Tolvaptan is a selective vasopressin V2 receptor antagonist used to treat hyponatremia. It works by blocking V2 receptors in the kidney collecting ducts, decreasing water reabsorption and increasing excretion to raise serum sodium levels. Tolvaptan is approved by the FDA to treat hyponatremia caused by congestive heart failure, cirrhosis, or SIADH. It has few side effects but can cause thirst, dry mouth, and polyuria. Care must be taken to avoid overly rapid correction of sodium levels which can cause serious neurological issues.

1. PRESENTED BY
SHREYA JHA

2.  also known as OPC-41061
 is a selective, competitive vasopressin receptor 2
antagonist
 Mainly used to treat hyponatremia (euvolemic and
hypervolemic) in cases of congestive cardiac failure,
cirrhosis of liver and SIADH.

3.  Tolvaptan was approved by the U.S. Food and Drug
Administration (FDA) on May 19, 2009.
 is sold by Otsuka Pharmaceutical Co. under the trade
name Samsca
 In India is manufactured & sold by MSN laboratories
Ltd. under the trade name Tolsama & Tolvat and by
Lupin under the brand name Resodim

4. MECHANISM
 selective vasopressor V2 receptor antagonist without
intrinsic agonist properties.
 29 times more affinity for v2 receptors than v1
receptors.
 Produces adequate aquaresis (water diuresis without
electrolyte excretion)
 Antagonism at the V2 receptor causes a decrease in the
number of aquaporin-2 channels in the renal
collecting tubules, resulting in decreased water
reabsorption, a net increase in free water excretion and
an increase in serum sodium concentrations.

6. Advantages of Tolvaptan
 Improves signs and symptoms of congestion
 Improves hyponatremia
 No effect on renal functions
 No effect on blood pressure
 No effect on electrolytes
 Oral route of administration
 No adverse effect on mortality

7. PHARMACOKINETICS
 The absolute bioavailability of a dose of tolvaptan is
unknown, but at least 40% of the drug is absorbed
after oral administration.
 The onset of effect is two to four hours after a dose is
taken, and peak effects occur four to eight hours after
administration.
 After absorption, it is 99% bound to circulating
plasma proteins.
 Volume of distribution is approximately 3 L/kg

8.  Tolvaptan is eliminated by the liver almost entirely by
CYP 3A4 to inactive metabolites, and it is an inhibitor
of P-glycoprotein.
 The plasma half-life is 12 hours;
 Increased serum sodium concentrations persist at 24
hours post-dose despite a return to baseline free water
excretion.

9. INDICATION
 Used in patient with hyponatremia < 125 meq /l in heart
failure (NYHA class III and IV)
 Used in SIADH for fluid restriction
 Patients with a serum sodium level of 125 to 134 mEq/L may
be treated if they have symptoms and have not responded
to fluid restriction
 Tolvaptan is also in fast-track clinical trials for polycystic
kidney disease

10. Starting dose is 15 mg per day and may be increased to
30 to 60 mg per day.
 Initiate therapy only in a hospital where serum sodium
levels can be monitored
 Too rapid correction of serum sodium can cause
serious neurologic sequel
 Do not administer it for more than 30 days to
minimize the risk of liver injury
 During initiation and titration, frequently monitor for
changes in serum electrolytes and volume

11.  Too rapid correction of serum sodium 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.

12. ADVERSE EFFECTS
 Most common are thirst(7.8 -16 %), dry mouth(4.2 –
13%) and polyuria(3.3%).
 It may cause fatal liver injury.
 GI bleeding may occur when prescribed in cirrhosis of
liver
 constipation
 Hyperglycemia
Should be used during pregnancy only if the potential
benefit justifies the potential risk to the fetus.

13. CONTRA-INDICATION
 Hypovolemic hyponatremia
 Anuric patient
 Concomitant use of strong or moderate CYP 3A
inhibitor (mainly grapefruit)
 Urgent need to raise serum sodium acutely

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