Tolvaptan (ADPKD)

How it works

It is a selective vasopressin V2-receptor antagonist that reduces cyclic-AMP-driven cyst-cell proliferation and fluid secretion in the kidney. Blocking V2 receptors also produces aquaresis (free-water diuresis).

Prescribing in practice

• Idiosyncratic hepatotoxicity can occur, so liver function must be checked before treatment, monthly initially and then regularly, with prompt discontinuation if transaminases or bilirubin rise — it is prescribed under a controlled-access scheme.
• Marked aquaresis causes thirst, polyuria and nocturia and risks dehydration and hypernatraemia, so patients must maintain adequate water intake.
• Avoid co-administration with strong CYP3A inhibitors, which substantially raise tolvaptan exposure.

Monitoring

Monitor liver function tests on the mandated schedule plus serum sodium, hydration status and body weight throughout treatment.

Counselling the patient

• Drink water in response to thirst, especially at night, to avoid dehydration.
• Report any nausea, abdominal pain, dark urine or yellowing of the skin or eyes immediately.
• Do not stop or skip the required blood tests for your liver.

Evidence & guidelines

The TEMPO 3:4 and REPRISE trials showed tolvaptan slows the decline in renal function and growth of kidney volume in ADPKD, supporting NICE-approved use in rapidly progressing disease.