Commentary to Michna et al.: The Elephant in the Room: Hydrocodone/Acetaminophen Combination Compounds and the Substitution Effect

Abstract

Michna et al. present a compelling case for re-examining the Food and Drug Administration (FDA) Advisory Committee's recent recommendation to eliminate prescription acetaminophen combination products [1]. They outline the significant methodological limitations of the research presented to the Advisory Committee that likely influenced its recommendations. In addition, the authors offer alternative actions that the FDA could recommend, other than completely eliminating opioid/acetaminophen combination products from the market and describe consequences that could be expected if the Advisory Committee's recommendation to remove opioid/acetaminophen combination products from the market were implemented, such as limited availability of treatment alternatives to patients and more frequent adverse events due to increased use of non-steroidal anti-inflammatory drugs (NSAIDS). Michna et al. clearly argue for the best interest of patients, but they do not address essential regulatory, clinical, and marketing factors that often contribute to the overuse of opioid/acetaminophen combination products and the occurrence of acetaminophen-related adverse events. Despite the FDA Advisory Committee focus on acetaminophen as the objectionable agent in these combination products, it must be stressed that the opioid component is almost certainly a driving force for excessive acetaminophen use. Therefore, even though the FDA Advisory Committee's stated goal is to reduce acetaminophen toxicity, this topic and their recommendations must be viewed with consideration of the contribution of the opioid component, especially hydrocodone. In reviewing this topic, the question of why for many years the class of hydrocodone/acetaminophen combination products has been the most frequently prescribed of all controlled or non-controlled medications in the United States deserves consideration [2]. The “elephant in the room” refers to the central issue associated with hydrocodone/acetaminophen combination products that can put patients at risk—that of the “substitution effect”[3], whereby physicians prescribe such products instead of more optimal and possibly safer opioid compounds, because they are …