2022-02-22-世界卫生组织-2021_ACSoMP_recommendations_4页_150kb

Summary of the 18th Meeting of the WHO Advisory Committee on the Safety of Medical Products

Core Content

The 18th meeting of the WHO Advisory Committee on the Safety of Medical Products (ACSoMP) took place virtually from 26–28 October 2021 and was co-chaired by Dr June Raine (MHRA, UK) and Dr Gerald Dal Pan (USFDA, USA). The meeting focused on enhancing global pharmacovigilance and vaccine safety monitoring, addressing safety concerns of specific medicines during pregnancy and in pediatric populations, and improving the safety oversight of leprosy and visceral leishmaniasis treatments.

Main Recommendations

1. Integrated Approach to Pharmacovigilance and Vaccine Safety Monitoring

• The WHO restructured its medicines and health products division, merging former safety teams into a unified pharmacovigilance unit.
• This integration is expected to improve global coordination in monitoring the safety of medicines and vaccines.
• The Committee recommended using models like the Tspano study to assess the safety of medicines and vaccines during pregnancy.
• Pregnancy exposure registries and birth defect surveillance systems in low- and middle-income countries (LMICs) are encouraged to support safety assessments.

2. Dolutegravir and Neural Tube Defects (NTDs)

• Dolutegravir (DTG) is an effective antiretroviral drug, but concerns arose in 2018 due to a potential link with NTDs in Botswana.
• Subsequent studies showed a decline in the risk signal, and the Tspano study demonstrated a positive benefit-to-risk balance.
• ACSoMP recommended correcting the misconception about DTG to facilitate regimen harmonization and scale-up of ART programs.
• The Committee emphasized the need for continued monitoring and data collection on medicines used during pregnancy.

3. Sodium Valproate and Pregnancy

• Sodium valproate was added to the WHO Essential Medicines List with a cautionary note regarding its use in pregnant women and women of childbearing potential.
• The drug is associated with a high risk of birth defects and developmental disorders.
• Recommendations include:
  • Avoiding valproate in women of childbearing age unless absolutely necessary.
  • Ensuring newer, safer alternatives are more available in LMICs.
  • Revisiting the safety monitoring of medicines during pregnancy in future meetings.

4. Monitoring Safety of Leprosy Medicines

• Leprosy medicines, many of which are old, have limited data on adverse drug reactions.
• ACSoMP recommended:
  • Developing a pharmacovigilance package with a watch list of adverse reactions, management strategies, and prevention advice.
  • Conducting further studies on the effectiveness of thalidomide for erythema nodosum leprosum (ENL) and follow-up cohort studies.
  • Learning from tuberculosis programs on active surveillance and IT-based data sharing.
  • Strengthening pharmacovigilance in the Kala-azar elimination program.

5. Tuberculosis and Delamanid-Induced Hallucinations

• Delamanid is used for treating multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB) in children.
• A safety signal of hallucinations was identified, requiring further evaluation.
• Recommendations include:
  • Engaging a specialist in childhood psychology and sleep disorders to review the evidence.
  • Facilitating an in-depth investigation by the Uppsala Monitoring Centre and other experts.
  • Encouraging direct reporting of adverse events to VigiBase.

6. Visceral Leishmaniasis and Ocular Adverse Events with Miltefosine

• Miltefosine is the only oral treatment for visceral leishmaniasis (VL) and is included in WHO’s Essential Medicines List.
• Ocular adverse events have been reported in a small number of patients, especially in India.
• Recommendations include:
  • Implementing risk management strategies and improving early detection and management of ocular events.
  • Conducting eye examinations to determine the cause of the adverse events.
  • Studying the safety of miltefosine beyond 28 days of treatment.
  • Performing laboratory tests to investigate potential impurities and drug quantities.
  • Establishing a multistakeholder subgroup to better understand the issue.
  • Strengthening pharmacovigilance in the Kala-azar elimination program.

7. African Trypanosomiasis and Fexinidazole

• Fexinidazole was approved by the EMA for the treatment of HAT (sleeping sickness) in 2018.
• A post-authorization safety study (PASS) is ongoing, but data collection has been slow due to the rarity of the disease and delays in reporting.
• Adverse events, including two deaths (one from suicide), have been reported.
• Suicidal ideation has been added to the formal description of fexinidazole.
• ACSoMP recommended proactive data collection and making EMA safety data available for future review.

Conclusion

The meeting underscored the importance of a robust, integrated pharmacovigilance system to ensure the safety of medicines in special populations, including pregnant women and children. It also highlighted the need for better data collection, transparency, and stakeholder engagement in global health programs.