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Naproxen

Class: Other Nonsteroidal Anti-inflammatory Agents
CAS Number: 22204-53-1
Brands: Aleve, Anaprox, Naprelan, Naprosyn

Medically reviewed by Drugs.com. Last updated on Nov 9, 2020.

Warning

Special Alerts:

[Posted 10/15/2020]

AUDIENCE: Consumer, Patient, Health Professional, Pharmacy

ISSUE: FDA is warning that use of NSAIDs around 20 weeks or later in pregnancy may cause rare but serious kidney problems in an unborn baby. This can lead to low levels of amniotic fluid surrounding the baby and possible complications.

For prescription NSAIDs, FDA is requiring changes to the prescribing information to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.

For over-the-counter (OTC) NSAIDs intended for use in adults, FDA will also update the Drug Facts labels, available at: [Web]. These labels already warn to avoid using NSAIDs during the last 3 months of pregnancy because the medicines may cause problems in the unborn child or complications during delivery. The Drug Facts labels already advise pregnant and breastfeeding women to ask a health care professional before using these medicines.

BACKGROUND:

NSAIDs

  • are a class of medicines available by prescription and OTC. They are some of the most commonly used medicines for pain and fever.

  • are used to treat medical conditions such as arthritis, menstrual cramps, headaches, colds, and the flu.

  • work by blocking the production of certain chemicals in the body that cause inflammation.

  • are available alone and combined with other medicines. Examples of NSAIDs include aspirin, ibuprofen, naproxen, diclofenac, and celecoxib.

Common side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas, heartburn, nausea, vomiting, and dizziness.

RECOMMENDATION:

Consumers/Patients

  • If you are pregnant, do not use NSAIDs at 20 weeks or later in pregnancy unless specifically advised to do so by your health care professional because these medicines may cause problems in your unborn baby.

  • Many OTC medicines contain NSAIDs, including those used for pain, colds, flu, and insomnia, so it is important to read the Drug Facts labels, available at: [Web], to find out if the medicines contain NSAIDs.

  • Talk to your health care professional or pharmacist if you have questions or concerns about NSAIDs or which medicines contain them.

  • Other medicines, such as acetaminophen, are available to treat pain and fever during pregnancy. Talk to your pharmacist or health care professional for help deciding which might be best.

Health Care Professionals

  • FDA recommends that health care professionals should limit prescribing NSAIDs between 20 to 30 weeks of pregnancy and avoid prescribing them after 30 weeks of pregnancy. If NSAID treatment is determined necessary, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours and discontinue the NSAID if oligohydramnios is found. FDA is warning that use of NSAIDs around 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.

  • These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation.

  • Oligohydramnios is often, but not always, reversible with treatment discontinuation.

  • Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.

  • If NSAID treatment is deemed necessary between 20 to 30 weeks of pregnancy, limit use to the lowest effective dose and shortest duration possible. As currently described in the NSAID labels, avoid prescribing NSAIDs at 30 weeks and later in pregnancy because of the additional risk of premature closure of the fetal ductus arteriosus.

  • The above recommendations do not apply to low-dose 81 mg aspirin prescribed for certain conditions in pregnancy.

  • Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if oligohydramnios occurs and follow up according to clinical practice.

For more information visit the FDA website at: [Web] and [Web].

Warning

    Cardiovascular Risk
  • Increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke). Risk may occur early in treatment and may increase with duration of use. (See Cardiovascular Thrombotic Effects under Cautions.)

  • Contraindicated in the setting of CABG surgery.

    GI Risk
  • Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine). Serious GI events can occur at any time and may not be preceded by warning signs and symptoms. Geriatric individuals are at greater risk for serious GI events. (See GI Effects under Cautions.)

Introduction

Prototypical NSAIA; propionic acid derivative.

Uses for Naproxen

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Consider potential benefits and risks of naproxen therapy as well as alternative therapies before initiating therapy with the drug. Use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.

Inflammatory Diseases

Symptomatic treatment of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. May be used in fixed combination with esomeprazole in patients at risk of developing gastric ulcers associated with NSAIA therapy.

Symptomatic treatment of tendinitis, bursitis, and acute gout.

Management of juvenile rheumatoid arthritis in children ≥2 years of age.

Pain

Relief of pain.

NSAIAs considered first-line agents for mild to moderate migraine attacks or for severe attacks that have responded in the past to NSAIAs or nonopiate analgesics.

Self-medication in children ≥12 years of age and adults for the temporary relief of minor aches and pain associated with the common cold, headache, toothache, muscular aches, backache, and minor pain of arthritis.

Dysmenorrhea

Symptomatic management of primary dysmenorrhea.

Self-medication for the temporary relief of minor aches and pain associated with menstrual cramps.

Fever

Self-medication for reduction of fever in children ≥12 years of age and adults.

Naproxen Dosage and Administration

General

  • Consider potential benefits and risks of naproxen therapy as well as alternative therapies before initiating therapy with the drug.

Administration

Oral Administration

Formulation Considerations

Naproxen oral suspension is the preferred dosage form for children because of suitability for providing the calculated dosage.

Naproxen sodium is preferred for management of acute painful conditions when prompt onset of pain relief is desired.

Naproxen delayed-release preparations are not recommended for management of acute gout, tendinitis, bursitis, acute pain, or dysmenorrhea because of slow onset of action.

Naproxen or Naproxen Sodium Conventional (Immediate-release) Tablets and Naproxen Suspension

Usually administered orally twice daily. When used for the management of osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis, the morning and evening doses may be unequal in size.

Administration with meal, milk, or antacids may minimize adverse GI effects.

Naproxen Delayed-release Tablets

Usually administered orally twice daily. When used for the management of osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis, the morning and evening doses may be unequal in size.

Do not break, crush, or chew naproxen delayed-release tablets.

Administration with meal, milk, or antacids may minimize adverse GI effects.

Naproxen Sodium Extended-release Tablets

Administer orally once daily.

Administration with meal, milk, or antacids may minimize adverse GI effects.

Tablets Containing Delayed-release Naproxen and Immediate-release Esomeprazole

Administer orally twice daily.

Swallow whole with liquid; do not split, chew, crush, or dissolve tablets.

Administer at least 30 minutes before meals; patient may use antacids during therapy.

Tablets Containing Naproxen Sodium and Sumatriptan

Administer with or without food; do not split, crush, or chew.

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as naproxen or naproxen sodium; each 220, 275, 412.5, or 550 mg of naproxen sodium is approximately equivalent to 200, 250, 375, or 500 mg of naproxen, respectively.

If changing from one strength to another or one dosage form to another, be aware that different dose strengths and formulations are not necessarily bioequivalent.

To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals. Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.

Pediatric Patients

Inflammatory Diseases
Juvenile Rheumatoid Arthritis
Oral

Naproxen 10 mg/kg daily in 2 divided doses.

Pain
Oral

Naproxen sodium self-medication in children ≥12 years of age: Initially, 440 mg; usual dosage is 220 mg every 8–12 hours.

Fever
Oral

Naproxen sodium self-medication in children ≥12 years of age: Initially, 440 mg; usual dosage is 220 mg every 8–12 hours.

Adults

Inflammatory Diseases
Osteoarthritis, Rheumatoid Arthritis, or Ankylosing Spondylitis
Oral

Preparation

Dosage

Naproxen conventional tablets, delayed-release tablets, or suspension

250–500 mg twice daily; may increase dosage to 1.5 g daily for up to 6 months

Naproxen sodium conventional tablets

275–550 mg twice daily; may increase dosage to 1.65 g daily for up to 6 months

Naproxen sodium extended-release tablets

825 mg or 1.1 g once daily; may increase dosage to 1.65 g daily for up to 6 months

Tablets containing delayed-release naproxen and immediate-release esomeprazole

375 or 500 mg of naproxen (with esomeprazole 20 mg) twice daily

Acute Tendinitis/Bursitis
Oral

Preparation

Dosage

Naproxen conventional tablets or suspension

500 mg initially, followed by 500 mg every 12 hours or 250 mg every 6–8 hours as needed

Naproxen sodium conventional tablets

550 mg initially, followed by 550 mg every 12 hours or 275 mg every 6–8 hours as needed

Naproxen sodium extended-release tablets

1.1 g once daily; may increase dosage to 1.65 g once daily for limited period

Gout
Oral

Preparation

Dosage

Naproxen conventional tablets or suspension

750 mg initially, followed by 250 mg every 8 hours until attack subsides

Naproxen sodium conventional tablets

825 mg initially, followed by 275 mg every 8 hours until attack subsides

Naproxen sodium extended-release tablets

1.1–1.65 g once on first day, followed by 1.1 g once daily until attack subsides

Pain
Oral

Preparation

Dosage

Naproxen conventional tablets or suspension

500 mg initially, followed by 500 mg every 12 hours or 250 mg every 6–8 hours as needed

Naproxen sodium conventional tablets

550 mg initially, followed by 550 mg every 12 hours or 275 mg every 6–8 hours as needed

Naproxen sodium extended-release tablets

1.1 g once daily; may increase dosage to 1.65 g once daily for limited period

Naproxen sodium for self-medication of minor aches and pain: Initially, 440 mg; usual dosage is 220 mg every 8–12 hours.

Acute Migraine Attack
Oral

Naproxen sodium/sumatriptan fixed combination: Naproxen sodium 500 mg (with sumatriptan 85 mg) as a single dose. Efficacy of >1 dose not established. If a second dose is administered, allow ≥2 hours to elapse between the first and second doses.

Dysmenorrhea
Oral

Preparation

Dosage

Naproxen conventional tablets or suspension

500 mg initially, followed by 500 mg every 12 hours or 250 mg every 6–8 hours as needed

Naproxen sodium conventional tablets

550 mg initially, followed by 550 mg every 12 hours or 275 mg every 6–8 hours as needed

Naproxen sodium extended-release tablets

1.1 g once daily; may increase dosage to 1.65 g once daily for limited period

Naproxen sodium self-medication: Initially, 440 mg; usual dosage is 220 mg every 8–12 hours.

Fever
Oral

Naproxen sodium self-medication: Initially, 440 mg; usual dosage is 220 mg every 8–12 hours.

Prescribing Limits

Pediatric Patients

Pain
Oral

Naproxen sodium self-medication in children ≥12 years of age: Maximum 440 mg in 8–12 hours; 660 mg in 24 hours. Self-medication should not exceed 10 days.

Fever
Oral

Naproxen sodium self-medication in children ≥12 years of age: Maximum 440 mg in 8–12 hours; 660 mg in 24 hours. Self-medication should not exceed 3 days.

Adults

Inflammatory Diseases
Osteoarthritis, Rheumatoid Arthritis, or Ankylosing Spondylitis
Oral

As naproxen, maximum 1.5 g daily.

As naproxen sodium, maximum 1.65 g daily.

Acute Tendinitis/Bursitis
Oral

As naproxen, maximum 1.25 g on the first day; thereafter, 1 g daily. Maximum 1.5 g daily for limited period.

As naproxen sodium, maximum 1.375 g on the first day; thereafter, 1.1 g daily. Maximum 1.65 g daily for limited period.

Pain
Oral

As naproxen, maximum 1.25 g on the first day; thereafter, 1 g daily. Maximum 1.5 g daily for limited period.

As naproxen sodium, maximum 1.375 g on the first day; thereafter, 1.1 g daily. Maximum 1.65 g daily for limited period.

Naproxen sodium for self-medication of minor aches and pain: Maximum 440 mg in 8–12 hours; 660 mg in 24 hours. Self-medication should not exceed 10 days.

Acute Migraine Attack
Oral

Naproxen sodium/sumatriptan fixed combination: Maximum 2 doses (total sumatriptan dosage of 170 mg) in any 24-hour period. Safety of treating an average of >5 headaches per 30-day period not established.

Dysmenorrhea
Oral

As naproxen, maximum 1.25 g on the first day; thereafter, 1 g daily.

As naproxen sodium, maximum 1.375 g on the first day; thereafter, 1.1 g daily.

Naproxen sodium self-medication: Maximum 440 mg in 8–12 hours; 660 mg in 24 hours.

Fever
Oral

Naproxen sodium self-medication: Maximum 440 mg in 8–12 hours; 660 mg in 24 hours. Self-medication should not exceed 3 days.

Special Populations

Hepatic Impairment

Dosage adjustment may be needed if high doses required. Consider reduced initial dosage. Use lowest effective dosage.

Tablets containing delayed-release naproxen and immediate-release esomeprazole not recommended for patients with severe hepatic impairment; an appropriate esomeprazole dosage is not available as a fixed-ratio preparation for twice-daily dosing.

Do not use tablets containing naproxen sodium and sumatriptan in patients with hepatic impairment; sumatriptan dosage cannot be appropriately adjusted.

Renal Impairment

Consider reduced initial dosage.

Not recommended for use in patients with moderate to severe renal impairment (Clcr <30 mL/minute).

Geriatric Patients

Dosage adjustment may be needed if high doses required. Consider reduced initial dosage. Use lowest effective dosage.

Maximum for self-medication, naproxen sodium 220 mg twice daily unless otherwise directed by a clinician.

Cautions for Naproxen

Contraindications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Known hypersensitivity to naproxen or any ingredient in the formulation.

  • History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.

  • In the setting of CABG surgery.

Warnings/Precautions

Warnings

Cardiovascular Thrombotic Effects

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) increase the risk of serious adverse cardiovascular thrombotic events (e.g., MI, stroke) in patients with or without cardiovascular disease or risk factors for cardiovascular disease.

Findings of FDA review of observational studies, meta-analysis of randomized controlled trials, and other published information indicate that NSAIAs may increase the risk of such events by 10–50% or more, depending on the drugs and dosages studied.

Relative increase in risk appears to be similar in patients with or without known underlying cardiovascular disease or risk factors for cardiovascular disease, but the absolute incidence of serious NSAIA-associated cardiovascular thrombotic events is higher in those with cardiovascular disease or risk factors for cardiovascular disease because of their elevated baseline risk.

Increased risk may occur early (within the first weeks) following initiation of therapy and may increase with higher dosages and longer durations of use.

In controlled studies, increased risk of MI and stroke observed in patients receiving a selective COX-2 inhibitor for analgesia in first 10–14 days following CABG surgery.

In patients receiving NSAIAs following MI, increased risk of reinfarction and death observed beginning in the first week of treatment.

Increased 1-year mortality rate observed in patients receiving NSAIAs following MI; absolute mortality rate declined somewhat after the first post-MI year, but the increased relative risk of death persisted over at least the next 4 years.

Some systematic reviews of controlled observational studies and meta-analyses of randomized studies suggest naproxen may be associated with lower risk of cardiovascular thrombotic events compared with other NSAIAs. FDA states that limitations of these studies and indirect comparisons preclude definitive conclusions regarding relative risks of NSAIAs.

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events throughout therapy, even in those without prior cardiovascular symptoms) and at the lowest effective dosage for the shortest duration necessary.

Some clinicians suggest that it may be prudent to avoid NSAIA use, whenever possible, in patients with cardiovascular disease. Avoid use in patients with recent MI unless benefits of therapy are expected to outweigh risk of recurrent cardiovascular thrombotic events; if used, monitor for cardiac ischemia. Contraindicated in the setting of CABG surgery.

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs. (See Specific Drugs under Interactions.)

GI Effects

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.

For patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol; alternatively, consider concomitant use of a proton-pump inhibitor (e.g., esomeprazole, omeprazole) or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).

Hypertension

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events. Use with caution in patients with hypertension; monitor BP.

Impaired response to ACE inhibitors, angiotensin II receptor antagonists, β-blockers, and certain diuretics may occur. (See Specific Drugs under Interactions.)

Heart Failure and Edema

Fluid retention and edema reported.

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) may increase morbidity and mortality in patients with heart failure.

NSAIAs may diminish cardiovascular effects of diuretics, ACE inhibitors, or angiotensin II receptor antagonists used to treat heart failure or edema. (See Specific Drugs under Interactions.)

Manufacturer recommends avoiding use in patients with severe heart failure unless benefits of therapy are expected to outweigh risk of worsening heart failure; if used, monitor for worsening heart failure.

Some experts recommend avoiding use, whenever possible, in patients with reduced left ventricular ejection fraction and current or prior symptoms of heart failure.

Sodium Content

Each 220-, 275-, 412.5-, or 550-mg naproxen sodium tablet contains about 0.87, 1, 1.5, or 2 mEq of sodium, respectively; each mL of naproxen suspension contains about 0.3 mEq of sodium. Caution in patients with fluid retention, hypertension, or heart failure.

Renal Effects

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.

Potential for overt renal decompensation. Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in patients with volume depletion, in geriatric patients, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist. (See Renal Impairment under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions reported.

Immediate medical intervention and discontinuance for anaphylaxis.

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning. Discontinue at first appearance of rash or any other sign of hypersensitivity (e.g., blisters, fever, pruritus).

General Precautions

Do not use multiple naproxen-containing preparations concomitantly.

Hepatic Effects

Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs.

Elevations of serum ALT or AST reported.

Monitor liver function periodically during long-term therapy. Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results. Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur or if liver function test abnormalities persist or worsen.

Hematologic Effects

Anemia reported rarely. Periodically determine hemoglobin concentrations during long-term therapy in patients with initial values ≤10 g/dL. Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia occur.

May inhibit platelet aggregation and prolong bleeding time.

CNS Effects

Drowsiness and dizziness reported; may impair ability to perform activities requiring mental alertness.

Ocular Effects

Visual disturbances reported; ophthalmic evaluation recommended if visual changes occur.

Other Precautions

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.

May mask certain signs of infection.

Obtain CBC and chemistry profile periodically during long-term use.

Use of Fixed Combinations

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category C. Avoid use in third trimester because of possible premature closure of the ductus arteriosus.

Lactation

Distributed into milk; use not recommended.

Pediatric Use

Safety and efficacy not established in children <2 years of age.

Should not be used for self-medication in children <12 years of age unless otherwise directed by a clinician.

Dosing recommendations for juvenile rheumatoid arthritis based on well-controlled studies.

Safety of extended-release naproxen sodium tablets not established in children.

Risk of overdosage and toxicity (including death) in children <2 years of age receiving OTC preparations containing antihistamines, cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection. Such preparations also may contain analgesics and antipyretics. Limited evidence of efficacy for these preparations in this age group; appropriate dosages not established. Therefore, FDA recommended not to use such preparations in children <2 years of age; safety and efficacy in older children currently under evaluation. Because children 2–3 years of age also are at increased risk of overdosage and toxicity, some manufacturers of oral nonprescription cough and cold preparations recently agreed to voluntarily revise the product labeling to state that such preparations should not be used in children <4 years of age. FDA recommends that parents and caregivers adhere to dosage instructions and warnings on the product labeling that accompanies the preparation and consult a clinician about any concerns.

Geriatric Use

Geriatric patients appear to tolerate GI ulceration and bleeding less well than other individuals. Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.

Select dosage with caution because of age-related decreases in renal function. May be useful to monitor renal function.

Caution advised if high dosages required.

Hepatic Impairment

Caution advised if high dosages required.

Renal Impairment

Use not recommended in patients with moderate to severe renal impairment (Clcr <30 mL/minute); close monitoring of renal function advised if used.

Metabolites eliminated principally via the kidney.

Common Adverse Effects

Abdominal pain, constipation, dizziness, drowsiness, dyspnea, edema, ecchymoses, headache, heartburn, nausea, pruritus, skin eruptions, tinnitus.

Interactions for Naproxen

Extensively metabolized by CYP1A2 and CYP2C9. Does not induce drug-metabolizing enzymes.

Protein-bound Drugs

Pharmacokinetic interaction possible; caution advised. Observe for adverse effects if used with other protein-bound drugs.

Drugs Affecting Gastric pH

Concomitant administration of delayed-release naproxen tablets with drugs that increase gastric pH not recommended; possible pharmacokinetic interaction.

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Reduced BP response to ACE inhibitor

Possible deterioration of renal function in individuals with renal impairment

Monitor BP

Alcohol

Increased risk of GI bleeding

Angiotensin II receptor antagonists

Reduced BP response to angiotensin II receptor antagonist

Possible deterioration of renal function in individuals with renal impairment

Monitor BP

Antacids

Delayed absorption of naproxen

Concomitant use of intensive antacid therapy with delayed-release naproxen tablets not recommended

Anticoagulants (warfarin)

Possible bleeding complications

Caution advised

Aspirin

Increased risk of GI ulceration and other complications

No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs

Concomitant administration may interfere with the antiplatelet effect of low-dose aspirin

Manufacturers state that concomitant use not recommended

β-Adrenergic blocking agents

Reduced BP response

Monitor BP

Cholestyramine

Delayed absorption of naproxen

Diuretics (furosemide, thiazides)

Reduced natriuretic effects

Monitor for diuretic efficacy and renal failure

Lithium

Increased plasma lithium concentrations

Monitor for lithium toxicity

Methotrexate

Possible toxicity associated with increased plasma methotrexate concentrations

Caution advised

Probenecid

Increased plasma concentrations and half-life of naproxen

Sucralfate

Delayed absorption of naproxen

Concomitant use with delayed-release naproxen tablets not recommended

Naproxen Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration; bioavailability is about 95%.

Extent of absorption similar for commercially available formulations; peak plasma concentrations also similar, although about 36% lower with conventional tablets containing naproxen sodium 500 mg and sumatriptan than with conventional naproxen sodium 550-mg tablets.

Rate of absorption varies depending on formulation used. Peak plasma concentration usually attained within about 1–2 hours (naproxen sodium conventional tablets), 2–4 hours (naproxen conventional tablets), 1–4 hours (naproxen suspension), 3 hours (tablets containing delayed-release naproxen and immediate-release esomeprazole), 3–5 hours (naproxen sodium extended-release tablets), 5 hours (conventional tablets containing naproxen sodium and sumatriptan), or 4–6 hours (naproxen delayed-release tablets).

Onset

Naproxen sodium conventional tablets and extended-release tablets provide pain relief within 30 minutes; naproxen conventional tablets provide pain relief within 1 hour.

Duration

Analgesic effect lasts up to 12 hours.

Food

Food delays time to peak plasma concentration by about 6–8 hours following administration as naproxen delayed-release tablets.

High-fat meal delays time to peak plasma naproxen concentration by 10 hours and decreases peak plasma naproxen concentration by about 12% following administration as tablets containing delayed-release naproxen and immediate-release esomeprazole.

Food does not substantially affect bioavailability of naproxen from naproxen sodium/sumatriptan tablets.

Distribution

Plasma Protein Binding

>99%.

Elimination

Metabolism

Extensively metabolized in the liver by CYP1A2 and CYP2C9 to 6-desmethylnaproxen.

Elimination Route

Excreted in urine (95%) mainly as conjugates of naproxen or 6-desmethylnaproxen.

Half-life

12–17 hours.

Special Populations

In patients with renal impairment, possible accumulation of naproxen metabolites.

Stability

Storage

Oral

Conventional and Delayed-release Tablets

15–30°C.

Extended-release Tablets

20–25°C.

Tablets Containing Delayed-release Naproxen and Immediate-release Esomeprazole

25°C (may be exposed to 15–30°C).

Tablets Containing Naproxen Sodium and Sumatriptan

25°C (may be exposed to 15–30°C). Store in original container with desiccant packet; do not repackage.

Suspension

15–30°C in light-resistant container.

Actions

  • Inhibits cyclooxygenase-1 (COX-1) and COX-2.

  • Pharmacologic actions similar to those of other prototypical NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.

  • When used for self-medication, importance of reading the product labeling.

  • When used for self-medication, importance of using the lowest effective dosage and of not exceeding the recommended dosage or duration of therapy.

  • When used for self-medication, importance of reviewing the warning information provided by the manufacturer.

  • Risk of serious cardiovascular events (e.g., MI, stroke).

  • Risk of GI bleeding and ulceration.

  • Risk of serious skin reactions. Risk of anaphylactoid and other sensitivity reactions.

  • Risk of hepatotoxicity.

  • Importance of seeking immediate medical attention if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.

  • Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding develop.

  • Importance of discontinuing naproxen and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop. Importance of seeking immediate medical attention if an anaphylactic reaction occurs.

  • Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.

  • Risk of heart failure or edema; importance of reporting dyspnea, unexplained weight gain, or edema.

  • Potential for naproxen to interfere with antiplatelet effect of low-dose aspirin. Importance of consulting clinician prior to taking low-dose aspirin concomitantly.

  • Important of not engaging in activities requiring alertness if adverse CNS effects (drowsiness, dizziness, vertigo, depression) occur.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Importance of avoiding naproxen in late pregnancy (third trimester).

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Naproxen

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Suspension

125 mg/5 mL*

Naproxen Suspension

Tablets

250 mg*

Naprosyn

Canton

Naproxen Tablets

375 mg*

Naprosyn

Canton

Naproxen Tablets

500 mg*

Naprosyn

Canton

Naproxen Tablets

Tablets, delayed-release (enteric-coated)

375 mg*

EC-Naprosyn

Canton

Naproxen Delayed-release Tablets

500 mg*

EC-Naprosyn (scored)

Canton

Naproxen Delayed-release Tablets

Naproxen Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, delayed-release core (naproxen only)

375 mg with Esomeprazole Magnesium 20 mg (of esomeprazole)

Vimovo

Horizon

500 mg with Esomeprazole Magnesium 20 mg (of esomeprazole)

Vimovo

Horizon

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Naproxen Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

220 mg (equivalent to naproxen 200 mg)*

Aleve Caplets

Bayer

Aleve Tablets

Bayer

Naproxen Sodium Tablets

Tablets, extended-release

412.5 mg (equivalent to 375 mg naproxen)

Naprelan

Almatica

550 mg (equivalent to 500 mg naproxen)

Naprelan

Almatica

825 mg (equivalent to 750 mg naproxen)

Naprelan

Almatica

Tablets, film-coated

275 mg (equivalent to naproxen 250 mg)*

Anaprox

Canton

Naproxen Sodium Film Coated Tablets

550 mg (equivalent to naproxen 500 mg)*

Anaprox DS (scored)

Canton

Naproxen Sodium Film Coated Tablets

Naproxen Sodium Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended release

220 mg (equivalent to 200 mg naproxen) with Pseudoephedrine Hydrochloride 120 mg

Aleve Cold and Sinus

Roche

Tablets, film-coated

500 mg (equivalent to 455 mg naproxen) with Sumatriptan Succinate 85 mg (of sumatriptan)

Treximet

GlaxoSmithKline

AHFS DI Essentials™. © Copyright 2021, Selected Revisions November 9, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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