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