SAMSCA*
Manufacturer DetailsOTUSKA INC
OTUSKA AMERICA PHARMACEUTICAL INC 2440 RESEARCH BLVD ROCKVILLE MD 98101
Compositions:
Tolvaptan 15mg/30mg/60mg tablets,
Tolvaptan 15mg/30mg/60mg tablets,
| Strength | Rate | Packing Style |
|---|---|---|
| mg | 0.00 | unit |
List of Related Indications:
- Treatment for patients with hypervolemic and euvolemic hyponatreamia
List Of Drugs:
- Tolvaptan - Samsca- @- Selective Vasopressor V2 Antagonist- (May 2009)
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
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 SAMSCA with strong inhibitors of CYP 3A and avoid concomitant use
with moderate CYP 3A inhibitors,
Avoid co-administration of CYP 3A inducers (e.g., rifampin, rifabutin, rifapentin,
barbiturates, phenytoin, carbamazepine, St. John’s Wort) with SAMSCA,
as this can lead to a reduction in the plasma concentration of tolvaptan and
decreased effectiveness of SAMSCA treatment. If coadministered with CYP 3A inducers,
the dose of SAMSCA may need to be increased
P-gp Inhibitors- The dose of SAMSCA may have to be reduced when
SAMSCA is co-administered with P-gp inhibitors, e.g., cyclosporine
Hyperkalemia or Drugs that Increase Serum Potassium
Grapefruit Juice
Co-administration of grapefruit juice and SAMSCA results in a 1.8-fold increase
in exposure to tolvaptan .
Treatment with tolvaptan is associated with an acute reduction of the extracellular
fluid volume which could result in increased serum potassium.
Serum potassium levels should be monitored after initiation of tolvaptan
treatment in patients with a serum potassium >5 mEq/L as well as those
who are receiving drugs known to increase serum potassium levels.
Indication:
Proprietary Name- Samsca
Established Name - Tolvaptan
Applicant- Otisuka America Pharmaceuticals Inc.
Indication-
Treatment for patients with hypervolemic and euvolemic hyponatreamia
Dosage-
Should be initiated in hospitals
Approved by FDA on 19-5-2009 (Ref- FDA approved List- 2009)
New Drugs Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
Tolvaptan Tablets 15/30mg 06-09-2012
For The Treatment of Clinically Significant Hypovalemic and Euvolemic
Hyponatremia ( Serum Sodium < 125ME E/L or less marked Hyponatremia
that is symptomatic and has resisted correction with Fluid restriction)
including Patients with Heart Failure , Cirhosis and syndrome of Inappropiate
Antidiuretic Hormone (SIADH)
Adverse Reaction:
Most common adverse reactions (.5% placebo) are thirst, dry mouth, asthenia,
constipation, pollakiuria or polyuria, and hyperglycemia
Contra-Indications:
CONTRAINDICATIONS
Need to raise serum sodium acutely
Patients who are unable respond appropriately to thirst
Hypovolemic hyponatremia
Concomitant use of strong CYP 3A inhibitors
Anuria
WARNINGS
INITIATE AND RE-INITIATE IN A HOSPITAL AND MONITOR SERUM SODIUM
See full prescribing information for complete boxed warning.
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.
PRECAUTIONS
Liver injury: Limit treatment duration to 30 days. If hepatic injury is suspected,
discontinue SAMSCA.
Avoid use in patients with underlying liver disease
Dehydration and hypovolemia may require intervention
Avoid use with hypertonic saline
Avoid use with CYP 3A inducers and moderate CYP 3A inhibitors
Consider dose reduction if co-administered with P-gp inhibitors
Monitor serum potassium in patients with potassium >5 mEq/L or on
drugs known to increase potassium
Dosages/ Overdosage Etc:
Indication-
Treatment for patients with hypervolemic and euvolemic hyponatreamia
INDICATIONS AND USAGE
SAMSCA is a selective vasopressin V2-receptor antagonist indicated for the
treatment of clinically significant hypervolemic and euvolemic hyponatremia
[serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic
and has resisted correction with fluid restriction], including patients with heart
failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
Important Limitations:
Patients requiring intervention to raise serum sodium urgently to prevent or
to treat serious neurological symptoms should not be treated with SAMSCA
It has not been established that SAMSCA provides a symptomatic benefit to patients
DOSAGE AND ADMINISTRATION
SAMSCA should be initiated and re-initiated in a hospital (2.1)
The recommended starting dose is 15 mg once daily.
Dosage may be increased at intervals .24 hr to 30 mg once daily,
and to a maximum of 60 mg once daily as needed to raise serum sodium.
Patient Information:
.
1 Concomitant Medication
Advise patients to inform their physician if they are taking or plan to take any
prescription or over-the-counter drugs since there is a potential for interactions.
Strong and Moderate CYP 3A inhibitors and Pg-p inhibitors
Advise patients to inform their physician if they use strong (e.g., ketoconazole,
itraconazole, clarithromycin, telithromycin, nelfinavir, saquinavir, indinavir, ritonavir)
or moderate CYP 3A inhibitors (e.g., aprepitant, erythromycin, diltiazem, verapamil,
fluconazol) or P-gp inhibitors (e.g., cyclosporine) [see Dosage and Administration
.
2 Nursing
Advise patients not to breastfeed an infant if they are taking SAMSCA
Pharmacology/ Pharmacokinetics:
Tolvaptan is a selective vasopressin V2-receptor antagonist with an affinity for
the V2-receptor that is 1.8 times that of native arginine vasopressin (AVP).
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.
Tolvaptan metabolites have no or weak antagonist activity for human
V2-receptors compared with tolvaptan.
Plasma concentrations of native AVP may increase
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
There is no need to adjust dose based on age, gender, race, or cardiac function .
Pregnancy
Pregnancy Category C.
There are no adequate and well controlled studies of SAMSCA use in pregnant women.
In animal studies, cleft palate, brachymelia, microphthalmia, skeletal malformations,
decreased fetal weight, delayed fetal ossification, and embryo-fetal death occurred.
SAMSCA should be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus.
Nursing Mothers
It is not known whether SAMSCA is excreted into human milk.
Tolvaptan is excreted into the milk of lactating rats.
Because many drugs are excreted into human milk and because of the
potential for serious adverse reactions in nursing infants from SAMSCA,
a decision should be made to discontinue nursing or SAMSCA, taking into
consideration the importance of SAMSCA to the mother.
Pediatric Use
Safety and effectiveness of SAMSCA in pediatric patients have not been established.
Geriatric Use
Of the total number of hyponatremic subjects treated with SAMSCA in clinical studies,
42% were 65 and over, while 19% were 75 and over.
No overall differences in safety or effectiveness were observed between these
subjects and younger subjects, and other reported clinical experience has
not identified differences in responses between the elderly and younger patients,
but greater sensitivity of some older individuals cannot be ruled out.
Increasing age has no effect on tolvaptan plasma concentrations
