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. Tolvaptan, as Jynarque, was granted approval for medical use in the United States in April 2018.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. The FDA granted Jynarque an orphan drug designation in April 2012, for the treatment of autosomal dominant polycystic kidney disease.Tolvaptan is available as a generic medication. Medical uses
Tolvaptan (Samsca) is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia.Tolvaptan (Jynarque) is indicated to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).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. 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.
Treatment
One form of LCA, in patients with LCA2 bearing a mutation in the RPE65 gene, has been successfully treated in clinical trials using gene therapy. The results of three early clinical trials were published in 2008 demonstrating the safety and efficacy of using adeno-associated virus to deliver gene therapy to restore vision in LCA patients. In all three clinical trials, patients recovered functional vision without apparent side effects. These studies, which used adeno-associated virus, have spawned a number of new studies investigating gene therapy for human retinal disease.The results of a phase 1 trial conducted by the University of Pennsylvania and Children’s Hospital of Philadelphia and published in 2009 showed sustained improvement in 12 subjects (ages 8 to 44) with RPE65-associated LCA after treatment with AAV2-hRPE65v2, a gene replacement therapy. Early intervention was associated with better results. In that study, patients were excluded based on the presence of particular antibodies to the vector AAV2 and treatment was only administered to one eye as a precaution. A 2010 study testing the effect of administration of AAV2-hRPE65v2 in both eyes in animals with antibodies present suggested that immune responses may not complicate use of the treatment in both eyes. On 19 December 2017, the U.S. Food and Drug Administration approved voretigene neparvovec-rzyl (Luxturna), an adeno-associated virus vector-based gene therapy for children and adults with biallelic RPE65 gene mutations responsible for retinal dystrophy, including Leber congenital amaurosis.