Regarding amendments to the instructions for medical use of medicinal products containing tamoxifen (tamoxifen)

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 evaluation of periodic safety update reports (PSURs) for medicinal products containing tamoxifen, PSUSA/00002846/202504, reached the following conclusions.

In view of the available data from the literature on decreased bone mineral density in premenopausal women, and in view of the probable mechanism of action, the PRAC considers that a causal relationship between the use of tamoxifen and decreased bone mineral density in premenopausal women is at least reasonably possible. The PRAC concluded that the instructions for medical use of medicinal products containing tamoxifen should be amended accordingly.

In view of the available data on QT interval prolongation on the electrocardiogram (ECG) from the literature and spontaneous reports, including in some cases a close temporal relationship, cases with a positive response to withdrawal of the medicinal product (de-challenge) and/or a positive response to re-administration (re-challenge), and in view of a probable mechanism of action, the PRAC considers that a causal relationship between the use of tamoxifen and QT interval prolongation on the ECG is at least reasonably possible. The PRAC concluded that the instructions for medical use of medicinal products containing tamoxifen 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 on tamoxifen (tamoxifen), CMDh considers that the benefit/risk balance of medicinal products containing tamoxifen (tamoxifen) remains unchanged, provided that the proposed changes are 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 and precaution should be added:

In studies conducted in premenopausal women who used tamoxifen to reduce the risk of breast cancer or as part of breast cancer treatment, a decrease in bone mineral density has been reported. Premenopausal women using <Name of the medicinal product > should be given advice on measures to maintain bone health in accordance with local clinical guidelines.

The following warning and precaution should be added:

<Name of the medicinal product> at the recommended dose may prolong the QTc interval on the electrocardiogram (ECG), especially in patients with existing risk factors for QT prolongation, including patients with concomitant heart disease or patients currently receiving treatment with other medicinal products known to prolong the QT interval (see the section “Interaction with other medicinal products and other forms of interaction”). ECG and electrolyte balance monitoring is recommended in such patients.

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

The following interaction information should be added:

<Name of the medicinal product> at the recommended dose may prolong the QTc interval on the electrocardiogram (ECG), and concomitant use of <Name of the medicinal product> with other medicinal products known to prolong the QT interval may further potentiate QT prolongation. Therefore, caution should be exercised in the event of such an interaction, and monitoring of the ECG and electrolyte balance is recommended in such patients (see section “Special warnings and precautions for use”).

“Adverse reactions” section

The following adverse reaction should be added to the System Organ Class (SOC) “Musculoskeletal and connective tissue disorders” with the frequency “not known”:

Decreased bone mineral density (in premenopausal women)

The following adverse reaction should be added to the System Organ Class (SOC) “Cardiac disorders” with the frequency “not known”:

Prolongation of the QT interval

“Overdose” section

If similar wording has not yet been included, the following warning should be added:

The scientific literature has reported that the use of tamoxifen at doses several times higher than the standard dose may be associated with QT interval prolongation on the ECG.

Changes to the safety information for medicinal products containing tamoxifen following the meeting of the Pharmacovigilance Risk Assessment Committee (PRAC) of 12 – 15 January 2026

The European Medicines Agency (EMA) has published the minutes of the Pharmacovigilance Risk Assessment Committee (PRAC) meeting of 12 – 15 January 2026. Following the meeting, a decision was made on the need to introduce safety-related changes to the registration materials/instructions for medical use of medicinal products containing tamoxifen.

Tamoxifen (tamoxifen) – PSUSA/00002846/202504

Tamoxifen is an antineoplastic (antitumor) hormonal agent indicated for the treatment of breast cancer, the prevention of breast cancer in women at increased risk, the treatment of anovulatory infertility, and also for the treatment of endometrial cancer under certain conditions.

Based on the evaluation of periodic safety update reports (PSURs), PRAC reviewed the benefit/risk balance of medicinal products containing tamoxifen and provided the relevant recommendations.

Summary of recommendations and conclusions

• Based on the analysis of safety and efficacy data, the benefit/risk ratio of medicinal products containing tamoxifen for the approved indications remains unchanged.
• At the same time, the instructions for medical use should be updated by adding a decrease in bone mineral density in premenopausal women as a warning and an adverse reaction with the frequency “not known,” as well as adding a warning on measures to support bone health in premenopausal women. In addition, the instructions for medical use should be updated by adding QT interval prolongation on the electrocardiogram (ECG) as a warning and an adverse reaction with the frequency “not known,” as well as a recommendation to monitor patients with existing risk factors for QT interval prolongation, including patients concomitantly receiving other medicinal products known to prolong the QT interval. Accordingly, the existing provisions of the instructions for medical use should be amended¹.
• In the next PSUR, all registration certificate holders (RCHs) must carefully monitor cases of diabetes mellitus and cognitive disorders, and also carry out a cumulative analysis of cases of decreased/lost sexual desire and related symptoms (for example, vulvovaginal dryness, dyspareunia) reported with the use of tamoxifen, including a discussion of the need to update the instructions for medical use, if necessary. In addition, the RCH Sandoz must provide any safety information relevant to the benefit/risk balance of tamoxifen obtained from study 2017-004554-42.

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¹Update of the sections "Special warnings and precautions for use", "Interaction with other medicinal products and other forms of interaction", "Adverse reactions" and "Overdose" of the package leaflet. The risk assessment report and the PRAC recommendation are forwarded to the CMDh for a decision.

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: