Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 27-30 September 2021

News 01/10/2021

EMA starts review of meningioma risk with nomegestrol- and chlormadinone-containing medicines

EMA has started a review of medicines containing the active substance nomegestrol or chlormadinone. These medicines can be used, alone or in combination with other active substances, to treat gynaecological disorders such as amenorrhea (absence of menstrual periods) and other menstrual disorders, uterine bleeding, endometriosis (a condition in which tissue similar to the lining of the womb grows elsewhere in the body), breast tenderness, as hormone replacement therapy or as contraceptives (birth control).

The review was requested by the French medicines agency (ANSM) following new data from two epidemiological studies carried out in France in women taking these medicines to investigate the risk of meningioma, a tumour of the membranes covering the brain and spinal cord. This tumour is usually non-malignant and is not considered to be a cancer, but due to their location in and around the brain and spinal cord, meningiomas can in rare cases cause serious problems.

In light of these new data concerning the risk of meningioma, EMA's safety committee (PRAC) will now examine the available evidence and make recommendations as to whether the marketing authorisations for nomegestrol- and chlormadinone-containing medicines should be amended across the EU.

For more information see EMA’s public health communication.

PRAC assessment of rare cases of venous thromboembolism with COVID-19 Vaccine Janssen

The PRAC has concluded that there is a possible link to rare cases of venous thromboembolism (VTE) with COVID-19 Vaccine Janssen.

VTE is a condition in which a blood clot forms in a deep vein, usually in a leg, arm or groin, and may travel to the lungs causing a blockage of the blood supply, with possible life-threatening consequences. This safety issue is distinct from the very rare side effect of thrombosis with thrombocytopenia syndrome (TTS) (i.e. blood clots with low blood platelets).  

VTE was included in the risk management plan for COVID-19 Vaccine Janssen as a safety concern to be investigated, based on a higher proportion of cases of VTE observed within the vaccinated group versus the placebo group in the large clinical study which was used to authorise this vaccine. The issue has been kept under close monitoring.

The PRAC has now reviewed new evidence from the study described above, as well as new evidence from another large clinical study. In this second study, there was no increase in venous thromboembolic events among individuals who received COVID-19 Vaccine Janssen. The PRAC also reviewed evidence from the post marketing setting - that is data gathered while the vaccine is used in the context of vaccination campaigns. When taking all evidence into account, the committee concluded that there is a reasonable possibility that rare cases of VTE are linked to vaccination with COVID-19 Vaccine Janssen.

The committee is therefore recommending listing VTE as a rare side effect of COVID-19 Vaccine Janssen in the product information, together with a warning to raise awareness among healthcare professionals and people taking the vaccine, especially those who may have an increased risk of VTE.

As part of the awareness-raising effort, the PRAC has agreed the content of a direct communication to healthcare professionals that is described further in this document, in the section ’New safety information for healthcare professionals’.

PRAC assessment of cases of immune thrombocytopenia with Vaxzevria and COVID-19 Vaccine Janssen

The PRAC assessed cases of immune thrombocytopenia (ITP) reported following vaccination with Vaxzevria (formerly AstraZeneca COVID-19 Vaccine) as well as COVID-19 Vaccine Janssen.

ITP is a condition in which the immune system mistakenly targets blood cells called platelets that are needed for normal blood clotting. Very low levels of blood platelets can be associated with bleeding, and have serious health consequences.

The committee assessed all the available data and recommended updating the product information of both vaccines to include ITP as an adverse reaction with an unknown frequency.

Furthermore, a warning statement has been agreed to highlight that cases of very low levels of blood platelets have been reported very rarely, usually within the first four weeks following vaccination with COVID-19 Vaccine Janssen or Vaxzevria.

If an individual has a history of ITP, the risk of developing low platelet levels should be considered before vaccination, and platelet monitoring is recommended after vaccination with either of these vaccines.

The PRAC will continue to monitor for new information and will take any further actions as necessary.

As part of the awareness-raising effort, the PRAC has agreed the content of a direct communication to healthcare professionals which is described further in this document, in the section ’New safety information for healthcare professionals’.

New safety information for healthcare professionals

As part of its advice on safety-related aspects, the PRAC agreed on direct healthcare professional communications (DHPCs) containing important safety information for COVID-19 Vaccine Janssen and Vaxzevria.

COVID-19 Vaccine Janssen: risk of immune thrombocytopenia and venous thromboembolism

This DHPC informs healthcare professionals about immune thrombocytopenia (ITP) and venous thromboembolism (VTE).

For ITP, the DHPC highlights that cases of ITP have been reported within the first four weeks after receiving COVID-19 Vaccine Janssen, and that it included serious cases with very low platelet counts.

If an individual has a history of ITP, healthcare professionals should consider the risk of developing low platelet levels prior to administering the vaccine. In individuals with a history of ITP, it is recommended to monitor platelet levels following vaccination with COVID-19 Vaccine Janssen.

For VTE, it is described that VTE has been observed rarely following vaccination with COVID-19 Vaccine Janssen and that the risk of VTE should be considered for individuals with increased risk factors for thromboembolism (blood clots).

Individuals diagnosed with thrombocytopenia within three weeks after vaccination with COVID-19 Vaccine Janssen should be actively investigated for signs of thrombosis. Similarly, individuals who present with thrombosis within three weeks of vaccination should be evaluated for thrombocytopenia.  This is important, to assess a potential diagnosis of thrombosis with thrombocytopenia syndrome (TTS), which requires specialised clinical management.

Vaxzevria: risk of thrombocytopenia including immune thrombocytopenia

This DHPC informs healthcare professionals of cases of thrombocytopenia (low levels of blood platelets) including immune thrombocytopenia (ITP) that have been reported with Vaxzevria, typically within the first four weeks after vaccination.

Very rarely, these events of thrombocytopenia presented with very low platelet levels and/or were associated with bleeding.

If an individual has a history of a thrombocytopenic disorder, healthcare professionals are advised to consider the risk of developing low platelet levels such as ITP, before administering the vaccine. Additionally, platelet monitoring is recommended after vaccination in an individual who has a history of ITP.

The DHPCs for COVID-19 Vaccine Janssen and Vaxzevria will be forwarded to EMA’s human medicines committee, the CHMP. Following the CHMP agreement, the DHPCs will be disseminated to healthcare professionals by the marketing authorisation holders, according to an agreed communication plan, and published on EMA’s website and in national registers in EU Member States.

Start of referral

PRAC statistics: October 2021

PRAC statistics: October 2021

Glossary:

  • 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.
  • Pandemic summary safety reports have been introduced as part of the enhanced safety monitoring of COVID-19 vaccines. Marketing authorisation holders are required to submit these reports to EMA on a monthly basis. Their submission complements the submission of PSURs. For more information see EMA’s pharmacovigilance plan for COVID-19 vaccines.

Ongoing referrals

Procedure

Status

Update

Amfepramone-containing medicinal products - Article -31 ReferralUnder evaluationPRAC continued its assessment

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