Asmaa Salah Abdelkhalek
Manager of pharmacovigilance postmarketing administration
Egyptian Drug Authority
Pharmacovigilance plays a crucial role in safeguarding public health by identifying and mitigating potential risks associated with medicinal products. Post-marketing real-world evidence generation often relies on cumulative global data, such as VigiBase, the WHO global database of adverse event reports for medicines and vaccines, to support the evaluation of a signal. Such was the case for Egypt’s safety assessment of vincristine, where swift action ensured patient safety after multiple cases were identified in the Egyptian pharmacovigilance database.
Detecting a potential signal
The Egyptian Drug Authority’s (EDA) pharmacovigilance signal management team first identified a potential safety signal for vincristine-associated necrotising soft tissue infections (NSTIs) through signal detection methods. Reports submitted to the national pharmacovigilance database VigiFlow highlighted cases of NSTIs, including necrotising fasciitis, in patients receiving vincristine as part of chemotherapy regimens.
Recognising the potential significance of these reports, the EDA signal management team conducted a thorough review of the global pharmacovigilance database, VigiBase, and used VigiLyze to assess the broader context of similar cases. The analysis identified 48 cases worldwide, with a statistically significant information component (IC025 = 3.1), confirming disproportionate reporting of this adverse event.
Investigating the risk of NSTIs with vincristine
Vincristine is an anti-tumour medication commonly used in polychemotherapy. NSTIs are life-threatening conditions characterised by rapid tissue destruction and severe morbidity. While vincristine labelling includes warnings about extravasation risks, its direct association with NSTIs had not been previously established in regulatory documents.
A deeper investigation of global data using Vigilyze revealed reported cases from published literature of eight documented cases, including five from an Egyptian national study linking NSTIs to vincristine and three cases from other countries, suggesting a possible link to extravasation during administration of vesicant chemotherapy products and immunocompromised states, further supporting the need for regulatory action.
The signal was evaluated collaboratively between the signal management trainee from Egypt and the signal management team at Uppsala Monitoring Centre during the face-to-face signal training in May 2023 and the results of this evaluation confirmed this signal. Given the severity of NSTIs and the emerging data from both national and global sources, the EPVC requested an urgent safety assessment from the Marketing Authorisation Holder (MAH) for the medicine. This resulted in strengthened safety communication to healthcare professionals, ensuring greater vigilance when administering vesicant chemotherapy products.
Key takeaways for global pharmacovigilance
- Early detection saves lives – Even a small number of well-documented national cases can provide a crucial early warning, preventing larger public health risks.
- Comprehensive data analysis is essential – Utilising global databases like VigiBase enhances the robustness of signal assessment, reinforcing local findings.
- Proactive regulatory engagement accelerates safety measures – Prompt collaboration with MAHs can lead to meaningful actions that improve patient outcomes.
- Face-to-face training added value – The face-to-face course in signal management provided by UMC builds confidence and trust in national safety signal management procedures, resulting in prompt regulatory actions.
A success story in patient safety
Egypt’s response to the potential signal of NSTIs with vesicant chemotherapy products highlights the strength of its pharmacovigilance alert system. The prompt identification and validation of the signal, followed by swift regulatory intervention, serves as a model for global pharmacovigilance efforts. As pharmacovigilance continues to evolve, proactive signal management remains a cornerstone in ensuring patient safety.
Disclaimer: Causal relationships between the event and a medicine or vaccine may be difficult to establish due to limitations in the data. The information and any results and conclusions drawn do not represent the opinions of Uppsala Monitoring Centre, the WHO Collaborating Centre for International Drug Monitoring, or the World Health Organization.