Pharmacovigilance

Pharmacovigilance

• Pharmacovigilance is the monitoring of medicinal products after authorization to ensure maximum safety and the best possible balance between benefits and risks
• Pharmacovigilance is a science and activities related to the detection, assessment, understanding, and prevention of adverse drug reactions (ADRs)
• The aim is to improve patient safety and contribute to public health protection

Historical Milestones

• Tragic crises like thalidomide tragedy in the 1960s were major drivers for change in pharmacovigilance
• Early pharmacovigilance initiatives, such as the WHO Programme for International Drug Monitoring, began in the 1960s
• The thalidomide tragedy led to increased awareness of the importance of monitoring drug safety
• Czechoslovakia was one of the first countries engaged in WHO's International Drug Monitoring Program

Adverse Drug Reactions (ADRs)

• ADR is a noxious and unintended response to a medicinal product, at doses used for prophylaxis, diagnosis or therapy of disease
• ADRs may occur within or outside the terms of the marketing authorization
• or from occupational exposure

Types of ADRs

• Serious ADRs: results in death, life-threatening, hospitalization, or prolongation of existing hospitalization, persistent or significant disability, or a birth defect
• Unexpected ADRs: nature or severity is not consistent with information in the summary of product characteristics (SmPC)

Types of Adverse Drug Reactions (classification)

• Augmented: dose-dependent, predictable (eg,anticoagulants → bleeding)
• Bizarre: hypersensitivity reactions (eg, penicillin → anaphylaxis)
• Chronic: cumulative (eg., amiodarone → pulmonary fibrosis)
• Delayed: (eg., teratogens: thalidomide, warfarin, lithium, valproate)
• End of Use: rebound phenomenon, withdrawal syndrome (eg., abrupt withdrawal of beta-blockers)
• Failure of Therapy: lack of effectiveness (eg., due to drug-interactions)
• Immediate: rapid titration (eg., ACEI → orthostatic hypotension)

Classification of ADRs by Frequency

• Very common: ≥ 1/10 patients
• Common: 1/100 to 1/10 patients
• Uncommon: 1/1000 to 1/100 patients
• Rare: 1/10 00 to 1/1000 patients
• Very rare: < 1/10 000 patients

Classification according to the organ system class

• Hematologic toxicity, hepatotoxicity, cardiac toxicity, nephrotoxicity & rhabdomyolysis

Stakeholders in Pharmacovigilance

• Health Care Providers (HCPs): report suspected serious or unexpected ADRs
• Marketing Authorization Holders (MAHs): collect, review, analyze information on suspected ADRs, and report to regulatory authorities
• Regulatory Authorities (e.g., EMA, FDA, SÚKL): manage ICSR databases, guidelines, inspections, benefit-risk assessment, and regulatory actions
• Patients and Patient Organisations: report directly to health authorities, and their views inform benefit-risk decision-making

Signal Detection

• Signal = information from multiple sources suggesting new causal associations between an intervention and an adverse event
• Signal detection involves gathering information from various sources and analyzing for potential relationships

Periodic Safety Update Reports (PSURs)

• MAHs provide comprehensive and critical analysis of the risk-benefit balance of a product.
• MAHs report this information to regulatory authorities

Regulatory Actions

• Withdrawal from the market: If risks outweigh benefits, the product may be removed.
• Risk Minimization Measures (RMMs): This is an intervention used to reduce the occurrence or severity of ADRs

Risk Minimization Measures

• Update of product summary and patient information leaflets (PIL)
• New drug warnings and contraindications
• Legal status changes (e.g., from OTC to prescription-only)
• Package changes to reduce risks (eg. maximum supply days)
• Communication; e.g., pregnancy prevention programs, medical education

Test your knowledge on pharmacovigilance, its historical milestones, and the significance of monitoring adverse drug reactions (ADRs). This quiz covers the evolution of safety practices in medication use and their impact on patient care and public health. Delve into the lessons learned from historical crises and current practices in drug safety monitoring.