Pharmacological and Clinical Aspects of Drug Safety

The course covers the pharmacology of adverse reactions, molecular mechanisms of toxicity, drug metabolism, drug-drug interactions and pharmacogenomics, pharmacokinetic and pharmacodynamic (PK/PD) aspects and allergic reactions. Examples of the most frequent and/or important adverse reactions with their clinical manifestations in different organ systems are described (nervous system, skin, gastrointestinal, liver, kidneys, cardiovascular, pulmonary, endocrine and metabolism). Characteristics of special populations and patients with specific risk factors for adverse effects are also presented, including the safety of drugs in pregnancy and lactation, paediatric patients and older adults. The course also comprises classification of adverse events (diagnostic terminology), evaluation (causality assessment, severity and seriousness), and reporting. Furthermore, the requirements for information recorded in individual case safety reports (ICSRs), guidelines and timelines for submission to regulatory authorities. The role of the marketing authorisation holder and periodic drug safety update Reports (PSURs) are also covered. Additionally, the possibility of preventing adverse effects, including individualised treatment (personalised medicine).

Topics are:

• Pharmacological aspects of adverse reactions
  • Types of adverse reactions
  • Molecular mechanisms (drug-receptor interactions, specific organ toxicity)
  • PK/PD aspects, drug metabolism and excretion
  • Drug-drug interactions leading to adverse effects
  • Pharmacogenetics and risk of adverse effects
  • Dose-time-response – acute and chronic drug effects
  • Immunological aspects: allergic reactions, immunosuppression and -stimulation
• Patient-related and clinical aspects
  • Clinical manifestation of adverse drug reactions in different body systems
  • Special populations and risk factors
  • Pregnancy and breastfeeding
  • Pregnancy outcomes and congenital malformations
  • The paediatric and the elderly population
  • Chronic diseases, hepatic or renal impairment
  • Drug addiction and abuse
  • Medication errors
  • Individualised treatment (personal medicine).
• Individual case safety reports (ICSRs)
  • Definitions: Adverse events, adverse reactions, seriousness and severity
  • Overdose, abuse, misuse, medication error or occupational exposure, lack of effect
  • When to suspect, how to diagnose and when to report an adverse event
  • Requirements for the content of ICSRs
  • Causality assessment principles
  • Coding terminology (MEDDRA)
  • Sources of reports (healthcare professionals, patients)
  • Regulatory requirements and processes related to the submission of ICSRs 
  • International guidelines (GVP, ICH, FDA).
  • Reporting to regulatory authorities and the content of PSURs