Naproxen

What it is

Naproxen is a non-steroidal anti-inflammatory drug (NSAID), often given as its sodium salt, which is absorbed faster. It is sold on prescription and, at lower strengths, over the counter. It relieves pain, inflammation and fever.

What the research says

The trial evidence shows naproxen relieves short-term pain well: in reviews of dental and surgical pain, about half of people got useful relief versus 15% on placebo. For period pain, NSAIDs as a class clearly beat placebo, though the evidence was rated low quality. For arthritis pain it helps, with larger doses doing more. On its own it is weak for migraine. The harms are real. Like all NSAIDs it raises the risk of stomach bleeding, heart failure and kidney injury, although among NSAIDs it has one of the lower signals for heart attack and stroke. A prevention trial found it did not prevent Alzheimer's disease.

Evidence grade: Well established.

How it works

Drug class: Non-selective non-steroidal anti-inflammatory drug (NSAID); propionic acid derivative

Naproxen blocks both forms of the cyclooxygenase enzyme (COX-1 and COX-2), which the body uses to make prostaglandins. Prostaglandins sensitise pain nerves and drive inflammation and fever. The label notes that the mechanism is not completely understood. (Source 1)

Boxed warning

WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS Cardiovascular Thrombotic Events Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use [see Warnings and Precautions (5.1) ]. Naproxen tablets and naproxen sodium tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications (4) , Warnings and Precautions (5.1) ]. Gastrointestinal Bleeding, Ulceration, and Perforation NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events [see Warnings and Precautions (5.2) ].

(Source 2)

What it is used for

• A Cochrane review of 15 trials found a single 500/550 mg dose gave at least 50% pain relief for about half of patients, against 15% on placebo (NNT 2.7). Evidence: established. (Source 3)
• In a Cochrane review, NSAIDs as a class relieved period pain better than placebo (OR 4.37). The evidence was rated low quality, side effects were more frequent, and no single NSAID was shown to be better than the others. Evidence: established. (Source 4)
• A network meta-analysis of 76 trials found every NSAID beat placebo for osteoarthritis pain, and naproxen had a significant dose-response. Naproxen was not among the six treatments with at least a 95% probability of a clinically important effect. Evidence: established. (Source 5)
• Naproxen beat placebo, but the NNT of 11 for being pain-free at two hours led Cochrane reviewers to call it not clinically useful on its own. A fixed combination with sumatriptan is a separate product that works better. Evidence: limited. (Source 6)
• The ADAPT randomised trial in people aged 70+ with a family history of Alzheimer's found that naproxen did not prevent the disease. The early hazard ratio pointed toward harm (2.35, not significant). Evidence: not-supported. (Source 7)

Interactions

• Low-dose aspirin (pharmacokinetic study): Taking naproxen before aspirin blunted aspirin's lasting antiplatelet effect in healthy volunteers. The effect was smaller when naproxen was taken 2 hours after aspirin. Whether this changes heart outcomes has not been tested in trials. (Source 8)
• SSRI antidepressants, anticoagulants, oral corticosteroids (label): The label lists these as risk factors for serious GI bleeding on NSAIDs. A meta-analysis of observational studies found SSRIs added to NSAIDs raised the odds of upper GI bleeding (OR 1.75). (Source 9)
• Alcohol (label): The label lists alcohol use as a risk factor for GI bleeding with NSAIDs. A case-control study found heavy drinking and NSAID use together gave the highest bleeding risk, but naproxen itself was not analysed. (Source 10)
• Magnesium oxide or aluminium hydroxide antacids, sucralfate (label): These can delay how quickly naproxen is absorbed. The label does not recommend taking them together. (Source 11)

Stopping it

• Naproxen causes no known dependence or withdrawal syndrome. Using acute headache medicines often (analgesics included) is linked to medication-overuse headache. A German guideline advises education and preventive treatment first, then pausing acute medication if those fail. (Source 12)

What goes wrong

NSAIDs used for period pain caused more side effects than placebo, mostly gastrointestinal and neurological. (Source 4)

• Systematic review, Low certainty.
• Size: 25 RCTs for overall adverse effects.
• Who: Women with primary dysmenorrhoea.
• How long: Menstrual cycles studied.
• Result: Overall adverse effects OR 1.29 (95% CI 1.11 to 1.51); an estimated 11-14% vs 10%.
• Funding: not stated in abstract.

The evidence suggests that if 10% of women taking placebo experience side effects, between 11% and 14% of women taking NSAIDs will do so.

All NSAID regimens studied, naproxen included, roughly doubled the risk of heart failure. (Source 13)

• Meta-analysis, Certainty not rated.
• Size: 754 randomised trials.
• Who: Trial participants on NSAIDs.
• How long: Trial durations.
• Result: Heart failure risk roughly doubled by all NSAIDs.
• Funding: independent (UK Medical Research Council, British Heart Foundation)

Heart failure risk was roughly doubled by all NSAIDs.

All NSAID regimens raised the risk of upper gastrointestinal complications (perforation, obstruction or bleeding). High-dose naproxen raised it about fourfold, the largest increase of the regimens compared. (Source 13)

• Meta-analysis, Certainty not rated.
• Size: 754 randomised trials.
• Who: Trial participants on NSAIDs.
• How long: Trial durations.
• Result: Upper GI complications: naproxen RR 4.22 (95% CI 2.71-6.56), ibuprofen 3.97, diclofenac 1.89, coxibs 1.81.
• Funding: independent (UK Medical Research Council, British Heart Foundation)

All NSAID regimens increased upper gastrointestinal complications (coxibs 1·81, 1·17-2·81, p=0·0070; diclofenac 1·89, 1·16-3·09, p=0·0106; ibuprofen 3·97, 2·22-7·10, p<0·0001; and naproxen 4·22, 2·71-6·56, p<0·0001).

In the PRECISION trial of arthritis patients at raised cardiovascular risk, naproxen had a cardiovascular event rate similar to celecoxib and ibuprofen, and more gastrointestinal events than celecoxib. (Source 14)

• Randomized trial, Certainty not rated.
• Size: 24,081 patients.
• Who: Adults with osteoarthritis or rheumatoid arthritis at increased cardiovascular risk.
• How long: Mean treatment 20.3 months; follow-up 34.1 months.
• Result: Primary CV outcome 2.5% naproxen vs 2.3% celecoxib vs 2.7% ibuprofen (ITT); 68.8% stopped study drug.
• Funding: industry-funded (Pfizer, maker of celecoxib)

a primary outcome event occurred in 188 patients in the celecoxib group (2.3%), 201 patients in the naproxen group (2.5%), and 218 patients in the ibuprofen group (2.7%)

Adding an SSRI antidepressant to an NSAID was associated with a higher risk of upper gastrointestinal bleeding than the NSAID alone. (Source 15)

• Meta-analysis, Certainty not rated.
• Size: 1 cohort and 9 case-control studies.
• Who: Patients taking NSAIDs with or without SSRIs.
• How long: Observational.
• Result: OR 1.75 (95% CI 1.32-2.33)
• Funding: not stated in abstract.

There was an additional increased risk of upper GI bleeding in patients on NSAIDs with concomitant SSRI use (OR 1.75, 95% CI = 1.32-2.33).

In adults aged 65 and over, systemic NSAID use for more than 14 days was associated with higher odds of acute kidney injury or high potassium (a class finding, not naproxen-specific). (Source 16)

• Cohort study, Certainty not rated.
• Size: 12,798 older adults.
• Who: Adults aged 65+ in Singapore public healthcare.
• How long: 30-day outcome.
• Result: Systemic NSAIDs >14 days adjusted OR 1.84 (95% CI 1.37-2.49); primary outcome occurred in 16.7% overall.
• Funding: not stated in abstract.

systemic NSAIDs > 14 days (adjusted OR 1.84, 95% CI 1.37-2.49) were independently associated with the primary outcome, compared with no NSAID.

In a case-control study, heavy drinking independently raised the risk of upper GI bleeding, and the risk was highest in heavy drinkers who also used aspirin or ibuprofen. Naproxen was not analysed separately. (Source 10)

• Case-control study, Certainty not rated.
• Size: 1224 cases, 2945 controls.
• Who: Adults in the US and Sweden.
• How long: Case-control.
• Result: UGIB relative risk rose to 2.8 in those drinking 21+ drinks/week; regular ibuprofen RR 2.7 among drinkers.
• Funding: not stated in abstract.

As heavy alcohol intake independently increases the risk, the incidence of UGIB is highest among persons who are both heavy drinkers and users of aspirin or ibuprofen.

What the evidence supports

A single 500/550 mg dose of naproxen gave at least 50% pain relief over four to six hours with an NNT of 2.7 in postoperative pain. (Source 3)

• Systematic review, Certainty not rated.
• Size: 15 studies, 1509 participants (784 in the 500/550 mg analysis)
• Who: Adults with moderate to severe acute postoperative pain.
• How long: Single dose, 4-6 hours.
• Result: NNT 2.7 (95% CI 2.3 to 3.2); median time to rescue medication 8.9 h vs 2.0 h on placebo.
• Funding: not stated in abstract.

In nine studies (784 participants) using 500/550 mg naproxen or naproxen sodium the NNT for at least 50% pain relief over four to six hours was 2.7 (95% CI 2.3 to 3.2).

About half of patients given naproxen got clinically useful pain relief, compared with 15% on placebo, and adverse events did not differ from placebo in single-dose use. (Source 3)

• Systematic review, Certainty not rated.
• Size: 15 studies, 1509 participants.
• Who: Adults after surgery.
• How long: Single dose.
• Result: About 50% vs 15% achieving useful relief.
• Funding: not stated in abstract.

About half of participants treated with these doses experienced clinically useful levels of pain relief, compared to 15% with placebo

NSAIDs as a class relieved primary dysmenorrhoea better than placebo, but the evidence was low quality. (Source 4)

• Systematic review, Low certainty.
• Size: 80 RCTs, 5820 women (35 RCTs in this comparison)
• Who: Women with primary dysmenorrhoea.
• How long: Menstrual cycles studied.
• Result: OR 4.37 (95% CI 3.76 to 5.09) for pain relief; an estimated 45-53% on NSAIDs vs 18% on placebo get moderate or excellent relief.
• Funding: not stated in abstract.

NSAIDs were more effective for pain relief than placebo (OR 4.37, 95% CI 3.76 to 5.09; 35 RCTs, I(2) = 53%, low quality evidence)

In knee and hip osteoarthritis, every NSAID improved pain compared with placebo, and only naproxen showed a significant linear dose-response. (Source 5)

• Meta-analysis, Certainty not rated.
• Size: 76 trials, 58,451 patients.
• Who: Adults with knee or hip osteoarthritis.
• How long: Up to the trial durations (varied)
• Result: Linear dose effect significant only for naproxen (p=0.034)
• Funding: independent (Swiss National Science Foundation)

Treatment effects increased as drug dose increased, but corresponding tests for a linear dose effect were significant only for naproxen (p=0·034).

What the evidence does not support

Naproxen was not among the six treatments with at least a 95% probability of a clinically important pain reduction in osteoarthritis, and diclofenac 150 mg/day ranked most effective. (Source 5)

• Meta-analysis, Certainty not rated.
• Size: 76 trials, 58,451 patients.
• Who: Adults with knee or hip osteoarthritis.
• How long: Varied.
• Result: Minimum clinically important effect set at ES -0.37; naproxen not among the treatments reaching 95% probability.
• Funding: independent (Swiss National Science Foundation)

For six interventions (diclofenac 150 mg/day, etoricoxib 30 mg/day, 60 mg/day, and 90 mg/day, and rofecoxib 25 mg/day and 50 mg/day), the probability that the difference to placebo is at or below a prespecified minimum clinically important effect for pain reduction (effect size [ES] -0·37) was at least 95%.

Naproxen did not prevent Alzheimer's disease in older adults with a family history, and the early hazard ratio pointed toward harm. (Source 7)

• Randomized trial, Certainty not rated.
• Size: ADAPT trial at six US sites (treatment suspended December 2004)
• Who: Adults aged 70+ with a family history of Alzheimer's disease.
• How long: Early years of treatment (suspended early)
• Result: HR for AD 2.35 (95% CI 0.95 to 5.77; p=0.06) naproxen vs placebo.
• Funding: not stated in abstract.

These results do not support the hypothesis that celecoxib or naproxen prevent Alzheimer dementia, at least within the early years after initiation of treatment.

Where the evidence is mixed

For acute migraine, naproxen alone beat placebo only modestly, and the Cochrane reviewers judged it not clinically useful as a stand-alone treatment. (Source 6)

• Systematic review, Moderate certainty.
• Size: 6 studies; 1241 took naproxen, 1092 placebo.
• Who: Adults with moderate or severe migraine attacks.
• How long: Single attack, 2-24 hours.
• Result: Pain-free at 2 h: 17% vs 8%, RR 2.0 (95% CI 1.6 to 2.6), NNT 11 (moderate quality)
• Funding: not stated in abstract.

Naproxen is statistically superior to placebo in the treatment of acute migraine, but the NNT of 11 for pain-free response at two hours suggests that it is not a clinically useful treatment.

In an individual-participant meta-analysis of randomised trials, high-dose naproxen did not significantly increase major vascular events (heart attack, stroke or vascular death). (Source 13)

• Meta-analysis, Certainty not rated.
• Size: 280 placebo-controlled trials (124,513 participants) and 474 NSAID-vs-NSAID trials (229,296 participants)
• Who: Trial participants on NSAIDs, including people at vascular risk.
• How long: Trial durations (person-years reported)
• Result: Major vascular events with naproxen RR 0.93 (0.69-1.27)
• Funding: independent (UK Medical Research Council, British Heart Foundation)

Naproxen did not significantly increase major vascular events (0·93, 0·69-1·27).

Where the research disagrees

Whether naproxen is the NSAID with the lowest cardiovascular risk

• Coxib and traditional NSAID Trialists' Collaboration (Lancet 2013), individual-participant meta-analysis of randomised trials: high-dose naproxen is associated with less vascular risk than other NSAIDs (Source 13)
• PRECISION investigators (NEJM 2016, Pfizer-funded), randomised non-inferiority trial with high drop-out: At moderate doses, celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety. (Source 14)

How much

• Reference intake: Dosing is set by the prescriber. The FDA label, as a position (DailyMed version effective 2026-09-24), advises the lowest effective dose for the shortest duration. (Source 17)
• Upper limit: For rheumatoid arthritis, osteoarthritis and ankylosing spondylitis, the label allows the dose to be raised to 1500 mg/day of naproxen for limited periods of up to 6 months when more anti-inflammatory or pain-relieving effect is needed, and says the prescriber should see enough extra benefit to offset the added risk. This is a regulatory position, not a target. (Source 18)
• Studied: Single doses of 200/220 to 500/550 mg in postoperative pain trials. (Source 3)
• Studied: Mean 852 mg/day in the PRECISION cardiovascular safety trial. (Source 14)
• Studied: Naproxen sodium 220 mg twice daily in the ADAPT Alzheimer prevention trial. (Source 7)

A common belief, and what the research shows

The belief: Naproxen is a good stand-alone migraine treatment because it is a strong, long-acting painkiller.

What the research shows: Cochrane found naproxen beat placebo for migraine, but: "the NNT of 11 for pain-free response at two hours suggests that it is not a clinically useful treatment."

Questions and answers

What is it?

Naproxen is a synthetic non-steroidal anti-inflammatory drug, available on prescription and over the counter. The body does not make it and it is not found in food. (Source 1)

What does it do in the body?

It blocks the COX-1 and COX-2 enzymes, which cuts prostaglandin production. That reduces pain, inflammation and fever. (Source 1)

Is it good or bad for you?

It depends on the setting. Short courses relieve acute pain and period pain well. All NSAIDs raise the risk of stomach bleeding, heart failure and kidney injury, and these risks grow in older people and with longer use. The reviewers say the size of these risks can be predicted. (Source 13)

How do you get more of it?

Does not apply as a nutrient. Naproxen is a medicine taken only as a product. The label, as a position, advises the lowest effective dose for the shortest time. (Source 17)

If it is harmful, what reduces it?

Naproxen leaves the body on its own once it is stopped. The label advises limiting dose and duration to reduce its harms. It causes no known withdrawal syndrome, but frequent use for headache is linked to medication-overuse headache. (Source 17)

Why might someone be low in it or missing it?

Does not apply. Naproxen is not a nutrient or body substance that anyone can be low in. (Source 1)

We searched: Europe PMC and the DailyMed label; naproxen is a synthetic drug with no physiological level

Which whole foods contain it or feed it?

Does not apply. No food contains naproxen. (Source 1)

We searched: DailyMed label and Europe PMC; no dietary source exists for a synthetic drug

What happens if you do not have it?

Does not apply. Not taking naproxen causes no deficiency. The only effect is losing its pain relief. (Source 1)

We searched: DailyMed label and Europe PMC

How can you test for it?

No routine blood test is used to guide naproxen dosing. For long-term use, the label says to consider checking blood counts and a chemistry panel periodically, because bleeding, liver injury and kidney injury can occur without warning. (Source 19)

References

1. US FDA-approved labeling via DailyMed (National Library of Medicine). Naproxen Tablets / Naproxen Sodium Tablets prescribing information (American Health Packaging), DailyMed SPL effective 2026-09-24. 2026. Read the source
2. US FDA-approved labeling via DailyMed (National Library of Medicine). Naproxen Tablets / Naproxen Sodium Tablets prescribing information (American Health Packaging), DailyMed SPL effective 2026-09-24. 2026. Read the source
3. The Cochrane database of systematic reviews. Single dose oral naproxen and naproxen sodium for acute postoperative pain in adults.. 2009. PMID 19160232, DOI 10.1002/14651858.cd004234.pub3. Read the source
4. The Cochrane database of systematic reviews. Nonsteroidal anti-inflammatory drugs for dysmenorrhoea.. 2015. PMID 26224322, DOI 10.1002/14651858.cd001751.pub3. Read the source
5. Lancet (London, England). Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis.. 2017. PMID 28699595, DOI 10.1016/s0140-6736(17)31744-0. Read the source
6. The Cochrane database of systematic reviews. Naproxen with or without an antiemetic for acute migraine headaches in adults.. 2013. PMID 24142263, DOI 10.1002/14651858.cd009455.pub2. Read the source
7. Neurology. Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial.. 2007. PMID 17460158, DOI 10.1212/01.wnl.0000260269.93245.d2. Read the source
8. Arthritis and rheumatism. Low-dose naproxen interferes with the antiplatelet effects of aspirin in healthy subjects: recommendations to minimize the functional consequences.. 2011. PMID 21360514, DOI 10.1002/art.30175. Read the source
9. US FDA-approved labeling via DailyMed (National Library of Medicine). Naproxen Tablets / Naproxen Sodium Tablets prescribing information (American Health Packaging), DailyMed SPL effective 2026-09-24. 2026. Read the source
10. The American journal of gastroenterology. The risk of acute major upper gastrointestinal bleeding among users of aspirin and ibuprofen at various levels of alcohol consumption.. 1999. PMID 10566713, DOI 10.1111/j.1572-0241.1999.01517.x. Read the source
11. US FDA-approved labeling via DailyMed (National Library of Medicine). Naproxen Tablets / Naproxen Sodium Tablets prescribing information (American Health Packaging), DailyMed SPL effective 2026-09-24. 2026. Read the source
12. Neurological research and practice. Management of medication overuse (MO) and medication overuse headache (MOH) S1 guideline.. 2022. PMID 36031642, DOI 10.1186/s42466-022-00200-0. Read the source
13. Lancet (London, England). Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials.. 2013. PMID 23726390, DOI 10.1016/s0140-6736(13)60900-9. Read the source
14. The New England journal of medicine. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis.. 2016. PMID 27959716, DOI 10.1056/nejmoa1611593. Read the source
15. Scientific reports. Selective serotonin reuptake inhibitors increase risk of upper gastrointestinal bleeding when used with NSAIDs: a systemic review and meta-analysis.. 2022. PMID 36002638, DOI 10.1038/s41598-022-18654-2. Read the source
16. Drugs & aging. Non-Steroidal Anti-Inflammatory Drugs and Risk of Acute Kidney Injury and Hyperkalemia in Older Adults: A Retrospective Cohort Study and External Validation of a Clinical Risk Model.. 2022. PMID 34888761, DOI 10.1007/s40266-021-00907-w. Read the source
17. US FDA-approved labeling via DailyMed (National Library of Medicine). Naproxen Tablets / Naproxen Sodium Tablets prescribing information, section 2.1 (American Health Packaging), DailyMed SPL effective 2026-09-24. 2026. Read the source
18. US FDA-approved labeling via DailyMed (National Library of Medicine). Naproxen Tablets / Naproxen Sodium Tablets prescribing information, section 2.2 (American Health Packaging), DailyMed SPL effective 2026-09-24. 2026. Read the source
19. US FDA-approved labeling via DailyMed (National Library of Medicine). Naproxen Tablets / Naproxen Sodium Tablets prescribing information (American Health Packaging), DailyMed SPL effective 2026-09-24. 2026. Read the source