II. Indications
- Hypervolemic or euvolemic Hyponatremia (Sodium <125 mEq/L) due to CHF or SIADH
- FDA approved for short-term use only
- Limit to hospitalized patients for close Serum Sodium monitoring
III. Contraindications
- Severe symptomatic Hyponatremia
- Hypovolemic Hyponatremia
- Anuria
- Creatinine Clearance <30 ml/min/1.73m2 (Conivaptan) or <10 ml/min/1.73m2 (Tolvaptan)
IV. Precautions
- Not currently recommended for Hyponatremia Management (European Society of Endocrinology)
- Risk of rapid Sodium over-correction
- No mortality benefit
- Spasovski (2014) Eur J Endocrinol 170(3): G1-47 [PubMed]
VI. Dosing
- Conivaptan (Vaprisol)
- Loading: 20 mg IV (in 100 ml D5W) infused over 30 minutes
- In moderate liver disease, use 10 mg IV over 30 minutes
- Maintenance: 20 mg IV over 24 hours for 2-4 days (max 40 mg/24 hours)
- In moderate liver disease, use 10 mg IV over 24 hours (max 20 mg/24 hours)
- Do not use longer than 4 days
- Loading: 20 mg IV (in 100 ml D5W) infused over 30 minutes
- Tolvaptan (Samsca)
- Start: 15 mg orally daily
- Increase to 30 mg daily after 24 hours if needed
- Titrate to maximum of 60 mg daily based on goal Sodium concentration
VII. Pharmacokinetics
- Metabolized by CYP3A4 (both Conivaptan and Tolvaptan)
- Half life
- Conivaptan: 5-8 hours
- Tolvaptan: 5-12 hours (onset at 2-4 hours, peaks at 4-8 hours)
- Excretion
- Primarily feces (Conivaptan is 12% renally excreted as metabolites)
VIII. Adverse Effects
- Conivaptan (Vaprisol) most common adverse effects
- Fever
- Hypokalemia
- IV site inflammation
- Orthostatic Hypotension
- Tolvaptan (Samsca) most common adverse effects
- Nausea
- Pollakuria
- Polyuria
- Thirst
- Xerostomia
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Related Studies
Concepts | Organic Chemical (T109) , Pharmacologic Substance (T121) |
MSH | C106389 |
SnomedCT | 421516006, 421858002 |
English | Conivaptan, Conivaptan (product), Conivaptan (substance), conivaptan, CONIVAPTAN, conivaptan [Chemical/Ingredient] |
Spanish | conivaptán (sustancia), conivaptán, conivaptán (producto) |
Ontology: tolvaptan (C1176308)
Concepts | Organic Chemical (T109) , Pharmacologic Substance (T121) |
MSH | C116664 |
SnomedCT | 442901006, 443058000 |
English | 7-Chloro-5-hydroxy-1-(2-methyl-4-(2-methylbenzoylamino)benzoyl)2,3,4,5-tetrahydro-1H-1-benzazepine, TOLVAPTAN, Tolvaptan (product), Tolvaptan, Tolvaptan (substance), 7-chloro-5-hydroxy-1-(2-methyl-4-(2-methylbenzoylamino)benzoyl)2,3,4,5-tetrahydro-1H-1-benzazepine, tolvaptan |
Spanish | tolvaptán, tolvaptán (sustancia), tolvaptán (producto) |
Ontology: Vasopressin Antagonist (C3537128)
Definition (NCI) | Substances that antagonize vasopressin, causing, disruption of extracellular fluid volume regulation, vasodilation, and decreased blood pressure and vascular resistance. |
Definition (MSH) | Endogenous compounds and drugs that inhibit or block the activity of ANTIDUIRETIC HORMONE RECEPTORS. |
Concepts | Pharmacologic Substance (T121) |
MSH | D065092 |
English | Vasopressin Antagonist, Antagonists, Vasopressin Receptor, Receptor Antagonists, Vasopressin, Antidiuretic Hormone Receptor Antagonists, Vasopressin Receptor Antagonists, Vasopressin Antagonists, Antidiuretic Hormone Antagonists, Hormone Antagonists, Antidiuretic, Antagonists, Vasopressin, Antagonists, Antidiuretic Hormone |