LEC 5: PHARMACOVIGILANCE

1. General Introduction

Pharmacovigilance is a crucial activity within the healthcare system, focused on ensuring the safety of drug users. This activity centers around monitoring, evaluating, understanding, and preventing adverse drug reactions (ADRs) to enhance treatment efficacy and patient well-being.

2. Four Core Tasks of Pharmacovigilance:

• Detection (of adverse reactions): Identifying and recording adverse events related to drug use, encompassing both ADRs and non-ADR adverse events.
• Evaluation: Conducting necessary supplementary tests to determine the cause, severity, and association between the adverse event and the drug.
• Understanding: Establishing the impact and risk level of the adverse event through data analysis and research on ADR reports.
• Prevention: Preventing potential adverse events in patients by issuing drug usage recommendations, updating drug safety information, and adjusting treatment regimens accordingly.

3. Scope of Pharmacovigilance:

• Drug Safety Surveillance: Monitoring and evaluating the safety of all drug types, including pharmaceuticals, biologicals, herbal medicines, traditional medicines, vaccines, veterinary drugs, etc.
• Substandard Drugs: Detecting and addressing issues related to drug quality, such as counterfeit drugs, expired drugs, contaminated drugs, etc.
• Medication Errors: Identifying and rectifying errors that occur during drug prescription, dispensing, use, and management.
• Poisoning: Detecting and managing drug poisoning cases.
• Drug-Related Deaths: Investigating and analyzing deaths linked to drug use.
• Adverse Drug-Drug, Drug-Food Interactions, etc.: Monitoring and evaluating potential adverse interactions between drugs, food, alcohol, etc.

The scope of pharmacovigilance may vary depending on regulations in each country and regulatory authority.

4. Target of Pharmacovigilance:

• Drugs: All drugs used for disease prevention, diagnosis, treatment, and altering physiological functions of the body.
• Healthcare Products: Blood products, biological origin drugs, vaccines, traditional medicine, cosmetics, dietary supplements, herbal medicine, medical devices, etc.

Pharmacovigilance should focus on products with a high risk of causing ADRs.

5. Pharmacovigilance Process:

5.1. Activities:

• Detection: Collecting and processing information about adverse events related to drugs.
• Evaluation: Determining the cause, severity, and association between the adverse event and the drug.
• Research: Analyzing data, evaluating ADR reports, and conducting research to gain a deeper understanding of drug safety.
• Prevention: Providing information about drug safety, issuing drug usage recommendations, updating treatment regimens, and implementing ADR prevention measures.

5.2. Targets:

• Drugs: Information about drugs, including composition, dosage, side effects, interactions, etc.
• Drug Quality: Information about drug quality, including manufacturing process, quality control, storage, transportation, etc.
• Treatment Failure: Information about treatment failure, including causes, symptoms, etc.
• ADRs: Reports of adverse drug reactions, including information about the patient, drug, reaction, etc.
• MEs: Information about medication errors, including prescription errors, dispensing errors, usage errors, etc.

The pharmacovigilance process should be established and implemented scientifically, effectively, ensuring accuracy and timeliness.

6. Objectives of Pharmacovigilance:

• Safe and Rational Drug Use: Raising awareness about drug safety, encouraging the appropriate, effective, and safe use of drugs.
• Enhancing Treatment Efficacy and Quality for Patients: Minimizing adverse events, increasing treatment success rates, improving patient health and quality of life.

7. Issues Related to Drug Safety:

• Adverse Drug Reactions (ADRs): Adverse reactions that occur when using drugs at normal doses for disease prevention, diagnosis, treatment, and altering physiological functions of the body.
• Medication Errors (MEs): Errors that occur during drug prescription, dispensing, use, and management.
• Drug Quality: Issues related to drug quality, including counterfeit drugs, substandard drugs, expired drugs, contaminated drugs, etc.

These issues need to be addressed promptly and effectively to ensure drug user safety.

8. Subjects of Drug Safety Research:

• Pharmaceuticals: Drugs manufactured from chemical compounds.
• Vaccines: Drugs used to generate immunity in the body against diseases.
• Medical Devices for Direct Human Use: Medical devices used for diagnosis, treatment, disease prevention, or improving health.
• Traditional Chinese Medicine: Drugs manufactured from herbal remedies using traditional methods.
• Herbal Medicines: Drugs manufactured from herbal remedies using scientific methods.

Drug safety research should be conducted scientifically, comprehensively, and objectively.

9. Eight Tasks of the Pharmacovigilance System in Vietnam:

• Collecting and Managing Reports: Collecting, processing, and managing reports on ADRs, MEs, and other adverse events.
• Coordinating Activities Related to Report Collection: Collaborating with relevant agencies to improve ADR report collection efficiency.
• Promptly Detecting and Handling Signals: Detecting unusual drug safety signals and addressing them promptly.
• Providing Information about Adverse Events: Providing information about adverse events to relevant agencies, healthcare professionals, and the public.
• Detecting and Contributing to Reducing Errors in Prescription, Prescription Copy, Dispensing, and Drug Use: Identifying and rectifying drug-related errors to enhance drug safety.
• Assessing and Managing Risks: Assessing and managing risks associated with drug safety.
• Communication: Communicating drug safety information to the community, raising awareness about ADRs and the importance of reporting ADRs.
• Strengthening and Developing Drug Information Activities: Providing drug information to patients, healthcare professionals, and the community.

These tasks should be implemented effectively and synchronously to ensure drug user safety.

10. Concepts of Adverse Event, Adverse Drug Reaction (ADR), Serious Adverse Event (SAE):

• Adverse Event (AE): Any adverse event that occurs during drug use due to treatment, which may or may not be caused by the treatment regimen.
• Adverse Drug Reaction (ADR): Any harmful reaction that occurs at the usual dose administered to humans for disease prevention, diagnosis, treatment, or altering physiological functions of the body.
• Serious Adverse Event (SAE): Adverse events that lead to one of the following consequences:
  • Death, life-threatening, requiring hospitalization or prolonging hospital stay.
  • Leaving severe or permanent sequelae for the patient.
  • Fetal: congenital malformations.
  • Any adverse reaction deemed to have serious clinical consequences for the patient.

It’s crucial to distinguish between AE, ADR, and SAE to implement appropriate handling measures.

11. Causes of Adverse Events Differentiated from Side Effects:

Besides adverse drug reactions, other causes contribute to adverse events, including:

• Drug Misuse: Errors in prescription, dispensing, use, and drug management.
• Counterfeit Drugs, Substandard Drugs: Counterfeit drugs, substandard drugs, expired drugs, contaminated drugs, etc.

Thoroughly consider relevant factors to accurately determine the cause of adverse events.

12. Classifying ADRs by Severity:

• Mild: No treatment needed, no detoxification, no prolonged hospitalization.
• Moderate: Changes in treatment, requiring specific treatment or prolonged hospitalization for at least one day.
• Severe: Life-threatening, leaving long-term sequelae or requiring intensive care measures.
• Fatal: Directly or indirectly related to patient death.

Classifying ADRs by severity helps determine the severity level of the adverse reaction and guide appropriate handling measures.

13. Classifying ADRs by Onset Time:

• Onset time is calculated from the last drug administration to the first symptom appearance.
• Acute: 0-60 minutes.
• Subacute: 1-24 hours.
• Late: 1 day – several weeks.

Classifying ADRs by onset time helps identify the relationship between drug administration time and the appearance of adverse reactions.

14. Classifying ADRs by Body System:

• Central Nervous System
• Cardiovascular System
• Endocrine and Metabolic System
• Gastrointestinal and Hepatic System
• Renal and Urinary System
• Hematology
• Skin
• Musculoskeletal System
• Respiratory System
• Sense Organs and Sensory Organs

Classifying ADRs by body system helps identify the organs affected by the adverse reaction.

15. Classifying ADRs by Frequency of Occurrence:

• Very common: >=1/10
• Common: 1/10 to 1/100
• Uncommon: 1/100 to 1/1000
• Rare: 1/1000 to 1/10000
• Very rare: Less than 1/10000

Classifying ADRs by frequency of occurrence helps assess the prevalence of adverse reactions.

16. Classifying ADRs by Pharmacological Action:

• A:
  • Predictable.
  • Dose-dependent.
  • High incidence.
  • Low mortality.
  • Dosage adjustment.
• B:
  • Unpredictable pharmacological action.
  • Not dose-dependent.
  • Low incidence.
  • High mortality.
  • Treatment: Stop the drug.

Classifying ADRs by pharmacological action helps understand the mechanism of adverse reaction causation.

17. Classifying ADRs by Extended Pharmacological Properties:

• C: Occurs only during prolonged treatment, related to dose and duration.
• D: Appears after discontinuing treatment for a period.
• E: Related to abrupt drug discontinuation, depending on the mechanism and duration.
• F: Loss of drug efficacy, related to drug quality.
• G: Related to genetics.

Classifying ADRs by extended pharmacological properties helps identify factors related to the appearance of adverse reactions.

18. Consequences of Adverse Drug Reactions:

• Prolonged Hospital Stay
• Increased Costs
• Increased Patient Numbers
• Decreased Treatment Adherence
• Increased Mortality Rate
• Economic and health damage to workers.

The consequences of ADRs can have serious implications for the health and economy of individuals and society.

19. Related Terms:

• ADE (Adverse Drug Event): Adverse event related to drugs.
• ADR (Adverse Drug Reaction): Adverse drug reaction.
• ME (Medication Error): Medication error.

Understanding these terms helps ensure accurate communication in pharmacovigilance activities.

20. Preventable ADRs:

• Dosage errors
• Incorrect route of administration
• Incorrect drug administration intervals
• Incorrect drug form used
• Expired drugs
• Incorrect drug storage
• Usage errors
• Incorrect indication
• Prescribing not suitable for patient characteristics
• Prescribing not suitable for clinical conditions
• Drug or drug group allergy history
• Known drug interactions
• Treatment overlap
• Not using the necessary drugs
• ….

These factors can be controlled to minimize the risk of ADRs.

21. Drugs Commonly Associated with ADRs:

• Cardiovascular drugs
• Hypoglycemic drugs
• Anticoagulants
• Statins: Cholesterol-lowering drugs
• Drugs acting on the CNS
• Theophylline: Bronchodilator, treating airway obstruction

These drugs should be used cautiously and under the guidance of healthcare professionals.

22. ADR Reporting:

ADR reporting needs to clarify three characteristics:

• Serious / non-serious
• Related / unrelated to treatment
• Predictable / unpredictable

23. Types of ADR Reports:

• Voluntary Reporting: Reports made by healthcare professionals based on their experience.
• Intentional Voluntary Reporting: Reports made by healthcare professionals with a specific purpose, such as monitoring a new drug.
• Active Surveillance Reporting (Mandatory): Reports made as required by the regulatory authority.

Selecting the appropriate type of report ensures the accuracy and timeliness of ADR information.

24. How to Detect ADRs:

• Clearly describe the reaction: Medical history, drug administration time, event occurrence time, tests, food consumed during drug administration.
• Stop the drug and re-administer: Monitor the body’s response after stopping the drug and re-administering it.
• Review the drug’s pharmacological action: Check if the adverse reaction is consistent with the drug’s pharmacological action.

Early ADR detection helps facilitate prompt handling and minimize ADR harm.

25. ADR Report Writers:

• Physicians, dentists
• Pharmacists
• Nurses, midwives, technicians,…
• Any healthcare worker involved in drug use or a group of healthcare workers jointly participating in report writing.

Anyone involved in drug use has a responsibility to report ADRs.

26. Prioritize which cases in ADR reporting:

• Serious ADRs
• New ADRs not previously known and described
• ADRs with a high frequency for a drug batch
• ADRs of new drugs not yet used in treatment at the healthcare facility

These cases should be reported promptly to provide early warnings about ADR risks.

27. Can multiple patients be grouped together in one ADR report?

Each patient needs a separate report.

28. If a drug treating an ADR causes another ADR, is it unnecessary to separate the report?

False.

Separate reports are needed.

29. Is it correct to submit the report as soon as possible, even if it is incomplete?

True.

Additional information can be added if collected.

30. What is the deadline for submitting serious ADR reports causing injuries?

7 days.

31. What is the deadline for submitting ADR reports on other serious adverse reactions not causing death?

15 days.

32. When should non-serious adverse reactions be reported?

Collected and submitted monthly, before the 5th of the following month.

33. Notes on ADR Reporting:

• Classify ADRs, prioritize classification by pharmacological properties: A, B,… and by severity level.
• Format: Online or by letter.

Timely, accurate, and comprehensive ADR reporting helps enhance drug safety and protect patient health.

Conclusion:

Pharmacovigilance is a critical activity within the healthcare system, aimed at ensuring the safety of drug users. Monitoring, evaluating, understanding, and preventing adverse drug reactions play crucial roles in enhancing treatment efficacy and promoting patient health.