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.
5.
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.
