SAMSCA TABLET 15MG

TABLET

**\[DOSAGE & ADMINISTRATION\]** 1. **Usual Dosage in Adults** Patients should be in a hospital for initiation and re-initiation of therapy to evaluate the therapeutic response and because too rapid correction of hyponatremia can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma and death. During initiation and titration, frequently monitor for change in serum electrolytes and volume. In order to avoid nocturnal urination, SAMSCA is recommended to be administered in the morning and swallowed whole with water regardless of meal. Fluid restriction during the first 24 hours of therapy with SAMSCA should generally be avoided. Patients receiving SAMSCA should continue ingestion of fluid in response to thirst. 1. _Hyponatremia_ The usual starting dose for SAMSCA is 15 mg administered once daily in adult. Increase the dose to 30 mg once daily, after at least 24 hours, to a maximum of 60 mg once daily, as needed to achieve the desired level of serum sodium. Do not administer SAMSCA for more than 30 days to minimize the risk of liver injury. 2. _Adjunct treatment of volume overload in heart failure_ SAMSCA should be used in combination with other diuretics, such as loop diuretics, thiazides, and aldosterone antagonists, since SAMSCA increases aquaresis but not natriuresis. There is no clinical experience of co-administration of SAMSCA with human atrial natriuretic peptide (hANP). The usual adult dose is 15 mg once daily but it is recommended to start from 7.5 mg/day for patients whose serum sodium is less than 125 mEq/L, patients in whom rapid plasma volume decrease is undesirable, elderly patients or patients with serum sodium concentration higher than 140 mEq/L. The starting dose of 7.5mg/day is recommended based on safety considerations. If clinical symptoms such as persistent thirst and dehydration are observed, dosage of SAMSCA should be reduced and appropriate measures such as fluid replenishment, including fluid therapy, should be taken in accordance with the symptoms. If there is no improvement in symptoms, SAMSCA should be discontinued. Administration of SAMSCA should not be continued after body weight has returned to the target level (body weight at which volume overload is appropriately controlled) or when conditions or symptoms due to volume overload are resolved. Administration of SAMSCA should not be continued if volume overload or body fluid retention is not improved. 2. **Drug Withdrawal** Following discontinuation from SAMSCA, patients should be advised to resume fluid restriction and should be monitored for changes in serum sodium and volume status. 3. **Co-Administration with CYP 3A Inhibitors, CYP 3A Inducers and P-gp Inhibitors** _CYP 3A Inhibitors_ SAMSCA is metabolized by CYP 3A, and use with strong CYP 3A inhibitors causes a marked (5-fold) increase in exposure. The effect of moderate CYP 3A inhibitors on SAMSCA exposure has not been assessed. Avoid co-administration of SAMSCA and moderate CYP 3A inhibitors. _CYP 3A Inducers_ Co-administration of SAMSCA with potent CYP 3A inducers (e.g., rifampin) reduces SAMSCA plasma concentrations by 85%. Therefore, the expected clinical effects of SAMSCA may not be observed at the recommended dose. Patient response should be monitored and the dose adjusted accordingly. _P-gp Inhibitors_ SAMSCA is a substrate of P-gp. Co-administration of SAMSCA with inhibitors of P-gp (e.g., cyclosporine) may necessitate a decrease in SAMSCA dose.