A safety signal is information on a new or known adverse event that may be caused by a medicine and requires further investigation.
Safety signals can be detected from a wide range of sources, such as spontaneous reports, clinical studies and scientific literature.
Eudravigilance veterinary is an important source of information on suspected adverse reactions and signals with veterinary medicines in the European Union (EU).
Marketing authorisation holders must continuously monitor the data on their medicines in Eudravigilance veterinary and inform EMA and the national competent authorities of validated signals detected in the database.
Guidance for marketing authorisation holders is available in the module on signal management of the guidelines on the veterinary good pharmacovigilance practices (VGVP).
The legal basis is Article 81 of the Veterinary Medicinal Products Regulation (Regulation (EU) 2019/6).
Marketing authorisation holders should report the outcomes of their signal management activities on an annual basis.
The recommended due dates for submitting these annual statements via EMA's IRIS platform for all veterinary medicines is available below.
More information on submitting annual statements is available in the VGVP guideline module on signal management.
Marketing authorisation holders should use the template below to provide their assessment of all signals detected and validated in the Union Pharmacovigilance database (EudraVigilance Veterinary(EVV)) or from any other sources, including the MAH’s own database.
This includes:
The template has been revised in order to provide MAHs with detailed guidance on the information required for signal submissions and to ensure a consistent approach for all types of validated signals.
Some of the main changes implemented refer to the inclusion of a standardised overview of signals (e.g. in terms of the VeDDRA terms linked to the submitted signal, the type of signal: in initial or follow-up), a more comprehensive guidance on what information should be included in each section of the assessment report template, reference to mandatory dates for analysis, EVV queries and to the creation of standardised statements for the outcome of the assessment, available in the conclusion section.
The template should be filled in considering also the guidance provided in the current version of the Veterinary Union Pharmacovigilance Database - Best Practice Guide, which was also recently updated to include practical advice in relation to the signal management process and its management through the EMA digital systems IRIS and EudraVigilance Veterinary Data Warehouse.
EMA and national competent authorities in EU Member States may carry out targeted signal management procedure for a given veterinary medicine or a group of veterinary medicines.
They can start a targeted signal management procedure at any time. The legal basis is Article 81(3) of Regulation (EU) 2019/6.
EMA publishes information on targeted signal management procedures initiated by EMA or national competent authorities below.
| Procedure | Targeted Signal Management for VMPs with ATCvet code QN03AA02 (Phenobarbital) |
| Status | Closed |
| Procedure start date | April 2024 |
| Procedure end date | May 2026 |
| Outcome |
National competent authorities have identified an increase in adverse event reporting for veterinary medicinal products under ATCvet code QN03AA02 (phenobarbital). These include ‘Anticonvulsant Hypersensitivity Syndrome’ in dogs and cats, ‘Pancreatitis’ in dogs, ‘Elevated serum lipids’ in dogs and ‘Elevated liver enzymes’ in dogs. Based on the review of available data on the topics of the TSM and taking into account any comments provided by the PhVWP-V, members of the CMDv and the involved MAHs, the CMDv considered that the benefit-risk balance of medicinal products containing the active substance of phenobarbital remains unchanged but recommended that the terms of the marketing authorisations should be varied to adequately reflect the risks of pancreatitis, elevated serum lipids and elevated liver enzymes in dogs. Furthermore, other risk minimisation measures were recommended regarding the signal in the non-target species of cats. Recommendations: ‘Pancreatitis’ in dogs The PhVWP-V recommended including ‘Pancreatitis’ in the adverse events table in SPC section 3.6 in the frequency category “uncommon”, with a footnote under the table: “The risk of pancreatitis increases further with combined treatment with potassium bromide”. Furthermore, it is recommended to update section 3.8 to include the warning: “Interaction with other medicinal products and other forms of phenobarbital”; “Concurrent use with potassium bromide increases the risk of pancreatitis.” ‘Elevated serum lipids’ in dogs The PhVWP-V recommended inclusion of a specific recommendation in SPC section 3.5 to monitor serum lipids (including cholesterol and triglycerides) along with the other monitoring recommendations mentioned: “Elevated serum lipids may be seen with phenobarbital therapy in dogs. Since chronically elevated serum lipids have been linked to an increased risk of pancreatitis in dogs, serum lipids (including cholesterol and triglycerides) should be periodically monitored”. ‘Elevated liver enzymes’ in dogs The PhVWP-V recommended inclusion of ‘Elevated liver enzymes’ in the adverse events table in section 3.6 in the frequency category “common”, with a footnote stating: “May not necessarily be indicative of hepatic dysfunction. See also section 3.5.” Furthermore, it is recommended to update section 3.5 to include further information on elevated liver enzymes. ‘Anticonvulsant Hypersensitivity Syndrome’ in cats The PhVWP-V found that the evidence supports a likely causal association between anticonvulsant hypersensitivity syndrome in cats and treatment with phenobarbital. The adverse event is considered serious and preventable, and therefore it is recommended to inform prescribers about this risk, taking into consideration that the adverse event occurs in a non-target species following use outside the terms of the marketing authorisation. ‘Anticonvulsant hypersensitivity syndrome’ (AHS) in dogs The PhVWP-V requested that the MAHs keep AHS in dogs under close monitoring for all VMPs belonging to the ATCvet code for phenobarbital (QN03AA02). Please note that the national translation process for the recommended SPC changes is still ongoing. Once the translations have been finalised, they will be published below. |
| Summary assessment report | Targeted signal management (TSM) for Phenobarbital in cats and dogs |
| Procedure | Anaphylactic reactions in cattle following the use of injectable veterinary medicinal products |
| Status | Closed |
| Procedure start date | March 2023 |
| Procedure end date | December 2024 |
| Outcome |
Between 2020 and 2022, it was observed a notable increase of adverse event reports (AERs) in cattle involving anaphylactic reactions following the use of injectable veterinary medicinal products (pharmaceuticals and vaccines). Since 2023, the number of these reactions has decreased and appears to have stabilised in the EU. Based on the information evaluated to date, and following the implementation of mitigation measures (communication towards veterinarians and changes in manufacturing processes of the main vaccines involved), this targeted signal management procedure can now be closed. However, adverse events will continue to be closely monitored by all competent authorities and the marketing authorisation holders. Should the need arise, additional mitigation measures and communication activities can be considered in the future. |
| Advice for veterinarians | Veterinarians are reminded to continue reporting any observed side effects, including anaphylactic reactions. |
An update log is available to show the date and summary of changes to this webpage. It does not include updates to linked documents or minor edits like typos or broken link fixes.
The tracking of updates begins in September 2026.
4 September 2026