What is the indication for Samsca (tolvaptan)?

Indications for Samsca (Tolvaptan)

Tolvaptan (Samsca) is 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). 1

Primary Indications

• Clinically significant hypervolemic hyponatremia associated with:
  • Heart failure 1
  • Cirrhosis 2
• Clinically significant euvolemic hyponatremia associated with:
  • Syndrome of Inappropriate Antidiuretic Hormone (SIADH) 1

Specific Criteria for Use

• Serum sodium <125 mEq/L 1
• OR less severe hyponatremia that is:
  • Symptomatic 1
  • Has resisted correction with fluid restriction 1

Important Limitations of Use

• Not indicated for patients requiring urgent correction of serum sodium to prevent or treat serious neurological symptoms 1
• Should not be used for autosomal dominant polycystic kidney disease (ADPKD) outside of FDA-approved REMS due to risk of hepatotoxicity 1
• Should not be used for more than 30 days to minimize risk of liver injury 1
• Not established that raising serum sodium with tolvaptan provides symptomatic benefit to patients 1

Contraindications

• Patients with ADPKD outside of FDA-approved REMS 1
• Patients unable to sense or respond to thirst 1
• Hypovolemic hyponatremia 1
• Patients taking strong CYP3A inhibitors 1
• Anuria 1
• Hypersensitivity to tolvaptan or components of the product 1

Administration Considerations

• Must be initiated and re-initiated in a hospital setting where serum sodium can be closely monitored 1
• Starting dose is 15 mg once daily, which can be titrated to 30 mg after 24 hours and up to 60 mg once daily as needed 1
• Careful monitoring is required to prevent too rapid correction of hyponatremia (>12 mEq/L/24 hours) which can cause osmotic demyelination syndrome 1, 2
• Fluid restriction should be avoided during the first 24 hours of therapy 1

Clinical Evidence and Guidelines

• In clinical trials, tolvaptan significantly increased serum sodium in patients with euvolemic/hypervolemic hyponatremia, including those with heart failure and cirrhosis 3, 4
• The American College of Cardiology Foundation/American Heart Association guidelines suggest that vasopressin antagonists may be considered in the short term for patients hospitalized with volume overload who have persistent severe hyponatremia and are at risk for or having active cognitive symptoms despite water restriction and maximization of guideline-directed medical therapy 2
• European Association for the Study of the Liver (EASL) guidelines note that tolvaptan has been approved in the USA for management of severe hypervolemic hyponatremia (<125 mmol/L) associated with cirrhosis, ascites, heart failure, and SIADH 2

Monitoring and Safety

• Serum sodium should be monitored closely to avoid increases of more than 8-10 mmol/L/day 2, 1
• Patients should be monitored for signs of dehydration, hypernatremia, and renal impairment 2
• Common side effects include thirst, dry mouth, and polyuria 3, 5
• Drug interactions with CYP3A inhibitors or inducers should be carefully considered 1, 6

Special Populations

• In patients with cirrhosis, tolvaptan should be used with caution due to potential safety concerns with long-term use 2
• Not recommended for patients with altered mental state (encephalopathy) who cannot drink appropriate amounts of fluid 2

Remember that tolvaptan should be used judiciously and only in appropriate clinical scenarios where the benefits of correcting hyponatremia outweigh the risks of treatment.