Naproxen

What Is Naproxen and What Is It Used For?

Naproxen belongs to the propionic acid class of NSAIDs, a group of medications that work by inhibiting cyclooxygenase (COX) enzymes. These enzymes—specifically COX-1 and COX-2—are responsible for the production of prostaglandins, lipid compounds that play a central role in mediating pain, inflammation, and fever throughout the body. By reducing prostaglandin synthesis, naproxen effectively addresses all three of these physiological responses simultaneously.

First developed in the 1970s by Syntex Corporation and approved by the U.S. Food and Drug Administration (FDA) in 1976, naproxen has become one of the most widely used pain relievers worldwide. It is available over the counter (OTC) in lower doses in many countries for short-term relief of mild to moderate pain, and by prescription at higher doses for chronic inflammatory conditions. The World Health Organization (WHO) includes naproxen on its Model List of Essential Medicines, recognizing its importance in global healthcare.

Approved Indications

Naproxen is indicated for a broad range of pain and inflammatory conditions. For adults and adolescents aged 12 years and older (weighing over 50 kg), naproxen is approved for the relief of temporary, mild to moderate pain conditions including:

• Headache – including tension-type headache and mild migraine
• Toothache – dental pain from various causes
• Muscle and joint pain – sprains, strains, and overuse injuries
• Back pain – acute musculoskeletal back pain
• Menstrual cramps (dysmenorrhea) – primary and secondary
• Acute migraine attacks – in adults aged 18 years and older

At prescription-strength doses, naproxen is also widely used for the management of chronic inflammatory and rheumatic conditions such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, juvenile arthritis, and gout. In these settings, the full anti-inflammatory benefit may take up to two weeks of regular use to develop, and treatment is typically supervised by a physician.

How Naproxen Works

Naproxen exerts its pharmacological effects through non-selective inhibition of both COX-1 and COX-2 enzymes. COX-2 is primarily induced at sites of tissue damage and inflammation, and its inhibition is largely responsible for the therapeutic anti-inflammatory and analgesic effects. COX-1, on the other hand, is constitutively expressed in the gastrointestinal mucosa, kidneys, and platelets, where it plays protective physiological roles. The inhibition of COX-1 explains many of the adverse effects associated with NSAIDs, particularly gastrointestinal irritation and impaired platelet function.

One of naproxen's distinguishing pharmacokinetic properties is its long elimination half-life of approximately 12 to 17 hours in healthy adults. This is considerably longer than ibuprofen (2–4 hours) or diclofenac (1–2 hours), which means naproxen provides sustained pain relief and typically only needs to be taken twice a day. The drug is well absorbed after oral administration, reaching peak plasma concentrations within 1 to 4 hours depending on the formulation. It is extensively bound to plasma proteins (approximately 99%) and is metabolized primarily in the liver before being excreted by the kidneys.

What Should You Know Before Taking Naproxen?

Contraindications

Naproxen is contraindicated in several clinical scenarios, and it is essential to be aware of these before starting treatment. You must not take naproxen if any of the following apply:

• Allergy to naproxen or other NSAIDs – If you have previously experienced allergic reactions such as asthma, rhinitis (runny nose), urticaria (hives), or angioedema after taking aspirin (acetylsalicylic acid) or any other NSAID, you must not take naproxen. Cross-reactivity between different NSAIDs is well documented.
• Active peptic ulcer disease – If you have or have had recurrent stomach ulcers or duodenal ulcers, or if you have developed ulcers during previous NSAID treatment, naproxen is contraindicated.
• Increased bleeding tendency – Naproxen inhibits platelet aggregation and prolongs bleeding time, making it unsuitable for patients with coagulation disorders.
• Severe liver disease – Advanced hepatic impairment significantly alters drug metabolism and increases the risk of adverse effects.
• Severe kidney disease – NSAIDs reduce renal blood flow by inhibiting prostaglandin-mediated vasodilation in the kidneys, which can worsen existing renal impairment.
• Severe heart failure – NSAIDs cause sodium and fluid retention, which can exacerbate cardiac failure.
• Third trimester of pregnancy – Naproxen is absolutely contraindicated during the last three months of pregnancy due to risks to the fetus and complications during delivery (see Pregnancy and Breastfeeding section below).

Warnings and Precautions

Even when naproxen is not strictly contraindicated, there are many situations in which extra caution is warranted. Always speak to your doctor before using naproxen if you have any of the following conditions or risk factors:

• Inflammatory bowel disease – Conditions such as ulcerative colitis and Crohn's disease may be worsened by NSAID use.
• Systemic lupus erythematosus (SLE) – NSAIDs can occasionally cause aseptic meningitis in patients with SLE.
• Asthma – Approximately 10–20% of asthma patients have NSAID-exacerbated respiratory disease. If you have asthma, particularly if accompanied by nasal polyps, use naproxen with extreme caution.
• Impaired kidney or liver function – Even mild to moderate impairment requires careful dose adjustment and monitoring.
• Heart failure or hypertension – NSAIDs may cause fluid retention and worsen blood pressure control.
• History of gastrointestinal problems – Previous GI bleeding, ulceration, or dyspepsia increases the risk of recurrence.
• Elderly patients – Older adults are at increased risk for all NSAID-related adverse effects, particularly gastrointestinal bleeding and renal impairment. The European Medicines Agency (EMA) and the American Geriatrics Society recommend using NSAIDs with caution in patients over 65 years.

Children and Adolescents

Naproxen should not be used in children under 12 years of age without medical supervision. In adolescents aged 12 and over who weigh more than 50 kg, OTC naproxen may be used for temporary mild to moderate pain. However, for migraine treatment, naproxen is only approved for adults aged 18 years and older. If you suspect your adolescent has migraine, consult a doctor for appropriate evaluation and management rather than self-medicating with naproxen.

Pregnancy and Breastfeeding

The safety of naproxen during pregnancy depends critically on the stage of pregnancy, and this information is vital for women of childbearing age:

First and second trimester (weeks 1–26): Naproxen should only be used during this period if clearly necessary and as advised by your doctor. If treatment is required, the lowest possible dose for the shortest possible time should be used. Importantly, from the 20th week of pregnancy onward, naproxen use for more than a few days can cause kidney problems in the fetus, potentially leading to reduced amniotic fluid (oligohydramnios) or premature closure of the ductus arteriosus in the fetal heart. If prolonged treatment is necessary during this period, your doctor may recommend additional monitoring.

Third trimester (weeks 27–40): Naproxen is absolutely contraindicated. It can cause serious harm to the unborn baby, including kidney and heart problems. It can also affect the mother's and baby's tendency to bleed and may delay or prolong labor. These risks are well documented for all NSAIDs and are reflected in regulatory guidance from the FDA, EMA, and WHO.

Breastfeeding: Naproxen passes into breast milk in small quantities. While it is unlikely to affect a breastfed infant at therapeutic doses, it is advisable to consult your doctor before using naproxen while breastfeeding, especially for prolonged periods. The American Academy of Pediatrics considers naproxen compatible with breastfeeding, but caution is still recommended.

Fertility: Naproxen may temporarily impair female fertility by inhibiting ovulation. If you are trying to conceive or experiencing difficulty becoming pregnant, discuss this with your doctor. This effect is reversible upon discontinuation of the drug.

Driving and Operating Machinery

Naproxen can cause side effects such as dizziness, drowsiness, and visual disturbances that may impair your ability to drive or operate machinery safely. You should be aware of how the medication affects you before engaging in activities requiring alertness, such as driving or performing precision work. If you experience any of these effects, avoid such activities until you feel fully capable.

How Does Naproxen Interact with Other Drugs?

Drug interactions are an important safety consideration when taking naproxen. Because NSAIDs affect prostaglandin synthesis, platelet function, and renal blood flow, they can interact with a wide range of other medications, potentially increasing the risk of adverse effects or reducing the efficacy of either drug. Always inform your doctor or pharmacist about all medications you are taking, including over-the-counter drugs and herbal supplements.

Major Interactions

The following interactions are considered clinically significant and may require dose adjustments, additional monitoring, or avoidance of concomitant use:

Moderate Interactions

These interactions are clinically relevant but may not always require avoidance. Monitoring and possible dose adjustments are typically recommended:

Food and Alcohol Interactions

Naproxen can be taken with or without food. Taking it with food does not reduce its effectiveness but may slightly delay the onset of action. Taking naproxen with food or milk can help reduce stomach irritation, which is a practical recommendation for patients who experience gastrointestinal discomfort.

Alcohol should be used with caution while taking naproxen. Both alcohol and NSAIDs irritate the gastric mucosa independently, and their combination significantly increases the risk of gastrointestinal bleeding. The FDA recommends that people who drink three or more alcoholic beverages daily should consult their doctor before using any NSAID, including naproxen.

What Is the Correct Dosage of Naproxen?

Correct dosing of naproxen is essential for achieving effective pain relief while minimizing the risk of adverse effects. The dose varies depending on the indication, the patient's age and weight, and whether the medication is used as OTC self-medication or as a prescription treatment. Always follow the instructions on the packaging or your doctor's specific directions.

Adults (18 years and older)

Adolescents (12–17 years, over 50 kg)

Elderly Patients

Older adults are at significantly increased risk for NSAID-related adverse effects, particularly gastrointestinal bleeding, renal impairment, and cardiovascular events. The following principles apply:

• Use the lowest effective dose for the shortest possible time
• Monitoring of renal function, blood pressure, and gastrointestinal symptoms is recommended
• Consider co-prescribing a proton pump inhibitor (PPI) for gastrointestinal protection
• Be alert to the signs and symptoms of GI bleeding, which may present without warning
• Regularly reassess the need for continued NSAID therapy

Missed Dose

If you forget to take a dose of naproxen, take it as soon as you remember unless it is nearly time for your next dose. In that case, skip the missed dose and continue with your regular schedule. Do not take a double dose to make up for a forgotten dose. When used as-needed for pain relief, a missed dose is generally not a concern—simply take the next dose when pain returns.

Overdose

What Are the Side Effects of Naproxen?

Like all medications, naproxen can cause side effects, although not everyone experiences them. The risk of side effects generally increases with higher doses and longer treatment duration, which is why the fundamental principle of NSAID use—lowest effective dose for the shortest possible time—is so important. Most common side effects are mild and resolve when the medication is discontinued.

Cardiovascular Risk

All NSAIDs carry a warning about potential cardiovascular risks. Medicines like naproxen may be associated with a small increased risk of heart attack or stroke, particularly when used at high doses and for long periods. However, it is worth noting that the 2013 meta-analysis by the Coxib and traditional NSAID Trialists' (CNT) Collaboration, published in The Lancet and analyzing over 600 randomized trials, found that naproxen was not associated with a significant increase in major vascular events, unlike some other NSAIDs. This has led regulatory agencies including the EMA to characterize naproxen as having a comparatively favorable cardiovascular profile among non-selective NSAIDs, though it is not entirely free of risk.

Gastrointestinal Risk

The gastrointestinal tract is the organ system most commonly affected by NSAID use. Naproxen, like all non-selective NSAIDs, inhibits COX-1 in the gastric mucosa, reducing the production of protective prostaglandins that maintain the mucosal barrier. This can lead to a spectrum of effects ranging from mild dyspepsia to serious complications such as peptic ulcers, gastrointestinal perforation, and hemorrhage. Risk factors for serious GI events include advanced age, history of peptic ulcer disease, concomitant use of anticoagulants or corticosteroids, and high-dose or prolonged NSAID use. For patients at increased GI risk who require NSAID therapy, co-prescribing a proton pump inhibitor (PPI) is strongly recommended by clinical guidelines including those from NICE and the American College of Gastroenterology.

How Should You Store Naproxen?

Proper storage of naproxen is important for maintaining the medication's effectiveness and safety. Follow these storage guidelines:

• Keep out of the reach and sight of children – This is the most critical storage requirement. Accidental ingestion by children is a medical emergency.
• Store at room temperature – Generally below 25°C (77°F), unless otherwise directed on the packaging. Avoid exposure to excessive heat, moisture, and direct sunlight.
• Check the expiration date – Do not use naproxen after the expiration date printed on the packaging (EXP). The expiration date refers to the last day of the indicated month.
• Proper disposal – Do not discard unused medications in household waste or flush them down the drain. Return unused naproxen to a pharmacy or use a medication take-back program to protect the environment.

If the tablets appear discolored, crumbled, or damaged, do not use them. Contact your pharmacist for a replacement if your medication shows signs of deterioration before the expiration date.

What Does Naproxen Contain?

Understanding the composition of naproxen tablets can be important, particularly if you have allergies or intolerances to specific excipients. While the active ingredient is the same across all brands, the inactive ingredients (excipients) may vary between manufacturers.

Active Ingredient

Each tablet contains naproxen as the active pharmaceutical ingredient. The most commonly available strengths are:

• 200 mg – soft capsule formulation (OTC)
• 250 mg – standard tablet formulation (OTC and prescription)
• 500 mg – tablet and enteric-coated tablet formulation (prescription)

Common Inactive Ingredients (Excipients)

Typical inactive ingredients found in naproxen tablets include:

• Lactose monohydrate (a milk sugar—inform your doctor if you have lactose intolerance)
• Corn starch (maize starch)
• Gelatin
• Talc
• Magnesium stearate
• Sodium starch glycolate

Available Formulations

Naproxen is available in several formulations designed to meet different clinical needs:

• Standard tablets – white, round, biconvex tablets with a score line for splitting; the most common formulation.
• Enteric-coated tablets – designed with a special coating that resists stomach acid, releasing naproxen in the small intestine instead. This may reduce direct gastric irritation but does not eliminate the systemic GI risks of NSAIDs.
• Soft capsules – contain naproxen in a liquid form within a soft gelatin shell, which may allow for faster absorption and onset of action.
• Modified-release tablets – formulations combining naproxen with other agents (e.g., esomeprazole) for enhanced gastric protection during long-term use.