II. Indications

  1. Hypervolemic or euvolemic Hyponatremia (Sodium <125 mEq/L) due to CHF or SIADH
    1. FDA approved for short-term use only
    2. Limit to hospitalized patients for close Serum Sodium monitoring

III. Contraindications

  1. Severe symptomatic Hyponatremia
  2. Hypovolemic Hyponatremia
  3. Anuria
  4. Creatinine Clearance <30 ml/min/1.73m2 (Conivaptan) or <10 ml/min/1.73m2 (Tolvaptan)

IV. Precautions

  1. Not currently recommended for Hyponatremia Management (European Society of Endocrinology)
    1. Risk of rapid Sodium over-correction
    2. No mortality benefit
    3. Spasovski (2014) Eur J Endocrinol 170(3): G1-47 [PubMed]

V. Efficacy

  1. SALT Trial: Tolvaptan increased Sodium levels in SIADH, Cirrhosis, CHF
    1. Schrier (2006) N Engl J Med 355(20): 2099-112 [PubMed]

VI. Dosing

  1. Conivaptan (Vaprisol)
    1. Loading: 20 mg IV (in 100 ml D5W) infused over 30 minutes
      1. In moderate liver disease, use 10 mg IV over 30 minutes
    2. Maintenance: 20 mg IV over 24 hours for 2-4 days (max 40 mg/24 hours)
      1. In moderate liver disease, use 10 mg IV over 24 hours (max 20 mg/24 hours)
    3. Do not use longer than 4 days
  2. Tolvaptan (Samsca)
    1. Start: 15 mg orally daily
    2. Increase to 30 mg daily after 24 hours if needed
    3. Titrate to maximum of 60 mg daily based on goal Sodium concentration

VII. Pharmacokinetics

  1. Metabolized by CYP3A4 (both Conivaptan and Tolvaptan)
  2. Half life
    1. Conivaptan: 5-8 hours
    2. Tolvaptan: 5-12 hours (onset at 2-4 hours, peaks at 4-8 hours)
  3. Excretion
    1. Primarily feces (Conivaptan is 12% renally excreted as metabolites)

VIII. Adverse Effects

  1. Conivaptan (Vaprisol) most common adverse effects
    1. Fever
    2. Hypokalemia
    3. IV site inflammation
    4. Orthostatic Hypotension
  2. Tolvaptan (Samsca) most common adverse effects
    1. Nausea
    2. Pollakuria
    3. Polyuria
    4. Thirst
    5. Xerostomia

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