PRAC reviewing cases of period irregularities with mRNA COVID-19 vaccines

The PRAC is assessing reported cases of heavy menstrual bleeding (heavy periods) and absence of menstruation (amenorrhea) with the COVID-19 vaccines Comirnaty and Spikevax.
The Committee had previously analysed reports of menstrual (period) disorders in the context of the safety summary reports for COVID-19 vaccines approved in the EU and concluded at the time that the evidence did not support a causal link between these vaccines and menstrual disorders.
In view of spontaneous reports of menstrual disorders with both vaccines and of findings from the literature, the PRAC decided to further assess occurrences of heavy periods or amenorrhea following vaccination.
Menstrual disorders are very common and can occur with a wide range of underlying medical conditions as well as from stress and tiredness. Cases of these disorders have also been reported following COVID-19 infection.
Heavy periods may be defined as bleeding characterised by a volume, which may interfere with the person’s physical, social, emotional and material quality of life. Amenorrhea may be defined as the absence of menstrual bleeding for three or more months in a row.
After reviewing the available evidence, the PRAC decided to request an in-depth evaluation of all available data, including reports from spontaneous reporting systems, clinical trials and the published literature.
At this stage, it is not yet clear whether there is a causal link between the COVID-19 vaccines and the reports of heavy periods or amenorrhea. There is also no evidence to suggest that COVID-19 vaccines affect fertility.
EMA will communicate further when more information becomes available.

Updated guidance on core requirements for risk management plans of COVID-19 vaccines

The PRAC has adopted updated guidance on core requirements for risk management plans (RMPs) of COVID-19 vaccines.
As for any medicinal product that is authorised in the EU, companies need to submit their RMP when applying for a marketing authorisation to detail their plan for the post-marketing surveillance and what measures they must put in place to further characterise and manage risks. In the context of the pandemic, EMA adopted specific RMP guidance for COVID-19 vaccines, which complements the existing guidelines on the RMP format in the EU and guidance on good pharmacovigilance practices.
Following discussion at the PRAC, this guidance has been updated in light of the experience accrued during the pandemic to include specific considerations on:

• content requirements for summary safety reports (formerly ‘Monthly summary safety reports’) to be submitted to EMA by marketing authorisation holders of newly authorised COVID-19 vaccines, and details on safety topics for which monitoring with the usual periodic safety update reports (PSURs) is more appropriate;
• considerations for summary safety reports’ frequency changes and when it is appropriate to remove the requirement to submit such safety reports.

The new version of the guidance is available on EMA’s website.

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 infliximab.

Advice to postpone use of live vaccines in infants exposed to infliximab during pregnancy or via breastfeeding

This DHPC informs healthcare professionals on the need to postpone the use of live vaccines in infants who are exposed to infliximab during pregnancy or via breastfeeding.
Infliximab is an anti-inflammatory medicine authorised for the treatment of adults with rheumatoid arthritis (an immune system disease causing inflammation of the joints), Crohn’s disease (a disease causing inflammation of the digestive tract), ulcerative colitis (a disease causing inflammation and ulcers in the lining of the gut), ankylosing spondylitis (a disease causing inflammation and pain in the joints of the spine), psoriatic arthritis (a disease causing red, scaly patches on the skin and inflammation of the joints) or psoriasis (a disease causing red, scaly patches on the skin). Infliximab is also authorised in patients aged between 6 and 17 years with severe, active Crohn’s disease or severely active ulcerative colitis, when they have not responded to or cannot take other medicines or treatments.
Following treatment during pregnancy, it has been reported that infliximab crosses the placenta and it has been detected in infants up to 12 months after birth. Live vaccines should not be given to infants for 12 months after birth if they have been exposed to infliximab during pregnancy. If infant infliximab serum levels are undetectable or infliximab administration was limited to the first trimester of pregnancy, administration of a live vaccine might be considered at an earlier time point if there is a clear clinical benefit for the individual infant.
Infliximab has also been detected at low levels in breast milk, therefore, administration of a live vaccine to a breastfed infant while the mother is receiving the medicine is not recommended unless infant infliximab serum levels are undetectable.
It is important that women treated with infliximab who become pregnant or who breastfeed their infant inform the healthcare professional responsible for vaccination of their infant about their treatment with infliximab.
The DHPC for infliximab 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 holders according to an agreed communication plan, and published on the Direct healthcare professional communications page and in national registers in the EU Member States.

Published on: 11 February 2022