PRAC June 2022 –Update of COVID-19 vaccins and new safety information for Xalkori.

date: 17/06/2022

During its June 2022 meeting, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA)  is continuing its assessment of cases of heavy menstrual bleeding (heavy periods) with the COVID-19 mRNA vaccines and the PRAC finds no link between mRNA COVID-19 vaccines and absence of menstruation. The PRAC also discussed a direct healthcare professional communication (DHPC) containing important safety information for Xalkori.

Update on review of cases of heavy menstrual bleeding with mRNA COVID-19 vaccines
The PRAC is continuing its assessment of cases of heavy menstrual bleeding (heavy periods) with the COVID-19 mRNA vaccines Comirnaty and Spikevax.

Heavy periods may be defined as bleeding characterised by an increased volume and/or duration which interferes with the person’s physical, social, emotional and material quality of life. Menstrual disorders are very common and can occur with a wide range of underlying medical conditions as well as from stress and tiredness. 

The PRAC has reviewed all the available data, including cases reported during the clinical trials, cases spontaneously reported in Eudravigilance and data from the literature. 

The committee agreed to continue the assessment of this safety signal and to request from the marketing authorisation holders an updated cumulative review of the cases of heavy periods.

EMA will communicate further as soon as more information is available.

PRAC finds no link between mRNA COVID-19 vaccines and absence of menstruation
The PRAC concluded that there was insufficient evidence to establish a causal association between the COVID-19 vaccines Comirnaty and Spikevax and cases of absence of menstruation (amenorrhoea).

Absence of menstruation is defined as no bleeding for a period of 90 days or more. 

The committee assessed all the available data, including findings from the literature and cases of amenorrhea reported to EudraVigilance after the administration of Comirnaty and Spikevax. 

Overall, the PRAC considered that the available data does not support causal association and an update of the product information for either vaccine. 

The committee will continue to carefully monitor this issue and has requested the marketing authorisation holders to include it in the next periodic safety update reports (PSURs) for Comirnaty and Spikevax.

Xalkori: risk of ocular toxicity and severe visual loss in paediatric patients
As part of its advice on safety-related aspects to other EMA committees, the PRAC discussed a direct healthcare professional communications (DHPCs) containing important information for Xalkori.
This DHPC informs healthcare professionals of the risk of ocular toxicity, severe visual loss and the need for monitoring in paediatric patients with Xalkori.

Xalkori (crizotinib) is a cancer medicine used to treat adults with a type of lung cancer called non-small cell lung cancer (NSCLC), when the disease is advanced. Xalkori has been studied in children from 6 to 18 as a monotherapy for the treatment of relapsed or refractory systemic anaplastic large cell lymphoma (ALCL) that is ALK positive or patients with unresectable, recurrent, or refractory ALK positive inflammatory myofibroblastic tumour (IMT).

Vision disorders have been reported in 61% of paediatric patients treated with crizotinib in clinical trials for these indications. 

Vision disorders and ocular toxicity are more challenging to detect in children. Young patients may not report or notice changes in vision without specific questioning of symptoms and examinations. Paediatric patients should be monitored for ocular toxicity, including the risk of severe vision loss. They should receive a baseline ophthalmologic examination prior to starting Xalkori with follow-up examinations. Healthcare professionals are advised to inform patients and caregivers of the symptoms and remind them to contact their doctor if any of these symptoms develop. Any visual symptoms should be reported to an eye specialist.

Healthcare professionals are also advised to consider a dose reduction of Xalkori for patients who develop Grade 2 ocular disorders. If Grade 3 and 4 ocular disorders occur, treatment with the medicine should be discontinued permanently, unless another cause is identified.  

The product information and the educational material for patients and caregivers have been updated with instructions/recommendations in children about the risk of ocular toxicity, including severe vision loss.

The DHPC for Xalkori 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 EU Member States.

Xalkori is authorised and marketed in Belgium

More information is available on the EMA website

Last updated on 17/06/2022