Tolvaptan
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.
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Trade names | Samsca, Jinarc, Jynarque |
Other names | OPC-41061 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a609033 |
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Routes of administration | Oral |
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Bioavailability | Unknown (40% absorbed) |
Protein binding | 99% |
Metabolism | Hepatic (CYP3A4-mediated)[1] |
Elimination half-life | 12 hours (terminal) |
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ECHA InfoCard | 100.219.212 ![]() |
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Formula | C26H25ClN2O3 |
Molar mass | 448.95 g·mol−1 |
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The FDA granted tolvaptan a fast-track designation for clinical trials investigating its use for the treatment of polycystic kidney disease.[2]
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.[3] When using to treat hyponatremia, it may cause too rapid correction of hyponatremia resulting in fatal osmotic demyelination syndrome.[4]
Pharmacology
Tolvaptan is a selective V2 receptor antagonist.[5]
Chemistry
Tolvaptan is a racemate, a 1:1 mixture of the following two enantiomers:[6]
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![]() (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.
- "Otsuka Maryland Research Institute, Inc. Granted Fast Track Designation For Tolvaptan In PKD". Medical News Today. Healthline Media UK Ltd. Retrieved 6 December 2018.
- "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)
- "SAMSCA (tolvaptan) tablets - Package Insert" (PDF). Otsuka Pharmaceutical Co., Ltd. Retrieved 6 December 2018.
- 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
- 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.