Conivaptan Hydrochloride
Pronouncation: (koe-NYE-vap-tan HYE-droe-KLOR-ide)Class: Vasopressin receptor antagonist
Trade Names:
Vaprisol
- Injection 5 mg/mL
Pharmacology
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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 membranes 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).
Pharmacokinetics
Absorption
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.
Distribution
Plasma protein binding is 99%.
Metabolism
Metabolism is via CYP3A4, and 4 metabolites have been identified.
Elimination
Mean terminal elimination t ½ 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.
Special Populations
Renal Function ImpairmentHas not been evaluated. AUC for oral administration was up to 80% higher in patients with renal function impairment.
Hepatic Function ImpairmentHas not been evaluated; increased systemic exposure occurs after oral administration to patients with stable cirrhosis and moderate hepatic function impairment.
ElderlyDrug exposure in elderly patients increased nearly 2-fold with the 60 mg dose compared with younger men.
Indications and Usage
Treatment of euvolemic and hypervolemic hyponatremia (eg, SIADH) in hospitalized patients.
Contraindications
Hypovolemic hyponatremia; coadministration with potent CYP3A4 inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, ritonavir); hypersensitivity to any component of the product.
Dosage and Administration
AdultsIV 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.
General Advice
- For IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, or intra-arterial administration.
- For loading dose, withdraw conivaptan 4 mL (20 mg) from 1 vial and add to infusion bag containing 100 mL of dextrose 5% injection; gently invert bag several times to completely mix solution.
- For continuous infusion containing conivaptan 20 mg, withdraw 4 mL (20 mg) from 1 vial and add to infusion bag containing 250 mL of dextrose 5% injection. Gently invert bag several times to completely mix solution.
- For continuous infusion containing conivaptan 40 mg, withdraw 4 mL (20 mg) from each of 2 vials and add to infusion bag containing 250 mL of dextrose 5% injection. Gently invert bag several times to completely mix solution.
- Use diluted solution immediately and complete administration within 24 h of mixing.
- Discard any unused contents in ampule. Do not save for future use.
- Conivaptan is compatible with dextrose 5% injection and is stable for up to 24 h after mixing. Do not combine with any other product in IV line or bag.
- Do not mix or administer with Ringer's lactate injection or sodium chloride 0.9% injection.
- Do not administer if solution is discolored, cloudy, or contains particulate matter.
Storage/Stability
Store ampules at controlled room temperature (59° to 86°F) in cardboard container and protect from light. Do not store below 59°F.
Drug Interactions
CYP3A4 inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, ritonavir)Conivaptan plasma levels may be elevated; coadministration is contraindicated.
DigoxinPlasma 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.
Laboratory Test Interactions
None well documented.
Adverse Reactions
Cardiovascular
Adverse cardiac failure events (32%); hypertension, orthostatic hypotension (6%); atrial dysrhythmias, hypotension (5%); atrial fibrillation (2%).
CNS
Headache (10%); thirst (6%); confusional state (5%); insomnia (4%).
Dermatologic
Pruritus (1%).
EENT
Pharyngolaryngeal pain (1%).
GI
Diarrhea, vomiting (7%); constipation (6%); nausea (5%).
Genitourinary
UTI (4%).
Hematologic-Lymphatic
Anemia (6%).
Local
Infusion-site phlebitis (32%); infusion-site reaction (19%); infusion-site erythema (6%); infusion-site pain (5%).
Metabolic-Nutritional
Hypokalemia (10%); hyponatremia (6%); hypomagnesemia (2%).
Respiratory
Pneumonia (2%).
Miscellaneous
Peripheral edema, sepsis (8%); pyrexia (5%).
Precautions
MonitorFrequently monitor serum sodium, vital signs, volume status, and neurologic status during conivaptan administration. Frequently assess administration site for reactions. |
Pregnancy
Category C .
Lactation
Undetermined.
Children
Safety and efficacy not established.
Renal Function
Use with caution.
Hepatic Function
Use with caution.
CHF
Safety in hyponatremic patients with underlying CHF not established.
Hypotension/Hypovolemia
Discontinue infusion if patient develops hypovolemia or hypotension. May resume conivaptan at a reduced dose once patient is euvolemic and no longer hypotensive.
Injection-site reactions
May cause significant injection-site reactions. Administer conivaptan only via large veins following proper dilution. Rotate injection sites every 24 h.
Overly rapid correction of serum sodium
Overly rapid increase in serum sodium (greater 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 and patient has had no evidence of neurologic sequelae.
Overdosage
Symptoms
No data available; however, hypotension and thirst occur more frequently at high doses.
Patient Information
- Advise patient or caregiver that medication will be prepared and administered by health care provider.
- Advise patient to immediately report any pain, redness, or swelling at injection site.
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Hyponatremia, euvolemic, SIADH
