Drug Monograph
Naproxen (Naprosyn, Aleve)
naproxen & naproxen sodium
Pharmacokinetic Profile
Half-Life
12–17 h
Metabolism
Hepatic (CYP2C9, CYP1A2 minor); glucuronidation
Protein Binding
>99% (albumin)
Bioavailability
~95%
Volume of Distribution
0.16 L/kg
Clinical Information
Drug Class
Non-selective NSAID
Available Doses
220 mg (OTC Na salt); 250, 375, 500 mg (Rx); 550 mg Na salt (Rx)
Route
Oral (tablet, DR tablet, suspension)
Renal Adjustment
Avoid if CrCl <30 mL/min
Hepatic Adjustment
Caution; avoid in severe impairment
Pregnancy
Avoid ≥20 weeks; contraindicated ≥30 weeks
Lactation
Excreted in milk (~1% plasma level); short-term use acceptable; ibuprofen often preferred
Schedule / Legal Status
OTC (220 mg Na salt) / Rx (higher doses)
Black Box Warning
Yes — CV thrombotic events & GI bleeding
Generic Available
Yes (widely available)
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Rheumatoid arthritis | Adults | Monotherapy or combination with DMARDs | FDA Approved |
| Osteoarthritis | Adults | Monotherapy | FDA Approved |
| Ankylosing spondylitis | Adults | Monotherapy | FDA Approved |
| Polyarticular juvenile idiopathic arthritis | ≥2 years | Monotherapy or adjunctive | FDA Approved |
| Acute pain | Adults | Monotherapy | FDA Approved |
| Primary dysmenorrhea | Adults | Monotherapy | FDA Approved |
| Acute tendonitis & bursitis | Adults | Monotherapy | FDA Approved |
| Acute gout | Adults | Monotherapy | FDA Approved |
Naproxen is one of the most widely used non-steroidal anti-inflammatory drugs globally, valued for its combination of analgesic, antipyretic, and anti-inflammatory properties. Its long half-life allows for twice-daily dosing in most clinical scenarios, and among traditional NSAIDs it is generally considered to carry a comparatively favorable cardiovascular risk profile (PRECISION trial, FDA PI). It is available without a prescription in lower-dose naproxen sodium formulations for short-term pain relief.
Off-Label Uses
Migraine (acute treatment) — Naproxen sodium 500–550 mg is used as monotherapy or in combination with a triptan for acute migraine attacks. Supported by multiple randomized trials and the combination product sumatriptan/naproxen (Treximet). Evidence quality: High.
Pericarditis — NSAIDs including naproxen are recommended as first-line therapy for acute and recurrent pericarditis by the ESC 2015 guidelines, typically 500 mg BID tapered over weeks. Evidence quality: High.
Chronic low back pain — NSAIDs are recommended as first-line pharmacotherapy by the ACP/APS guidelines. Evidence quality: Moderate.
Dosing
Adult Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Chronic inflammatory arthritis (RA, OA, AS) — long-term control | 250–500 mg BID | 250–500 mg BID | 1500 mg/day Max 1500 mg/day for ≤6 months only | Adjust dose to lowest effective level; morning and evening doses need not be equal EC-Naprosyn 375 or 500 mg BID is an alternative for GI-sensitive patients |
| Acute musculoskeletal pain, dysmenorrhea, tendonitis, bursitis | 550 mg naproxen sodium Then 550 mg q12h or 275 mg q6–8h | 550 mg q12h | Day 1: 1375 mg; thereafter 1100 mg/day | Naproxen sodium (Anaprox DS) preferred for acute pain due to faster absorption Alternative: naproxen base 500 mg then 250 mg q6–8h; max 1250 mg/day |
| Acute gout flare | 750 mg naproxen base Then 250 mg q8h until flare subsides | 250 mg q8h | 1250 mg/day (base) | Continue until flare fully resolved (typically 5–7 days); do not use EC formulation (delayed absorption) Anaprox DS alternative: 825 mg then 275 mg q8h |
| Acute pericarditis (off-label) | 500 mg BID | 500 mg BID × 1–2 weeks, then taper | 1000 mg/day | Taper over 3–4 weeks; co-prescribe colchicine per ESC 2015 guidelines Add gastroprotection if risk factors present |
| OTC self-care (minor aches, headache, fever) | 220 mg naproxen sodium | 220 mg q8–12h | 660 mg/day | Adults and children ≥12 years; max 10 days for pain or 3 days for fever without medical consultation Adults <65: first dose may be 440 mg; adults ≥65: use 220 mg q12h and consult prescriber for use >10 days |
Pediatric Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Juvenile idiopathic arthritis (≥2 years) | 5 mg/kg BID | 5 mg/kg BID | 10 mg/kg/day | Liquid formulation preferred for weight-based dosing; tablets only suitable for children ≥50 kg 5 mg/kg produces plasma levels similar to adults receiving 500 mg (FDA PI) |
Clinical Pearl: Naproxen vs. Naproxen Sodium
Naproxen sodium 550 mg is equivalent to naproxen base 500 mg (the additional 50 mg is sodium). The sodium salt dissolves more rapidly, yielding a faster Tmax (~1 h vs. 2 h for base), making it the preferred formulation for acute pain. Different formulations are not interchangeable milligram-for-milligram. Always specify whether dosing refers to naproxen base or sodium salt.
Special Population Adjustments
| Population | Adjustment | Rationale |
|---|---|---|
| Elderly (≥65 years) | Use lowest effective dose; consider starting at 220–250 mg BID | Increased unbound fraction despite unchanged total plasma levels; higher GI and CV risk |
| Renal impairment (CrCl <30 mL/min) | Not recommended; metabolites may accumulate | Decreased elimination of conjugated metabolites; risk of further renal deterioration |
| Hepatic impairment | Caution with mild-moderate; avoid in severe | Altered disposition kinetics; elevated bleeding risk due to coagulopathy |
| Heart failure | Avoid unless benefits outweigh risks; monitor for fluid retention | NSAIDs increase risk of hospitalisation for heart failure; blunt diuretic efficacy |
Pharmacology
Mechanism of Action
Naproxen is a 2-arylpropionic acid derivative that exerts its pharmacological effects through non-selective, reversible inhibition of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. By blocking COX-mediated conversion of arachidonic acid to prostaglandins and thromboxane A2, naproxen reduces prostaglandin synthesis at sites of inflammation, injury, and fever generation. The anti-inflammatory effect stems primarily from COX-2 inhibition in inflammatory tissues, while analgesia involves both peripheral prostaglandin reduction and possible central mechanisms. Its relatively low COX-2 selectivity ratio compared to coxibs is thought to contribute to a more balanced prostacyclin-thromboxane profile, which may partly explain the comparatively favourable cardiovascular safety signal observed in large-scale trials such as PRECISION.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Oral bioavailability ~95%; Tmax 1–2 h (IR tablets), 2–4 h (EC/DR tablets); Na salt Tmax ~1 h | Nearly complete absorption; food does not significantly affect total bioavailability; use sodium salt when rapid onset is desired |
| Distribution | Vd 0.16 L/kg; >99% albumin-bound; penetrates synovial fluid | Highly confined to plasma compartment; saturable protein binding at doses >500 mg/day leads to increased free fraction and clearance; substantial concentrations in synovial fluid support joint-targeted action |
| Metabolism | Hepatic: O-demethylation to 6-O-desmethylnaproxen (CYP2C9, CYP1A2 minor substrates); further conjugation to acyl glucuronides | Not a significant CYP3A4 inducer or inhibitor; CYP2C9 polymorphisms may alter clearance but clinical impact is modest; minimal first-pass metabolism |
| Elimination | t½ 12–17 h; ~95% excreted renally as conjugated metabolites; <1% unchanged in urine; clearance 0.13 mL/min/kg | Long half-life supports BID dosing; steady state in 4–5 days; metabolite accumulation in renal impairment; ~1% excreted in breast milk |
Side Effects
Adverse reaction data from controlled clinical trials in 960 patients treated for RA or OA and 962 patients treated for acute pain or dysmenorrhea (FDA PI, revised 11/2024). GI reactions were more frequent and severe with daily doses of 1500 mg naproxen compared to 750 mg.
≥10%
Very Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| ALT/AST elevation (<3× ULN) | Up to 15% | Usually transient and asymptomatic; clinically significant elevations (≥3× ULN) occur in ~1% of NSAID-treated patients; monitor if symptoms of hepatotoxicity develop (FDA PI section 5.3) |
1–10%
Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Dyspepsia / heartburn | 3–9% | Most common adverse effect overall; dose-related and more frequent with chronic use (GI reactions reported 2–10× more often in chronic vs. short-term studies); co-prescribe PPI or H2RA if high risk |
| Abdominal pain | 3–9% | May signal developing ulceration; evaluate if persistent or worsening |
| Nausea | 3–9% | Taking with food or milk may reduce symptoms without affecting bioavailability |
| Headache | 3–9% | Often self-limiting; differentiate from medication overuse headache with chronic use |
| Dizziness | 3–9% | Advise caution with driving or operating machinery at initiation |
| Drowsiness | 3–9% | May be potentiated by concurrent CNS depressants |
| Pruritus / skin eruptions | 3–9% | Discontinue if rash progresses; assess for photosensitivity in sun-exposed patients |
| Ecchymosis / bruising | 3–9% | Reflects platelet function inhibition; higher risk when combined with anticoagulants |
| Tinnitus | 3–9% | Usually reversible with dose reduction; assess hearing if persistent |
| Peripheral edema | 1–3% | Due to renal sodium retention; monitor weight and blood pressure; caution in heart failure |
| Constipation | 1–3% | Encourage adequate hydration and dietary fibre |
| Diarrhoea | 1–3% | Consider enteric-coated formulation if recurrent |
| Flatulence | 1–3% | NSAID class effect; usually mild |
Serious
Serious Adverse Effects (Regardless of Frequency)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| GI bleeding, ulceration, perforation | ~1% at 3–6 months; 2–4% at 1 year | Any time; may occur without warning | Discontinue immediately; urgent endoscopy; haemodynamic stabilisation |
| Cardiovascular thrombotic events (MI, stroke) | Increased relative risk (lower vs. other NSAIDs) | May begin in first weeks; increases with duration | Use lowest effective dose for shortest duration; avoid post-CABG; monitor CV symptoms |
| Severe hepatotoxicity (fulminant hepatitis, liver necrosis) | Rare (<0.1%); ALT/AST ≥3× ULN in ~1% | Weeks to months | Discontinue if symptomatic LFT elevation or ≥3× ULN; full hepatic workup |
| Acute kidney injury / renal papillary necrosis | Uncommon; higher in dehydrated/elderly | Days to weeks, especially with volume depletion | Discontinue; IV hydration; monitor creatinine; avoid rechallenge in acute setting |
| Severe skin reactions (SJS, TEN, DRESS) | Very rare | 1–4 weeks after initiation | Discontinue immediately at first sign of rash or mucosal involvement; dermatology consultation; permanent discontinuation |
| Anaphylaxis / anaphylactoid reactions | Very rare | Minutes to hours after dose | Emergency management (epinephrine, airway support); permanent discontinuation of all NSAIDs |
| Heart failure exacerbation / fluid overload | ~2-fold increased hospitalisation risk (NSAID class) | Days to weeks | Discontinue; manage fluid overload; avoid NSAIDs in severe heart failure |
| Agranulocytosis / thrombocytopenia | Very rare | Variable | Discontinue; CBC with differential; haematology referral |
| Aseptic meningitis | Very rare; higher in SLE patients | Hours to days | Discontinue; CSF analysis to exclude infectious cause; typically resolves on withdrawal |
Discontinuation
Discontinuation Rates
Chronic Use (RA/OA Trials)
~10–15%
Top reasons: GI intolerance (dyspepsia, abdominal pain, nausea), CNS effects (headache, dizziness), skin reactions
Short-term Acute Pain Studies
~3–5%
Top reasons: GI upset; GI adverse events were 2–10× less frequent in short-term vs. chronic use
| Reason for Discontinuation | Incidence | Context |
|---|---|---|
| GI intolerance (dyspepsia, nausea, abdominal pain) | 5–8% | Most common reason in chronic trials; higher at 1500 mg/day |
| CNS effects (headache, dizziness, drowsiness) | 1–3% | More frequent with chronic use |
| Dermatologic reactions (rash, pruritus) | 1–2% | Mandate discontinuation if suggestive of serious skin reaction |
| Peripheral edema / hypertension | <1% | More relevant in patients with pre-existing CV or renal disease |
GI Risk Management
Gastrointestinal toxicity is the most clinically significant concern with naproxen. Co-prescribe a proton pump inhibitor in patients with risk factors: age ≥65, prior peptic ulcer disease, concurrent aspirin, anticoagulants, corticosteroids, or SSRIs. H. pylori testing and eradication should be considered before starting long-term NSAID therapy. Upper GI ulcers and bleeding occurred in approximately 1% of patients at 3–6 months and 2–4% at one year of chronic NSAID use (FDA PI).
Drug Interactions
Naproxen is a minor CYP2C9 and CYP1A2 substrate and is not a significant inducer or inhibitor of CYP3A4. Its high protein binding (>99%) creates the potential for displacement interactions, though most are not clinically significant at therapeutic doses. The most important interactions involve additive bleeding risk and interference with antihypertensive and renal-protective therapies.
Major
Warfarin & oral anticoagulants
MechanismAdditive antiplatelet effect (COX-1 inhibition) + protein-binding displacement + potential GI mucosal injury
EffectSignificantly increased risk of GI and other bleeding events, including fatal haemorrhage
ManagementAvoid combination if possible; if essential, monitor INR closely (especially first 2 weeks), add PPI, and educate patient on bleeding signs
FDA PI
Major
Methotrexate
MechanismReduced renal clearance of methotrexate; possible protein-binding displacement
EffectElevated methotrexate plasma concentrations with increased toxicity risk (pancytopenia, mucositis, hepatotoxicity)
ManagementCaution with low-dose MTX (≤25 mg/week); withhold naproxen on day of and 48 h around high-dose MTX; monitor CBC and renal function
FDA PI
Major
Lithium
MechanismDecreased renal lithium clearance via prostaglandin-mediated reduction in renal blood flow
EffectIncreased serum lithium levels and risk of toxicity (tremor, ataxia, renal impairment)
ManagementMonitor lithium levels when initiating, adjusting, or discontinuing naproxen; may need lithium dose reduction
FDA PI
Major
Aspirin (analgesic doses)
MechanismAdditive GI mucosal injury and antiplatelet effects; naproxen may interfere with irreversible COX-1 acetylation by aspirin
EffectIncreased GI bleeding risk; potentially blunted cardioprotective effect of low-dose aspirin
ManagementAvoid concurrent analgesic-dose aspirin; if low-dose aspirin needed for CV protection, take aspirin ≥2 h before naproxen and add PPI
FDA PI
Moderate
ACE Inhibitors / ARBs
MechanismReduced prostaglandin-mediated vasodilation and natriuresis
EffectBlunted antihypertensive effect; increased risk of acute kidney injury (especially in elderly, volume-depleted, or CKD patients)
ManagementMonitor blood pressure and renal function; ensure adequate hydration; “triple whammy” risk (NSAID + RAAS inhibitor + diuretic) warrants avoidance
FDA PI
Moderate
Diuretics (loop & thiazide)
MechanismProstaglandin inhibition reduces renal sodium and water excretion
EffectReduced natriuretic and antihypertensive efficacy of diuretics
ManagementMonitor blood pressure, weight, and renal function; may need to increase diuretic dose temporarily
FDA PI
Moderate
SSRIs / SNRIs
MechanismSSRIs reduce platelet serotonin uptake, impairing platelet aggregation; additive with naproxen’s antiplatelet effect
EffectIncreased risk of GI bleeding (estimated 2–3 fold increase vs. either alone)
ManagementCo-prescribe PPI; use lowest naproxen dose for shortest duration; educate patient on bleeding signs
Lexicomp
Moderate
Digoxin
MechanismReduced renal clearance of digoxin
EffectIncreased serum digoxin levels; prolonged half-life; risk of toxicity
ManagementMonitor serum digoxin levels when initiating or discontinuing naproxen
FDA PI
Moderate
Oral corticosteroids
MechanismBoth agents impair GI mucosal defences through complementary mechanisms
EffectSignificantly increased risk of GI ulceration and bleeding
ManagementMandatory PPI co-prescription; use lowest effective doses of both; limit duration of combination
FDA PI
Moderate
Cyclosporine
MechanismAdditive nephrotoxicity from prostaglandin inhibition combined with cyclosporine’s vasoconstrictive renal effects
EffectIncreased risk of nephrotoxicity
ManagementMonitor renal function closely; use the lowest NSAID dose for shortest duration
FDA PI
Minor
Antacids
MechanismMay slightly delay absorption of naproxen
EffectMildly delayed Tmax; no clinically significant change in total bioavailability
ManagementNo dose adjustment required; antacids may be taken concurrently
FDA PIMonitoring
-
Blood Pressure
Baseline, then periodically
Routine NSAIDs can raise blood pressure by 3–5 mmHg on average. Check within 2–4 weeks of initiation, then every 3–6 months during chronic use. More frequent in patients on antihypertensives. -
Renal Function
Baseline, then q6–12 months
Routine Serum creatinine and eGFR. More frequent monitoring in elderly, diabetic, heart failure, or patients on concurrent nephrotoxic drugs. Check within 1–2 weeks if high-risk. -
Hepatic Function
Baseline; if symptoms arise
Trigger-based ALT/AST at baseline for chronic use. Recheck if patient develops fatigue, nausea, jaundice, or pruritus. Mild transaminase elevations (<3× ULN) occur in up to 15% of patients and may be monitored; ≥3× ULN requires discontinuation. -
CBC
Baseline; then if signs of anaemia or bleeding
Trigger-based Haemoglobin/haematocrit to detect occult GI blood loss. Check urgently if patient presents with melena, haematemesis, unexplained anaemia, or fatigue. -
GI Symptoms
Every visit
Routine Ask about dyspepsia, abdominal pain, dark stools, haematemesis at every follow-up. Low threshold for endoscopy if new or worsening symptoms. Ensure PPI co-prescription in high-risk patients. -
CV Symptoms
Every visit
Routine Screen for chest pain, dyspnoea, unilateral weakness, fluid retention, and oedema. Reassess risk-benefit periodically in patients with CV risk factors. -
Weight & Fluid Balance
First 4 weeks; then as needed
Trigger-based Monitor for oedema and weight gain, particularly in patients with heart failure or on diuretics. -
Serum Potassium
If on RAAS inhibitors
Trigger-based NSAIDs reduce aldosterone secretion; risk of hyperkalaemia when combined with ACE inhibitors, ARBs, or potassium-sparing diuretics. Check within 1–2 weeks of adding naproxen.
Contraindications & Cautions
Absolute Contraindications
- Known hypersensitivity to naproxen or any component of the formulation, including history of anaphylaxis or serious skin reactions to naproxen
- Aspirin-exacerbated respiratory disease (AERD) — history of asthma, urticaria, or allergic-type reactions triggered by aspirin or other NSAIDs
- Peri-operative setting of coronary artery bypass graft (CABG) surgery — increased risk of MI and stroke demonstrated in two large controlled trials of COX-2 selective NSAIDs
- Pregnancy ≥30 weeks gestation — risk of premature closure of the fetal ductus arteriosus, fetal renal dysfunction, and oligohydramnios
- Active gastrointestinal bleeding or perforation
Relative Contraindications (Specialist Input Recommended)
- Moderate to severe renal impairment (CrCl <30 mL/min) — risk of metabolite accumulation and further deterioration of renal function; use only if expected benefit clearly outweighs risk with close monitoring
- Severe hepatic impairment — altered drug disposition and increased bleeding risk due to coagulopathy
- Pregnancy 20–30 weeks — FDA recommends limiting NSAID use in this window due to risk of oligohydramnios and fetal renal dysfunction
- Active peptic ulcer disease or recent GI bleed (within 6 months) — significantly elevated risk of recurrence; if NSAID essential, requires specialist co-management and mandatory PPI
- Severe, uncontrolled heart failure (NYHA III–IV) — NSAIDs increase risk of decompensation and hospitalisation
- Concurrent high-dose methotrexate (>25 mg/week) — risk of severe methotrexate toxicity
Use with Caution
- Elderly patients (≥65 years) — increased risk of GI, CV, and renal adverse events; start at lowest effective dose
- Known cardiovascular disease or multiple CV risk factors — use lowest dose for shortest duration; reassess benefit-risk periodically
- Hypertension — NSAIDs can elevate blood pressure; monitor and adjust antihypertensives as needed
- Mild hepatic impairment — monitor LFTs periodically
- Concurrent anticoagulant, antiplatelet, corticosteroid, or SSRI therapy — additive bleeding risk; consider GI prophylaxis
- History of asthma (without aspirin sensitivity) — monitor for exacerbation of bronchospasm
- Dehydration or hypovolemia — correct fluid status before initiating; risk of acute kidney injury
- SLE or mixed connective tissue disease — increased susceptibility to NSAID-induced aseptic meningitis
FDA Boxed Warning
Risk of Serious Cardiovascular and Gastrointestinal Events
Cardiovascular Thrombotic Events: NSAIDs cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may begin early in treatment and may increase with duration of use. Naproxen is contraindicated in the setting of CABG surgery.
Gastrointestinal Bleeding, Ulceration, and Perforation: NSAIDs cause an increased risk of serious 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.
Patient Counselling
Purpose of Therapy
Naproxen reduces pain, swelling, and stiffness by blocking chemicals in the body that cause inflammation. It is not a cure for conditions like arthritis but helps manage symptoms so that daily activities become more comfortable. The medication works best when taken regularly at the prescribed dose rather than only when pain is at its worst.
How to Take
Swallow tablets whole with a full glass of water. Take with food or milk to reduce stomach upset. Do not crush, break, or chew delayed-release (EC) tablets. Avoid lying down for at least 30 minutes after taking. Do not combine prescription naproxen with over-the-counter naproxen (Aleve) or other NSAID products, as they contain the same active compound and stacking doses increases risk of serious side effects.
Stomach Problems & GI Bleeding
Tell patient
Take with food to reduce stomach irritation. Avoid alcohol, as it compounds GI risk. Stomach bleeding can occur without prior pain or warning. If a proton pump inhibitor has been prescribed alongside naproxen, take it daily as directed.
Call prescriber
Black or tarry stools, vomiting blood or material resembling coffee grounds, persistent or severe stomach pain, unexplained weight loss.
Heart & Circulation Risks
Tell patient
All NSAIDs carry a small risk of heart attack or stroke, even in people who have never had heart problems. This risk is minimised by using the lowest dose for the shortest time needed. Naproxen is thought to have a lower cardiovascular risk than some other NSAIDs, but the risk is not zero.
Call prescriber
Chest pain, shortness of breath, sudden weakness or numbness on one side of the body, slurred speech, or unexplained swelling of the legs.
Kidney & Fluid Retention
Tell patient
Stay well-hydrated, especially in hot weather or during exercise. Naproxen can cause the body to retain fluid, leading to swollen ankles or weight gain. This is usually mild but can worsen pre-existing kidney or heart conditions.
Call prescriber
Significant swelling of the hands, feet, or ankles; decrease in urine output; rapid weight gain (>2 kg in one week); fatigue or confusion.
Skin Reactions
Tell patient
Rarely, naproxen can cause serious skin reactions. Any new rash while taking this medication should be reported. Naproxen can also increase sun sensitivity, so use sunscreen and protective clothing.
Call prescriber
Any rash, blistering, peeling skin, or sores in the mouth. Seek emergency care if rash is accompanied by fever, swollen lymph nodes, or difficulty breathing.
Drowsiness & Dizziness
Tell patient
Some people feel drowsy or dizzy, especially at the start of treatment. Use caution when driving or operating machinery until you know how naproxen affects you. This effect usually diminishes within the first week.
Call prescriber
If dizziness is persistent or accompanied by visual changes, hearing loss, or ringing in the ears.
Pregnancy & Fertility
Tell patient
Naproxen should be avoided after 20 weeks of pregnancy unless specifically directed by a healthcare provider. It may make it harder to become pregnant; this is usually reversible after stopping. Inform your doctor if you are pregnant, planning pregnancy, or breastfeeding.
Call prescriber
If pregnancy is confirmed while taking naproxen, especially after 20 weeks gestation.
Medication Interactions
Tell patient
Do not take other NSAID products (ibuprofen, aspirin for pain, other naproxen products) at the same time. Always tell your doctor about all medications, including over-the-counter products and supplements, particularly blood thinners, blood pressure medications, and antidepressants.
Call prescriber
If you need to start any new medication while taking naproxen, or if you experience unusual bruising or bleeding.
Sources
Regulatory (PI / SmPC)
- Naprosyn (naproxen), EC-Naprosyn, Anaprox DS — Full Prescribing Information. Revised 11/2024. U.S. FDA Reference ID: 5482791. accessdata.fda.gov Primary source for all approved indications, dosing, contraindications, boxed warning, and adverse reactions data cited throughout this monograph.
- Naproxen Sodium Extended-Release Tablets — Full Prescribing Information. DailyMed. dailymed.nlm.nih.gov Provides extended-release formulation-specific dosing and pharmacokinetic data including modified Tmax profiles.
- FDA Drug Safety Communication: FDA recommends avoiding use of NSAIDs in pregnancy at 20 weeks or later. October 2020. fda.gov Source for the 2020 FDA safety communication on NSAID-related oligohydramnios and fetal renal dysfunction in pregnancy.
Key Clinical Trials
- Nissen SE, Yeomans ND, Solomon DH, et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med. 2016;375(26):2519–2529. doi:10.1056/NEJMoa1611593 The PRECISION trial: largest randomised CV safety trial of NSAIDs (N=24,081); found naproxen non-inferior to celecoxib for major adverse cardiovascular events.
- Bhala N, Emberson J, Merhi A, et al. (Coxib and traditional NSAID Trialists’ Collaboration). Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382(9894):769–779. doi:10.1016/S0140-6736(13)60900-9 Individual participant data meta-analysis (N>300,000 participants); key source for NSAID-class cardiovascular and GI risk estimates including heart failure hospitalisation data.
- Derry CJ, Derry S, Moore RA. Naproxen with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2013;(10):CD009455. doi:10.1002/14651858.CD009455.pub2 Cochrane review supporting naproxen 500–550 mg efficacy for acute migraine treatment (off-label use evidence base).
Guidelines
- Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases. Eur Heart J. 2015;36(42):2921–2964. doi:10.1093/eurheartj/ehv318 Recommends NSAIDs (including naproxen) as first-line therapy for acute pericarditis alongside colchicine.
- Qaseem A, Wilt TJ, McLean RM, et al. Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2017;166(7):514–530. doi:10.7326/M16-2367 ACP guideline recommending NSAIDs as first-line pharmacotherapy for acute and chronic low back pain.
Mechanistic / Basic Science
- Vane JR, Botting RM. Mechanism of action of nonsteroidal anti-inflammatory drugs. Am J Med. 1998;104(3A):2S–8S. doi:10.1016/S0002-9343(97)00203-9 Seminal review on COX-1/COX-2 mechanisms underpinning the therapeutic and adverse effects of non-selective NSAIDs.
- Angiolillo DJ, Weisman SM. Clinical pharmacology and cardiovascular safety of naproxen. Am J Cardiovasc Drugs. 2017;17(2):97–107. doi:10.1007/s40256-016-0200-5 Comprehensive review of naproxen’s COX selectivity, platelet effects, and the pharmacological basis for its comparatively favourable CV risk profile.
Pharmacokinetics / Special Populations
- Davies NM, Anderson KE. Clinical pharmacokinetics of naproxen. Clin Pharmacokinet. 1997;32(4):268–293. doi:10.2165/00003088-199732040-00002 Definitive PK review covering absorption, protein binding, distribution, metabolism (CYP2C9), and elimination kinetics across populations.
- Runkel R, Chaplin M, Boost G, et al. Absorption, distribution, metabolism, and excretion of naproxen in various laboratory animals and human subjects. J Pharm Sci. 1972;61(5):703–708. doi:10.1002/jps.2600610507 Original ADME characterisation study; source for bioavailability (~95%), Vd (0.16 L/kg), and renal excretion data.
- Frost C, Song Y, Yu Z, et al. The effect of naproxen on the pharmacokinetics and pharmacodynamics of apixaban. Br J Clin Pharmacol. 2014;78(4):877–885. doi:10.1111/bcp.12393 Source for naproxen CYP2C9/CYP1A2 substrate data and documentation that naproxen does not inhibit CYP3A4.
- Weisman SM, Brunton S. Efficacy and safety of naproxen for acute pain. Pract Pain Manag. 2020. pceconsortium.org Comprehensive clinical review summarising OTC and prescription naproxen safety data, including pooled adverse event rates and GI risk comparisons.