Nonrenal toxicities of acetaminophen, aspirin, and nonsteroidal anti-inflammatory agents

Approximately 2% of the United States population consumes an analgesic, antipyretic, or nonsteroidal antiinflammatory drug (NSAID) each day. Aspirin and acetaminophen have been available to the public without a prescription (over-the-counter) for decades, while most NSAIDs are still only available with a prescription from a physician. The recent trend of switching NSAIDs from prescription to over-the-counter status may be perceived by some as an indication of their inherent safety. However, all these agents have been associated with a unique but overlapping safety profile. In fact, significant adverse events (AEs) on multiple organ systems, including the kidney and gastrointestinal tract, have been reported with most of these agents. In this review, the incidence of the nonrenal AEs of aspirin, acetaminophen, and selected NSAIDs are tabulated. The strengths of the causative associations are highlighted, the relative risks for the gastrointestinal and cardiovascular AEs are discussed, and the relationship to patient risk factors and drug characteristics, such as dose and half-life, are reviewed. The selection of the optimal agent for an individual patient depends on the balance between the desired pharmacodynamic response, the patient's pharmacotherapy history, and the degree of AE risk one is willing to accept. Therapy should be initiated in all settings with the lowest possible dosage since the incidence of the major AEs is dose related.