Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 11-14 May 2020

News 15/05/2020

PRAC concludes review of new information on the known risk of breast cancer with hormone replacement therapy

EMA’s safety committee (PRAC) recommends updating the current safety information for hormone replacement therapy (HRT) used to treat symptoms of the menopause.

The updates are based on evidence from a large study published in The Lancet[1] in August 2019, which confirmed the known higher risk of breast cancer in women using HRT. Furthermore, the results showed that the risk may continue to be increased for ten years or more after stopping HRT, if it has been used for more than five years.

Having assessed all available evidence, the PRAC recommends changes in the product information for implementation by authorities to reflect the following updates:

  • For combined oestrogen-progestagen and oestrogen-only HRT, the updated product information will reflect that the known higher risk of breast cancer in women using HRT becomes clear after approximately three years of use. After stopping HRT, the extra risk will decrease with time, and the time needed to return to baseline depends on the duration of prior HRT use. The new information indicates that the risk may persist for ten years or more in women who have used HRT for more than five years.
  • For conjugated oestrogens/bazedoxifene (Duavive), the effect on the risk of breast cancer is unknown. However, as Duavive contains conjugated oestrogens, the product information will be updated to reflect the new information related to oestrogen-only therapy.
  • For tibolone-containing HRT, the updated product information will reflect that no data for persistence of risk after stopping treatment are available, but a similar pattern cannot be ruled out.
  • For low dose vaginally applied oestrogen, the product information will be updated to reflect that the evidence has not shown an increase in breast cancer risk in women who had no breast cancer in the past. It is not known if it can be safely used in women who had breast cancer in the past.

The PRAC stresses that, as already indicated in the product information of HRT medicines, women should only take hormone replacement therapy for the treatment of symptoms of menopause at the lowest dose and for the shortest possible time that works for them. Women should also have regular check-ups, including breast screening, in line with current recommendations, and seek medical attention if they notice any changes in their breasts.

PRAC recommends new measures to avoid handling errors with Leuprorelin depot medicines

The PRAC is recommending measures to avoid handling errors in the preparation and administration of leuprorelin depot medicines, which are used to treat prostate cancer, breast cancer, certain conditions that affect the female reproductive system and early puberty.

A review by the PRAC found that some handling errors, such as the incorrect use of the needle or syringe, causing the medicine to leak from the syringe, and failure to inject leuprorelin properly, resulted in some patients receiving insufficient amounts of their medicine.

The Committee is therefore recommending that only healthcare professionals familiar with the preparation and administration steps should handle and administer the medicines to patients. Patients should not prepare or inject these medicines themselves. This information will be added to the product information of all medicines. 

For the medicine Eligard, the product information will be updated with warnings to strictly follow the instructions for preparation and administration and to monitor patients if a handling error occurs. In addition, the company marketing Eligard has been requested to replace the current device used to administer the medicine with one that is easier to handle by October 2021.  

For the medicine Lutrate Depot, the PRAC recommended that instructions for handling the medicine be revised to make them easier to follow and its packaging changed so the instructions are easier to find.

More information is available below.

[1] Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet. 2019 Sep 28;394(10204):1159-1168

PRAC statistics: May 2020

PRAC statistics: May 2020


  • Safety signal assessments. A safety signal is information on a new or known adverse event that is potentially caused by a medicine and that warrants further investigation. Signals are generated from several sources such as spontaneous reports, clinical studies and the scientific literature. More information can be found under Signal management.
  • Periodic safety update reports, abbreviated as PSURs, are reports prepared by the marketing authorisation holder to describe the worldwide safety experience with a medicine in a defined period after its authorisation. PSURs for medicinal products that contain the same active substance or the same combination of active substances, but have different marketing authorisations and are authorised in different EU Member States, are jointly assessed in a single assessment procedure. More information can be found under .
  • Risk management plans, abbreviated as RMPs, are detailed descriptions of the activities and interventions designed to identify, characterise, prevent or minimise risks relating to medicines. Companies are required to submit an RMP to EMA when applying for a marketing authorisation. RMPs are continually updated throughout the lifetime of the medicine as new information becomes available. More information is available under Risk management plans.
  • Post-authorisation safety studies, abbreviated as PASSs, are studies carried out after a medicine has been authorised to obtain further information on its safety, or to measure the effectiveness of risk-management measures. The PRAC assesses the protocols (aspects related to the organisation of a study) and the results of PASSs. More information can be found under Post-authorisation safety studies (PASS).
  • Referrals are procedures used to resolve issues such as concerns over the safety or benefit-risk balance of a medicine or a class of medicines. In a referral related to safety of medicines, the PRAC is requested by a Member State or the European Commission to conduct a scientific assessment of a particular medicine or class of medicines on behalf of the EU. More information can be found under Referral procedures: human medicines.

Ongoing referrals




Article-31 referral: Ifosfamide solutions

Under evaluation PRAC continued its assessment.

Article-31 referral: Ulipristal acetate 5mg medicinal products

Under evaluation PRAC continued its assessment.

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