Cardiorenal Safety of OTC Analgesics

Over-the-counter analgesics are used globally for the relief of acute pain. Although effective, these agents can be associated with adverse effects that may limit their use in some people. In the early 2000s, observations from clinical trials of prescription-strength and supratherapeutic doses of nonselective and cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs) raised safety concerns regarding the risk of cardiovascular adverse effects with the use of these medications. Subsequently, the US Food and Drug Administration mandated additional study of the cardiovascular safety of NSAIDs for a more comprehensive understanding of their risk. As these data were being collected, and based on a comprehensive review of prescription data and the recommendations of the US Food and Drug Administration Advisory Committee, the warning labels of over-the-counter NSAIDs were updated to emphasize the potential cardiovascular risks of these agents. The recently reported "Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen" (PRECISION) trial, in which participants with osteoarthritis or rheumatoid arthritis and underlying cardiovascular risk factors were treated with prescription-strength celecoxib, ibuprofen, or naproxen, revealed similar rates of cardiovascular events (death from cardiovascular causes including hemorrhagic death, nonfatal myocardial infarction, or nonfatal stroke) among the 3 treatment groups. Although informative, the cardiovascular safety findings derived from PRECISION cannot be extrapolated to the safety of the over-the-counter pain relievers ibuprofen and naproxen, given that the doses used were higher (mean [standard deviation]: ibuprofen, 2045 [246] mg; naproxen, 852 [103] mg) and the durations of use longer (∼20 months) than recommended with over-the-counter use of NSAIDs, which for ibuprofen is up to 10 days. This review discusses the cardiorenal safety of the most commonly used over-the-counter analgesics, ibuprofen, naproxen, and acetaminophen. Available data suggest that there is little cardiovascular risk when over-the-counter formulations of these agents are used as directed in their labels.