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Chemical compound
Tolvaptan
Trade names Samsca, Jinarc, Jynarque, others Other names OPC-41061
AHFS /
Drugs.com
Monograph
MedlinePlus
a609033
License data
Pregnancy category
Routes of administration
By mouth
ATC code
Legal status
Bioavailability Unknown (40% absorbed)
Protein binding 99%
Metabolism
Liver (
CYP3A4 -mediated)
[8]
Elimination half-life 12 hours (terminal)
N -(4-{[(5R )-7-Chloro-5-hydroxy-2,3,4,5-tetrahydro-1H -1-benzazepin-1-yl]carbonyl}-3-methylphenyl)-2-methylbenzamide
CAS Number
PubChem
CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (
EPA )
ECHA InfoCard
100.219.212
Formula C 26 H 25 Cl N 2 O 3
Molar mass 448.95 g·mol−1 3D model (
JSmol )
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
N Y
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(verify)
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]
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
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
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
Tolvaptan is a selective vasopressin V2 receptor antagonist.
[15]
[16]
Chemistry
Tolvaptan is a
racemate , a 1:1 mixture of the following two enantiomers:
[20]
Enantiomers of tolvaptan
(R )-TolvaptanCAS number: 331947-66-1
(S )-TolvaptanCAS number: 331947-44-5
References
^
"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. <
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm350185.htm >[
dead link ]
^ 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 )
^ 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
External links
"Tolvaptan" . Drug Information Portal . U.S. National Library of Medicine.