Tolvaptan is a selective
arginine vasopressin (AVP) V(2) receptor blocker used to induce free water diuresis in the treatment of euvolemic or hypervolemic
hyponatremia. Currently the orally active medication is in the final stages prior to approval by the FDA for outpatient
therapy. It appears to be safe and effective at promoting aquaresis and raising serum
sodium levels in both short- and long-term studies.
Tolvaptan is also effective for treatment of
congestive heart failure (CHF) exacerbation, but whether there are long standing beneficial effects on CHF is still controversial. Prolonged use of
tolvaptan leads to increased endogenous levels of AVP and perhaps over-stimulation of V(1A) receptors. Theoretically this activation could lead to increased afterload and cardiac myocyte
fibrosis, causing progression of CHF. However, after 52 weeks of
tolvaptan therapy there was no worsening of left ventricular dilatation. In addition,
tolvaptan is metabolized by the
CYP3A4 system; thus physicians should be aware of the potential for increased interactions with other medications.
Tolvaptan is a breakthrough in the
therapy of
hyponatremia as it directly combats elevated AVP levels associated with the syndrome of inappropriate secretion of
antidiuretic hormone,
congestive heart failure, and
cirrhosis of the liver.