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tolvaptan (Samsca, Jynarque)

Indications: 1) congestive heart failure* 2) hepatic cirrhosis 3) hyponatremia due to SIADH [2,4,6] (in-hospital use, Samsca only) 4) autosomal-dominant polycystic kidney disease [7] (Jynarque only) * in hospitalized patients with acute heart failure, addition of tolvaptan to intravenous loop diuretic did not improve dyspnea despite greater weight loss & fluid loss [9] Dosage: - 30-90 mg PO QD - limit use to < 30 days to avoid hepatotoxicity [5] tablets: 15 mg, 30 mg, 60 mg Adverse effects: 1) dry mouth & thirst (most common) 2) weakness 3) constipation 4) polyuria, urinary frequency 5) hyperglycemia 6) no adverse effects on heart rate, blood pressure, serum K+, or renal function 7) osmotic demyelination syndrome (central pontine myelinolysis) 8) hepatoxicity [5] - serum ALT & serum AST elevations begin ~2-3 months after initiation of tolvaptan, levels start to decline after 18 months [8] Mechanism of action: 1) direct vasopressin V2 receptor antagonist 2) 60 mg QD increases serum Na+ from 130-135 meq/L See EVEREST trial: [3] - safe, but no long-term benefit over standard therapy for CHF

General

vasopressin receptor antagonist (vaptan)

Properties

INHIBITS: vasopressin

Database Correlations

PUBCHEM correlations

References

  1. Journal Watch 24(12):97-98, 2004 - Gheorghiade M, Gattis WA, O'Connor CM, Adams KF Jr, Elkayam U, Barbagelata A, Ghali JK, Benza RL, McGrew FA, Klapholz M, Ouyang J, Orlandi C; Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Congestive Heart Failure (ACTIV in CHF) Investigators. Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA. 2004 Apr 28;291(16):1963-71. PMID: 15113814 - Francis GS, Tang WH. Vasopressin receptor antagonists: will the "vaptans" fulfill their promise? JAMA. 2004 Apr 28;291(16):2017-8. No abstract available. PMID: 15113822
  2. Schrier RW et al, Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia N Engl J Med 2006, 355:2099 PMID: 17105757
  3. Gheorghiade M et al for the Everest Investigators Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: The EVEREST clinical status trials. JAMA 2007, 297:1332 PMID: 17384438
  4. FDA News Release FDA Approves Samsca to treat Hyponatremia http://www.fda.gov/bbs/topics/NEWS/2009/NEW02017.html
  5. FDA MedWatch. Jan 25, 2013 Samsca (tolvaptan): Drug Warning - Potential Risk of Liver Injury. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm336669.htm - FDA MedWatch. April 30, 2013 Samsca (Tolvaptan): Drug Safety Communication - FDA Limits Duration and Usage Due To Possible Liver Injury Leading to Organ Transplant or Death. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm350185.htm
  6. Berl T, Quittnat-Pelletier F, Verbalis JG Oral tolvaptan is safe and effective in chronic hyponatremia. J Am Soc Nephrol. 2010 Apr;21(4):705-12. PMID: 20185637 Free PMC Article
  7. Torres VE, Chapman AB, Devuyst O et al Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012 Dec 20;367(25):2407-18. PMID: 23121377 Free PMC Article - Torres VE, Chapman AB, Devuyst O et al Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease. N Engl J Med 2017; 377:1930-1942. November 16, 2017 PMID: 29105594 Free Article http://www.nejm.org/doi/full/10.1056/NEJMoa1710030
  8. Alpers DH, Lewis JH, Hunt CM et al Clinical Pattern of Tolvaptan-Associated Liver Injury in Trial Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD): An Analysis of Pivotal Clinical Trials. Am J Kidney Dis. 2022 Sep 30:S0272-6386(22)00921-0. PMID: 36191725 Free article
  9. Felker GM, Mentz RJ, Cole RT et ak Efficacy and Safety of Tolvaptan in Patients Hospitalized With Acute Heart Failure. J Am Coll Cardiol. 2017 Mar 21;69(11):1399-1406. Epub 2016 Sep 18. PMID: 27654854 Free article. Clinical Trial.
  10. Medscape (Rx) Tolvaptan https://reference.medscape.com/drug/samsca-jynarque-tolvaptan-999103