Tolvaptan

Synthesis

Fugure 1: Synthesis of Tolvaptan

Precautions

Tolvaptan(SAMSCA) should be initiated and re-initiated in patients only in a hospital where serum sodium can be monitored closely. Too rapid correction of hyponatremia (e.g., >12 mEq/L/24 hours) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma and death. In susceptible patients, including those with severe malnutrition, alcoholism or advanced liver disease, slower rates of correction may be advisable. Tolvaptan(SAMSCA) is contraindicated in the following conditions: Urgent need to raise serum sodium acutely Inability of the patient to sense or appropriately respond to thirst Hypovolemic hyponatremia Concomitant use of strong CYP 3A inhibitors Anuric patients Hypersensitivity (e.g. anaphylactic shock, rash generalized) to tolvaptan or its components

Biochem/physiol Actions

Tolvaptan (OPC 41061) is a potent, orally active non-peptide vasopressin V2 selective antagonist. IC50 = 3 nM at the rat V2 receptor; 29 times more selective for the V2 than for V1a. Tolvaptan has also been shown to inhibit the development of polycystic kidney disease in several animal models.

Side effects

The most common adverse events were thirst, dry mouth, asthenia, constipation, pollakiuria or polyuria, and hyperglycemia. The recommended starting dose is 15 mg daily with a daily 15-mg adjustment to a maximum of 60 mg daily to raise serum sodium concentration. Initiation should be in a hospital setting where serum sodium and volume status may be monitored since too rapid correction of hyponatremia (>12 mEq/L/24 h) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, spastic quadriparesis, seizures, coma, and death. In addition to avoiding concomitant use of strong CYP3A4 inhibitors, tolvaptan is contraindicated in settings of urgent need to raise serum sodium acutely, in patients with an inability to sense or appropriately respond to thirst, in hypovolemic hyponatremia conditions, and in anuric patients.

references

[1] miyazaki t, fujiki h, yamamura y, et al. tolvaptan, an orally active vasopressin v2-receptor antagonist-pharmacology and

Brand name

Samsca