Adverse Drug Reactions in Children: The Double‐Edged Sword of Therapeutics

Abstract

Adverse drug reactions (ADRs) represent a major health problem worldwide, with high morbidity and mortality rates. ADRs are classified into Type A (augmented) and Type B (bizarre) ADRs, with the former group being more common and the latter less common but often severe and clinically more problematic due to their unpredictable nature and occurrence at any dose. Pediatric populations are especially vulnerable to ADRs due to the lack of data for this age group from the drug development process and because of the wide use of off-label and unlicensed use of drugs. Children are more prone to specific types of ADRs because of the level of maturity of body systems involved in absorption, metabolism, transportation, and elimination of drugs. This state-of-the-art review provides an overview of definitions, classifications, epidemiology, and pathophysiology of ADRs and discusses the available evidence for related risk factors and causes of ADRs in the pediatric population.

Adverse Drug Reactions Across the Age Continuum: Epidemiology, Diagnostic Challenges, Prevention, and Treatments

“…These have enabled health care providers to control—and even, in many cases, cure—common and important disorders in children. However, in biology nothing comes for free, and the double‐edged sword of therapeutics is that drugs that have beneficial effects also have toxic effects …”

“…Within this population are 2 distinct groups; most children receive no or 1 prescription a year, but children with complex and often chronic problems—approximately 20% of children—receive 70% of all prescription drugs . Thus it is not surprising that, in the latter group of children, ADRs would be expected to be both common and important problems . For the majority of children, there is a low risk for an ADR for the simple fact that they rarely take medication, and when they do, short courses of monotherapy are most common.…”

“…The management of most ADRs as noted above includes ensuring that the primary diagnosis has been addressed, when appropriate discontinuing the drug(s) in question and symptomatic management. In the case of serious and potentially life threatening ADRs such as Stevens‐Johnson syndrome or toxic epidermal necrolysis there is an ongoing controversy as to what constitutes optimal management . This problem is in part due to continuing uncertainty as to the precise pathophysiological mechanisms involved in evoking these ADRs.…”

“…The value of immunomodulation—for example, with corticosteroids or intravenous immunoglobulin—remains an issue of debate, with some data suggesting benefit, some no benefit and some suggesting harm . Nonetheless, these 2 facts are clear: excellent supportive care is a key to a successful outcome, and these patients should be managed by clinicians expert in the care of these uncommon but very serious ADRs …”

Allergen-Based Diagnostic: Novel and Old Methodologies with New Approaches

“…The pathophysiological mechanisms of Type B reactions are not well understood. Some cases are mediated by type I hypersensitivity (true allergy), but other cases are related with the generation of reactive metabolites that react nonenzymatically on multiple proteins to form immunogenic-drugs complexes that induce a cascade of cell-based reactions and result in a wide range of severe clinical symptoms [56]. Due to the complexity of ADR, only Type B reactions could be explored by basophil activation test (BAT).…”