Elsevier

The Lancet

Volume 356, Issue 9237, 7 October 2000, Pages 1255-1259
The Lancet

Adverse Drug Reactions
Adverse drug reactions: definitions, diagnosis, and management

https://doi.org/10.1016/S0140-6736(00)02799-9Get rights and content

Summary

We define an adverse drug reaction as “an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product, which predicts hazard from future administration and warrants prevention or specific treatment, or alteration of the dosage regimen, or withdrawal of the product.” Such reactions are currently reported by use of WHO's Adverse Reaction Terminology, which will eventually become a subset of the International Classification of Diseases. Adverse drug reactions are classified into six types (with mnemonics): dose-related (Augmented), non-dose-related (Bizarre), dose-related and time-related (Chronic), time-related (Delayed), withdrawal (End of use), and failure of therapy (Failure). Timing, the pattern of illness, the results of investigations, and rechallenge can help attribute causality to a suspected adverse drug reaction. Management includes withdrawal of the drug if possible and specific treatment of its effects. Suspected adverse drug reactions should be reported. Surveillance methods can detect reactions and prove associations.

Section snippets

Definitions

WHO's definition of an adverse drug reaction, which has been in use for about 30 years, is “a response to a drug that is noxious and unintended and occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function"1. However, in its use of the word “noxious” (defined in the Oxford English Dictionary as “injurious, hurtful, harmful”), this definition is vague; does it, for example, include all adverse reactions, no matter how

Classification

The forerunner of the modern pharmacological classification of adverse drug reactions distinguished dose-related and non-dose-related reactions, which were first called type A and type B, respectively9. Later, for mnemonic purposes, they were labelled “Augmented” and “Bizarre"10. Subsequently, two further types of reaction were added: reactions related to both dose and time, and delayed reactions11, later labelled types C and D12. The last of these categories can be split into two: time-related

Diagnosis and attribution of causality

The diagnosis of an adverse drug reaction is part of the broader diagnosis in a patient. If a patient is taking medicines, the differential diagnosis should include the possibility of an adverse drug reaction. The first problem is to find out whether a patient is taking a medicinal product, including: over-the-counter formulations; products that may not be thought of as medicines (such as herbal or traditional remedies, recreational drugs, or drugs of abuse); and long-term treatments that the

Management

Rapid action is sometimes important because of the serious nature of a suspected adverse drug reaction, for example anaphylactic shock. Emergency treatment and withdrawal of all medicines is occasionally essential, in which case cautious reintroduction of essential medicines should be considered. Otherwise, using clinical benefit-risk judgment, together with help from investigations, one decides which medicine or medicines should be withdrawn as a trial. A problem immediately arises if one or

Surveillance

Surveillance methods for drug reactions, and population methods for proving associations are summarised in table 2. 18, 19, 20. Outside of formal surveillance systems, all health-care professionals have a responsibility to inform their colleagues about clinically important adverse drug reactions that they detect, even if a well-recognised or causal link is uncertain. Information on what has happened and how the diagnosis has been made should be forwarded to a national centre with responsibility

Future developments

The work of the WHO monitoring programme in Uppsala is described in detail elsewhere21. The programme also supports the European Pharmacovigilance Research Group, which has allowed regulators and drug-safety specialists from a variety of European countries to come together to plan coordinated drug-safety exercises. Initiatives like these may pave the way for much more logical development and investigation of drug safety signals worldwide. Among the developments planned for the WHO programme are:

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