Regarding amendments to the package inserts of medicinal products containing α-tocopheryl, α-tocopherol, vitamin E (a-tocopheril, a-tocopherol, vitamin E)

In accordance with paragraph 8 of Section IV of the Procedure for Expert Evaluation, the applicant must amend the instructions for medical use of the medicinal product upon receipt of new data, including bringing the instructions for medical use into line with the approved instructions for medical use of the original (reference) medicinal product, and ensure that the information on the medicinal product corresponds to current scientific knowledge.

The Pharmacovigilance Risk Assessment Committee (PRAC), based on the analysis of Periodic Safety Update Reports (PSURs) for medicinal products containing (a-tocopheril, a-tocopherol, vitamin E), PSUSA/00003186/202511, reached the following conclusions.

Given the available data presented in literature publications and spontaneous reports regarding the risk of coagulation disorders and hemorrhagic events associated with vitamin E overdose, as well as the risk of coagulation disorders leading to hemorrhagic events associated with the use of vitamin E in patients with vitamin K deficiency or during concomitant therapy with anticoagulants – vitamin K antagonists, and also given the plausible mechanism of action and the fact that this risk is already reflected in the instructions for medical use of vitamin K antagonists and of some medicinal products containing vitamin E that are part of this PSUSA procedure, PRAC considers that a causal relationship between α-tocopheryl, α-tocopherol, vitamin E (a-tocopheril, a-tocopherol, vitamin E) and this risk is at least reasonably possible. PRAC concluded that the instructions for medical use of medicinal products containing α-tocopheryl, α-tocopherol, vitamin E (a-tocopheril, a-tocopherol, vitamin E) should be amended accordingly.

Having considered the PRAC recommendations, the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) agrees with the overall conclusions of the PRAC and the grounds for the recommendations.

Based on the scientific conclusions regarding α-tocopheryl, α-tocopherol, vitamin E (a-tocopheril, a-tocopherol, vitamin E), the CMDh considers that the benefit/risk balance of medicinal products containing α-tocopheryl, α-tocopherol, vitamin E (a-tocopheril, a-tocopherol, vitamin E) remains unchanged, subject to the proposed amendments being made to the instructions for medical use.

Changes to be made to the relevant sections of the instruction for medical use (new text underlined and in bold).

“Special precautions for use” section

The following warning should be added:

It has been reported that <active substance> alters coagulation parameters (INR, prothrombin time) in patients with vitamin K deficiency or during concomitant therapy with anticoagulants – vitamin K antagonists, which may increase the risk of hemorrhagic events. Treatment with <active substance> may require a review and/or adjustment of the dose of the vitamin K antagonist (see section “Interaction with other medicinal products and other forms of interaction”).

Section "Interaction with other medicinal products and other forms of interaction"

The following interaction should be added:

In patients receiving therapy with vitamin K antagonist anticoagulants, <active substance> may increase the risk of hemorrhagic events. Caution should be exercised during concomitant use, and dose adjustment of anticoagulants may be required (see section “Special warnings and precautions for use”).

• “Overdose” section

The following recommendations for the management of overdose should be added:

In case of overdose, treatment with < active substance > must be discontinued. In patients with active bleeding or changes in coagulation parameters, specific treatment should be considered.

TO ANALYZE THE PUBLISHED INFORMATION AND SUBMIT THE RELEVANT APPLICATION FOR AMENDMENTS TO THE REGISTRATION MATERIALS, THE APPLICANT MUST USE THE ORIGINAL TEXT AVAILABLE AT THE FOLLOWING LINKS: