Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as hydrochloride:
Vaprisol: 20 mg (100 mL)
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
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%
Use in Specific Populations
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.
Use: Off Label
Heart failure (with persistent severe hypervolemic hyponatremia)yes
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.
Dosage and Administration
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).
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
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
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
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
Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Bosentan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. 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 (Systemic): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic). Avoid combination
Budesonide (Topical): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased. Consider therapy modification
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
Cobimetinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cobimetinib. Management: Avoid the concomitant use of cobimetinib and moderate CYP3A4 inhibitors. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose to 20 mg daily. Avoid combination
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. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. 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. 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
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
Naloxegol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol. Avoid combination
Neratinib: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Neratinib. Avoid combination
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. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. 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
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
Ticagrelor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor. Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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
Zuclopenthixol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol. Monitor therapy
Adverse Reactions
>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).
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
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
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.
Frequently reported side effects of this drug
- Increased thirst
- Constipation
- Diarrhea
- Nausea
- Vomiting
- Sore throat
- Trouble sleeping
- Injection site irritation
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- 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
- Difficulty swallowing
- Difficulty 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 a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of 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 brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
