Pharmacovigilance for Herbal and Traditional Medicines: Advances, Challenges and International Perspectives

Prologue
Preface
Acknowledgement
Contents
Contributors
Part I: Advances and Challenges in Pharmacovigilance for Herbal Medicines
Chapter 1: The Historical Development of Pharmacovigilance for Herbal Medicines
1.1 Introduction
1.2 Early Texts
1.3 Awareness of Adverse Effects of Medicines and Resulting Adverse Reactions
1.4 Systematic Approaches to Gathering Reports of Adverse Drug Effects and Reactions
1.4.1 Louis Lewin
1.4.2 Secret Remedies
1.4.3 The US Federal Food, Drug, and Cosmetic Act, 1938
1.4.4 Meyler’s Side Effects of Drugs
1.4.5 The UK Medicines Act, 1968
1.5 Conclusions
References
Chapter 2: Prevalence of Use of Herbal and Traditional Medicines
2.1 Herbal and Traditional Medicines: Descriptions and Characteristics
2.2 Regulation of Herbal and Traditional Medicines
2.3 Global Use of Herbal and Traditional Medicines
2.4 Issues Relating to the Use of Herbal and Traditional Medicines
References
Chapter 3: Pyrrolizidine Alkaloids in Herbal Medicines and Food: A Public Health Issue
3.1 Pyrrolizidine Alkaloids and Their Occurrence in Herbal Medicines
3.2 Plant Species Containing Pyrrolizidine Alkaloids
3.3 Chemistry of Pyrrolizidine Alkaloids
3.4 Pyrrolizidine Alkaloid Toxicity
3.5 Quality Control Methods Used to Detect PAs in Herbal Materials
3.5.1 Botanical Identification
3.5.2 DNA Methods of Detecting PA-Containing herbs
3.5.3 Chemical Tests and Assays
3.6 Pharmacovigilance for Pyrrolizidine Alkaloid Toxicity
References
Chapter 4: Pharmacovigilance for Herbal and Traditional Medicine-Induced Liver Injury
4.1 Introduction
4.2 An Epidemiological Overview of Herbal and Traditional Medicines (HTMs) and Drug-Induced Liver Injury (DILI)
4.2.1 Description and Epidemiology of HTM DILI
4.2.2 Proportions of HTM DILI in All-Cause DILI
4.3 Species Implicated in HTM DILI
4.4 Main Risk Factors for HTM DILI
4.4.1 Risk Factors Related to Herbs and Drugs Combination
4.4.2 Risk Factors Related to Quality Problems
4.4.3 Risk Factors Related to HTM Product Use
4.5 Mechanisms of HTM DILI
References
Chapter 5: Herb-Drug Interactions: Fundamental Mechanisms, Prevalence and Challenges in Their Identification
5.1 General Introduction
5.2 Origin and Evolution of Awareness and Research on HDI
5.3 Fundamental Mechanisms of Herb-Drug Interaction and Potential HDI
5.3.1 Overview
5.3.2 Absorption
5.3.3 Drug Metabolism
5.3.3.1 Phase I Metabolism (Cytochrome P450)
Induction of Drug-Metabolising Enzymes
Inhibition of Drug-Metabolising Enzymes
5.3.3.2 Phase II Metabolism (Conjugation Reactions)
5.3.4 Distribution and Plasma Concentrations
5.3.5 Excretion
5.4 Clinically Relevant Interactions
5.5 Prevalence of Herb-Drug Interactions
5.6 Sources for information on Herb-Drug Interactions
5.7 Challenges and Solutions
5.8 Conclusions
References
Chapter 6: Safety and Pharmacovigilance of Herbal Medicines in Pregnancy
6.1 Safety and Pharmacovigilance of Herbal Medicines in Pregnancy
6.1.1 Therapeutic Drug Use in Pregnancy
6.1.2 Herbal Medicine Use in Pregnancy
6.1.3 Prevalence of Use of Herbal Medicines in Pregnancy
6.2 Safety Concerns Associated with Use of Herbal Medicines During Pregnancy
6.2.1 Adulteration and Contamination of Herbal Medicines
6.2.2 Herbal Medicine Interactions with Conventional Medicines
6.2.3 Issues Relating to Formulations, Routes of Exposure, Dose, and Dosage
6.2.4 The Availability of Information on the Use of Herbal Medicines in Pregnancy
6.3 Herbal Medicines Commonly Used to Treat Pregnancy-Related Conditions
6.3.1 Ginger Root (Zingiber officinale Roscoe)
6.3.2 Chamomile (Chamaemelum nobile (L.) All)
6.3.3 Cranberry (Vaccinium macrocarpon Aiton)
6.3.4 Echinacea (Echinacea spp.: E. angustifolia DC., E. pallida (Nutt.) Nutt., E. purpurea (L.) Moench)
6.3.5 Other Herbs with Known Adverse Effects in Pregnancy
6.4 Safety Monitoring Systems for Medicines Used in Pregnancy
6.4.1 Reporting of Adverse Reactions Associated with Herbal Medicine Use in Pregnancy
6.4.2 Safety Monitoring Systems for the Collection of Herbal Medicine Exposure Data in Pregnancy
6.5 Conclusions
References
Chapter 7: Advances in Methods and Techniques in Pharmacovigilance for Herbal and Traditional Medicines and Other Natural Health Products
7.1 Introduction
7.1.1 The Need for Pharmacovigilance for Herbal Medicines
7.1.2 Advocacy and Drivers for Change in Pharmacovigilance for Herbal Medicines
7.1.2.1 Regulatory Pharmacovigilance for Herbal Medicines as a Driver for Change
7.1.2.2 Traditional-Medicine/Natural-Health Practitioner-Focused Drivers for Change
7.2 Passive Surveillance in Pharmacovigilance for Herbal Medicines
7.2.1 Developments in Spontaneous Reporting for Herbal Medicines
7.2.1.1 Direct Patient Reporting of ADRs Associated with Herbal and Traditional Medicines
7.2.1.2 Promotional Campaigns for Spontaneous Reporting Schemes
7.2.1.3 Modified Spontaneous Reporting Forms
7.2.1.4 Bespoke Spontaneous Reporting Schemes for Herbal Medicines
7.2.2 Numbers of Spontaneous Reports of Suspected ADRs Associated with Herbal Medicines
7.2.3 Challenges in Spontaneous Reporting for Herbal and Traditional Medicines
7.2.4 Published Reports of Suspected ADRs Associated with Herbal Medicines
7.3 Active Surveillance Methods in Pharmacovigilance for Herbal Medicines
7.3.1 Active Surveillance Studies Involving Herbal and Traditional Medicines and Other Natural Health Products
7.3.2 Intensive Monitoring Methods Involving Herbal and Traditional Medicines and Other Natural Health Products
7.3.3 Registries
7.4 ‘Real-World’ Health Data
7.4.1 Electronic Medical/Health Record Data
7.4.2 Patient Experience Data
7.4.2.1 Mobile Applications and Social Media
7.5 Traditional Observational Study Designs
7.6 Randomised Clinical Trials
7.7 Signal Detection in Pharmacovigilance for Herbal Medicines
7.7.1 Application of Statistical Methods for Signal Detection in Pharmacovigilance for Herbal Medicines
7.7.2 Challenges in Statistical Methods of Signal Detection for Herbal Medicines
7.8 Conclusion
References
Chapter 8: Botanical Nomenclature for Herbal Medicines and Natural Products: Its Significance for Pharmacovigilance
8.1 Introduction
8.1.1 Names and Identity
8.1.2 Plants, Ingredients, Drugs and Names
8.2 The Need for Scientific Names
8.2.1 Common Names and Their Limitations
8.2.2 Pharmacopoeia Names: A Poor Remedy
8.2.3 Scientific Names and Why They Should Be Used
8.2.4 Structure of Scientific Names
8.2.4.1 Genera, Subspecies and Varieties
8.2.4.2 Autonyms
8.2.5 Nomenclature Versus Taxonomy
8.2.6 Taxonomic Reference Sources of Relevance to Pharmacovigilance
8.3 Challenges Inherent in Using Scientific Names
8.3.1 Too Many Scientific Names
8.3.1.1 Why Do Synonyms Occur?
8.3.1.2 Accepted Names: Establishing Taxonomic Position
8.3.1.3 Issues with Multiple Synonyms
8.3.2 Homonyms
8.3.3 Names Keep Changing
8.3.4 Conflicting and Out-of-Date Reference Sources
8.3.5 Cultivars, Landraces and Chemical Variants
8.3.6 Misapplied Names
8.4 Consequences of Misusing or Not Using Scientific Names
8.4.1 Imprecision in the Scientific Literature
8.4.2 A Failure to Protect Traditional Knowledge
8.4.3 Ambiguity in Monographs and Pharmacopoeias
8.4.4 Difficulties Recording and Utilising Adverse Reaction Reports
8.5 Solutions
8.5.1 The MPNS Data Resource
8.5.2 Using the MPNS Portal
8.5.3 MPNS Network and Services
8.5.4 IDMP: A New Drug Standard
8.6 What Does Best Practice Look Like?
8.6.1 Documenting Identity
8.6.2 Using Scientific Names to Communicate and Publish Effectively
8.6.3 Locating Publications and Data
8.6.4 Interpretation of the Literature
8.6.5 Creating and Interpreting Adverse Reaction Reports Involving Herbal Substances
8.7 Conclusion
References
Chapter 9: Coding Reports Involving Herbal Medicines in a Pharmacovigilance Database
9.1 Background
9.2 Challenges in Coding and Classifying Herbal Medicinal Products
9.3 Current Approaches in Coding and Classification
9.3.1 Botanical Nomenclature
9.3.2 The Herbal Anatomical Therapeutic Chemical (ATC) Classification System
9.3.3 Other Coding Methods
9.4 Solutions Towards Better Coding
9.4.1 Coding Options
9.5 Final Considerations
References
Chapter 10: Causality Assessment in Pharmacovigilance for Herbal Medicines
10.1 Introduction
10.2 Definitions
10.2.1 Herbal Medicines
10.2.2 Traditional Herbal Medicines
10.3 Principles of Causality Assessment
10.3.1 Herbal Product Identification, Quality and Usage Modalities
10.3.2 Temporal Association
10.3.3 Confounding Variables
10.3.4 Systematic Causality Evaluation
10.4 Causality Assessment Methods
10.4.1 Global Introspection Approaches
10.4.1.1 Ad hoc Approach
10.4.1.2 WHO Method for Standardized Case Causality Assessment
10.4.1.3 DILIN Method
10.4.2 Standardized Algorithm Approaches
10.4.2.1 Naranjo Scale
10.4.2.2 RUCAM
10.4.2.3 MV Scale
10.4.2.4 TTK Scale
10.4.3 Probabilistic Approach Derived from Bayes’ Theorem
10.5 Diagnostic Biomarkers
10.6 Herb-Herb and Herb-Drug Interactions
10.7 Herbal Pharmacovigilance Challenges and Future Perspectives
10.8 Conclusions
References
Chapter 11: The Value of Complementary Approaches to Causality Assessment for Individual Case Safety Reports: The Example of Artemisia annua and Hepatotoxicity
11.1 Introduction
11.2 Causality Assessment for Individual Case Safety Reports
11.3 Causality Assessment for Case Series
11.4 Focused Causality Assessment Methods
11.5 Artemisia annua L. and Liver Injury: Linking Methodologies for Causality Assessment
11.6 Conclusion
References
Chapter 12: Development of a Natural Health Product Active Surveillance Method in Outpatient Centers in Canada
12.1 Background
12.2 Development of the Study of Natural Health Product Adverse Reactions (SONAR) Method
12.2.1 Active Surveillance
12.2.2 Causality Assessment and Laboratory Analysis
12.3 Community Pharmacy SONAR Results
12.4 Specialty SONAR
12.4.1 Mental Health
12.4.2 Oncology
12.4.3 Evolution of SONAR
12.5 Future Directions
References
Chapter 13: Ethnopharmacovigilance and Traditional Medicines
13.1 Ethnopharmacovigilance: Concepts and Methods
13.2 Ethnopharmacovigilance in Published Literature: An Overview
References
Chapter 14: Pharmacovigilance for Herbal Medicines: A Perspective from the Herbal Medicines Industry
14.1 Introduction
14.2 Under-Reporting of Adverse Reactions Associated with Herbal Medicines
14.3 The Need for Pharmacovigilance for Herbal Medicines
14.4 Regulatory Obligations for Pharmacovigilance in the Herbal Medicines Industry
14.5 Challenges for the Herbal Medicines Industry
14.6 The Future
14.7 Conclusion
References
Chapter 15: Pharmacovigilance and Risk Communication for the Safe Use of Herbal and Traditional Medicines: How to Promote Evidence and Keep People Safe
15.1 Background
15.2 The Radical Problems of Risk Communication in all Aspects of Traditional and Modern Medicine
15.3 Challenges of Risk Communication in Adverse Effect Reporting
15.4 Communicating Herbal Medicine Safety Concerns
15.5 Multiple Conditions for Herbal Medicine Use
15.6 Professional Collaboration and Education
15.7 Obstacles and Solutions in Risk Communication for Herbal Medicines
15.8 Product Labelling and Safety Information
15.9 Phytovigilance in the Age of Covid-19 (SARS-CoV-2)
15.10 Conclusion
References
Part II: International Perspectives in Pharmacovigilance for Herbal Medicines
Chapter 16: Reports for Herbal Medicines in the Global Suspected ADR Database VigiBase
16.1 Background
16.2 Reports Involving Herbal Medicines
16.3 Considerations
References
Chapter 17: The Italian Phytovigilance Spontaneous Reporting Scheme
17.1 Introduction
17.2 Safety Issues Identified Through the Phytovigilance System
17.3 Conclusion
References
Chapter 18: Pharmacovigilance for Herbal and Traditional Medicines in Bosnia and Herzegovina
18.1 Pharmacovigilance in Bosnia and Herzegovina
18.2 Herbal and Traditional Medicines in Bosnia and Herzegovina
18.3 Pharmacovigilance for Herbal and Traditional Medicines in Bosnia and Herzegovina
18.4 Future Perspectives
References
Chapter 19: Pharmacovigilance for Herbal Products: A Canadian Perspective
19.1 Introduction
19.2 Regulation of NHPs in Canada
19.3 Pharmacovigilance for NHPs in Canada
19.4 Spontaneous Adverse Reaction Reports Associated with NHPs in Canada
19.5 Challenges in Signal Evaluation for NHPs
19.6 Risk Management Strategies
19.7 Risk Communication Strategies
19.8 Collaborative Efforts
19.9 Future Perspectives and Challenges
References
Chapter 20: Pharmacovigilance of Cannabis Products for Medical and Non-medical Purposes
20.1 Legal Status of Cannabis
20.2 Canadian Legislative and Regulatory Framework for Cannabis Products
20.2.1 A Public Health Approach to Cannabis Legalization
20.2.2 Cannabis Regulations
20.2.3 Adverse Reaction Reporting Requirements
20.3 Vigilance Framework for Cannabis Products
20.4 Pharmacovigilance Databases for Cannabis Products
20.5 Sources of Adverse Reactions with Cannabis Products
20.6 Signal Management Process with Cannabis Products
20.7 Challenges in the Vigilance of Cannabis Products
20.7.1 Limited Evidence on Cannabis Products
20.7.2 Variability of Cannabis Products
20.7.3 International Nomenclature
20.8 Conclusion
References
Chapter 21: Pharmacovigilance for Herbal Medicines in Brazil
21.1 Introduction
21.2 Herbal Medicinal Products Regulatory Framework
21.2.1 Marketing Authorization
21.2.2 Manufacturing and Compounding
21.3 Pharmacovigilance
21.3.1 Work Processes
21.3.2 Regulatory Frameworks
21.3.2.1 Resolution-RDC No. 36/2013
21.3.2.2 Resolution-RDC No. 406/2020 and Normative Instruction N° 63/2020
21.3.2.3 Ordinance GM/MS N° 1660/2009
21.3.3 Pharmacovigilance for Herbal Medicinal Products
21.4 Final Considerations
References
Chapter 22: Pharmacovigilance for Indian Traditional Medicines
22.1 Introduction
22.2 AYUSH Medicines Regulation
22.3 Pharmacovigilance System for Ayurveda, Siddha, Unani and Homoeopathy (ASU&H) Medicines
22.4 Structural Framework of NPP-ASU&H
22.5 ADR Reporting Criteria
22.6 Implementation and Monitoring of NPP-ASU&H
22.7 Assessment of Adverse Events Associated with ASU&H Medicines
22.8 Overview of Spontaneous Reports with Respect to ASU&H Medicines
22.9 Challenges in Pharmacovigilance for ASU&H Medicines in India
References
Chapter 23: Pharmacovigilance for Traditional Chinese Medicinal Drugs in China
23.1 Introduction
23.2 Regulatory Oversight and Management for TCMDs in China
23.2.1 Introduction of Updated Regulations on Pharmacovigilance Under the New Regulatory Situation
23.2.2 Regulations on Safety Surveillance Throughout the Whole Product Life Cycle for TCMDs
23.2.2.1 Chinese Patent Medicines (CPMs)
23.2.2.2 Prepared Slices of Chinese Crude Drugs (PSCCDs)
23.3 Current Status of Pharmacovigilance for TCMDs
23.3.1 Signal Detection for TCMDs Safety Concerns from NADRMS
23.3.2 China ADR Sentinel Surveillance Alliance (CASSA) and CHPS
23.4 Challenges and Strategies in Safety Monitoring for TCMDs
23.4.1 Establishing Post-marketing Surveillance Models for TCMDs Led by Detecting Important Signals from NADRMS, and Widening the Channels for Collecting ICSRs
23.4.2 Establishing Post-marketing Surveillance Approaches in Accordance with the Characteristics of TCMDs
23.4.3 Strengthening Surveillance of PSCCDs, and Healthcare Products Containing PSCCDs Approved by NMPA
23.4.4 Implementing Responsibilities for MAHs in the Whole Product Life Cycle for Benefit-Harm Assessment of TCMDs
References
Chapter 24: Pharmacovigilance for Herbal and Traditional Medicines in Japan
24.1 Types of Herbal Products in Japan
24.1.1 Traditional Medicines Commonly Known as Kampo
24.1.2 Non-Kampo Herbal Medicines
24.1.3 Herbal Products as Health Foods or Unlicensed Medicines
24.2 Current Regulatory Framework for Herbal Products
24.3 The Practice and Use of Herbal Medicine in Japan
24.4 Safety Issues Associated with Herbal Products in Japan
24.5 Safety Monitoring of Adverse Events Associated with Herbal Products in Japan
24.5.1 Spontaneous Adverse Events Monitoring Scheme
24.5.2 Reporting Suspected Adverse Reactions Associated with Health Foods and Unlicensed Medicines
24.6 Safety Information for Herbal Products in Japan
24.7 Future Perspectives and Challenges
References
Chapter 25: Pharmacovigilance for Herbal Medicines in Iraq
25.1 Introduction
25.2 Epidemiology of Herbal Medicines in Iraq
25.3 Regulation of Herbal and Traditional Medicines
25.3.1 Unit One: Regulatory System for Crude Herbal Drugs
25.3.2 Unit Two: Regulatory System for Manufactured Natural and Botanical Medicines
25.4 Pharmacovigilance for Herbal Medicines
25.5 Reporting Scenario and Reports Handling
25.6 Signal Management for Herbal Medicines
25.7 Awareness of Herbal Medicines Reporting
References
Chapter 26: Pharmacovigilance for Herbal and Traditional Medicines in the Sultanate of Oman
26.1 Introduction
26.2 Regulatory Framework for Herbal Medicines in Oman
26.3 Pharmacovigilance for Herbal Medicines
26.3.1 Safety/Risk Communication Strategies for Herbal Medicines and Other “Natural Health” Products
26.3.2 International Collaboration in Pharmacovigilance for Herbal Medicines
References
Chapter 27: Pharmacovigilance for Herbal Medicines in Sudan
27.1 Introduction
27.2 Adverse Reactions Associated with Sudanese Herbal and Traditional Medicines
27.3 Regulation of Herbal and Traditional Medicines in Sudan
27.4 Pharmacovigilance for Herbal and Traditional Medicines in Sudan
27.5 Conclusion
References
Epilogue