Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 4-7 April 2022
mRNA COVID-19 vaccines: PRAC finds no link with autoimmune hepatitis
The PRAC has concluded that available evidence does not support a causal link between COVID-19 vaccines Comirnaty and Spikevax and very rare cases of autoimmune hepatitis (AIH).
AIH is a serious chronic inflammatory condition in which the immune system attacks and damages the liver. Signs and symptoms of autoimmune hepatitis vary from person to person and may include yellowing of the skin (jaundice), build-up of fluid in the legs (oedema) or belly (ascites) and gastrointestinal symptoms.
The committee’s assessment is based on data from medical literature, cases of AIH spontaneously reported in the EudraVigilance database and further data and analyses provided by the marketing authorisation holders.
EMA will continue to closely monitor any new reports of the condition and take appropriate measures if necessary.
New safety information for healthcare professionals
As part of its advice on safety-related aspects to other EMA committees, the PRAC discussed a direct healthcare professional communication (DHPC) containing important safety information for Nulojix.
Nulojix: Risk of medication errors due to change in maintenance dose
This DHPC aims to inform healthcare professionals of the risk of medication errors due to a change in the maintenance dose to 6 mg/kg.
Nulojix (belatacept) is used in adults to prevent the body from rejecting a transplanted kidney. It is used together with corticosteroids and mycophenolic acid (other medicines used to prevent organ rejection). Nulojix is a powder that is made up into a solution for infusion (drip into a vein). Doses are calculated using the patient’s weight. In the initial phase, which lasts three months, it is given at a dose of 10 mg per kilogram of body weight. After that phase, Nulojix is given at a maintenance dose every four weeks.
The maintenance dose for Nulojix will be changed from 5 mg/kg to 6 mg/kg as a consequence of the implementation of a new manufacturing process. However, for approximately one to two months, Nulojix from both manufacturing processes will coexist on the market, and therefore two different dose recommendations will apply. A mix-up between the products may lead to medication errors resulting in over- or underdosing. Healthcare professionals are advised to carefully check the dose for the specific product to be administered, to make appropriate adjustments for weight-based dosing calculations.
The DHPC for Nulojix will be forwarded to EMA’s human medicines committee, the CHMP. Following the CHMP decision, the DHPC will be disseminated to healthcare professionals by the marketing authorisation holder, according to an agreed communication plan, and published on the Direct healthcare professional communications page and in national registers in EU Member States.
- Safety signal assessments. A safety signal is information which suggests a new potentially causal association, or a new aspect of a known association between a medicine and an adverse event that warrants further investigation. Safety 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 'Periodic safety update reports: questions and answers'.
- 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'.
- 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.
- 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, starting on a monthly basis. Their submission complements the submission of PSURs. For more information see EMA’s pharmacovigilance plan for COVID-19 vaccines.
|Amfepramone-containing medicinal products - Article - 31 Referral||Under evaluation||PRAC continued its assessment|
|Janus Kinase inhibitors (JAKi) – Article 20 Referral||Under evaluation||PRAC continued its assessment|
|Nomegestrol and chlormadinone - Article - 31 Referral||Under evaluation||PRAC continued its assessment|
|Terlipressin-containing medicinal products-Article 31 Referral||Under evaluation||PRAC continued its assessment|
- Comirnaty: EPAR
- Nulojix: EPAR
- Spikevax (previously COVID-19 Vaccine Moderna): EPAR
- Amfepramone-containing medicinal products: Article 31 referrals
- Janus kinase inhibitors (JAKi): Article 20 procedures
- Nomegestrol and chlormadinone: Article 31 referrals
- Terlipressin-containing medicinal products indicated in the treatment of hepatorenal syndrome: Article 31 referrals