Adverse Drug Reactions

Definitions

Several well-accepted definitions of ADRs exist. The World Health Organization defines an ADR as a noxious or unintended response to a drug occurring in prophylaxis, diagnosis, and therapy, apart from failure to accomplish the intended purpose. This ADR definition refers to injuries that occur at usual medication doses. A source of confusion in the literature is the interchangeable use of the terms adverse drug reactions and adverse drug events (ADEs). The Institute of Medicine defines an ADE as injury consequential to drug use. Under this definition, an ADE not only includes an ADR, or an injury that occurs at usual doses, but also an injury that occurs with inappropriate use or overdose.

Epidemiology

Complications of ADEs may include hospitalization, increased hospital stays and health care expenditures, morbidity, and death. The incidence of ADEs varies by type of health care setting (e.g., ambulatory clinic, hospital, nursing home). In a cohort of older Medicare enrollees, the rate of ADEs was 50.1 per 1,000 person-years. In long-term care facilities, the rates of ADEs were reported as 1.9 to 9.8 per 100 resident-months. ADEs are a common cause of hospital admission of older adults and were responsible for 6% to 24% of all hospital admissions. Of all ADEs, 23% to 28% were categorized as serious.

Approximately one quarter to one half of ADEs are considered to be preventable. Errors are most likely to occur at the time of prescribing a medication or during monitoring of therapy. Prescribing errors include choosing an inappropriate medication, prescribing a medication that interacts with another medication in the individual's regimen, and prescribing a drug in the face of an established drug allergy. Errors in monitoring of therapy may include failing to obtain necessary laboratory values to monitor drug therapy and not responding promptly to signs, symptoms, or laboratory evidence of drug toxicity.

Many researchers have attempted to identify risk factors for ADEs, an endeavor that has been disappointing. The most persistent risk factor for ADEs is [Page 10]use of multiple medications; thus, it is important that patients be maintained on the fewest number of medications needed to manage their health conditions. Researchers have not found ADEs to vary substantially according to age or sex. Several factors are important to keep in consideration to minimize ADEs, even though they have not been identified as independent risk factors. Prescribers should keep in mind the age-related changes in kidney and liver function that may cause the body to be less efficient in eliminating medications and should adjust medication doses appropriately in older adults. Although specific medication types have not consistently been identified as independent risk factors for ADEs, certain medications may be more likely to cause ADEs if they have a narrow therapeutic window; for example, a blood level that causes the desired pharmacological effect may be similar to the blood level that causes ADEs.

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