Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 25-28 November 2024
Doxycycline: currently available evidence not supporting link with risk of suicidality
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Doxycycline: currently available evidence not supporting link with risk of suicidality
EMA’s safety committee (PRAC) has concluded that the currently available evidence is not sufficient to establish a causal relationship between the use of the antibiotic doxycycline and the risk of suicidality.
Doxycycline is a broad-spectrum antibiotic, widely used to treat a wide range of infections caused by bacteria such as acne, urinary and lower respiratory tract infections, dental infections, and skin infections. It is also used to prevent the development of certain infections, such as malaria.
A safety signal on the risk of suicidality, suicidal thoughts or actions with doxycycline was raised based on cases reported to the Finnish national competent authority, as well as further cases reported to EudraVigilance, the centralised European database of suspected side effects reports, and the medical literature.
The PRAC started its review in November 2023 and requested the marketing authorisation holders for doxycycline to perform a cumulative review of the data from all relevant sources.
The PRAC also requested a study based on real-world evidence, which includes data from electronic health records and disease registries, through DARWIN EU to facilitate the assessment of the signal. After reviewing all available evidence from spontaneous reports, the literature, the discussion on possible mechanisms and the study performed via DARWIN EU, the PRAC considered that the evidence is not sufficient to establish a causal relationship and that no update to the product information of doxycycline is warranted.
Suicide-related events in relation to doxycycline will be closely monitored and any new evidence will be discussed in the Periodic Safety Update Reports (PSURs).
New safety information for healthcare professionals
Veoza (fezolinetant): new recommendations to minimise risk of liver injury
The PRAC has agreed to a direct healthcare professional communication (DHPC) informing of the risk of drug-induced liver injury (DILI) with Veoza (fezolinetant) and has recommended monitoring of liver function before and during treatment.
Veoza is a medicine used to treat moderate-to-severe vasomotor symptoms (also referred to as hot flushes or night sweats) associated with menopause.
The committee considered a review of the potential risk of fezolinetant to cause drug-induced liver injury based on information from all available sources, including reports of suspected side effects and studies published in the scientific literature.
Severe elevations of the liver enzymes alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (>10x upper limit of normal) with concurrent elevations in bilirubin and/or alkaline phosphatase (ALP) have been reported post marketing in women taking Veoza. In some cases, elevated liver function tests (LFTs) were associated with signs or symptoms suggestive of liver injury such as fatigue, pruritus, jaundice, dark urine, decreased appetite, or abdominal pain.
PRAC recommends LFTs must be performed before treatment is started. During the first three months of treatment, monthly LFTs must be carried out, and thereafter based on clinical judgement. During treatment, LFTs must be conducted if symptoms suggestive of liver injury occur. Monitoring of liver function should be maintained until they have normalised.
Treatment should be discontinued in certain cases of transaminase and bilirubin elevations or if liver enzyme elevations are accompanied by symptoms suggestive of liver injury.
The summary of product characteristics and package leaflet of Veoza are being updated to reflect the new risk information and recommendations.
Once adopted, the DHPC for Veoza 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.
Agenda
PRAC statistics: December 2024
Glossary
- 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.
Ongoing referrals
| Procedure | Status | Update |
| Finasteride- and dutasteride-containing medicinal products - referral | Under evaluation | PRAC continued its assessment |