Naproxen

Aleve®, Anaprox®, Naprelan®, Napron X®, Naprosyn® | Aflaxen™ | Aleve® Caplet | Anaprox® DS | Mediproxen® | Naprelan® 375 | Naprelan® 500

Classification:
Analgesics

• Nonsteroidal Antiinflammatory Drugs (NSAIDs)

Musculoskeletal Agents

• Antiinflammatory Agents
  
  • Nonsteroidal antiinflammatory drugs (NSAIDs)

Description: Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) of the propionic acid chemical class. Naproxen possesses antipyretic and analgesic properties. Naproxen is a propionic acid derivative related to ibuprofen, ketoprofen, flurbiprofen, and fenoprofen. Many pharmacodynamic similarities exist among these agents, which are usually better tolerated than aspirin or indomethacin. All NSAIDs including naproxen carry an increased risk of serious gastrointestinal adverse effects including bleeding, ulceration, and perforation of the stomach or intestines and may cause an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke. The lowest effective naproxen dose for the shortest possible duration is recommended, as the risk for adverse effects may increase with duration of use. A retrospective review by FDA Advisory Committees of short-term efficacy trials of non-prescription strength naproxen indicated that an increase in CV events was not apparent during the studies. Therefore, a cardiovascular boxed warning in non-prescription product labeling (e.g., Aleve®, Midol® Extended Relief) is not required at this time. However, it is important to note that CV risk was not the focus of the studies, and further information is needed to determine if a cause and effect relationship exists between non-prescription strength NSAID use and adverse cardiovascular outcomes. Naproxen is available as the anion and as the sodium salt; all formulations liberate naproxen as the active drug. Naproxen has been shown superior to ergotamine in the treatment of migraine. Naproxen tablets were approved by the FDA in 1976. On January 11, 1994, the FDA granted permission to market naproxen in a nonprescription form (e.g., Aleve®). The FDA approval dates for naproxen suspension, naproxen delayed-release tablets, naproxen sodium tablets, and naproxen sodium extended-release tablets are March 1987, October 1994, September 1987, and January 1996, respectively.

Naproxen competitively inhibits both cyclooxygenase (COX) isoenzymes, COX-1 and COX-2, by blocking arachidonate binding resulting in analgesic, antipyretic, and anti-inflammatory pharmacologic effects. The enzymes COX-1 and COX-2 catalyze the conversion of arachidonic acid to prostaglandin G2 (PGG2), the first step of the synthesis prostaglandins and thromboxanes that are involved in rapid physiological responses. COX isoenzymes are also responsible for a peroxidase reaction, which is not affected by NSAIDs. In addition, NSAIDs do not suppress leukotriene synthesis by lipoxygenase pathways. COX-1 is constitutively expressed in almost all tissues, while COX-2 appears to only be constitutively expressed in the brain, kidney, bones, reproductive organs, and some neoplasms (e.g., colon and prostate cancers). COX-1 is responsible for prostaglandin synthesis in response to stimulation by circulating hormones, as well as maintenance of normal renal function, gastric mucosal integrity, and hemostasis. However, COX-2 is inducible in many cells in response to certain mediators of inflammation (e.g., interleukin-1, tumor necrosis factor, lipopolysaccharide, mitogens, and reactive oxygen intermediates).