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

14. THANK YOU !!!!!!!!!