Tolvaptan

Tolvaptan
Clinical data
Trade names	Samsca, Jinarc, Jynarque, others
Other names	OPC-41061
AHFS/Drugs.com	Monograph
MedlinePlus	a609033
License data	EU EMA: by INN; US DailyMed: Tolvaptan; US FDA: Tolvaptan;
Pregnancy; category	US: C (Risk not ruled out) ;
Routes of; administration	By mouth
ATC code	C03XA01 (WHO) ;
Legal status
Legal status	UK: POM (Prescription only) ; US: ℞-only ;
Pharmacokinetic data
Bioavailability	Unknown (40% absorbed)
Protein binding	99%
Metabolism	Hepatic (CYP3A4-mediated)[1]
Elimination half-life	12 hours (terminal)
Identifiers
	IUPAC name 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 ;
PubChem CID	216237;
IUPHAR/BPS	2226;
DrugBank	DB06212 ;
ChemSpider	187438 ;
UNII	21G72T1950;
KEGG	D01213;
ChEMBL	ChEMBL344159 ;
CompTox Dashboard (EPA)	DTXSID3048780 ;
ECHA InfoCard	100.219.212
Chemical and physical data
Formula	C26H25ClN2O3
Molar mass	448.95 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Cc1ccccc1C(=O)Nc2cc(C)c(cc2)C(=O)N3c4ccc(Cl)cc4[C@H](O)CCC3;
	InChI 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) ; Key:GYHCTFXIZSNGJT-UHFFFAOYSA-N ;
	(what is this?) (verify)

Tolvaptan (trade names Samsca, Jinarc, and 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.[2] Tolvaptan, as Jynarque, was granted approval for medical use in the United States in April 2018.[3]

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.[4] The FDA granted Jynarque an orphan drug designation in April 2012, for the treatment of autosomal dominant polycystic kidney disease.[5]

Tolvaptan is available as a generic medication.[6]

Medical uses

Tolvaptan (Samsca) is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia.[7]

Tolvaptan (Jynarque) is indicated to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).[8]

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.[9] When using to treat hyponatremia, it may cause too rapid correction of hyponatremia resulting in fatal osmotic demyelination syndrome.[10]

Pharmacology

Tolvaptan is a selective vasopressin V₂ receptor antagonist.[7][8]

Chemistry

Tolvaptan is a racemate, a 1:1 mixture of the following two enantiomers:[11]

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

References

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.
"Drug Approval Package: Samsca (Tolvaptan) Tablets NDA #022275". U.S. Food and Drug Administration (FDA). 21 July 2009. Retrieved 15 August 2020. Lay summary (PDF).
"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.
"Samsca- tolvaptan tablet". DailyMed. 28 May 2019. Retrieved 15 August 2020.
"Jynarque- tolvaptan kit Jynarque- tolvaptan tablet". DailyMed. 31 March 2020. Retrieved 15 August 2020.
"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>
Goodman & Gilman's the pharmacological basis of therapeutics. Brunton, Laurence L, Knollmann, Björn C, Hilal-Dandan, Randa (Thirteenth ed.). New York. ISBN 9781259584732. OCLC 994570810.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.

External links

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

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[pk-1] 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.

[2] "Drug Approval Package: Samsca (Tolvaptan) Tablets NDA #022275". U.S. Food and Drug Administration (FDA). 21 July 2009. Retrieved 15 August 2020. Lay summary (PDF).

[3] "Drug Approval Package: Jynarque (tolvaptan)". U.S. Food and Drug Administration (FDA). 8 June 2018. Retrieved 15 August 2020.

[Otsuka-4] "Otsuka Maryland Research Institute, Inc. Granted Fast Track Designation For Tolvaptan In PKD". Medical News Today. Healthline Media UK Ltd. Retrieved 6 December 2018.

[5] "Tolvaptan Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 6 April 2012. Retrieved 15 August 2020.

[6] "Drugs@FDA: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 15 August 2020.

[Samsca_FDA_label-7] "Samsca- tolvaptan tablet". DailyMed. 28 May 2019. Retrieved 15 August 2020.

[Jynarque_FDA_label-8] "Jynarque- tolvaptan kit Jynarque- tolvaptan tablet". DailyMed. 31 March 2020. Retrieved 15 August 2020.

[9] "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>

[10] Goodman & Gilman's the pharmacological basis of therapeutics. Brunton, Laurence L, Knollmann, Björn C, Hilal-Dandan, Randa (Thirteenth ed.). New York. ISBN 9781259584732. OCLC 994570810.CS1 maint: others (link)

[Rote_Liste-11] 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.