Pharmacovigilance Overview

Pharmacovigilance

• Pharmacovigilance is the science and activities related to the detection, assessment, understanding, and prevention of adverse drug reactions (ADRs).
• It involves continual monitoring of the safety and efficacy of pharmaceutical products, especially after authorization for use in the general population.
• The goal of pharmacovigilance is to identify, evaluate, and minimize risks associated with drug use, ensuring safe and effective medication use.

History of Pharmacovigilance

• Early Beginnings: Early physicians, like Hippocrates, recognized the importance of observing drug effects but lacked systematic methods for tracking adverse reactions. The 17th-18th centuries saw growing awareness of drug risks, albeit with rudimentary safety concepts.
• Early 20th Century: The 1900s saw physicians begin documenting adverse drug reactions (ADRs), particularly as new drugs like morphine and aspirin were introduced.
• 1930s - Thalidomide Disaster: Thalidomide, marketed as a safe sedative in the 1950s and 60s, caused widespread birth defects. This tragedy was a critical catalyst in the development of modern pharmacovigilance, prompting regulatory reforms and the establishment of formal systems for monitoring drug safety
• 1960s - WHO and International Cooperation: In response to the thalidomide disaster, the World Health Organization (WHO) played a key role in advancing pharmacovigilance. The International Drug Monitoring Program was established in 1968 to facilitate global data collection and analysis of adverse drug reactions.
• 1962 - US Drug Amendments: The Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act were passed in the US, requiring manufacturers to provide evidence of drug safety and efficacy before approval. These led to the creation of adverse drug reaction reporting systems, increasing post-market surveillance.
• 1980s-90s: National pharmacovigilance systems expanded, with the Uppsala Monitoring Centre coordinating global efforts. Yellow Card Scheme (UK) and MedWatch (US) systems became prominent for ADR reporting.
• 2000s-Present: Technological advances, including AI and big data, improved ADR detection. International Council of Harmonisation (ICH) pharmacovigilance guidelines standardized practices across countries, and patient involvement in ADR reporting increased.

Key Objectives of Pharmacovigilance

• Identify and assess adverse drug reactions (ADRs).
• Improve patient care and safety through timely ADR identification.
• Ensure continual monitoring of drug safety after market approval.
• Aid regulatory decision-making regarding product safety, labeling, and use recommendations.
• Promote rational drug use by informing healthcare professionals and the public about potential medication risks.

Pharmacovigilance Activities

• Collect and manage data on the safety of medicines.
• Analyze data to detect "signals" (new or changing safety issues).
• Make decisions regarding safety issues based on data.
• Implement proactive risk management to minimize potential risks.
• Protect public health through appropriate regulatory action.
• Communicate with stakeholders, including the public.
• Regularly audit outcomes and key processes involved.

Those Involved in Pharmacovigilance

• Patients (users of medication)
• Doctors, pharmacists, nurses, and other healthcare professionals
• Regulatory authorities (WHO, FDA, EMA, national authorities)
• EMA's Pharmacovigilance Risk Assessment Committee (PRAC)
• Pharmaceutical companies and companies importing/distributing medicines

Role of Pharmacists in Pharmacovigilance

• Monitor adverse drug reactions (ADRs).
• Encourage reporting of adverse events.
• Educate patients about medication risks and benefits.
• Conduct medication therapy management (MTM) to prevent and manage ADRs.

Challenges in Pharmacovigilance

• Underreporting of adverse drug reactions (ADRs).
• Inaccurate or incomplete ADR reports.
• Limitations in post-market surveillance, due to less control over how drugs are used in the real world.
• Variations in infrastructure and practices between countries.

What is an Adverse Drug Reaction (ADR)?

• An undesired or harmful response to a medication.
• Occurring at the doses used in disease prevention, diagnosis, or treatment.
• Often occurring after administration, even with correct prescription.
• The goal of monitoring ADRs is to detect and assess potential risks of medication use, especially once a medicine is on the market.

Importance of Reporting ADRs

• Detect new, unexpected ADRs.
• Assess severity, frequency, and causes of ADRs to determine actions like product recalls, label changes, or restrictions.
• Protect public health by refining drug usage recommendations and safety measures.

Challenges in ADR Reporting

• Under-reporting due to lack of awareness, time constraints, or skepticism about the significance of certain reactions.
• Incomplete or inaccurate reporting which hinders analysis of ADR data.
• Reporting burdens on healthcare professionals that can lead to inconsistent data submissions.

Key Characteristics of ADRs

• Harmful effects ranging from mild (headaches, nausea) to severe (anaphylaxis, liver failure).
• Some ADRs are dose-dependent (occur more frequently with higher doses), but others are dose-independent (can occur at any normal dose).

Types of ADRs

• Type A (Augmented): Predictable, dose-related reactions (e.g., sedation with antihistamines).
• Type B (Bizarre): Unpredictable, not dose-related (e.g., allergic reactions, idiosyncratic reactions).
• Type C (Chronic): Related to long-term drug use (e.g., kidney damage).
• Type D (Delayed): Appearing after prolonged use or a latency period (e.g., cancer).
• Type E (End-of-treatment): Occurring after medication is discontinued (e.g., withdrawal syndrome).
• Type F (Failure): Occurs when the drug fails to achieve the desired therapeutic effect (e.g., antibiotic resistance).

Causes of ADRs

• Pharmacological effects (direct, predictable drug effects on the body)
• Idiosyncratic reactions (rare, unpredictable reactions, often linked to genetics or immune system)
• Allergic reactions (hypersensitive reactions where the immune system treats the medication as harmful)
• Drug interactions (ADRs caused by combined effects of two or more medications)
• Patient factors (age, gender, genetics, existing conditions, and liver, kidney function that influence response to medications.)

Severity of ADRs

• Mild: Self-limited reactions (e.g., mild rash, drowsiness).
• Moderate: Requires medical intervention, typically not life-threatening (e.g., nausea, dizziness).
• Severe: Potentially life-threatening, requiring hospitalization or leading to permanent damage (e.g., anaphylaxis).

Reporting and Monitoring of ADRs

• Pharmacovigilance systems are in place to monitor ADRs globally:
• Reporting ADRs detects new, unexpected reactions.
• Common reporting systems (FDA's MedWatch, Yellow Card Scheme, VigiBase).
• Risk management for ADRs includes dose adjustments, medication changes, patient education, and discontinuation of problematic medications.
• Pharmacovigilance aims to understand the benefits and risks of medications.

Key Stakeholders in ADR Reporting

• Healthcare Providers (Doctors, Pharmacists, Nurses): First to notice ADRs during patient care.
• Patients: Can report ADRs directly through websites, apps, or toll-free numbers.
• Pharmaceutical Companies: Required to report ADRs from their products, especially if the reaction significantly affects public health.

Monitoring and Reporting Medication Errors

• What are Medication Errors? Preventable events leading to inappropriate medication use or patient harm.
• Key Elements: Prescribing, Dispensing, Administration. Errors can occur at any stage:
  • Prescribing: Incorrect drug, dose, or route.
  • Dispensing: Mislabeling or wrong medication.
  • Administration: Wrong time or patient.

Types of Medication Errors

• Prescribing Errors: Inappropriate drug selection, dose, or route based on patient's condition. (e.g., wrong beta-blocker).
• Dispensing Errors: Errors during preparation and provision of medication; look-alike or sound-alike drugs. (e.g., Lasix vs. Losec).
• Administration Errors: Mistakes in the direct administration of medication to a patient (e.g., wrong injection site).
• Monitoring Errors: Failure to monitor medication effects properly, leading to undetected adverse effects or failure of treatment (e.g., neglecting to check potassium levels in a digoxin patient).

Consequences of Medication Errors

• Patient Impact: Adverse drug reactions, prolonged illness, or death.
• Healthcare Provider Impact: Guilt, legal consequences, and loss of trust from patients and colleagues.
• Healthcare System Impact: Increased healthcare costs due to prolonged hospital stays and additional treatments.

Importance of Monitoring Medication Errors

• Error Identification: Helps detect patterns in errors.
• Preventive Measures: Enables practitioners to implement measures to prevent future errors.
• Enhancing Patient Trust: Demonstrates that the system actively identifies and corrects errors and builds trust.

Reporting Medication Errors

• Reporting errors promotes transparency, accountability, and learning within the healthcare system.
• Follow institutional protocols such as incident report forms.
• Use standardized reporting systems like NCCMERP or FDA MedWatch.
• Include clear descriptions, patient details, drugs involved, circumstances, and outcomes of the incident (e.g., wrong dose).

Drug Incompatibilities

• Drug incompatibility refers to physical, chemical, or therapeutic reactions between drugs that make them unsuitable for use.
• Key Types: Physical incompatibility, chemical incompatibility, therapeutic incompatibility

Understanding Drug Incompatibilities

• Prevent therapeutic failure: Ensures intended effects are achieved
• Avoid adverse effects or toxicity: Prevents dangerous outcomes.
• Ensure drug stability and safety: Ensuring medications remain safe and effective for patients

Defining Drug Incompatibilities

• Physical Incompatibility: Drugs physically altering each other affecting appearance, solubility or viscosity when mixed. (e.g., precipitation, cloudiness or separation).

  • Precipitation: Forms insoluble solids, happens when incompatible solutions are mixed.
  • Adsorption/Absorption: Drugs sticking to containers or tubing reducing the drug's dosage, common with insulin.

• Chemical Incompatibility: Changes in the chemical properties of drugs that cause the loss of potency or formation of harmful substances (oxidation, hydrolysis, reduction, pH-dependence).

  • Oxidation: Drugs lose electrons causing degradation (e.g., oxidation of Vit. C)
  • Hydrolysis: Breakdown of chemicals in the presence of water (e.g., breakdown of aspirin).
  • pH Dependence: Drug stability is affected by changes in the pH of its environment (e.g., amphotericin is unstable in acidic solutions).

• Therapeutic Incompatibility: Combination of drugs that leads to undesired therapeutic effects such as additive (intensified), antagonistic (reduced) or synergistic effects (unusually enhanced).

  • Additive: Combined effects of similar drugs (e.g., aspirin and clopidogrel both inhibit platelets, increasing risk of bleeding).
  • Antagonistic: Opposing effects reducing efficacy (e.g., naloxone reversing opioid effects).
  • Synergistic: Enhanced effect when combined (e.g., Raltegravir and Tenofovir enhance HIV treatment).

Drug-Food Interactions

• Food can delay, enhance, or interfere with the effects of certain drugs. (e.g., High fat meals increasing absorption).

Clinical Implications and Risk Factors

• Risk Factors: Polypharmacy, Age, Chronic diseases, Genetic factors.
• Prevention: Review medication history and use drug interaction checkers.

Pharmacist's Role in Drug Interaction Management

• Identify and assess drug interactions using databases and clinical knowledge.
• Collaborate with healthcare providers to discuss potential interactions.
• Educate patients about risks of interactions and advise on proper drug use.
• Monitor patient response and adjust treatments as needed to ensure safety.

Case Studies (Specific Examples)

• Warfarin and Amoxicillin: Interaction alters warfarin metabolism increasing likelihood of bleeding.
• Hydrochlorothiazide (diuretic) and Lithium: Interaction increases lithium's blood level resulting in toxicity.

Conclusion

• Pharmacovigilance is critical in safeguarding patient safety.
• It involves reporting both adverse reactions and medication errors to optimize outcomes.
• Effective management of medication involves identifying, assessing, and mitigating risks to ensure safe and effective treatment.
• Collaboration among healthcare providers, regulatory agencies, and patients is vital for the effective delivery of medications.