Acetaminophen in Perspective.

Abstract

To the Editor: Osteoarthritis is the most common arthropathy in the Western world and the most-frequent cause of disability in the United States. The disease is manifested by accelerated degeneration of the articular cartilage. Initial presentation is in the form of minor pain and stiffness, with pain becoming more debilitating and contributing to the development of muscle weakness, deformity, and sleep deprivation as the disease becomes more advanced. The incidence of osteoarthritis continues to increase. An estimated 26.9 million people in the United States have been diagnosed with osteoarthritis.1 In 2009, it was the fourth most-common cause of hospitalization, with 905,000 hip or knee replacements, at a cost of $42.3 billion.2 The number of U.S. adults with osteoarthritis is projected to rise to 67 million by 2030.3 Treatment of osteoarthritis remains focused on symptom reduction, without the ability to arrest or reverse the process. Joint replacement remains the only “cure” but at a cost and potential risk to the individual. Pharmacological interventions address the symptoms of pain but do not alter disease progression. Intra-articular corticosteroid injections, hyaluronate injections, prescription nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids have all had varying degrees of success but also potential serious side effects. The Food and Drug Administration (FDA) has approved duloxetine, but it must be obtained by prescription.4 There are limitations based on potential side effects, drug-to-drug interactions, and recommendations not to combine it with other therapies for depression. Acetaminophen therapy has been the mainstay of osteoarthritis pain since the 1950s, and its efficacy and safety are still promoted today. No long-term toxicity has been demonstrated with up to 4 g of acetaminophen per day for various sources of pain.5 Other options for systemic analgesia such as NSAIDS and opioids can be effective but have limitations. NSAIDS have been found to have in short- and long-term toxicities in cardiovascular disease and hypertension and mortality in gastrointestinal bleeding. NSAIDs are widely used in the treatment of osteoarthritis and pain. They are readily available over the counter and have 17 prescription variants. NSAIDs have underlying risks. Hypertension, cardiovascular, renal, hepatic, central nervous system, and gastrointestinal complications can be profound and even lethal.6 The FDA revised the warning and precaution on all nonaspirin forms of NSAIDs in July 2015. The new FDA warning includes greater risk of heart attack or stroke as early as the first few weeks of use. This risk is greater with higher doses and exists for individuals with or without cardiac risk factors, and greater mortality is associated with NSAID use after myocardial infarction.7 Opioids, although effective, have complications including sedation, constipation, drug diversion, polypharmacy, and respiratory depression. The use of acetaminophen in the vast majority of individuals with osteoarthritis makes it a viable choice based on a blend of efficacy, safety, and cost. Monitoring is important, especially when taken with other acetaminophen-containing products or in severe hepatic disease. Intentional misuse is rare, and hepatic consequences with the use of even maximum doses of 4 g per day are almost nonexistent. Health Canada conducted a retrospective review in July 2015 of 4 billion doses in 1 year. Two hundred fifty individuals developed serious liver consequences only when exceeding the maximum dose of 4 g because of suicide attempts or unintentional overdoses. No evidence was found that doses of 4 g were toxic.8 It is important to be aware of all of potential sources of acetaminophen, including combination products, and the cumulative dose of acetaminophen so as not to exceed the maximal dose in 24 hours. Physicians and allied health professionals should educate people about the efficacy of acetaminophen and the unsurpassed safety of this class of drugs. The costs of education and monitoring of medications are minimal. In summary, people trust that the pharmacological options for their osteoarthritis pain are safe. The abundant, long-term clinical trial data for acetaminophen support its use in the management of osteoarthritis pain. Conflict of Interest: Dr. Sulich is a consultant for Abbvie, Genetech, Celgene, and Crescendo Bioscience and has conducted research for Genetech, GSK, and Celgene. Author Contributions: Dr. Sulich was solely responsible for the concept and preparation of this letter. Sponsor's Role: None.