Reporting adverse drug reactions.

Reported in this month’s edition of the Southern Medical Journal is a case of ischemic colitis potentially caused by sumatriptan. The authors do an excellent job of describing the patient history and linking the adverse event to the potential causative drug. Although these adverse drug reports are somewhat commonplace, reporting these “post-marketing” events is necessary since preapproval studies do not always provide the complete scope of a drug’s adverse event profile. Because pharmacotherapy plays such a vital role in medicine, it is essential for practitioners to understand how adverse drug reactions (ADRs) are classified, identified and reported. As defined by the World Health Organization, an adverse drug reaction is “any response to a drug which is noxious and unintended, and which occurs at doses normally used in humans for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function.” Adverse drug reactions then, are essentially any type of untoward event related to a drug’s administration regardless of etiology. It is also important to determine if the reaction was a drug side effect or if it was induced by human error (eg, an inappropriate dose). ADRs can be subdivided into “hypersensitivity reactions,” which are defined as immune-mediated effects (hypersensitivity reactions can be further subdivided); and “drug allergies,” which are specific to an IgE-mediated drug response. These terms are sometimes used inappropriately when referring to an ADR. Once an ADR is identified it can be further defined. The US Food and Drug Administration (FDA) classifies ADRs in various ways. ADRs can be assigned as mild, moderate, severe, or lethal based on the severity of the patient response. The term “serious” has been defined by the FDA as an adverse drug reaction that “results in death, a birth defect, disability, or hospitalization; is life-threatening; or requires intervention to prevent harm.” Based on preapproval studies and postmarketing reports, the frequency of a particular ADR can also be hypothesized. ADR frequency definitions for adverse events are generally defined as: very common ( 1/10); common ( 1/100 but 1/10); uncommon ( 1/1,000 but 1/ 100); rare ( 1/10,000 but 1/1,000); and very rare ( 1/ 10,000). These basic definitions are utilized to describe and classify adverse drug events. Although new drugs undergo extensive review and the FDA requires a significant amount of safety data before approving a new drug for use, most new drugs are only studied in a few thousand patients. This means that generally, only those ADRs which are the most prevalent will be identified in preapproval, Phase I, Phase II, and Phase III clinical trials. Those less common events will not manifest themselves until the drug enters the market postapproval and the drug is utilized in several thousand more patients. Unfortunately, preapproval studies are unable to duplicate the exact patient populations in which a new drug may be utilized. Older or younger patients, with various comorbidities, potentially receiving many different drugs, may pose a completely different risk of developing an ADR from a new agent than those subjects included in premarketing trials. For all of these reasons, reporting postmarketing adverse drug reactions is a vital necessity. Identifying a causal relationship between a drug and a particular adverse event can be problematic, especially if a patient is receiving many medications. Various tools have been developed by the FDA and others to assess the probability of ADRs. One tool that is used extensively is the Naranjo ADR Probability Scale, which assigns a score to a particular event based on a series of questions. The derived score then determines the general probability of that particular drug causing a specific adverse drug reaction. Assessing the “causeeffect” of an ADR is especially important for these postmarketing reports, as the drug is used in a less controlled environment compared to the premarketing randomized controlled trials. All health care professionals must share in the responsibility of reporting adverse drug reactions. The information From the University of Missouri–Kansas City (UMKC), School of Medicine, Kansas City, MO.