Annex I. Scientific conclusions and grounds for the variation to the terms of the Marketing Authorisation(s)

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1 Annex I Scientific conclusions and grounds for the variation to the terms of the Marketing Authorisation(s) 1

2 Scientific conclusions Taking into account the PRAC Assessment Report on the PSUR(s) for sodium iodide (131i), the scientific conclusions are as follows: Incidences of severe hyponatraemia have been reported in thyroid cancer patients undergoing radioactive iodine therapy. The mechanism described in the scientific literature is multifactorial: hypothyroidism due to thyroid hormone replacement withdrawal prior to the radioactive iodine (RAI) treatment, prolonged low-iodine (low-sodium) diet, excessive hydration or use of thiazide diuretics. Although hyponatraemia has not been regarded as a direct adverse drug reaction of sodium iodide ( 131 i), in a large retrospective study severe hyponatremia appeared to occur more frequently after RAI therapy. Severe hyponatraemia may result in life-threatening complications such as brain oedema and demyelination. Several publications recommend monitor sodium concentration especially in elderly patients undergoing RAI therapy. Although sodium iodide ( 131 i) itself does not directly cause the hyponatremia, the instructions in the SmPC to increase efficacy (withdrawal thyroid hormone, low iodine diet) as well as those to decrease radiation exposure (strong hydration) do contribute to the phenomenon in this specific patient group and therefore a warning is considered necessary in the product information. Potentially life-threatening consequences of severe hyponatraemia may be preventable when healthcare professionals identify this rare side effect and initiate prompt intervention. The CMDh agrees with the scientific conclusions made by the PRAC. Grounds for the variation to the terms of the Marketing Authorisation(s) On the basis of the scientific conclusions for sodium iodide (131i) the CMDh is of the opinion that the benefit-risk balance of the medicinal product(s) containing sodium iodide (131i) is unchanged subject to the proposed changes to the product information. The CMDh reaches the position that the marketing authorisation(s) of products in the scope of this single PSUR assessment should be varied. To the extent that additional medicinal products containing sodium iodide (131i) are currently authorised in the EU or are subject to future authorisation procedures in the EU, the CMDh recommends that such marketing authorisations are varied accordingly. 2

3 Annex II Amendments to the product information of the nationally authorised medicinal product(s) 3

4 Amendments to be included in the relevant sections of the Product Information (new text underlined and in bold, deleted text strike through) Summary of Product Characteristics Section 4.4 A warning should be added as follows: Hyponatraemia: Serious manifestations of hyponatraemia have been reported after sodium iodide [ 131 I] therapy in elderly patients who have undergone total thyroidectomy. Risk factors include older age, female sex, use of thiazide diuretics and hyponatraemia at the start of sodium iodide [ 131 I] therapy. Regular serum electrolytes measurements shall be considered for these patients. Package Leaflet Section 2 Warnings and precautions Low sodium blood levels have been observed in elderly patients who have had their thyroid removed. This event is most likely to occur in women and in patients taking medicines that increase the amount of water and sodium that is excreted in the urine (diuretics, such as hydrochlorothiazide). If you are included in some of these groups, your doctor may perform regular blood tests to check the amount of electrolytes (e.g. sodium) in your blood. 4

5 Annex III Timetable for the implementation of this position 5

6 Timetable for the implementation of this position Adoption of CMDh position: November 2017 CMDh meeting Transmission to National Competent Authorities of the translations of the annexes to the position: Implementation of the position by the Member States (submission of the variation by the Marketing Authorisation Holder): 23 December February