European Medicines Agency

Doc. Ref.: EMEA/501291/2009 EMEA/H/C/980



EPAR summary for the public

This document is a summary of the European Public Assessment Report (EPAR). It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the studies performed, to reach their recommendations on how to use the medicine.

If you need more information about your medical condition or your treatment, read the Package Leaflet (also part of the EPAR) or contact your doctor or pharmacist. If you want more information on the basis for the CHMP recommendations, read the Scientific Discussion (also part of the EPAR)._

What is Samsca?

Samsca is a medicine that contains the active substance tolvaptan. It is available as blue tablets (triangular: 15 mg; round: 30 mg).

What is Samsca used for?

Samsca is used to treat adults with hyponatraemia (abnormally low levels of sodium in the blood) caused by a condition called ‘syndrome of inappropriate antidiuretic hormone secretion’ (SIADH). SIADH occurs when there is an excessive amount of a hormone called ‘antidiuretic hormone’ or ‘vasopressin’, which reduces urine output by retaining water in the blood. This results in the blood becoming diluted, lowering the level of sodium.

The medicine can only be obtained with a prescription.

How is Samsca used?

Treatment with Samsca should be started in hospital so that healthcare professionals can determine the most appropriate dose and monitor the patient’s level of blood sodium and blood volume.

The starting dose is 15 mg once a day. This may be increased to a maximum of 60 mg once a day to achieve an appropriate level of blood sodium and blood volume.

The tablets should be swallowed whole with a glass of water. They should not be taken with grapefruit juice.

How does Samsca work?

People with SIADH have an amount of vasopressin, leading to decreased urine production and dilution of the blood. The active substance in Samsca, tolvaptan, is a ‘vasopressin-2 receptor antagonist’. This means that it blocks one type of receptor (a protein) to which the hormone vasopressin normally attaches itself. By blocking this receptor, Samsca prevents vasopressin from having its effect. This leads to an increase in urine production, decreasing the amount of water in the blood and increasing the blood sodium level.

How has Samsca been studied?

The effects of Samsca were first tested in experimental models before being studied in humans.

Samsca was compared with placebo (a dummy treatment) in two main studies involving 424 adults with low sodium levels caused by SIADH and other conditions such as liver and heart problems. The

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main measure of effectiveness was based on the change in the amount of sodium in the blood over the first 30 days of treatment. The study also looked specifically at effect of treatment in the different disease groups.

What benefit has Samsca shown during the studies?

Samsca was more effective than placebo at increasing sodium levels in the blood in all diseases, but Samsca was more effective in patients with SIADH than with liver or heart problems. Sodium levels were around 129 mmol/l at the start of the study. In patients with SIADH, the levels had increased by an average of 4.8 mmol/l by day 4 in those who took Samsca, compared with 0.2 mmol/l in those who took placebo. By day 30, sodium had increased by an average of 7.4 mmol/l in patients who took Samsca, compared with 1.5 mmol/l in patients receiving placebo.

What is the risk associated with Samsca?

The most common side effects with Samsca (seen in more than 1 patient in 10) are thirst and nausea (feeling sick). For the full list of all side effects reported with Samsca, see the Package Leaflet. Samsca should not be used in people who may be hypersensitive (allergic) to tolvaptan or any of the other ingredients. It must not be used in patients with anuria (an inability to pass urine), very low blood volume, low blood sodium levels with low blood volume, hypernatremia (abnormally high levels of sodium in the blood) or in patients who cannot perceive thirst. It must also not be used in women who are pregnant or breast-feeding.

Why has Samsca been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Samsca’s benefits are greater than its risks for the treatment of adult patients with hyponatraemia secondary to SIADH. The Committee recommended that Samsca be given marketing authorisation.

Other information about Samsca:

The European Commission granted a marketing authorisation valid throughout the European Union for Samsca to Otsuka Pharmaceutical Europe Ltd on 3 August 2009.

The full EPAR for Samsca can be found here.

This summary was last updated in 06-2009.