Pharmacovigilance Risk Assessment Committee (PRAC), which is responsible for assessing and monitoring the safety of human medicines from European medicines agency (EMA) has published new significant safety information (signals) for medicines which were identified from their monthly PRAC meeting held during the period of 28 Sep-2020 to 01 Oct 2020.

PRAC Recommendations for regulatory action

Based on the sufficient safety evidence (studies, published literature etc.,) to demonstrate the relationship between Drug-ADR pair, PRAC recommends Committee for Medicinal Products for Human Use (CHMP) for endorsement when the signal concerns Centrally Authorised Products (CAPs), and to the Co-ordination Group for Mutual Recognition and Decentralized Procedures – Human (CMDh) for information in the case of Nationally Authorised Products (NAPs) and the MAH(s) for corresponding medicine are obliged to take actions such as product label update.

Below signals are recommended by PRAC to CHMP/CMDh for regulatory actions:

1. Postpartum haemorrhage associated with Selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitor (SNRIs):

This is a signal identified for antidepressant class of medicines. PRAC identified the association between haemorrhagic events and to the drugs of these two pharmacological classes based on the observational studies (Bruning et al 2015 and Jiang et al 2016, as well as from Heller at al 2017, Huybrechts at al 2020, Palmsten et al in 2013 and 2020 and Skalkidou et al in 2020) and recommended to update the product label for these class of medicines by including the risk of postpartum haemorrhage in special warnings and precautions, pregnancy sections and adding this signal as an additional event under undesirable effects section of summary of product characteristics (SmPC). PRAC also recommended to update package leaflet by adding “heavy vaginal bleeding shortly after birth (postpartum haemorrhage)” as a possible side effect for these class of medicines.

2. Sjogren’s syndrome associated with the use of Pembrolizumab:

Pembrolizumab is a humanized antibody used in cancer immunotherapy belongs to the class of monoclonal antibodies. Sjogren’s syndrome is an autoimmune disorder in which body’s immune system attacks the cells of organs responsible for tears and saliva. So, this disorder is characterized by dry eyes and dry mouth.

PRAC identified the causal association between pembrolizumab and Sjogren’s syndrome based on the safety evidence available from the case reports at EudraVigilance database and from medical literature. PRAC recommended to add this safety signal as a new adverse reaction under undesirable effects section of SmPC with uncommon frequency (may affect 1 in 100 people) and under possible side effects section of package leaflet with uncommon and rare occurrences (1 in 1000).

Marketing authorization holders (MAH) for these respective drugs and drug-class are obliged to update the product labels/package leaflets, per PRAC recommendations and submit the variation within the 2-month timeline.