What Is an Adverse Drug Reaction?

An Adverse Drug Reaction (ADR) is a harmful, unintended and clinically significant response to a medicinal product when it is used at doses normally used for prevention, diagnosis or treatment of disease, or for modification of physiological function.

ADRs can range from relatively mild effects such as nausea or drowsiness to severe and potentially life-threatening reactions such as anaphylaxis, severe cutaneous reactions, organ toxicity or serious bleeding.

ADR vs Adverse Drug Event

An adverse drug event (ADE) is a broader term describing harm associated with medication use. An ADE can include adverse drug reactions as well as medication errors, overdoses, inappropriate use and other preventable or non-preventable medication-related harms.

ADR Quick Facts

Classification of Adverse Drug Reactions

The traditional pharmacological classification divides ADRs into Type A through Type F. This classification is useful for understanding predictability, dose relationship and mechanisms.

Mechanisms of Adverse Drug Reactions

ADRs may result from exaggerated pharmacological effects, direct toxicity, immune-mediated reactions, genetic susceptibility, altered drug exposure or interactions with other medicines.

1. Pharmacological Mechanisms

The ADR results from excessive or unwanted expression of the known pharmacological action of the drug.

2. Immune-Mediated Mechanisms

Some drug reactions involve immune recognition of the drug or a drug-associated antigen. Clinical presentations may include urticaria, angioedema, bronchospasm or anaphylaxis.

3. Genetic Susceptibility

Genetic differences can influence drug metabolism, transport, pharmacodynamic responses and susceptibility to certain severe reactions.

4. Altered Pharmacokinetics

Changes in absorption, distribution, metabolism or elimination can increase drug exposure and increase the probability of toxicity.

Risk Factors for ADRs

• Advanced age or very young age
• Polypharmacy
• Renal impairment
• Hepatic impairment
• Previous history of drug reactions
• Drug-drug interactions
• Drug-food interactions
• Genetic differences in drug metabolism
• High doses or narrow therapeutic index medicines
• Long treatment duration
• Pregnancy and other special physiological states
• Multiple comorbidities

Severity of Adverse Drug Reactions

Examples of Serious Adverse Drug Reactions

Common Drug-Related Adverse Reactions

The following examples illustrate common relationships between medicines and adverse reactions. Actual risk depends on dose, patient factors, concomitant medicines and clinical circumstances.

Management of Adverse Drug Reactions

Management depends on the severity, mechanism, suspected medicine, patient condition and availability of alternative treatment.

General Approach

1. Recognize and assess the suspected reaction.
2. Evaluate the severity and immediate clinical risk.
3. Identify the suspected medicine and recent medication changes.
4. Assess timing between drug exposure and reaction.
5. Consider alternative causes and differential diagnoses.
6. Stop, reduce or substitute the suspected medicine when clinically appropriate.
7. Provide supportive and specific treatment when indicated.
8. Monitor the patient and document the reaction clearly.
9. Consider reporting the suspected ADR through the appropriate pharmacovigilance system.

Prevention of Adverse Drug Reactions

• Obtain an accurate medication history.
• Document previous drug allergies and reactions.
• Check for clinically important drug interactions.
• Consider renal and hepatic function before prescribing where relevant.
• Use appropriate doses and treatment durations.
• Monitor drugs with narrow therapeutic ranges.
• Educate patients about expected and concerning symptoms.
• Use medication reconciliation during transitions of care.
• Review polypharmacy regularly.
• Use pharmacogenomic information where clinically validated and appropriate.

ADR Reporting & Pharmacovigilance

Pharmacovigilance is concerned with the detection, assessment, understanding and prevention of adverse effects or other medicine-related problems.

Why Report Suspected ADRs?

Individual reports can contribute to the identification of previously unrecognized safety signals. Accumulated evidence may lead to changes in prescribing information, warnings, monitoring requirements or other risk-minimization measures.

What Information Is Useful?

• Patient characteristics relevant to the reaction
• Suspected medicine and dose
• Route and frequency of administration
• Start and stop dates
• Description of the reaction
• Timing of onset
• Concomitant medicines
• Relevant laboratory or diagnostic findings
• Outcome of the reaction
• Dechallenge and rechallenge information where available

ADR Causality Assessment

Causality assessment attempts to estimate how likely it is that a medicine caused the reported event.

Adverse Drug Reaction vs Side Effect vs Allergy

Patient Safety Considerations

Patients should be encouraged to maintain an up-to-date list of all prescription medicines, over-the-counter products, supplements and herbal products they use.

When a suspected drug reaction occurs, the medicine and reaction should be documented clearly so that future healthcare professionals can take the information into account.

Patients should not independently discontinue essential medicines without professional advice unless they are experiencing an emergency requiring immediate medical attention.

Frequently Asked Questions

Key Reference Areas

• World Health Organization pharmacovigilance resources
• International Council for Harmonisation safety and pharmacovigilance guidance
• Regulatory authority adverse event reporting systems
• Clinical pharmacology and pharmacovigilance textbooks
• Drug product prescribing information and safety communications