Adverse Drug Reactions (ADRs) PDF

ADVERSE DRUG REACTIONS Sandra Knowles, BScPhm Sunnybrook Health Sciences Centre  ADVERSE DRUG REACTIONS What are ADRs? Terminology Classification of ADRs Approach to patients with ADRs Causality assessment  Adverse Drug Reaction (ADR) Health Canada: Adverse reacti...

ADVERSE DRUG REACTIONS Sandra Knowles, BScPhm Sunnybrook Health Sciences Centre  ADVERSE DRUG REACTIONS What are ADRs? Terminology Classification of ADRs Approach to patients with ADRs Causality assessment  Adverse Drug Reaction (ADR) Health Canada: Adverse reactions are undesirable effects to health products (including drugs, medical devices and natural health products). – Drugs include both prescription and nonprescription pharmaceuticals; biologically- derived products such as vaccines, serums, and blood derived products; cells, tissues and organs; disinfectants; and radiopharmaceuticals WHO: any noxious and untended response to a medicinal product Why are ADRs so important?  Impact of ADRs  Common  30% of hospitalized patients will experience an ADR  2-5% of all admissions due to an ADR  Expensive – ADR health care costs: cost of drug-related morbidity and mortality has been estimated as $136 billion annually – ADRs cause an average 2 day increase in hospital stays  Serious  serious/fatal reactions are fifth leading cause of death  JAMA 1998;279:200-5  Often preventable How do I know that the reaction is related to a drug?  ADR Detection Sometimes easy – Well recognized ADR – Patient’s medication history simple Most often not – ADR not recognized as being related to drug – Other complicating diagnosis (e.g., viral infections) – Complicated medication history – High background incidence Recognizing an ADR  Adverse Drug Reactions: Causality assessment  determine probability of association (or did the drug cause the reaction) When did the reaction occur in relationship to the drug? Did the reaction occur only after the drug was started? Did anything else change around the time of the ADR other than the suspected drug? Did the reaction improve when the drug was stopped or specific treatment given? Was there ever intentional or accidental use of the drug following the ADR?  Onset of the reaction Banerji et al. J Allergy Clin Immunol Pract 2023;11:356-68 What drugs cause ADRs?  Drugs causing ADRs Outpatient leading to Outpatient leading to ED admission to hospital visits NSAIDs (30%) Anticoagulants (17.6%) Diuretics (27%) Antibiotics (16.1%) Warfarin (11%) Diabetes agents (13.3%) ACEI/ARBs (8%) Opioids (6.8%) Antidepressants (7%) Antiplatelets (6.6%) Beta-blockers (7%) ACEI/ARBs (3.5%) Opioids (6%) Pirmohamed M, et al. BMJ Antineoplastics (3.0%) 2004;329:15-9. Sedatives (3.0%) Shehab et al. JAMA 2016;316:2115-25.  Drugs causing ADRs Consider excipients especially in patients with hypersensitivity to systemic corticosteroids, vaccines and biologics – e.g., carboxymethylcellulose, gelatin, polyethylene glycols – Caballero 2021 PMID 33737254 How are ADRs classified?  Classification of ADRs Drug Reaction Predictable Reactions Unpredictable Reactions “on-target” ADRs “off-target” ADRs  On-target (Predictable) Reactions  Augmentation of the pharmacology of the drug  Dose-dependent  80% of all ADRs  Examples:  Traditional antihistamines: sedation  Warfarin: increase in INR possible leading to bleeding  Antibiotic-associated diarrhea Examples of Predictable Reactions Toxicity: hepatic failure with high-dose acetaminophen Side effect: sedation with antihistamines Secondary effect: development of diarrhea with antibiotic treatment Drug interaction: theophylline toxicity with concomitant erythromycin  Classification of ADRs Drug Reaction Predictable Reactions Unpredictable Reactions “on-target” ADRs “off-target” ADRs 1. Antibody-mediated (immunologic) 2. Cell-mediated a. Single-organ disease b. Isolated cutaneous disease c. Systemic or multisystem disease 3. Non-IgE-mediated  Off-target (Unpredictable) ADRs  cannot be explained on the basis of the known pharmacology of the drug  do not exhibit a simple relationship between dose and occurrence of toxicity Antibody-mediated (immunologic) reactions  occur on reexposure to a drug or during second week of a course of treatment  occur at lower doses than required for pharmacologic effect  produce reactions that are characteristic of known allergic drug reactions (e.g., urticaria, angioedema)  symptoms usually subside within 3 to 5 days after drug is discontinued  Unpredictable Reactions: antibody-mediated Presentation Chronology/onset Examples IgE-mediated Urticaria,