Drug Safety-related Labeling Changes (SrLC)

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SAMSCA (NDA-022275)


Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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04/23/2018 (SUPPL-16)

Approved Drug Label (PDF)

Boxed Warning

Addition of the following:


Because of the risk of hepatoxicity, tolvaptan should not be used for ADPKD outside of the FDA-approved REMS

4 Contraindications

Addition of the following subsection:

4.1 Use in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) outside of FDA approved REMS

Tolvaptan can cause serious and potentially fatal liver injury. Tolvaptan should not be prescribed or used outside of the FDA-approved Risk Evaluation and Mitigation Strategy (REMS) for ADPKD patients.

5 Warnings and Precautions

5.2 Liver Injury

Additions and/or revisions underlined:

Tolvaptan can cause serious and potentially fatal liver injury. In placebo-controlled studies and an open label extension study of chronically administered tolvaptan in patients with ADPKD, cases of serious liver injury attributed to tolvaptan, generally occuring during the first 18 months of therapy, were observed. In postmarketing experience with tolvaptan in ADPKD, acute injury resulting in liver failure requiring liver transplantation has been reported. Tolvaptan should not be used to treat ADPKD outside of the FDA-approved risk evaluation and mitigation strategy (REMS) for ADPKD patients … Patients with symptoms that may indicate liver injury …

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)


What is the most important information I should know about SAMSCA?

Addition of the following:

3) If you have autosomal dominant polycystic kidney disease (ADPKD), do not use SAMSCA because you should receive the medicine (tolvaptan) through a program that ensures laboratory monitoring of your liver.

06/01/2017 (SUPPL-15)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Too Rapid Correction of Serum Sodium Can Cause Serious Neurologic Sequelae

(additions underlined)

Osmotic demyelination syndrome is a risk associated with too rapid correction of hyponatremia (e.g., >12 mEq/L/24 hours). Osmotic demyelination results in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma or death. In susceptible patients, including those with severe malnutrition, alcoholism or advanced liver disease, slower rates of correction may be advisable. In controlled clinical trials in which tolvaptan was administered in titrated doses starting at 15 mg once daily, 7% of tolvaptan-treated subjects with a serum sodium <130 mEq/L had an increase in serum sodium greater than 8 mEq/L at approximately 8 hours and 2% had an increase greater than 12 mEq/L at 24 hours. Approximately 1% of placebo-treated subjects with a serum sodium <130 mEq/L had a rise greater than 8 mEq/L at 8 hours and no patient had a rise greater than 12 mEq/L/24 hours. Osmotic demyelination syndrome has been reported in association with SAMSCA therapy [see Adverse Reaction. Patients treated with SAMSCA should be monitored to assess serum sodium concentrations and neurologic status, especially during initiation and after titration. Subjects with SIADH or very low baseline serum sodium concentrations may be at greater risk for too-rapid correction of serum sodium. In patients receiving SAMSCA who develop too rapid a rise in serum sodium, discontinue or interrupt treatment with SAMSCA and consider administration of hypotonic fluid. Fluid restriction during the first 24 hours of therapy with SAMSCA may increase the likelihood of overly-rapid correction of serum sodium, and should generally be avoided. Co-administration of diuretics also increases the risk of too rapid correction of serum sodium and such patients should undergo close monitoring of serum sodium.

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