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Tolvaptan

December 20, 2023

Tolvaptan, sold under the brand name Samsca among others, is an aquaretic drug that functions as a selective, competitive vasopressin receptor 2 (V2) antagonist used to treat hyponatremia (low blood sodium levels) associated with congestive heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone (SIADH). Tolvaptan was approved by the U.S. Food and Drug Administration (FDA) on May 19, 2009, and is sold by Otsuka Pharmaceutical Co. under the trade name Samsca.[9] Tolvaptan, as Jynarque, was granted approval for medical use in the United States in April 2018.[10]

Tolvaptan
Clinical data
Trade namesSamsca, Jinarc, Jynarque, others
Other namesOPC-41061
AHFS/Drugs.comMonograph
MedlinePlusa609033
License data
Pregnancy
category
  • UK: Contraindicated
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityUnknown (40% absorbed)
Protein binding99%
MetabolismLiver (CYP3A4-mediated)[8]
Elimination half-life12 hours (terminal)
Identifiers
  • N-(4-{[(5R)-7-Chloro-5-hydroxy-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl]carbonyl}-3-methylphenyl)-2-methylbenzamide
CAS Number
  • 150683-30-0 N
PubChem CID
  • 216237
IUPHAR/BPS
  • 2226
DrugBank
  • DB06212 Y
ChemSpider
  • 187438 Y
UNII
  • 21G72T1950
KEGG
  • D01213
ChEMBL
  • ChEMBL344159 Y
CompTox Dashboard (EPA)
  • DTXSID3048780
ECHA InfoCard100.219.212
Chemical and physical data
FormulaC26H25ClN2O3
Molar mass448.95 g·mol−1
3D model (JSmol)
  • Interactive image
  • Cc1ccccc1C(=O)Nc2cc(C)c(cc2)C(=O)N3c4ccc(Cl)cc4[C@H](O)CCC3
  • InChI=1S/C26H25ClN2O3/c1-16-6-3-4-7-20(16)25(31)28-19-10-11-21(17(2)14-19)26(32)29-13-5-8-24(30)22-15-18(27)9-12-23(22)29/h3-4,6-7,9-12,14-15,24,30H,5,8,13H2,1-2H3,(H,28,31) Y
  • Key:GYHCTFXIZSNGJT-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

The U.S. Food and Drug Administration (FDA) granted tolvaptan a fast track designation for clinical trials investigating its use for the treatment of polycystic kidney disease.[11] The FDA granted Jynarque an orphan drug designation in April 2012, for the treatment of autosomal dominant polycystic kidney disease.[12]

Tolvaptan is available as a generic medication.[13][14]

Medical uses edit

Tolvaptan (Samsca) is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia.[15]

Tolvaptan (Jynarque) is indicated for slow kidney-function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).[16]

Tolvaptan phosphate is a prodrug of tolvaptan, developed for intravenous administration. Tolvaptan phosphate is converted into the active drug tolvaptan in the human body following administration.[17]

Side effects edit

The FDA has determined that tolvaptan should not be used for longer than 30 days and should not be used in patients with underlying liver disease because it can cause liver injury, potentially leading to liver failure.[18] When using to treat hyponatremia, it may cause too rapid correction of hyponatremia resulting in fatal osmotic demyelination syndrome.[19]

Pharmacology edit

Tolvaptan is a selective vasopressin V2 receptor antagonist.[15][16]

Chemistry edit

Tolvaptan is a racemate, a 1:1 mixture of the following two enantiomers:[20]

Enantiomers of tolvaptan
 
(R)-Tolvaptan
CAS number: 331947-66-1 		 
(S)-Tolvaptan
CAS number: 331947-44-5

References edit

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ "Samsca 15 mg tablets - Summary of Product Characteristics (SmPC)". (emc). Retrieved 14 December 2020.
  3. ^ "Jinarc 15 mg tablets - Summary of Product Characteristics (SmPC)". (emc). 21 April 2020. Retrieved 14 December 2020.
  4. ^ "Jynarque- tolvaptan kit Jynarque- tolvaptan tablet". DailyMed. 31 March 2020. Retrieved 14 December 2020.
  5. ^ "Samsca- tolvaptan tablet". DailyMed. 26 October 2020. Retrieved 14 December 2020.
  6. ^ "Samsca EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 14 December 2020.
  7. ^ "Jinarc EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 14 December 2020.
  8. ^ Shoaf S, Elizari M, Wang Z, et al. (2005). "Tolvaptan administration does not affect steady state amiodarone concentrations in patients with cardiac arrhythmias". J Cardiovasc Pharmacol Ther. 10 (3): 165–71. doi:10.1177/107424840501000304. PMID 16211205. S2CID 39158242.
  9. ^ "Drug Approval Package: Samsca (Tolvaptan) Tablets NDA #022275". U.S. Food and Drug Administration (FDA). 21 July 2009. Retrieved 15 August 2020.
  10. ^ "Drug Approval Package: Jynarque (tolvaptan)". U.S. Food and Drug Administration (FDA). 8 June 2018. Retrieved 15 August 2020.
  11. ^ "Otsuka Maryland Research Institute, Inc. Granted Fast Track Designation For Tolvaptan In PKD". Medical News Today. Healthline Media UK Ltd. Retrieved 6 December 2018.
  12. ^ "Tolvaptan Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 6 April 2012. Retrieved 15 August 2020.
  13. ^ "Drugs@FDA: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 15 August 2020.
  14. ^ "Tolvaptan Accord: Pending EC decision". European Medicines Agency (EMA). 26 January 2023. Retrieved 28 January 2023.
  15. ^ a b "Samsca- tolvaptan tablet". DailyMed. 28 May 2019. Retrieved 15 August 2020.
  16. ^ a b "Jynarque- tolvaptan kit Jynarque- tolvaptan tablet". DailyMed. 31 March 2020. Retrieved 15 August 2020.
  17. ^ "Otsuka Obtains Approval in Japan for SAMTASU® for I.V. Infusion, a V2 -Receptor Antagonist for the Treatment of Cardiac Edema" (Press release). March 28, 2022. Retrieved June 11, 2022.
  18. ^ "U.S. Food and Drug Administration." Samsca (Tolvaptan): Drug Safety Communication. N.p., 30 Apr. 2013. Web. 1 June 2014. <http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm350185.htm>[dead link]
  19. ^ Goodman & Gilman's the pharmacological basis of therapeutics. Brunton, Laurence L, Knollmann, Björn C, Hilal-Dandan, Randa (Thirteenth ed.). New York. 5 December 2017. ISBN 9781259584732. OCLC 994570810.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: others (link)
  20. ^ Rote Liste Service GmbH (Hrsg.): Rote Liste 2017 - Arzneimittelverzeichnis für Deutschland (einschließlich EU-Zulassungen und bestimmter Medizinprodukte). Rote Liste Service GmbH, Frankfurt/Main, 2017, Aufl. 57, ISBN 978-3-946057-10-9, S. 222.

Further reading edit

  • Gheorghiade M, Niazi I, Ouyang J, et al. (2003). "Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial". Circulation. 107 (21): 2690–6. doi:10.1161/01.CIR.0000070422.41439.04. PMID 12742979.

External links edit

  • "Tolvaptan". Drug Information Portal. U.S. National Library of Medicine.

December 20, 2023
tolvaptan, sold, under, brand, name, samsca, among, others, aquaretic, drug, that, functions, selective, competitive, vasopressin, receptor, antagonist, used, treat, hyponatremia, blood, sodium, levels, associated, with, congestive, heart, failure, cirrhosis, . Tolvaptan sold under the brand name Samsca among others is an aquaretic drug that functions as a selective competitive vasopressin receptor 2 V2 antagonist used to treat hyponatremia low blood sodium levels associated with congestive heart failure cirrhosis and the syndrome of inappropriate antidiuretic hormone SIADH Tolvaptan was approved by the U S Food and Drug Administration FDA on May 19 2009 and is sold by Otsuka Pharmaceutical Co under the trade name Samsca 9 Tolvaptan as Jynarque was granted approval for medical use in the United States in April 2018 10 TolvaptanClinical dataTrade namesSamsca Jinarc Jynarque othersOther namesOPC 41061AHFS Drugs comMonographMedlinePlusa609033License dataEU EMA by INN US DailyMed Tolvaptan US FDA TolvaptanPregnancycategoryUK ContraindicatedRoutes ofadministrationBy mouthATC codeC03XA01 WHO Legal statusLegal statusUK POM Prescription only 2 3 US WARNING 1 Rx only 4 5 EU Rx only 6 7 Pharmacokinetic dataBioavailabilityUnknown 40 absorbed Protein binding99 MetabolismLiver CYP3A4 mediated 8 Elimination half life12 hours terminal IdentifiersIUPAC name N 4 5R 7 Chloro 5 hydroxy 2 3 4 5 tetrahydro 1H 1 benzazepin 1 yl carbonyl 3 methylphenyl 2 methylbenzamideCAS Number150683 30 0 NPubChem CID216237IUPHAR BPS2226DrugBankDB06212 YChemSpider187438 YUNII21G72T1950KEGGD01213ChEMBLChEMBL344159 YCompTox Dashboard EPA DTXSID3048780ECHA InfoCard100 219 212Chemical and physical dataFormulaC 26H 25Cl N 2O 3Molar mass448 95 g mol 13D model JSmol Interactive imageSMILES Cc1ccccc1C O Nc2cc C c cc2 C O N3c4ccc Cl cc4 C H O CCC3InChI InChI 1S C26H25ClN2O3 c1 16 6 3 4 7 20 16 25 31 28 19 10 11 21 17 2 14 19 26 32 29 13 5 8 24 30 22 15 18 27 9 12 23 22 29 h3 4 6 7 9 12 14 15 24 30H 5 8 13H2 1 2H3 H 28 31 YKey GYHCTFXIZSNGJT UHFFFAOYSA N Y N Y what is this verify The U S Food and Drug Administration FDA granted tolvaptan a fast track designation for clinical trials investigating its use for the treatment of polycystic kidney disease 11 The FDA granted Jynarque an orphan drug designation in April 2012 for the treatment of autosomal dominant polycystic kidney disease 12 Tolvaptan is available as a generic medication 13 14 Contents 1 Medical uses 2 Side effects 3 Pharmacology 4 Chemistry 5 References 6 Further reading 7 External linksMedical uses editTolvaptan Samsca is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia 15 Tolvaptan Jynarque is indicated for slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease ADPKD 16 Tolvaptan phosphate is a prodrug of tolvaptan developed for intravenous administration Tolvaptan phosphate is converted into the active drug tolvaptan in the human body following administration 17 Side effects editThe FDA has determined that tolvaptan should not be used for longer than 30 days and should not be used in patients with underlying liver disease because it can cause liver injury potentially leading to liver failure 18 When using to treat hyponatremia it may cause too rapid correction of hyponatremia resulting in fatal osmotic demyelination syndrome 19 Pharmacology editTolvaptan is a selective vasopressin V2 receptor antagonist 15 16 Chemistry editTolvaptan is a racemate a 1 1 mixture of the following two enantiomers 20 Enantiomers of tolvaptan nbsp R TolvaptanCAS number 331947 66 1 nbsp S TolvaptanCAS number 331947 44 5References edit FDA sourced list of all drugs with black box warnings Use Download Full Results and View Query links nctr crs fda gov FDA Retrieved 22 Oct 2023 Samsca 15 mg tablets Summary of Product Characteristics SmPC emc Retrieved 14 December 2020 Jinarc 15 mg tablets Summary of Product Characteristics SmPC emc 21 April 2020 Retrieved 14 December 2020 Jynarque tolvaptan kit Jynarque tolvaptan tablet DailyMed 31 March 2020 Retrieved 14 December 2020 Samsca tolvaptan tablet DailyMed 26 October 2020 Retrieved 14 December 2020 Samsca EPAR European Medicines Agency EMA 17 September 2018 Retrieved 14 December 2020 Jinarc EPAR European Medicines Agency EMA 17 September 2018 Retrieved 14 December 2020 Shoaf S Elizari M Wang Z et al 2005 Tolvaptan administration does not affect steady state amiodarone concentrations in patients with cardiac arrhythmias J Cardiovasc Pharmacol Ther 10 3 165 71 doi 10 1177 107424840501000304 PMID 16211205 S2CID 39158242 Drug Approval Package Samsca Tolvaptan Tablets NDA 022275 U S Food and Drug Administration FDA 21 July 2009 Retrieved 15 August 2020 Drug Approval Package Jynarque tolvaptan U S Food and Drug Administration FDA 8 June 2018 Retrieved 15 August 2020 Otsuka Maryland Research Institute Inc Granted Fast Track Designation For Tolvaptan In PKD Medical News Today Healthline Media UK Ltd Retrieved 6 December 2018 Tolvaptan Orphan Drug Designations and Approvals U S Food and Drug Administration FDA 6 April 2012 Retrieved 15 August 2020 Drugs FDA FDA Approved Drugs U S Food and Drug Administration FDA Retrieved 15 August 2020 Tolvaptan Accord Pending EC decision European Medicines Agency EMA 26 January 2023 Retrieved 28 January 2023 a b Samsca tolvaptan tablet DailyMed 28 May 2019 Retrieved 15 August 2020 a b Jynarque tolvaptan kit Jynarque tolvaptan tablet DailyMed 31 March 2020 Retrieved 15 August 2020 Otsuka Obtains Approval in Japan for SAMTASU for I V Infusion a V2 Receptor Antagonist for the Treatment of Cardiac Edema Press release March 28 2022 Retrieved June 11 2022 U S Food and Drug Administration Samsca Tolvaptan Drug Safety Communication N p 30 Apr 2013 Web 1 June 2014 lt http www fda gov Safety MedWatch SafetyInformation SafetyAlertsforHumanMedicalProducts ucm350185 htm gt dead link Goodman amp Gilman s the pharmacological basis of therapeutics Brunton Laurence L Knollmann Bjorn C Hilal Dandan Randa Thirteenth ed New York 5 December 2017 ISBN 9781259584732 OCLC 994570810 a href Template Cite book html title Template Cite book cite book a CS1 maint location missing publisher link CS1 maint others link Rote Liste Service GmbH Hrsg Rote Liste 2017 Arzneimittelverzeichnis fur Deutschland einschliesslich EU Zulassungen und bestimmter Medizinprodukte Rote Liste Service GmbH Frankfurt Main 2017 Aufl 57 ISBN 978 3 946057 10 9 S 222 Further reading editGheorghiade M Niazi I Ouyang J et al 2003 Vasopressin V2 receptor blockade with tolvaptan in patients with chronic heart failure results from a double blind randomized trial Circulation 107 21 2690 6 doi 10 1161 01 CIR 0000070422 41439 04 PMID 12742979 External links edit Tolvaptan Drug Information Portal U S National Library of Medicine Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Tolvaptan amp oldid 1170129292, wikipedia, wiki, book, books, library,

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