Tolvaptan for the treatment of liver cirrhosis oedema

Abstract

No alternative therapeutic option exists if liver cirrhosis patients have insufficient response to conventional diuretics and/or experience conventional diuretic-related adverse events. In 2013, tolvaptan (7.5 mg/day), an arginine vasopressin V₂ receptor antagonist, was approved in Japan for the treatment of liver cirrhosis with oedema. Short-term use of tolvaptan produced decreases in body weight, reduction in ascites volume and increases in urine volume when compared to placebo, despite the use of conventional diuretics. Additionally, approximately 60% of patients with oedema-related symptoms improved. Low-dose tolvaptan, 3.75 mg, was also efficacious. Even in patients with low serum albumin (<2.5 g/dL), decrease in body weight was greater with tolvaptan than with placebo. For future research, the efficacy and safety of lower tolvaptan doses for the treatment of liver cirrhosis patients with oedema should be confirmed in Japan. The results of this research could be used as an indicator or a guideline for physicians around the world.

Keywords::

• albumin
• ascites
• bothersome symptom
• cirrhotic patient
• hyponatraemia
• sodium
• tolvaptan

Acknowledgements

Thank you to Koji Nakajima (Otsuka pharmaceutical) who advised on this draft.

Financial & competing interests disclosure

I Sakaida is a consultant for Otsuka Pharmaceutical. I Sakaida received a research grants from Otsuka Pharmaceutical, Takeda Pharmaceutical, MSD and Chugai Pharmaceutical. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Tolvaptan was approved in liver cirrhosis patients with edema in Japan.

• No alternative therapeutic options exist if patients have insufficient response to conventional diuretics and/or have conventional diuretic-related adverse events.

• Even low-dose tolvaptan, 7.5 mg/day, produced measurable efficacy in reducing ascites in liver cirrhosis patients with volume overload.

• Tolvaptan treatment did not result in a reduction in serum sodium despite furosemide use.

• Bothersome symptoms associated with liver cirrhosis can decrease patients quality of life. Approximately 60% of patients treated with tolvaptan experienced a measurable improvement in their symptoms within 7 days.

• The frequency of albumin use in the placebo group was significantly higher than that of the tolvaptan group, approximately twofold. These results support the cost-effective use of tolvaptan.

• Future research should focus on safety assessments including the potential for liver injury in liver cirrhosis patients using low-dose tolvaptan. The results of future research could be used as an indicator or a guideline for physicians around the world.

Notes