Adverse drug reactions and pharmacovigilance — formative SAQs

SAQ 1 — Classification and causality (10 marks, 15 minutes)

Question. Define an adverse drug reaction and distinguish it from an adverse drug event and a medication error. Outline the Rawlins and Thompson classification (Type A and Type B) and the DoTS extension, and explain how you would apply the Naranjo algorithm to assess causality in a child with a suspected reaction. [2]

Model answer — a full-marks answer names the definitions, the contrast, and the operational tool. [1]

1. Definition of an ADR (1 mark). A noxious and unintended response to a medicine that occurs at doses normally used in humans. The phrase "normally used" is essential — it excludes overdose and error.
2. Distinction from an ADE and a medication error (2 marks). An adverse drug event is any harm from a medicine whether or not the dose was correct, so it captures both true ADRs and harm from medication errors. A medication error is the process failure itself (wrong drug, dose, route, time or patient) that may or may not reach the child and may or may not cause harm.
3. Rawlins and Thompson classification (3 marks). Type A (augmented): an exaggerated primary pharmacological effect that is predictable, dose-related, common, and usually of low mortality (for example opioid respiratory depression, beta-agonist tachycardia). Type B (bizarre): a qualitatively abnormal response that is unpredictable, largely dose-independent, rare, and potentially lethal; it is immune-mediated (anaphylaxis, SJS/TEN, DRESS) or idiosyncratic (G6PD haemolysis). Mention the alphabet extension: Type C chronic, Type D delayed, Type E end-of-use (withdrawal), Type F failure of therapy.
4. DoTS extension (2 marks). DoTS classifies each reaction across three axes — Dose-relatedness (standard, low or high), Time-relatedness (early, intermediate, late or cumulative), and Susceptibility (age, genotype, organ function, disease, interacting drugs). It complements Type A/B by explaining mixed patterns.
5. Naranjo application (2 marks). Score the ten items (previous conclusive reports, temporal relationship to the suspected drug, improvement on withdrawal, recurrence on rechallenge, alternative causes, placebo response, drug detected in blood, dose-dependent reaction, prior exposure, objective confirmation). Sum and band the score: 0 to 4 doubtful, 5 to 6 possible, 7 to 13 probable, 14 to 18 definite. [1]

SAQ 2 — Severe cutaneous adverse reaction (10 marks, 15 minutes)

Question. A 9-year-old boy of Han Chinese ancestry presents two weeks after starting carbamazepine for new focal epilepsy with a blistering rash, mouth ulcers and fever. Outline your immediate and definitive management, including classification of the reaction, causality assessment, and your reporting obligations. [1]

Model answer — structure it as recognise, assess, treat, report, prevent. [1]

1. Recognise and classify (2 marks). Suspect Stevens-Johnson syndrome or toxic epidermal necrolysis. Confirm by estimating the percentage of body surface area with epidermal detachment: under 10 percent SJS, 10 to 30 percent SJS-TEN overlap, over 30 percent TEN. Examine all mucous membranes and assess for the HLA-B*15:02 association typical of carbamazepine-induced SJS/TEN in Han Chinese and Southeast Asian ancestry.
2. Immediate management (3 marks). Stop carbamazepine immediately and withdraw all non-essential medicines. Resuscitate using airway, breathing and circulation priorities. Admit to a high-dependency or PICU setting. Treat as a burn: fluids titrated to the area of detachment, meticulous wound care, eye review by ophthalmology within 24 hours, nutritional support and pain relief. Avoid prophylactic antibiotics. Seek specialist advice on immunomodulation (intravenous immunoglobulin or ciclosporin).
3. Causality and severity assessment (2 marks). Apply the Naranjo algorithm (strong temporal relationship to carbamazepine, improvement on withdrawal, no rechallenge expected, plausible alternative causes excluded) to assign probable causality. Grade severity with the Hartwig scale. Reconsider the differential (staphylococcal scalded skin syndrome, Kawasaki disease, severe viral exanthem) and exclude each.
4. Reporting (2 marks). Report to the national pharmacovigilance system — the TGA in ANZ, MHRA Yellow Card in the UK, FDA MedWatch in the US — even though causality is still being assessed, because carbamazepine is a high-risk drug and the report reaches WHO VigiBase through the national centre. Reporting is a professional duty and is independent of certainty.
5. Prevention and disposition (1 mark). Document the reaction and the allergy status, issue a MedicAlert, avoid cross-reactive aromatic anticonvulsants, substitute a structurally unrelated agent such as levetiracetam, counsel the family, and offer pharmacogenomic counselling to first-degree relatives. [2]