same IV line with other drugs.
Dilution
Loading dose: Add 4 mL (20 mg) of conivaptan hydrochloride concentrate to 100 mL of 5% dextrose injection.
Continuous infusion: Add 4 mL (20 mg) or 8 mL (40 mg) of conivaptan hydrochloride concentrate to 250 mL of 5% dextrose injection.
Do not use diluents other than 5% dextrose injection.
Invert bag gently several times to ensure complete mixing.
Rate of Administration
Administer loading dose over 30 minutes.
Administer the continuous IV infusion over 24 hours.
Complete administration within 24 hours of mixing IV infusion.
Administration Risks
Administer only through large veins; change infusion site every 24 hours to decrease risk of venous irritation. (See Infusion Site Reactions under Cautions.)
Dosage
Available as conivaptan hydrochloride; dosage expressed in terms of the salt.
Adults
Euvolemic or Hypervolemic Hyponatremia
IV
Initially, 20 mg as a loading dose over 30 minutes, followed by continuous infusion of 20 mg over 24 hours for 2–4 days.
If serum sodium is not increasing at the desired rate, may increase dosage to 40 mg daily by continuous infusion.
Monitor vital signs, serum sodium, and neurologic and volume status.
Discontinue drug if serum sodium concentration increases too rapidly (by >12 mEq/L in 24 hours). Carefully monitor serum sodium and neurologic status. Do not resume conivaptan if serum sodium continues to rise; however, if hyponatremia persists or recurs, and patient has no evidence of neurologic sequelae of rapid serum sodium rise, may resume conivaptan at a reduced dose. (See Overly Rapid Correction of Serum Sodium Concentration under Cautions.)
If hypotension or hypovolemia develops, discontinue conivaptan. Monitor volume status and vital signs frequently; once euvolemic and normotensive, and if hyponatremia persists, may resume conivaptan at a reduced dose.
Prescribing Limits
Adults
Euvolemic or Hypervolemic Hyponatremia
IV
Maximum (after loading dose): 40 mg daily.
Maximum duration of therapy: 4 days.
Special Populations
Hepatic Impairment
Increased systemic exposure possible; however, no specific dosage recommendations at this time. (See Hepatic Impairment under Cautions.)
Renal Impairment
Increased systemic exposure possible; however, no specific dosage recommendations at this time. (See Renal Impairment under Cautions.)
Geriatric Patients
Increased systemic exposure possible at higher dosages; however, no specific dosage recommendations at this time. (See Geriatric Use under Cautions and also Special Populations under Pharmacokinetics.)
Cautions
Contraindications
Hypovolemic hyponatremia.
Concomitant use of potent inhibitors of CYP3A4. (See Interactions.)
Warnings/Precautions
Major Toxicities
Infusion Site Reactions
Mild to severe infusion site reactions possible (>60% of patients receiving 40 mg daily); may require discontinuation. May occur even when properly prepared and administered. Administer diluted solution only into a large vein; change infusion site every 24 hours.
General Precautions
CHF
Insufficient number of patients with hypervolemic hyponatremia and underlying heart failure to establish safety in this patient population; the manufacturer recommends use in patients with underlying heart failure only when the expected clinical benefit outweighs the increased risk of adverse effects.
Conivaptan is not indicated for the treatment of CHF; safety and efficacy are not established for this indication. (See Euvolemic or Hypervolemic Hyponatremia under Uses.)
Overly Rapid Correction of Serum Sodium Concentration
Increases in serum sodium of >12 mEq/L in 24 hours may cause serious sequelae (e.g., osmotic demyelination syndrome). Monitor fluid status, serum sodium concentrations, and neurologic status carefully; if serum sodium concentrations increase too rapidly, discontinue conivaptan and monitor patient carefully. (See Dosage under Dosage and Administration.)
Hypovolemia and Hypotension
If hypovolemia or hypotension occurs, discontinue conivaptan and monitor fluid status and vital signs frequently.
Specific Populations
Pregnancy
Category C.
Lactation
Distributed into milk in rats; caution if used in nursing women.
Pediatric Use
Safety and efficacy not established in children <18 years of age.
Geriatric Use
Potential for increased systemic exposure, especially at high doses; use with caution in geriatric patients. Adverse effects similar to those in younger adults. (See Special Populations under Pharmacokinetics.)
Hepatic Impairment
Potential for increased systemic exposure; use with caution in patients with hepatic impairment.
Renal Impairment
Potential for increased systemic exposure; use with caution in patients with renal impairment.
Metabolized extensively by CYP3A4; potent inhibitor of CYP3A4.
Drugs Affecting Hepatic Microsomal Enzymes
Potent CYP3A4 inhibitors: Potential pharmacokinetic interaction (increased plasma concentrations of conivaptan); concomitant use contraindicated.
Drugs Metabolized by Hepatic Microsomal Enzymes
CYP3A4 substrates: Potential pharmacokinetic interaction (increased plasma concentrations and AUC of CYP3A4 substrate); monitor closely or avoid concomitant use. If treatment is suspended during conivaptan therapy, wait ≥24 hours after discontinuing conivaptan before restarting CYP3A4 substrate.
V2antagonism of AVP in renal collecting ducts results in increased free water excretion (i.e., effective water clearance); and, typically, 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).
Advice to Patients
Risk of orthostatic hypotension (e.g., lightheadedness, syncope).
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Conivaptan Hydrochloride
Routes
Dosage Forms
Strengths
Brand Names
Manufacturer
Parenteral
For injection concentrate, for IV use only
20 mg (5 mg/mL)
Vaprisol® (with propylene glycol 1.2 g and alcohol 400 mg)
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
Sign up with Facebook
