Tolvaptan

Hyponatremia is a common complication in patients with heart failure, cirrhotic ascites and syndrome of inappropriate antidiuretic hormone secretion. Traditional diuretic therapy is often associated with risks such as electrolyte disorders and renal impairment, and there has been a long-term lack of precise and targeted treatment options in clinical practice. Tolvaptan is the world's first selective vasopressin V2 receptor antagonist. It specifically blocks the V2 receptors on the surface of renal tubular epithelial cells and inhibits the reabsorption of free water, thereby increasing serum sodium levels without increasing electrolyte excretion. It is currently the only oral drug approved for the treatment of isovolemic/hypervolemic hyponatremia, and can also be used for volume management in patients with heart failure who have poor response to traditional diuretic therapy, especially suitable for people with fluid retention complicated by renal impairment and hyponatremia.

At present, the global tolvaptan market size is stably maintained at more than 1.2 billion US dollars, and the annual growth rate of the Chinese market is maintained at around 18%. In 2023, the terminal sales of domestic public medical institutions exceeded 1.8 billion yuan. In terms of competitive landscape, the original research product still accounts for about 62% of the market share. Generic preparations from 4 domestic enterprises have passed the consistency evaluation, and this variety has been included in the seventh batch of national centralized drug procurement. The maximum price reduction of the selected products compared with the original research is as high as 94%, which has greatly improved clinical accessibility, driven the continuous rise in demand for upstream API, and the enthusiasm for domestic API registration and declaration has increased year by year.

The original research enterprise of tolvaptan is Otsuka Pharmaceutical, with the original research brand name "Samsca", and its compound patent in China expired in 2020. The main dosage form approved for the original research is tablet, with specifications of 15mg and 30mg. It has been included in the *Catalogue of Reference Preparations of Chemical Drugs* of China, and is also a reference preparation listed by FDA. Up to now, there are 12 tolvaptan API registration numbers in China, among which 8 are in status A (approved for use in marketed preparations). In addition, tolvaptan oral preparations from more than 20 enterprises have been approved for marketing, among which 11 have passed the consistency evaluation. (Data as of October 2024, please refer to the official website of CDE for the latest information)

CATO can provide a full set of tolvaptan impurity reference standards. All products meet the compliance requirements of multiple regulatory systems such as the Chinese Pharmacopoeia and FDA. Most products support spot supply. Spot orders placed before 16:00 can be shipped on the same day, which can fully meet the reference standard needs in the stages of API R&D, quality research and batch production.