Naproxen, sold under the brand name Aleve among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, menstrual cramps, inflammatory diseases such as rheumatoid arthritis, gout and fever. It is taken orally. It is available in immediate and delayed release formulations. Onset of effects is within an hour and lasts for up to twelve hours.Common side effects include dizziness, headache, bruising, allergic reactions, heartburn, and stomach pain. Severe side effects include an increased risk of heart disease, stroke, gastrointestinal bleeding, and stomach ulcers. The heart disease risk may be lower than with other NSAIDs. It is not recommended in people with kidney problems. Use is not recommended in the third trimester of pregnancy.Naproxen is a nonselective COX inhibitor. 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 was patented in 1967, and approved for medical use in the United States in 1976. In the United States it is available over the counter and as a generic medication. In 2019, it was the 61st most commonly prescribed medication in the United States, with more than 11 million prescriptions. Medical uses
Naproxens 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).
Interactions
Drug–drug interactions
Naproxen may interact with antidepressants, lithium, methotrexate, probenecid, warfarin and other blood thinners, heart or blood pressure medications, including diuretics, or steroid medicines such as prednisone.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. Alcohol consumption increases the risk of gastrointestinal bleeding when combined with NSAIDs like naproxen in a dose-dependent manner (that is, the higher the dose of naproxen, the higher the risk of bleeding). The risk is highest for people who are heavy drinkers. Pharmacology
Mechanism of action
Naproxen works by reversibly inhibiting both the COX-1 and COX-2 enzymes as a non-selective coxib. Pharmacokinetics
Naproxen is a minor substrate of CYP1A2 and CYP2C9. It is extensively metabolized in the liver to 6-O-desmethylnaproxen, and both the parent drug and the desmethyl metabolite undergo further metabolism to their respective acylglucuronide conjugated metabolites. An analysis of two clinical trials shows that naproxens time to peak plasma concentration occurs between 2–4 hours after oral administration, though naproxen sodium reaches peak plasma concentrations within 1–2 hours. Pharmacogenetics
The pharmacogenetics of naproxen has been studied in an effort to better understand its adverse effects.