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Naproxen, sold under the brand names Aleve and Naprosyn among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, menstrual cramps, inflammatory diseases such as rheumatoid arthritis, and fever. It is taken by mouth. It is available in immediate and delayed release formulations. Onset of effects is within an hour and last for up to twelve hours.

Naproxen is a nonselective COX inhibitor. It is in the propionic acid class of medications. As an NSAID, naproxen appears to exert its anti-inflammatory action by reducing the production of inflammatory mediators called prostaglandins. It is metabolized by the liver to inactive metabolites.[

Naproxen's medical uses are related to its mechanism of action as an anti-inflammatory compound. Naproxen is used to treat a variety of inflammatory conditions and symptoms that are due to excessive inflammation, such as pain and fever (naproxen has fever-reducing, or antipyretic, properties in addition to its anti-inflammatory activity). Notably, not all medications that reduce fever are anti-inflammatory compounds (such as paracetamol). Inflammatory sources of pain that may respond to naproxen's anti-inflammatory activity are conditions such as migraine, osteoarthritis, kidney stones, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, menstrual cramps, tendinitis, and bursitis.

COX-2 selective and nonselective NSAIDs have been linked to increases in the number of serious and potentially fatal cardiovascular events, such as myocardial infarctions and strokes. Naproxen is, however, associated with the smallest overall cardiovascular risks. Cardiovascular risk must be considered when prescribing any nonsteroidal anti-inflammatory drug. The drug had roughly 50% of the associated risk of stroke compared with ibuprofen, and was also associated with a reduced number of myocardial infarctions compared with control groups.

NSAIDs such as naproxen may interfere with and reduce the efficacy of SSRI antidepressants, as well as increase the risk of bleeding greater than the individual bleeding risk of either class of agent when taken together. Naproxen is not contraindicated in the presence of SSRIs, though concomitant use of the medications should be done with caution.

Naproxen works by reversibly inhibiting both the COX-1 and COX-2 enzymes as a non-selective coxib. This results in the inhibition of prostaglandin synthesis. Prostaglandins act as signaling molecules in the body, inducing inflammation. Thus, by inhibiting COX-1/2, naproxen induces an anti-inflammatory effect.

The pharmacogenetics of naproxen has been studied in an effort to better understand its adverse effects. In 1998, a small pharmacokinetic (PK) study failed to show that differences in a patient's ability to clear naproxen from the body could account for differences in a patient's risk of experiencing the adverse effect of a serious gastrointestinal bleed while taking naproxen. However, the study failed to account for differences in the activity of CYP2C9, a drug metabolizing enzyme responsible for clearing naproxen. Studies on the relationship between CYP2C9 genotype and NSAID-induced gastrointestinal bleeds have shown that genetic variants in CYP2C9 that reduce the clearance of major CYP2C9 substrates (like naproxen) increase the risk of NSAID-induced gastrointestinal bleeds, especially for homozygous defective variants.

Naproxen has been used to differentiate between infectious fevers and neoplastic or connective tissue disease-related fevers. Although the literature is inconclusive, it is thought that naproxen may help differentiate between infectious fevers and neoplastic fevers by its efficacy in reducing them; in some studies, naproxen reduced neoplastic fevers better than it reduced infectious fevers.