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Conivaptan

Medically reviewed by Drugs.com. Last updated on July 15, 2020.

Pronunciation

(koe NYE vap tan)

Index Terms

  • Conivaptan HCl/D5W
  • Conivaptan Hydrochloride
  • YM087

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous, as hydrochloride:

Vaprisol: 20 mg (100 mL)

Brand Names: U.S.

  • Vaprisol

Pharmacologic Category

  • Vasopressin Antagonist

Pharmacology

Conivaptan is an arginine vasopressin (AVP) receptor antagonist with affinity for AVP receptor subtypes V1A and V2. The antidiuretic action of AVP is mediated through activation of the V2 receptor, which functions to regulate water and electrolyte balance at the level of the collecting ducts in the kidney. Serum levels of AVP are commonly elevated in euvolemic or hypervolemic hyponatremia, which results in the dilution of serum sodium and the relative hyponatremic state. Antagonism of the V2 receptor by conivaptan promotes the excretion of free water (without loss of serum electrolytes) resulting in net fluid loss, increased urine output, decreased urine osmolality, and subsequent restoration of normal serum sodium concentrations.

Metabolism

Hepatic via CYP3A4 to four minimally-active metabolite

Excretion

Feces (~83%); urine (12%)

Half-Life Elimination

5.3 to 8.1 hours

Protein Binding

99%

Special Populations: Hepatic Function Impairment

AUC increased (2.3 to 2.5-fold) and plasma protein binding decreased (~27% and 50%) respectively in moderate and severe hepatic impairment.

Use: Labeled Indications

Euvolemic or hypervolemic hyponatremia: Treatment of euvolemic and hypervolemic hyponatremia in hospitalized patients.

Limitations of use: Conivaptan is not approved for use in heart failure; however, conivaptan has been shown to be effective in improving sodium levels and intracardiac pressures, and increasing urine output (especially in combination with loop diuretics) in patients with heart failure (Goldsmith 2008; Goldsmith 2011; Udelsen 2001). Conivaptan has not been shown to be effective for treating symptoms of heart failure.

Off Label Uses

Heart failure (with persistent severe hypervolemic hyponatremia)

Based on the American College of Cardiology Foundation/American Heart Association guidelines for the management of heart failure, the short-term use of vasopressin antagonists may be considered to improve serum sodium concentrations in patients with heart failure who have persistent severe hyponatremia (despite water restriction and maximized guideline directed medical therapy) and are at risk for or having ongoing cognitive symptoms. Long-term safety and efficacy studies are still needed to establish the role of conivaptan in patients with heart failure. Specific dosing in this population cannot be recommended at this time.

Contraindications

Hypovolemic hyponatremia; concurrent use with strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, indinavir, and clarithromycin); anuria.

Dosing: Adult

Euvolemic or hypervolemic hyponatremia: IV: 20 mg infused over 30 minutes as a loading dose, followed by a continuous infusion of 20 mg over 24 hours (0.83 mg/hour) for 2 to 4 days; may increase to a maximum dose of 40 mg over 24 hours (1.7 mg/hour) if serum sodium not rising sufficiently; total duration of therapy not to exceed 4 days. Note: If patient requires 40 mg/24 hours, may administer two consecutive 20 mg/100 mL premixed solutions over 24 hours (ie, 20 mg over 12 hours followed by 20 mg over 12 hours).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Administration

For intravenous use only; infuse into large veins and change infusion site every 24 hours to minimize vascular irritation. Do not administer with any other product in the same intravenous line or container.

Storage

Store at 25°C (77°F); brief excursions permitted up to 40°C (104°F). Avoid excessive heat. Protect from light and freezing. Do not remove protective overwrap until ready for use.

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Consider therapy modification

Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Apixaban: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Apixaban. Monitor therapy

Aprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Aprepitant. Avoid combination

Asunaprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Asunaprevir. Avoid combination

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Barnidipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Barnidipine. Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Bortezomib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bortezomib. Monitor therapy

Bosutinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib. Avoid combination

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination

Budesonide (Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Oral Inhalation). Monitor therapy

Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Avoid combination

Cannabidiol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabidiol. Monitor therapy

Cannabis: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Codeine: CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Codeine. Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Conivaptan. Avoid combination

CYP3A4 Substrates (High risk with Inhibitors): Conivaptan may increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Digoxin: Conivaptan may increase the serum concentration of Digoxin. Monitor therapy

Dofetilide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dofetilide. Monitor therapy

Domperidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Domperidone. Avoid combination

Dronabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Estrogen Derivatives: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Estrogen Derivatives. Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin. Management: Use of flibanserin with moderate CYP3A4 inhibitors is contraindicated. If starting flibanserin, start 2 weeks after the last dose of the CYP3A4 inhibitor. If starting a CYP3A4 inhibitor, start 2 days after the last dose of flibanserin. Avoid combination

Fosaprepitant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosaprepitant. Avoid combination

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Ifosfamide: CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy

Imatinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Imatinib. Monitor therapy

Ivabradine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine. Avoid combination

Lemborexant: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lemborexant. Avoid combination

Levamlodipine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Levamlodipine. Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Monitor therapy

Lomitapide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide. Avoid combination

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Lumateperone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lumateperone. Avoid combination

Lurbinectedin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurbinectedin. Management: Avoid concomitant use of lurbinectedin and moderate CYP3A4 inhibitors when possible. If combined, consider a lurbinectedin dose reduction as clinically indicated. Consider therapy modification

Meperidine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Meperidine. Monitor therapy

Midostaurin: Conivaptan may increase the serum concentration of Midostaurin. Management: Seek alternatives to the concomitant use of midostaurin and conivaptan if possible. If concomitant use cannot be avoided, monitor patients for increased risk of adverse reactions. Consider therapy modification

MiFEPRIStone: Conivaptan may increase the serum concentration of MiFEPRIStone. Management: Limit mifepristone adult dose, when used for treatment of hyperglycemia in Cushing's syndrome, to a maximum of 600 mg/day when combined with conivaptan. Monitor for increased mifepristone toxicity regardless of dose or indication. Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naldemedine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naldemedine. Monitor therapy

Nalfurafine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nalfurafine. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy

Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Monitor therapy

Pimozide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimozide. Avoid combination

Propafenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinidine (Non-Therapeutic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Quinidine (Non-Therapeutic). Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir. Avoid combination

Tetrahydrocannabinol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Toremifene: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Toremifene. Monitor therapy

Ulipristal: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combination should be monitored for ulipristal toxicity. Avoid combination

Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Monitor therapy

Vindesine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine. Monitor therapy

Vorapaxar: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vorapaxar. Monitor therapy

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Orthostatic hypotension (6% to 14%)

Endocrine & metabolic: Hypokalemia (10% to 22%)

Local: Injection site reaction (63% to 73%; including erythema at injection site, injection site pain, injection site phlebitis, swelling at injection site)

Miscellaneous: Fever (5% to 11%)

1% to 10%:

Cardiovascular: Hypertension (6% to 8%), hypotension (5% to 8%), peripheral edema (3% to 8%), phlebitis (5%), atrial fibrillation (2% to 5%), ECG abnormality (≤5%)

Central nervous system: Headache (8% to 10%), insomnia (4% to 5%), confusion (≤5%), pain (2%)

Dermatologic: Pruritus (1% to 5%), erythema (3%)

Endocrine & metabolic: Hyponatremia (6% to 8%), increased thirst (3% to 6%), hypomagnesemia (2% to 5%), hyperglycemia (≤3%), hypoglycemia (≤3%), dehydration (2%)

Gastrointestinal: Constipation (6% to 8%), vomiting (5% to 7%), diarrhea (≤7%), nausea (3% to 5%), xerostomia (4%), oral candidiasis (2%)

Genitourinary: Urinary tract infection (4% to 5%), hematuria (2%)

Hematologic & oncologic: Anemia (5% to 6%)

Renal: Polyuria (5% to 6%)

Respiratory: Pneumonia (2% to 5%), pharyngolaryngeal pain (1% to 5%)

<1%, postmarketing, and/or case reports: Atrial arrhythmia, sepsis

Warnings/Precautions

Concerns related to adverse effects:

• Hypotension: Discontinue if hypotension occurs; may correct and resume at a reduced dose if necessary.

• Hypovolemia: Discontinue if hypovolemia occurs; may correct and resume at a reduced dose if necessary.

• Injection-site reactions: May occur and may be severe.

• Osmotic demyelination syndrome: May occur with overly rapid correction of hyponatremia (ie, >12 mEq/L per 24 hours), resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma or death. In susceptible patients, including those with severe malnutrition, alcoholism or advanced hepatic disease, use slower rates of correction.

Disease-related concerns:

• Heart failure: Although short-term use may be considered in patients with heart failure and persistent severe hypervolemic hyponatremia who are at risk for or having ongoing cognitive symptoms, evidence for routine use in these patients is limited (ACCF/AHA [Yancy 2013]).

• Hepatic impairment: Use caution in patients with moderate (Child-Pugh class B) and severe (Child Pugh class C) hepatic impairment; dosage adjustment required.

• Renal impairment: Not recommended in patients with severe renal impairment (CrCl <30 mL/minute).

Other warnings/precautions:

• Appropriate use: Monitor serum sodium concentrations and neurological status closely during administration. Discontinue use if rate of serum sodium increase is undesirable. If the serum sodium concentration continues to rise, do not resume therapy. May reinitiate infusion (at reduced dose) if hyponatremia persists or recurs (after initial discontinuation for an undesirably rapid rate of rise of serum sodium concentration) in the absence of neurological symptoms.

Monitoring Parameters

Rate of serum sodium increase, vital signs, volume status; neurologic status

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies.

Patient Education

What is this drug used for?

• It is used to treat low sodium levels.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Increased thirst

• Constipation

• Diarrhea

• Nausea

• Vomiting

• Sore throat

• Trouble sleeping

• Injection site irritation

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, severe dizziness, passing out, fast heartbeat, increased thirst, seizures, loss of strength and energy, lack of appetite, not able to pass urine or change in amount of urine passed, dry mouth, dry eyes, or nausea or vomiting

• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain

• Trouble swallowing

• Trouble speaking

• Swelling of arms or legs

• Severe headache

• Severe dizziness

• Passing out

• Vision changes

• Severe injection site redness, burning, pain, swelling, blisters, or sores

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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