title: Need to develop new nonsteroidal anti-inflammatory drug formulations.
abstract: BACKGROUND
  In the management of pain, primary care physicians are often the first to diagnose and treat acute or chronic painful conditions. This places them in an important intersection to manage pain, in which safe and effective therapeutic options are paramount for their patients. For decades, NSAIDs have been routinely prescribed for relief of mild to moderate acute and chronic pain. Yet, safety and tolerability concerns associated with the use of this class of drugs continue to be an issue for patients and clinicians.
  
  
  OBJECTIVE
  The objective of this review was to discuss the unmet medical needs of patients in the management of pain and inflammation, review the dose-dependent safety data associated with use of NSAIDs, and discuss the need to develop new NSAID formulations to improve safety and tolerability while maintaining efficacy.
  
  
  METHODS
  We performed literature searches of the PubMed and Cochrane Library databases through December 2012 for articles in English that reported dose-dependent safety and tolerability data associated with use of NSAIDs.
  
  
  RESULTS
  The risk of serious, dose-dependent adverse events involving the gastrointestinal tract, cardiovascular system, and kidneys is associated with use of NSAIDs. On the basis of these findings, the US Food and Drug Administration has requested that the package insert for all NSAIDs be revised to include a boxed warning highlighting the potential increased risk of cardiovascular events and the risk of serious, and potentially life-threatening, gastrointestinal tract bleeding. While using lower dosages of a particular NSAID may be associated with lower rates of adverse events, maintaining the clinical efficacy of standard NSAID dosages remains a challenge.
  
  
  CONCLUSIONS
  There is a need to develop new and effective NSAID formulations to minimize the safety and tolerability concerns associated with currently available NSAIDs, yet maintain efficacy in management of inflammation and pain.
authors.affiliation: Neighborhood Healthcare, Escondido, California, USA. drknowpain@cox.net
authors.forename: Bill
authors.initials: B
authors.lastname: McCarberg
authors.forename: Allan
authors.initials: A
authors.lastname: Gibofsky
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004348:Drug Labeling; D006301:Health Services Needs and Demand; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy*; D010818:Practice Patterns, Physicians'; D011320:Primary Health Care / Q000379:methods; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal