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Drugs reference index «Conivaptan Hydrochloride»

Conivaptan Hydrochloride

Pronunciation: (KOE-nye-VAP-tan HYE-droe-KLOR-ide)Class: Vasopressin receptor antagonist

Trade Names:Vaprisol- Injection, liquid 5 mg/mL

Trade Names:Vaprisol- Premixed in Dextrose, injection, solution 0.2 mg/mL

Pharmacology

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 membrane 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 half-life 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 Impairment

Has not been evaluated. AUC for oral administration was up to 80% higher in patients with renal function impairment.

Hepatic Function Impairment

Has not been evaluated; increased systemic exposure occurs after oral administration to patients with stable cirrhosis and moderate hepatic function impairment.

Elderly

Drug 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 corn or corn products (premixed solution); or any component of the product.

Dosage and Administration

Adults

IV 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.
  • Do not administer if solution is discolored, cloudy, or contains particulate matter.
  • Ampules
  • 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.

Storage/Stability

Ampules

Store at controlled room temperature (59° to 86°F) in cardboard container and protect from light. Do not store below 59°F.

Premixed

Store at 77°F. Avoid excessive heat. Protect from freezing. Protect from light until ready to use.

Drug Interactions

CYP3A4 inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, ritonavir)

Conivaptan plasma levels may be elevated; coadministration is contraindicated.

Digoxin

Plasma 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, ECG ST segment depression, 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

Monitor

Frequently 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.

Elderly

Adverse reactions profile in elderly patients is similar to that seen in general population.

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 (more 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 of conivaptan 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.

Copyright © 2009 Wolters Kluwer Health.

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