Long-Term Experience of Tolvaptan: Is Hepatotoxicity Still a Concern?

托伐普坦的长期经验:肝毒性仍然是一个令人担忧的问题吗?

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Abstract

In Canada, tolvaptan (JINARC) is approved for the treatment of adults with autosomal dominant polycystic kidney disease to slow the progression of kidney enlargement and kidney function decline. Safety data from the pivotal Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO 3:4) study suggested the potential for increased risk of liver injury with tolvaptan, which led to the establishment of the Canadian Hepatic Safety Monitoring and Distribution Programme in 2015. This review summarizes data regarding hepatic safety from clinical trials and presents data from established risk mitigation programs and real-world evidence. Data show that frequent liver function monitoring allows timely detection of drug-induced liver injury and prompt treatment interruption. To date, this approach has led to the absence of serious liver injury or liver failure in more than 2800 patients treated with tolvaptan in Canada over the past 10 years.

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