Naproxen, sold under the brand name Aleve among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, , and 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.][ Naproxen is also available in salt form, naproxen sodium, which has better solubility when taken orally.]
Common side effects include dizziness, headache, bruising, allergic reactions, heartburn, and stomach pain.[ 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.][
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Naproxen is a nonselective Cyclooxygenase inhibitor.[ As an NSAID, naproxen appears to exert its anti-inflammatory action by reducing the production of inflammatory mediators called prostaglandins.][
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Naproxen was patented in 1967 and approved for medical use in the United States in 1976.
Medical uses
Naproxen's medical uses are related to its mechanism of action as an anti-inflammatory compound.
Naproxen sodium is used as a "bridge therapy" in medication-overuse headache to slowly take patients off other medications.
Available formulations
Naproxen sodium is available as both an immediate-release and an extended-release tablet. The extended-release formulations (sometimes called "sustained release", or "enteric coated") take longer to take effect than the immediate-release formulations and therefore are less useful when immediate pain relief is desired. Extended-release formulations are more useful for the treatment of chronic, or long-lasting, conditions, in which long-term pain relief is desirable.
File:Naproxen2016.jpg|250mg tablet of naproxen
File:Naproxen.JPG|220mg tablet of naproxen sodium. Imprint L490 (upside-down). Round, light blue tablet
Pregnancy and lactation
As with all non-steroidal anti-inflammatory medications (NSAIDs), naproxen use should be avoided in pregnancy due to the importance of prostaglandins in vascular and renal function in the fetus. NSAIDs should especially be avoided in the third trimester. Small amounts of naproxen are excreted in breast milk.[ However, adverse effects are uncommon in infants breastfed from a mother taking naproxen.]
Adverse effects
Common adverse effects include dizziness, drowsiness, headache, rash, bruising, and gastrointestinal upset.[ Heavy use is associated with an increased risk of end-stage renal disease and kidney failure.]
In October 2020, the U.S. Food and Drug Administration (FDA) required the prescribing information to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.[ ][ ]
Gastrointestinal
As with other non-COX-2 selective NSAIDs, naproxen can cause gastrointestinal problems, such as heartburn, constipation, diarrhea, ulcers and stomach bleeding.[ Naproxen poses an intermediate risk of stomach ulcers compared with ibuprofen, which is low-risk, and indometacin, which is high-risk.]
Cardiovascular
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 .[
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A study found that high-dose naproxen induced near-complete suppression of platelet thromboxane throughout the dosing interval and appeared not to increase cardiovascular disease (CVD) risk, whereas other non-aspirin high-dose NSAID regimens had only transient effects on platelet COX-1 and were associated with a small but definite vascular hazard. Conversely, naproxen was associated with higher rates of upper gastrointestinal bleeding complications compared with other NSAIDs.[
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Drug-drug interactions
Naproxen may drug interaction with , lithium, methotrexate, probenecid, warfarin and other blood thinners, heart or blood pressure medications, including , or steroid medicines such as prednisone.[
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NSAIDs such as naproxen may interfere with and reduce the efficacy of SSRI antidepressants,
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.
Pharmacogenetics
The pharmacogenetics of naproxen has been studied to better understand its adverse effects.
Chemistry
Naproxen is a member of the 2-arylpropionic acid (profen) family of NSAIDs.
Synthesis
Naproxen has been industrially produced by Syntex starting from 2-naphthol as follows:
Society and culture
Brand names
Naproxen and naproxen sodium are marketed under various , including Accord, Aleve,
Access restrictions
Syntex first marketed naproxen in 1976, as the prescription drug Naprosyn. They first marketed naproxen sodium under the brand name Anaprox in 1980. It remains a prescription-only drug in much of the world. In the United States, the Food and Drug Administration (FDA) approved it as an over-the-counter (OTC) drug in 1994. OTC preparations of naproxen in the U.S. are mainly marketed by Bayer USA under the brand name Aleve and generic store brand formulations in 220mg tablets.
Ecological effects
Naproxen has been found in groundwater and drinking water in concentrations high enough to have adverse effects on invertebrates including fungi, algae, bacteria and .
Research
Naproxen may have antiviral activity against influenza. In laboratory research, it blocks the RNA-binding groove of the nucleoprotein of the virus, preventing the formation of the ribonucleoprotein complex—thus taking the viral nucleoproteins out of circulation.
Lay summary at:
Veterinary use
Horses
Naproxen is given by mouth to horses at a dose of 10mg/kg and has shown to have a wide safety margin (no toxicity when given at three times the recommended dose for 42 days).
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