Tolvaptan (Jinarc(®)) is a highly selective
vasopressin V2 receptor antagonist indicated for use in patients with
autosomal dominant polycystic kidney disease (
ADPKD).
Tolvaptan is the first
pharmaceutical agent to be approved in Europe for delaying the progression of
ADPKD in adults with stage 1-3
chronic kidney disease at initiation of treatment. In the large phase III TEMPO 3:4 trial in adults with
ADPKD, 3 years' treatment with oral
tolvaptan significantly reduced growth in total kidney volume and slowed renal function decline relative to placebo.
Tolvaptan was also associated with a significantly lower rate of events for the composite secondary endpoint of time to investigator-assessed
clinical progression relative to placebo, an effect that was largely attributable to reductions in the risk of worsening renal function and the risk of worsening kidney
pain. Many of the most common adverse events in the
tolvaptan group were related to its aquaretic mechanism of action (e.g.
polyuria,
nocturia,
polydipsia and thirst).
Tolvaptan was also associated with idiosyncratic elevations of liver
enzymes which were reversible on discontinuation of the
drug. Although the use of
tolvaptan requires careful consideration and balancing of benefits and risks, current evidence suggests that
tolvaptan is a promising new treatment option for patients with
ADPKD.