Adverse Drug Reactions and Pharmacovigilance
On this page
Direct answer
An adverse drug reaction is a harmful, unintended response to a medicine given at doses used in humans for prophylaxis, diagnosis or therapy, and pharmacovigilance is the science of detecting and preventing such reactions. Reactions are classified as types A to F, with type A dose-dependent and predictable and type B bizarre and idiosyncratic, while causality is judged by algorithms such as WHO-UMC and Naranjo. In India, clinicians report suspected reactions to the Pharmacovigilance Programme of India, coordinated by the Indian Pharmacopoeia Commission.
What you must remember
- Type A: Augmented and dose-dependent, predictable from pharmacology, and the commonest type, such as warfarin bleeding or insulin hypoglycaemia.
- Type B: Bizarre, idiosyncratic and not dose-related, including hypersensitivity and anaphylaxis; unpredictable and often serious.
- Type C: Chronic and dose-dependent with long exposure, such as HPA axis suppression from corticosteroids or analgesic nephropathy.
- Type D: Delayed reactions appearing long after exposure, such as teratogenicity or carcinogenicity.
- Type E: End-of-use reactions on withdrawal, such as rebound hypertension after stopping clonidine.
- Type F: Failure of therapy, such as contraceptive failure caused by enzyme-inducing drugs.
- Naranjo score: 9 or more is definite, 5 to 8 probable, 1 to 4 possible, and 0 or less doubtful.
- Serious reactions: Fatal, life-threatening, hospitalisation-causing, disabling, congenital anomaly or medically important reactions get reporting priority.
Working out causality for a rash after a new antibiotic
A 45-year-old man develops a maculopapular rash nine days after starting co-trimoxazole for a urinary infection. The rash began after the drug was started, improved within days of stopping it, and no other drug or infection plausibly explains it.
Causality is assessed through the structured Naranjo questions, and each answer adds or subtracts points.
- Previous reports: Conclusive reports of such a reaction exist, scoring one point.
- Timing: The reaction appeared after the suspected drug, scoring two.
- Dechallenge: It improved on stopping, scoring one.
- Rechallenge: Rechallenge is avoided because it could be dangerous, so that item scores zero.
- Alternative causes: No alternative cause could have produced the rash on its own, scoring two.
- Objective evidence: A rash documented on examination adds one point, giving a total of seven, which falls in the probable category.
The WHO-UMC system would reach a similar probable conclusion using its own criteria. The clinician then records the reaction on a suspected ADR form and advises the patient to avoid the drug in future. If the rash had blistered or involved mucosa, the reasoning would change, because severe cutaneous reactions are emergencies that outrank causality scoring and demand immediate drug cessation and urgent referral.
Where the exam tries to catch you
Most ADR errors come from mixing up classes, scores and reporting duties.
- Trap: assuming every type B reaction is an allergy Correct: allergy is only one immunological mechanism within type B, which is bizarre, idiosyncratic and not dose-related.
- Trap: confusing type C with type D Correct: chronic steroid suppression of the axis is type C because it depends on cumulative exposure, whereas teratogenicity is type D because it appears much later.
- Trap: using Naranjo and WHO-UMC as if they were interchangeable Correct: they are not interchangeable, and the point-based system is Naranjo, which the exam may ask about.
- Trap: waiting for a causality score before acting on a serious reaction Correct: reporting to PvPI is voluntary for most clinicians, but the duty to recognise and stop a dangerous drug is not, so serious reactions should never wait for a score.
Frequently asked questions
What distinguishes type A from type B adverse drug reactions?
Type A reactions are dose-dependent and predictable from the drug's pharmacology, and they make up most adverse reactions. Type B reactions are bizarre, idiosyncratic and largely independent of dose, so hypersensitivity reactions cannot usually be prevented by dose reduction.
Which ADR type covers corticosteroid-induced adrenal suppression?
Adrenal suppression from long-term corticosteroid use is a type C reaction, being chronic, dose-dependent and linked to prolonged exposure. Analgesic nephropathy from prolonged analgesic use is another type C reaction, showing that cumulative exposure rather than a single dose drives harm.
What does a Naranjo score of 7 indicate?
A Naranjo score of 7 indicates a probable adverse drug reaction, since scores from 5 to 8 fall in that category. Scores of 9 or more are definite, 1 to 4 possible, and 0 or less doubtful.
How does a clinician report a suspected adverse drug reaction in India?
Clinicians report suspected adverse drug reactions to the Pharmacovigilance Programme of India, coordinated by the Indian Pharmacopoeia Commission, using its suspected ADR reporting form. Serious reactions, such as those causing hospitalisation or death, should be prioritised for reporting.
Which features define a serious adverse drug reaction for reporting?
Serious reactions are those that are fatal, life-threatening, cause hospitalisation or prolong it, produce disability, cause a congenital anomaly, or are otherwise medically important. Recognising seriousness sets the priority and urgency of reporting, so it should be judged at the bedside before any causality score is calculated.