Tolvaptan is indicated in-
Hypervolemic or euvolemic hyponatremia.
Autosomal dominant polycystic kidney disease.
Other Drugs Affecting Exposure to Tolvaptan:
CYP 3A Inhibitors: Tolvaptan is a substrate of CYP 3A. CYP 3A inhibitors can lead to a marked increase in Tolvaptan concentrations. Do not use Tolvaptan with strong inhibitors of CYP 3A and avoid concomitant use with moderate CYP 3A inhibitors.
CYP 3A Inducers: Avoid co-administration of CYP 3A inducers (e.g., Rifampin, Rifabutin, Rifapentin, Barbiturates, Phenytoin, Carbamazepine) with Tolvaptan, as this can lead to a reduction in the plasma concentration of Tolvaptan and decreased effectiveness of Tolvaptan treatment. If co-administered with CYP 3A inducers, the dose of Tolvaptan may need to be increased.
P-gp Inhibitors: The dose of Tolvaptan may have to be reduced when Tolvaptan is co-administered with P-gp inhibitors, e.g., Cyclosporine.
Hypersensitivity to the active substance or to any of the excipients, anuria, volume depletion, hypovolemic hyponatremia, hypernatremia, Patients who cannot perceive thirst, pregnancy, breast-feeding.
The most common side effects of Tolvaptan are: thirst, dry mouth, weakness, constipation, making large amounts of urine and urinating often & increased blood sugar levels.
Too rapid correction of serum sodium can cause serious neurologic sequelae.
Single doses up to 480 mg and multiple doses up to 300 mg per day for 5 days have been well tolerated in clinical trials in healthy volunteers. There is no specific antidote for Tolvaptan intoxication. The signs and symptoms of an acute overdose can be anticipated to be those of excessive pharmacologic effect: a rise in serum sodium concentration, polyuria, thirst and dehydration/ hypovolemia (profuse and prolonged aquaresis). In patients with suspected Tolvaptan overdose, assessment of vital signs, electrolyte concentrations, ECG and fluid status is recommended. Appropriate replacement of water and/or electrolytes must continue until aquaresis abates. Dialysis may not be effective in removing Tolvaptan because of its high binding affinity for human plasma protein (>98%).
Store at below 25°C in a dry place, protected from light. Keep out of reach of children.
Selective vasopressin V2-receptor antagonist
Tolvaptan is a selective vasopressin V2-receptor antagonist. Tolvaptan affinity for the V2-receptor is 29 times greater than for the V1a-receptor. When taken orally, 15 to 60 mg doses of Tolvaptan antagonize the effect of vasopressin and cause an increase in urine water excretion that results in an increase in free water clearance (aquaresis), a decrease in urine osmolality, and a resulting increase in serum sodium concentrations. Urinary excretion of sodium and potassium and plasma potassium concentrations are not significantly changed.
There are no or limited amount of data from the use of Tolvaptan in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. Tolvaptan is contraindicated during pregnancy. Women of childbearing potential have to use effective contraception during Tolvaptan treatment. It is unknown whether Tolvaptan is excreted in human milk.
