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Conivaptan Hydrochloride

Pronunciation: KOE-ni-VAP-tan HYE-droe-KLOR-ide
Class: Vasopressin receptor antagonist

Trade Names

- Injection, solution 20 mg per 100 mL premixed in dextrose 5%


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 healthy 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).



C max is 619 ng/mL and occurs at the end of loading dose. C min occurs approximately 12 h after start of loading dose and increases to a mean concentration of 188 ng/mL at the end of infusion.


Plasma protein binding is 99%.


Metabolism is via CYP3A4, and 4 metabolites have been identified.


Mean terminal elimination half-life is 5 h and mean Cl is 253.3 mL/min. Approximately 83% is excreted in feces and 12% in urine over a period of several days.

Special Populations

Renal Function Impairment

IV administration has not been evaluated. AUC for oral administration in patients with renal impairment (CrCl 30 to 60 mL/min or CrCl 10 to 29 mL/min) was 70% to 85% higher, respectively, compared with those with healthy renal function. IV conivaptan resulted in higher exposure than oral conivaptan in study subjects without renal impairment. Use in patients with severe renal impairment (CrCl less than 30 mL/min) is not recommended.

Hepatic Function Impairment

IV administration has not been evaluated. Increased systemic exposure (up to a mean 2.8-fold increase) after oral administration has been seen in patients with stable cirrhosis and moderate hepatic impairment. IV conivaptan resulted in higher exposure than oral conivaptan in study subjects without hepatic impairment.

Indications and Usage

To raise serum sodium in hospitalized patients with euvolemic and hypervolemic hyponatremia.


Anuric patients; coadministration with potent CYP3A4 inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, ritonavir); hypersensitivity to corn, corn products, or any component of the product; hypovolemic hyponatremia.

Dosage and Administration


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 an 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 a maximum dosage of 40 mg/day. Total infusion duration should not exceed 4 days.

Hepatic Function Impairment Child-Pugh class A to C

10 mg IV loading dose over 30 min followed by a continuous IV infusion of 10 mg over 24 h for 2 days to a maximum of 4 days. May be titrated upward to 20 mg over 24 h if serum sodium is not increasing at the desired rate.

Renal Function Impairment Moderate impairment (CrCl 30 to 60 mL/min)

10 mg IV loading dose over 30 min followed by a continuous infusion of 10 mg IV over 24 h for 2 days to a maximum of 4 days. Dosage may be titrated upward to 20 mg over 24 h if serum sodium is not rising at desired rate.

Severe impairment (CrCl less than 30 mL/min)

Not recommended.

General Advice

  • For IV infusion only.
  • Do not administer if solution is discolored or cloudy, or contains particulate matter.
  • Administer through large veins and change the infusion site every 24 h to minimize the risk of vascular irritation.
  • For single use only; discard any unused contents in flexible container.
  • Do not use plastic containers in series connections; such use could result in air embolism.
  • Conivaptan is compatible with dextrose 5% injection and is physically and chemically compatible with sodium chloride 0.9% injection for up to 22 h when the 2 solutions are coadministered via a Y-site connection.
  • Do not mix or administer with Ringer's lactate injection or combine with any other product in the same IV line.
  • For patients who develop an undesirably rapid rate of rise of serum sodium, hypovolemia, or hypotension, conivaptan should be discontinued.


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.


Plasma levels may be elevated, increasing the risk of toxicity. Monitor digoxin concentrations and adjust the digoxin dose as needed.

Drugs primarily metabolized by CYP3A4 (eg, amlodipine, midazolam, simvastatin)

Conivaptan may elevate plasma levels of the agents, increasing the risk of adverse reactions. Treatment with a CYP3A substrate should not be initiated sooner than 1 wk after completion of conivaptan infusion.


Coadministration with warfarin may increase the S-warfarin C max and AUC. Prothrombin time and INR may not be changed.

Adverse Reactions


Orthostatic hypotension (14%); hypertension, hypotension (8%); atrial fibrillation, ECG ST-segment depression (5%).


Headache (10%); confusional state, insomnia (5%).


Pruritus (5%).


Constipation (8%); diarrhea, vomiting (7%); thirst (6%); nausea, postprocedural diarrhea (5%).


UTI (5%).


Anemia (6%).


Infusion-site phlebitis (51%); infusion-site reaction (22%); infusion-site erythema (6%); infusion-site pain (5%).


Hypokalemia (22%); hyponatremia (8%); hypomagnesemia (5%).


Pharyngolaryngeal pain, pneumonia (5%).


Pyrexia (11%); peripheral edema (8%).



Frequently monitor serum sodium, vital signs, volume status, and neurologic status during conivaptan administration. Frequently assess administration site for reactions.


Category C .




Safety and efficacy not established.


The adverse reaction profile in elderly patients is similar to that of the general population.

Renal Function

Dosage adjustment is necessary in patients with moderate renal impairment (CrCl 30 to 60 mL/min). Use in patients with severe renal impairment (CrCl less than 30 mL/min) is not recommended.

Hepatic Function

Patients with hepatic impairment (Child-Pugh class A to C) require dosage adjustment.

Heart failure

Safety data in patients with hypervolemic hyponatremia associated with heart failure is limited.


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.

Rapid correction of serum sodium

Osmotic demyelination syndrome is a risk associated with overly rapid correction of hyponatremia (ie, more than 12 mEq/L per 24 h). Discontinue conivaptan if patient develops an overly rapid rate of rise of serum sodium or neurologic changes and do not resume if serum sodium continues to rise. May resume at a reduced dose if hyponatremia persists or recurs after initial discontinuation of conivaptan and if patient has had no evidence of neurologic sequelae.



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 a health care provider.
  • Advise patient to immediately report any pain, redness, or swelling at the injection site.
  • Ask patients if they have any allergies to corn or corn products because solutions containing dextrose should not be used in these patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.