Naproxen, sold under the brand name Aleve among others, is a
nonsteroidal anti-inflammatory drug (NSAID) used to treat pain,
menstrual cramps, and
inflammatory diseases such as
rheumatoid arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...
,
gout
Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of pain in a red, tender, hot, and Joint effusion, swollen joint, caused by the deposition of needle-like crystals of uric acid known as monosodium urate crysta ...
and
fever
Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
.
[ 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
In chemistry, solubility is the ability of a chemical substance, substance, the solute, to form a solution (chemistry), solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form su ...
when taken orally.
Common side effects include dizziness, headache
A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...
, bruising, allergic reactions, heartburn
Heartburn is a burning sensation felt behind the breastbone. It is a symptom that is commonly linked to acid reflux and is often triggered by food, particularly fatty, sugary, spicy, chocolate, citrus, onion-based and tomato-based products. Ly ...
, and stomach pain. Severe side effects include an increased risk of heart disease
Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina pectoris, angina, myocardial infarction, heart attack), heart failure, ...
, stroke
Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...
, 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 2022, it was the 88th most commonly prescribed medication in the United States, with more than 7million prescriptions.
Medical uses
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
Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
, such as pain
Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...
and fever
Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
(naproxen has fever-reducing, or antipyretic, properties in addition to its anti-inflammatory activity). Naproxen's anti-inflammatory properties may relieve pain caused by inflammatory conditions such as migraine, osteoarthritis, kidney stones, rheumatoid arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...
, psoriatic arthritis, gout
Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of pain in a red, tender, hot, and Joint effusion, swollen joint, caused by the deposition of needle-like crystals of uric acid known as monosodium urate crysta ...
, ankylosing spondylitis, menstrual cramps, tendinitis, and bursitis. Naproxen has also proven effective for acute post-operative pain.
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
File:Teva-naproxen-ec-500.png, Naproxen extended release 500mg, back and front
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.] Naproxen may cause muscle cramps in the legs in 3% of people.
In October 2020, the U.S. Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA) required the drug label 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. They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.[ ][ ]
Gastrointestinal
As with other non- COX-2 selective NSAIDs, naproxen can cause gastrointestinal problems, such as heartburn, constipation, diarrhea, ulcers and stomach bleeding. Naproxen should be taken orally with, or just after food, to decrease the risk of gastrointestinal
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. ...
side effects. Persons with a history of ulcers or inflammatory bowel disease
Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine ...
should consult a doctor before taking naproxen. In U.S. markets, naproxen is sold with boxed warnings about the risk of gastrointestinal ulceration or bleeding.[ Naproxen poses an intermediate risk of stomach ulcers compared with ibuprofen, which is low-risk, and indometacin, which is high-risk. To reduce stomach ulceration risk, it is often combined with a proton-pump inhibitor (a medication that reduces stomach acid production) during long-term treatment of those with pre-existing stomach ulcers or a history of developing stomach ulcers while on NSAIDs.]
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 stroke
Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...
s. 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.[
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
Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...
(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.[
]
Interactions
Drug–drug interactions
Naproxen may interact with antidepressant
Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction.
Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...
s, lithium
Lithium (from , , ) is a chemical element; it has chemical symbol, symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard temperature and pressure, standard conditions, it is the least dense metal and the ...
, methotrexate, probenecid, warfarin and other blood thinners, heart or blood pressure medications, including diuretics, or steroid medicines such as prednisone
Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...
.[
NSAIDs such as naproxen may interfere with and reduce the efficacy of ]SSRI
Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.
SSRIs primarily work by ...
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
Alcohol may refer to:
Common uses
* Alcohol (chemistry), a class of compounds
* Ethanol, one of several alcohols, commonly known as alcohol in everyday life
** Alcohol (drug), intoxicant found in alcoholic beverages
** Alcoholic beverage, an alco ...
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
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...
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
Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
shows that naproxen's time to peak plasma concentration occurs between 2 and 4 hours after oral administration, though naproxen sodium reaches peak plasma concentrations within 1–2 hours.
Pharmacogenetics
The pharmacogenetics of naproxen has been studied 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 that is necessary for clearing naproxen. Studies on the relationship between CYP2C9 genotype
The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
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.
Chemistry
Naproxen is a member of the 2-arylpropionic acid (profen) family of NSAIDs. The free acid is an odorless, white to off-white crystalline substance. Naproxen free base is lipid
Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...
-soluble and practically insoluble in water, while naproxen sodium and many other salts are freely soluble in water, often soluble in methanol, and sparingly soluble in alcohol; check the specific solubility of each salt before use. Naproxen has a melting point
The melting point (or, rarely, liquefaction point) of a substance is the temperature at which it changes state of matter, state from solid to liquid. At the melting point the solid and liquid phase (matter), phase exist in Thermodynamic equilib ...
of 152–155 °C, while naproxen salts tend to have higher melting points.
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 brand name
A brand is a name, term, design, symbol or any other feature that distinguishes one seller's goods or service from those of other sellers. Brands are used in business, marketing, and advertising for recognition and, importantly, to create and ...
s, including Accord, Aleve, Anaprox, Antalgin, Apranax, Feminax Ultra, Flanax, Inza, Maxidol, Nalgesin, Naposin, Naprelan, Naprogesic, Naprosyn, Narocin, Pronaxen, Proxen, Soproxen, and Xenifar. It is also available as the combination naproxen/esomeprazole magnesium in delayed-release tablets under the brand name Vimovo.
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
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(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 HealthCare under the brand name Aleve and generic store brand formulations in 220mg tablets. In Australia, packets of 275mg tablets of naproxen sodium are Schedule 2 pharmacy medicines, with a maximum daily dose of five tablets or 1375mg. In the United Kingdom, 250mg tablets of naproxen were approved for OTC sale under the brand name Feminax Ultra in 2008, for the treatment of primary dysmenorrhoea in women aged 15 to 50. In the Netherlands, 220mg and 275mg tablets are available OTC in drugstores, 550mg is OTC only at pharmacies. Aleve became available over the counter in some provinces in Canada on 14 July 2009, but not British Columbia
British Columbia is the westernmost Provinces and territories of Canada, province of Canada. Situated in the Pacific Northwest between the Pacific Ocean and the Rocky Mountains, the province has a diverse geography, with rugged landscapes that ...
, Quebec
Quebec is Canada's List of Canadian provinces and territories by area, largest province by area. Located in Central Canada, the province shares borders with the provinces of Ontario to the west, Newfoundland and Labrador to the northeast, ...
or Newfoundland and Labrador
Newfoundland and Labrador is the easternmost province of Canada, in the country's Atlantic region. The province comprises the island of Newfoundland and the continental region of Labrador, having a total size of . As of 2025 the populatio ...
; it subsequently became available OTC in British Columbia in January 2010 and Quebec in 2023.
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 . Naproxen is not thoroughly removed by conventional water treatment methods, and its degradation pathways in the environment are limited. Some methods more successfully remove naproxen from wastewater, including metal-organic complexes and porous carbon. Although the levels are generally low enough to not be acutely toxic, sub-lethal effects may still occur, such as reduced photosynthetic ability.
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). It is more effective for myositis than the commonly used NSAID phenylbutazone, and has shown especially good results for treatment of equine exertional rhabdomyolysis, a disease of muscle breakdown; it is less commonly used for musculoskeletal disease.
References
External links
{{Authority control
Antipyretics
Drugs developed by Bayer
Equine medications
Naphthol ethers
Nonsteroidal anti-inflammatory drugs
Propionic acids
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