Medications are designed to help patients recover, relieve symptoms, or manage ongoing conditions. However, there are situations where drugs can cause unintended harm instead of benefit. Two terms often used to describe medication-related harm are Adverse Drug Events (ADEs) and Adverse Drug Reactions (ADRs). Although they may sound similar, the difference between them is important for clinical practice, medical documentation, and pharmacovigilance.
Adverse Drug Events (ADEs) refer to any harmful and unintended consequences associated with the use of a medication.
According to the American Society of Health-System Pharmacists (ASHP), an ADE is an unexpected, undesirable, harmful event where a medication was implicated.2 These events include harm caused directly by the drug, such as adverse drug reactions and overdoses, as well as harm resulting from the use of the drug, which includes complications from abrupt discontinuation or dose reductions.1
Liver failure following an acetaminophen overdose
Bleeding complications from excessive warfarin dosing
Respiratory depression after oxycodone overdose
Complications from stopping a medication too abruptly
Harm resulting from a medication error
ADEs may be classified based on severity into:
Adverse Drug Reactions (ADRs), or
Adverse effects (also known as side effects)
An Adverse Drug Reaction (ADR) is a specific subtype of ADE characterized by an unexpected, unintended, or excessive response to a drug that can lead to harm, disability, or even death.
The International Conference on Harmonization, which includes the World Health Organization and the FDA as members, defines an ADR as "a response to a drug which is noxious and unintended, and which occurs at doses normally used for prophylaxis, diagnosis, or therapy of disease or the modification of physiologic function."
ADRs occur at normal therapeutic doses and typically do not result from medication errors, overdoses, or noncompliance. 2
Gastritis from nonsteroidal anti-inflammatory drugs
Nephrotoxicity caused by aminoglycoside antibiotics
Drug-induced lupus from hydralazine, isoniazid, or phenytoin
Stevens-Johnson syndrome from certain medications 3
ADRs are broadly classified into two categories:
These reactions occur due to the known pharmacological properties of the drug and account for 85 to 90% of all ADRs. They include side effects, drug interactions, and predictable dose-dependent reactions.
These reactions are unpredictable and not related to the known pharmacological profile of the drug. They include hypersensitivity, idiosyncratic, and pseudoallergic reactions. Although less common, they are often more severe.
In 2022, more than 1.25 million serious adverse events were reported to the FDA's Adverse Event Reporting System, including nearly 175,000 deaths. 3
Studies show that ADRs contribute to up to 6% of hospital admissions, and approximately 3 out of every 1,000 admissions result in patient death due to an ADR. 4
The key distinction lies in causation and the circumstances under which the event occurs.
Include any medication-related injury
Can be preventable or non-preventable
May result from errors, overdoses, inappropriate use, or discontinuation
Encompass all forms of harm linked to medication use
Are noxious and unintended responses to a drug
Occur at normal therapeutic doses
Represent the body's unique response to the medication
Are a subset of ADEs
Understanding the difference between ADEs and ADRs has significant clinical and regulatory implications.
Identifying whether the harm was caused by the drug itself or by an error affects treatment decisions, monitoring strategies, and future prescribing.
Regulatory bodies track ADRs to identify safety issues and emerging risks. The withdrawal of rofecoxib (Vioxx) highlights how early detection of ADR patterns can prevent widespread harm.
Correct classification impacts patient records, future treatments, and insurance claims. A documented ADR may permanently contraindicate a drug for a patient, while an ADE may simply require dosage adjustment or closer monitoring.
How an event is classified influences reporting obligations and potential liability.
Detection, documentation, and reporting fall under the field of pharmacovigilance.
Pharmacovigilance is the science focused on identifying, assessing, understanding, and preventing adverse effects and other drug-related problems.
Despite their importance, fewer than 5% of ADEs are reported, even when reporting is mandatory. This underreporting allows rare but serious reactions to remain unidentified for long periods. 1
Healthcare professionals are encouraged to report all suspected ADRs, especially serious events causing death, life-threatening conditions, disability, or congenital anomalies.
In the United States, ADEs and ADRs can be reported through the FDA MedWatch voluntary reporting system.
A valid report mainly include four components:
An identifiable patient
A description of the adverse event
The suspect medication
An identifiable reporter 1
While adverse drug events and adverse drug reactions are related terms, recognizing the difference between them is essential for accurate documentation, safer prescribing, and effective drug surveillance.
An ADE refers to any harm related to medication use, while an ADR specifically describes harm caused directly by the drug when used in usually prescribed normal doses. Clear understanding of this distinction supports patient safety, strengthens pharmacovigilance efforts, and promotes more informed clinical decisions.
1. Bailey, C., Peddie, D., Wickham, M. E., Badke, K., Small, S. S., Doyle-Waters, M. M., Balka, E., and Hohl, C. M. (2016) Adverse drug event reporting systems: a systematic review. Br J Clin Pharmacol, 82: 17–29. doi: 10.1111/bcp.12944.
2. Ray, Sidhartha D., Joshua P. Gray, Sidney J. Stohs, and Henry Cohen. 2019. “ADRs, ADEs and SEDs: A Bird's Eye View.” In Side Effects of Drugs Annual, edited by Sidhartha D. Ray, vol. 41, xxvii–xlviii. Elsevier. https://doi.org/10.1016/S0378-6080(19)30058-3
3. Kommu S, Carter C, Whitfield P. Adverse Drug Reactions. [Updated 2024 Jan 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK599521/
4. Trontell, Anne E. 2001. “How the US Food and Drug Administration Defines and Detects Adverse Drug Events.” Current Therapeutic Research 62 (9): 641–49. https://doi.org/10.1016/S0011-393X(01)80070-9
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