tolvaptan (Samsca, Jynarque)
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Indications
- congestive heart failure*
- hepatic cirrhosis
- hyponatremia due to SIADH[2][4][6] (in-hospital use, Samsca only)
- 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
- dry mouth & thirst (most common)
- weakness
- constipation
- polyuria, urinary frequency
- hyperglycemia
- no adverse effects on heart rate, blood pressure, serum K+, or renal function
- osmotic demyelination syndrome (central pontine myelinolysis)
- hepatoxicity[5]
Mechanism of action
- direct vasopressin V2 receptor antagonist
- 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
More general terms
References
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/15113822 - ↑ 2.0 2.1 Schrier RW et al, Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia N Engl J Med 2006, 355:2099 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17105757
- ↑ 3.0 3.1 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: https://www.ncbi.nlm.nih.gov/pubmed/17384438
- ↑ 4.0 4.1 FDA News Release FDA Approves Samsca to treat Hyponatremia http://www.fda.gov/bbs/topics/NEWS/2009/NEW02017.html
- ↑ 5.0 5.1 5.2 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 - ↑ 6.0 6.1 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: https://www.ncbi.nlm.nih.gov/pubmed/20185637 Free PMC Article
- ↑ 7.0 7.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29105594 Free Article <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1710030 - ↑ 8.0 8.1 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: https://www.ncbi.nlm.nih.gov/pubmed/36191725 Free article
- ↑ 9.0 9.1 Felker GM, Mentz RJ, Cole RT et al 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: https://www.ncbi.nlm.nih.gov/pubmed/27654854 Free article. Clinical Trial.
- ↑ Medscape: Tolvaptan (Rx) https://reference.medscape.com/drug/samsca-jynarque-tolvaptan-999103