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Acetaminophen: Old Drug, New Issues

Published:February 28, 2015DOI:https://doi.org/10.1016/j.joen.2015.01.024

      Highlights

      • Although acetaminophen (APAP) is considered a safe drug, new concerns and warnings because of acetaminophen overdose and liver failure have resulted in the US Food and Drug Administration (FDA) mandating new labeling on acetaminophen packaging.
      • The FDA has asked acetaminophen manufacturers to lower the strength of acetaminophen in prescription drug products to 325 mg in opioid combination products.
      • Recent evidence also suggests that acetaminophen is a hormone disrupter and thus may not be considered a safe drug during pregnancy.
      • APAP may increase the risk of asthma in children, cause serious allergic reaction and toxicity, potentiate the effect of warfarin, and increase the risk of hematologic malignancies.
      • Finally, within the past decade, the mechanism of action of this drug has been reported to have a central analgesic effect, which inhibits prostaglandin synthesis in the central nervous system.

      Abstract

      Introduction

      The purpose of this review was to discuss new issues related to safety, labeling, dosing, and a better understanding of the analgesic effect of acetaminophen.

      Methods

      The MEDLINE, Embase, Cochrane, and PubMed databases were searched. Additionally, the bibliography of all relevant articles and textbooks were manually searched. Two reviewers independently selected the relevant articles.

      Results

      Concerns about acetaminophen overdose and related liver failure have led the US Food and Drug Administration to mandate new labeling on acetaminophen packaging. In addition, large-scale epidemiologic studies increasingly report evidence for second-generation adverse effects of acetaminophen. Prenatal exposure to acetaminophen is associated with neurodevelopmental and behavioral disorders. Recent studies also suggest that acetaminophen is a hormone disrupter (ie, it interferes with sex and thyroid hormone function essential for normal brain development) and thus may not be considered a safe drug during pregnancy. Finally, emerging evidence suggests that although the predominant mechanism by which acetaminophen exerts its therapeutic effect is by inhibition of cyclooxygenase, multiple other mechanisms also contribute to its analgesic effect.

      Conclusions

      Available evidence suggests that indiscriminate usage of this drug is not warranted. and its administration to a pregnant patient should be considered with great caution.

      Key Words

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