Chemistry:Tolvaptan
-Tolvaptan_Structural_Formula_V1.svg) | |
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| Trade names | Samsca, Jinarc, Jynarque, others |
| Other names | OPC-41061 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a609033 |
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| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Bioavailability | Unknown (40% absorbed) |
| Protein binding | 99% |
| Metabolism | Liver (CYP3A4-mediated)[7] |
| Elimination half-life | 12 hours (terminal) |
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| Chemical and physical data | |
| Formula | C26H25ClN2O3 |
| Molar mass | 448.95 g·mol−1 |
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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.[8] Tolvaptan, as Jynarque, was granted approval for medical use in the United States in April 2018.[9]
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.[10] The FDA granted Jynarque an orphan drug designation in April 2012, for the treatment of autosomal dominant polycystic kidney disease.[11]
Tolvaptan is available as a generic medication.[12][13]
Medical uses
Tolvaptan (Samsca) is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia.[14]
Tolvaptan (Jynarque) is indicated for slow kidney-function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).[15]
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.[16]
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.[17] When using to treat hyponatremia, it may cause too rapid correction of hyponatremia resulting in fatal osmotic demyelination syndrome.[18]
Pharmacology
Tolvaptan is a selective vasopressin V2 receptor antagonist.[14][15]
Chemistry
Tolvaptan is a racemate, a 1:1 mixture of the following two enantiomers:[19]
| Enantiomers of tolvaptan | |
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-Tolvaptan_Structural_Formula_V1.svg) (R)-Tolvaptan CAS number: 331947-66-1 |
-Tolvaptan_Structural_Formula_V1.svg) (S)-Tolvaptan CAS number: 331947-44-5 |
References
- ↑ "Samsca 15 mg tablets - Summary of Product Characteristics (SmPC)". https://www.medicines.org.uk/emc/product/6635/smpc.
- ↑ "Jinarc 15 mg tablets - Summary of Product Characteristics (SmPC)". 21 April 2020. https://www.medicines.org.uk/emc/product/6849/smpc.
- ↑ "Jynarque- tolvaptan kit Jynarque- tolvaptan tablet". 31 March 2020. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3febc0a1-9e5a-4ce0-843d-210f21d862c4.
- ↑ "Samsca- tolvaptan tablet". 26 October 2020. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5526617c-c7b9-4556-886d-729bbabbc566.
- ↑ "Samsca EPAR". 17 September 2018. https://www.ema.europa.eu/en/medicines/human/EPAR/samsca.
- ↑ "Jinarc EPAR". 17 September 2018. https://www.ema.europa.eu/en/medicines/human/EPAR/jinarc.
- ↑ "Tolvaptan administration does not affect steady state amiodarone concentrations in patients with cardiac arrhythmias". J Cardiovasc Pharmacol Ther 10 (3): 165–71. 2005. doi:10.1177/107424840501000304. PMID 16211205.
- ↑ "Drug Approval Package: Samsca (Tolvaptan) Tablets NDA #022275". 21 July 2009. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022275s000TOC.cfm.
- ↑ "Drug Approval Package: Jynarque (tolvaptan)". 8 June 2018. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000TOC.cfm.
- ↑ "Otsuka Maryland Research Institute, Inc. Granted Fast Track Designation For Tolvaptan In PKD". Healthline Media UK Ltd. https://www.medicalnewstoday.com/releases/38392.php.
- ↑ "Tolvaptan Orphan Drug Designations and Approvals". 6 April 2012. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=20113473.
- ↑ "Drugs@FDA: FDA-Approved Drugs". https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=211891.
- ↑ "Tolvaptan Accord: Pending EC decision". 26 January 2023. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/tolvaptan-accord.
- ↑ 14.0 14.1 "Samsca- tolvaptan tablet". 28 May 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5526617c-c7b9-4556-886d-729bbabbc566.
- ↑ 15.0 15.1 "Jynarque- tolvaptan kit Jynarque- tolvaptan tablet". 31 March 2020. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3febc0a1-9e5a-4ce0-843d-210f21d862c4.
- ↑ "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>[|permanent dead link|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.
- ↑ 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
- "Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial". Circulation 107 (21): 2690–6. 2003. doi:10.1161/01.CIR.0000070422.41439.04. PMID 12742979.
External links
- "Tolvaptan". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/tolvaptan.
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