Samsca Special Precautions

Careful Administration: Dehydration: SAMSCA therapy induces copious aquaresis, which is normally partially offset by fluid intake. Dehydration can occur, especially in patients receiving diuretics or those who are fluid restricted. In multiple-dose, placebo-controlled trials in which 607 hyponatremic patients were treated with SAMSCA, the incidence of dehydration was 3.3% for SAMSCA and 1.5% for placebo-treated patients. Patients' condition, such as thirst, should be monitored and body weight, blood pressure, pulse rate, and urine volume should be frequently measured. Patients receiving SAMSCA should continue ingestion of fluid in response to thirst. If sensation of thirst persists, dose reduction should be considered.
Hypovolemia patients: Hypovolemia can occur, especially in potentially volume-depleted patients receiving diuretics or those who are fluid restricted. In patients receiving SAMSCA who develop medically significant signs or symptoms of hypovolemia, interrupt or discontinue SAMSCA therapy and provide supportive care with careful management of vital signs, fluid balance and electrolytes. Fluid restriction during therapy with SAMSCA may increase the risk of hypovolemia. Patients receiving SAMSCA should continue ingestion of fluid in response to thirst.
Diabetes mellitus: Diabetic patients with an elevated glucose concentration (e.g. in excess of 300mg/dl) may present with pseudohyponatremia. This condition should be excluded prior and during treatment with SAMSCA.
SAMSCA may cause hyperglycemia. Therefore, diabetic patients treated with SAMSCA should be managed cautiously. In particular this applies to patients with inadequately controlled type II diabetes.
Patients with serious coronary artery disease or cerebrovascular disease and elderly patients: Rapid volume decrease or hemoconcentration associated with rapid diuresis may induce thromboembolism.
Patients with Hyperkalemia or Drugs that Increase Serum Potassium: Treatment with SAMSCA is associated with an acute reduction of the extracellular fluid volume which could result in increased serum potassium and may lead to ventricular fibrillation and ventricular tachycardia. Serum potassium levels should be monitored after initiation of SAMSCA treatment in patients with a serum potassium > 5 mEq/L as well as those who are receiving drugs known to increase serum potassium levels.
Urinary outflow obstruction: Patients with partial obstruction of urinary outflow, for example patients with prostatic hypertrophy or impairment of micturition, have an increased risk of developing acute retention.
Patients with renal impairment: Dose adjustment of SAMSCA is not required in patients with renal impairment. No clinical trials in hyponatremic subjects with a creatinine clearance <10 mL/min or in patients undergoing dialysis have been conducted.
Co-administration with hypertonic saline: Concomitant use with hypertonic saline is not recommended.
Other drugs affecting exposure to SAMSCA: CYP 3A Inhibitors: SAMSCA is a substrate of CYP 3A. CYP 3A inhibitors can lead to a marked increase in SAMSCA concentrations. Do not use SAMSCA with strong inhibitors of CYP3A and avoid concomitant use with moderate CYP 3A inhibitors.
CYP 3A Inducers: 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 SAMSCA and decreased effectiveness of SAMSCA treatment. If co-administered 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.
General Precautions: 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 hyponatremia patients.
When driving vehicles or using machines it should be taken into account that occasionally dizziness, asthenia or syncope may occur.
Fluid and electrolyte balance: Fluid and electrolyte status must be monitored in all patients. Administration of SAMSCA induces copious aquaresis and may cause dehydration and increases in serum sodium and is contraindicated in hypernatraemic patients. Serum creatinine, electrolytes and symptoms of electrolyte imbalances (e.g. dizziness, fainting, palpitations, confusion, weakness, gait instability, hyper-reflexia, seizures, coma) have to be assessed prior to and after starting SAMSCA to monitor for dehydration.
Adjunct treatment of volume overload in heart failure: As the aquaretic effect of SAMSCA is most potent within 24 hours after initial administration, serum sodium concentration should be measured at least at 4 to 6 hours and 8 to 12 hours after administration on the first day of administration. From the second to around the seventh day of administration, serum sodium concentration should be measured every day, and if administration is continued further, serum sodium concentration should be measured at appropriate intervals.
Use in specific populations: There is no need to adjust dose based on gender, race, or cardiac function.
Use in Patients with Hepatic Impairment: While moderate and severe hepatic impairment do not affect exposure to SAMSCA to a clinically relevant extent, there are limited data on the risk of hepatic injury in such patients. Therefore, one should avoid use of SAMSCA in patients with underlying liver disease.
Use in patients with Renal impairment: No dose adjustment is necessary based on renal function. There are no clinical trial data in patients with CrCl <10 mL/min, and, because drug effects on serum sodium levels are likely lost at very low levels of renal function, use in patients with a CrCl <10 mL/min is not recommended. No benefit can be expected in patients who are anuric.
Use in Patients with Congestive Heart Failure: Heart failure increases the bioavailability of SAMSCA and increases the volume of distribution of SAMSCA but not clinically relevant. No dose adjustment is necessary.
Use in Children: Safety and effectiveness of SAMSCA in children and adolescents under the age of 18 years have not been established.
Use in the Elderly: A rapid decrease in circulating plasma volume or hemoconcentration associated with rapid diuresis may induce thromboembolism. SAMSCA should be administered with care and the patient's condition should be closely monitored. Elderly patients generally have reduced physiological function and are known to be susceptible to dehydration.
Hyponatremia: 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 SAMSCA plasma concentrations.
Adjunct treatment of volume overload in heart failure: In Japanese trials in cardiac edema, the age eligibility criteria were age 20 to < 80 years in one phase 2 trial and 20 to 85 years, inclusive, in three phase 3 trials, and the trials included many elderly subjects (generally defined in Japan as aged ≥ 65). There were no notable safety concerns observed in the elderly subjects when starting administration at a dose of 15 mg in those trials. However, in a Japanese post marketing safety survey comprising of 3349 patients, the results indicated an increased risk of hypernatremia-related adverse drug reactions in patients' age ≥ 85. The incidence of hypernatremia in elderly patients was 3.1% for a starting dose of 7.5 mg and 6.9% for a starting dose of 15 mg, indicating a significantly high incidence of hypernatremia for a starting dose of 15 mg.
Initiation of SAMSCA at half dose (7.5mg) is recommended in elderly patients with volume overload due to heart failure, because elderly patients were found to be at risk for hypernatremia.