(na PROKS en)
Acute gout/Ankylosing spondylitis/Bursitis/Juvenile arthritis/Juvenile rheumatoid arthritis/Osteoarthritis/Rheumatoid arthritis/Tendonitis (Rx products only): For the relief of the signs and symptoms of acute gout, ankylosing spondylitis, bursitis, juvenile arthritis (excluding ER tablets), juvenile rheumatoid arthritis (oral suspension only), osteoarthritis, rheumatoid arthritis, and tendonitis. Delayed-release naproxen is not recommended for initial treatment of acute pain.
Pain/Primary dysmenorrhea (Rx and OTC products): For the relief of mild to moderate pain and the treatment of primary dysmenorrhea. Delayed-release naproxen is not recommended for initial treatment of acute pain.
Migraine prophylaxis
Hypersensitivity to naproxen, aspirin, other NSAIDs, or any component of the formulation; treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery
Canadian labeling: Additional contraindications (not in U.S. labeling): Active peptic ulcers; active GI bleeding; cerebrovascular bleeding or other bleeding disorders; active GI inflammatory disease; severe liver impairment or active liver disease; severe renal impairment (Crcl <30 mL/minute) or deteriorating renal disease; severe uncontrolled heart failure; known hyperkalemia; third trimester of pregnancy; breast-feeding; inflammatory lesions or recent bleeding of the rectum or anus (suppository only); use in patients <16 years of age (suppository only); use in patients <18 years of age (naproxen enteric coated and sustained release tablets and naproxen sodium tablets); use in children <2 years (naproxen tablets and suspension).
Nonsteroidal anti-inflammatory drugs (NSAIDs) may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
Naproxen is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
Gastrointestinal risk: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 are at greater risk for serious GI events
Note: Dosage expressed as naproxen base; 200 mg naproxen base is equivalent to 220 mg naproxen sodium. For relief of acute pain, naproxen sodium may be preferred due to more rapid absorption and onset; naproxen base may also be used however EC-Naprosyn is not recommended.
Ankylosing spondylitis, osteoarthritis, rheumatoid arthritis: Oral: 500 to 1,000 mg daily in 2 divided doses; in patients who require higher level of anti-inflammatory/analgesic activity and have tolerated lower doses, may increase to 1,500 mg/day for limited time period (<6 months)
Naproxen extended-release tablets: Initial: 750 to 1,000 mg once daily; in patients who require higher level of anti-inflammatory/analgesic activity and have tolerated lower doses, may temporarily increase to 1,500 mg once daily
Rectal suppository [Canadian product]: Insert one 500 mg suppository into the rectum once daily (Note: Suppository may be used to substitute for one oral dose in patients receiving 1,000 mg naproxen daily).
Gout, acute: Oral: Initial: 750 mg, followed by 250 mg every 8 hours until attack subsides
Naproxen extended-release tablets: Initial: 1,000 to 1,500 mg once daily followed by 1,000 mg once daily until attack subsides
Pain (mild to moderate), dysmenorrhea, acute tendonitis, bursitis: Oral: Initial: 500 mg, followed by 500 mg every 12 hours or 250 mg every 6 to 8 hours; maximum daily dose: Day 1: 1,250 mg; subsequent daily doses should not exceed 1,000 mg
Naproxen extended-release tablets: Oral: Initial: 1,000 mg once daily; may temporarily increase to 1,500 mg once daily if greater pain relief is needed. Dose should be subsequently reduced to a maximum of 1,000 mg daily.
Migraine, acute (off label use): Initial: 750 mg; an additional 250 to 500 mg may be given if needed (maximum: 1,250 mg in 24 hours) (Andersson, 1989; Nestvold, 1985).
OTC labeling: Pain, fever: 200 mg every 8 to 12 hours; if needed, may take 400 mg for the initial dose; maximum: 400 mg in any 8- to 12-hour period or 600 mg/24 hours
Use with caution; dosage adjustment may be required. Refer to adult dosing.
CrCl <30 mL/minute
U.S. labeling: Use is not recommended.
Canadian labeling: Use is contraindicated.
Manufacturer 's labeling suggests that a reduced dose should be considered; use with caution in chronic disease (eg, alcoholic liver disease), particularly at higher doses; dose adjustment may be required. Canadian labeling contraindicates use in severe impairment or active liver disease.
Oral: Administer with food, milk, or antacids to decrease GI adverse effects
Suspension: Shake suspension well before administration.
Tablet, delayed or extended release: Swallow tablet whole; do not break, crush, or chew.
Rectal suppository [Canadian product]: Insert suppository into rectum.
Drug may cause GI upset, bleeding, ulceration, perforation; take with food or milk to minimize GI upset.
Store at 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F); suspension should not be exposed to excessive heat (>40 ‚ °C [104 ‚ °F]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral, as sodium:
Aleve: 220 mg [contains brilliant blue fcf (fd&c blue #1)]
Cream, External:
EnovaRX-Naproxen: 10% (60 g, 120 g) [contains cetyl alcohol]
Equipto-Naproxen: 10% (120 g)
Naproderm: 15% (60 g [DSC])
Kit, Combination:
Flanax Pain Relief: 500 mg [contains cetearyl alcohol, cremophor el, propylparaben]
Naproxen Comfort Pac: 500 mg [contains methylparaben, trolamine (triethanolamine)]
Suspension, Oral:
Naprosyn: 125 mg/5 mL (480 mL)
Generic: 125 mg/5 mL (500 mL)
Tablet, Oral:
Naprosyn: 250 mg [DSC] [scored]
Naprosyn: 375 mg [DSC]
Naprosyn: 500 mg [scored]
Naproxen Kit: 500 mg [scored]
Generic: 250 mg, 375 mg, 500 mg
Tablet, Oral, as sodium:
Aleve: 220 mg [contains fd&c blue #2 aluminum lake]
All Day Pain Relief: 220 mg [contains fd&c blue #2 aluminum lake]
All Day Pain Relief: 220 mg [gluten free; contains fd&c blue #2 aluminum lake]
All Day Relief: 220 mg
All Day Relief: 220 mg [DSC] [contains fd&c blue #2 aluminum lake]
All Day Relief: 220 mg [gluten free; contains fd&c blue #2 aluminum lake]
Anaprox: 275 mg [DSC]
Anaprox DS: 550 mg [scored]
Flanax Pain Relief: 220 mg [contains fd&c blue #2 (indigotine)]
Mediproxen: 220 mg
Generic: 220 mg, 275 mg, 550 mg
Tablet Delayed Release, Oral:
EC-Naprosyn: 375 mg, 500 mg
Naproxen DR: 375 mg, 500 mg
Tablet Extended Release 24 Hour, Oral, as sodium [strength expressed as base]:
Naprelan: 375 mg, 500 mg, 750 mg, 500 mg (14s) and 750 mg (6s) [DSC]
Generic: 375 mg, 500 mg
5-ASA Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of 5-ASA Derivatives. Monitor therapy
ACE Inhibitors: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of ACE Inhibitors. Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Monitor therapy
Alcohol (Ethyl): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of GI bleeding may be increased with this combination. Monitor therapy
Aliskiren: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren. Management: Monitor renal function periodically in patients receiving aliskiren and any nonsteroidal anti-inflammatory agent. Patients at elevated risk of renal dysfunction include those who are elderly, are volume depleted, or have pre-existing renal dysfunction. Monitor therapy
Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants. Monitor therapy
Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Monitor therapy
Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Anticoagulants: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants. Monitor therapy
Antidepressants (Tricyclic, Tertiary Amine): May enhance the antiplatelet effect of NSAID (Nonselective). Monitor therapy
Apixaban: Naproxen may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Naproxen may increase the serum concentration of Apixaban. Consider therapy modification
Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Consider therapy modification
Bisphosphonate Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Monitor therapy
Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy
Corticosteroids (Systemic): May enhance the adverse/toxic effect of NSAID (Nonselective). Monitor therapy
CycloSPORINE (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Specifically, elevated diclofenac concentrations have been reported. Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (e.g., hypertension) during concomitant therapy with NSAIDs. Consider therapy modification
Dabigatran Etexilate: NSAID (Nonselective) may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of dabigatran and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Consider therapy modification
Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Monitor therapy
Deferasirox: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy
Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy
Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Desmopressin. Monitor therapy
Dexketoprofen: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination
Diclofenac (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Seek alternatives to the combined use of diclofenac with other nonsteroidal anti-inflammatory agents (NSAIDs). Avoid the use of diclofenac/misoprostol with other NSAIDs. Consider therapy modification
Digoxin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin. Monitor therapy
Drospirenone: Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Drospirenone. Monitor therapy
Edoxaban: NSAID (Nonselective) may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of edoxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Consider therapy modification
Eplerenone: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone. Monitor therapy
Floctafenine: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination
Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Haloperidol: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Haloperidol. Specifically including drowsiness and confusion. Monitor therapy
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Consider therapy modification
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Management: Concomitant treatment with these agents should generally be avoided. If used concomitantly, increased diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds) must be employed. Consider therapy modification
HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. Monitor therapy
Ibritumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy
Ketorolac (Nasal): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination
Ketorolac (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination
Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. Consider therapy modification
Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Monitor for evidence of kidney injury or decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concurrent use in CHF or cirrhosis. Concomitant use of bumetanide with indomethacin is not recommended. Consider therapy modification
Methotrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Methotrexate. Management: Alternative anti-inflammatory therapy should be considered whenever possible, especially if the patient is receiving higher, antineoplastic doses of methotrexate. Consider therapy modification
Morniflumate: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination
Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of other Nonsteroidal Anti-Inflammatory Agents. Monitor therapy
NSAID (COX-2 Inhibitor): Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of NSAID (COX-2 Inhibitor). Avoid combination
Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy
Omacetaxine: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of nonsteroidal antiinflammatory drugs (NSAIDs) with omacetaxine in patients with a platelet count of less than 50,000/uL. Avoid combination
Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
PEMEtrexed: NSAID (Nonselective) may increase the serum concentration of PEMEtrexed. Management: Patients with mild-to-moderate renal insufficiency (estimated creatinine clearance 45-79 mL/min) should avoid NSAIDs for 2-5 days prior to, the day of, and 2 days after pemetrexed. Consider therapy modification
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy
Potassium-Sparing Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy
PRALAtrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Closely monitor for increased pralatrexate serum levels and/or toxicity if used concomitantly with an NSAID. Monitor for decreased pralatrexate serum levels with NSAID discontinuation. Monitor therapy
Probenecid: May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Prostaglandins (Ophthalmic): Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents may also enhance the therapeutic effects of Prostaglandins (Ophthalmic). Monitor therapy
Quinolone Antibiotics: Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolone Antibiotics. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolone Antibiotics. Monitor therapy
Rivaroxaban: NSAID (Nonselective) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of rivaroxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Consider therapy modification
Salicylates: NSAID (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. NSAID (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of NSAID (Nonselective). Exceptions: Choline Magnesium Trisalicylate. Consider therapy modification
Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). NSAID (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider using alternative analgesics, when appropriate, and/or addition of a gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. Consider therapy modification
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). Monitor therapy
Sodium Phosphates: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with NSAIDs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Consider therapy modification
Tacrolimus (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tacrolimus (Systemic). Monitor therapy
Talniflumate: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination
Tenofovir Products: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Consider therapy modification
Tenoxicam: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination
Thiazide and Thiazide-Like Diuretics: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy
Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy
Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Tositumomab and Iodine I 131 Tositumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Monitor therapy
Treprostinil: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Monitor therapy
Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Avoid combination
Vancomycin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin. Monitor therapy
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy
Vitamin E: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Vitamin E (Oral): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Vitamin K Antagonists (eg, warfarin): NSAID (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists. Consider therapy modification
Occult blood loss, periodic liver function test, CBC, BUN, serum creatinine; urine output; blood pressure (hypertensive patients); ophthalmic exam (for vision changes/disturbances)
Naproxen may interfere with 5-HIAA urinary assays; due to an interaction with m-dinitrobenzene, naproxen should be discontinued 72 hours before adrenal function testing if the Porter-Silber test is used. May interfere with urine detection of cannabinoids and barbiturates (false-positives).
1% to 10%:
Cardiovascular: Edema (3% to 9%), palpitations (<3%)
Central nervous system: Dizziness ( ≤9%), drowsiness (3% to 9%), headache (3% to 9%), vertigo (<3%)
Dermatologic: Pruritus (3% to 9%), skin rash (3% to 9%), ecchymoses (3% to 9%), diaphoresis (<3%)
Endocrine & metabolic: Fluid retention (3% to 9%), increased thirst (<3%)
Gastrointestinal: Abdominal pain (3% to 9%), constipation (3% to 9%), nausea (3% to 9%), heartburn (3% to 9%), diarrhea (<3%), dyspepsia (<3%), stomatitis (<3%), flatulence, gastrointestinal hemorrhage, gastrointestinal perforation, gastrointestinal ulcer, vomiting
Hematologic & oncologic: Hemolysis (3% to 9%), purpura (<3%), anemia, prolonged bleeding time
Hepatic: Increased liver enzymes
Ophthalmic: Visual disturbance (<3%)
Otic: Tinnitus (3% to 9%), auditory disturbance (<3%)
Renal: Renal function abnormality
Respiratory: Dyspnea (3% to 9%)
<1% (Limited to important or life-threatening): Abnormal dreams, agranulocytosis, alopecia, anaphylactoid reaction, anaphylaxis, angioedema, aphthous stomatitis, aseptic meningitis, asthma, blurred vision, cardiac arrhythmia, cardiac failure, cognitive dysfunction, colitis, coma, confusion, conjunctivitis, cystitis, depression, dysuria, eosinophilia, eosinophilic pneumonitis, erythema multiforme, exfoliative dermatitis, fever, glossitis, granulocytopenia, hallucination, hematemesis, hepatic failure, hepatitis, hepatotoxicity (idiosyncratic) (Chalasani, 2014), hyperglycemia, hypertension, hypoglycemia, hypotension, infection, interstitial nephritis, melena, jaundice, leukopenia, lymphadenopathy, menstrual disease, malaise, myalgia, myasthenia, myocardial infarction, oliguria, pancreatitis, pancytopenia, paresthesia, pneumonia, polyuria, proteinuria, rectal hemorrhage, renal failure, renal papillary necrosis, respiratory depression, sepsis, skin photosensitivity, Stevens-Johnson syndrome, tachycardia, seizure, syncope, thrombocytopenia, toxic epidermal necrolysis, vasculitis
Metabolites and conjugates may accumulate.
Concerns related to adverse effects:
- Anaphylactoid reactions: Even in patients without prior exposure anaphylactoid reactions may occur; patients with aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Do not use in patients who experience bronchospasm, asthma, rhinitis, or urticaria with NSAID or aspirin therapy.
- Cardiovascular events: [U.S. Boxed Warning]: NSAIDs are associated with an increased risk of adverse cardiovascular thrombotic events, including MI and stroke. Risk may be increased with duration of use or preexisting cardiovascular risk factors or disease. Carefully evaluate individual cardiovascular risk profiles prior to prescribing. Use caution with fluid retention. Avoid use in heart failure (ACCF/AHA [Yancy, 2013]). Concurrent administration of ibuprofen, and potentially other nonselective NSAIDs, may interfere with aspirin 's cardioprotective effect. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.
- CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Discontinue use with blurred or diminished vision and perform ophthalmologic exam. Periodically evaluate vision in all patients receiving long term therapy.
- Gastrointestinal events: [U.S. Boxed Warning]: NSAIDs may increase risk of gastrointestinal irritation, inflammation, ulceration, bleeding, and perforation. These events may occur at any time during therapy and without warning. Risk for serious events is greater in elderly patients. Use caution with a history of GI disease (bleeding or ulcers). Canadian labeling contraindicates use with active peptic ulcers, GI bleeding, or inflammatory bowel disease. Use caution with concurrent therapy with aspirin, anticoagulants and/or corticosteroids, smoking, use of alcohol, the elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with aspirin, a substantial increase in the risk of gastrointestinal complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended (Bhatt, 2008).
- Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).
- Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE-inhibitors). Canadian labeling contraindicates use in patients with known hyperkalemia. Monitor potassium closely.
- Skin reactions: NSAIDs may cause serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); discontinue use at first sign of skin rash or hypersensitivity.
Disease-related concerns:
- Aseptic meningitis: May increase the risk of aseptic meningitis, especially in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders.
- Asthma: Do not administer to patients with aspirin-sensitive asthma; severe bronchospasm may occur. Use caution in patients with other forms of asthma.
- Coronary artery bypass graft surgery: [U.S. Boxed Warning]: Use is contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery. Risk of MI and stroke may be increased with use following CABG surgery.
- Hepatic impairment: Use with caution in patients with decreased hepatic function. Closely monitor patients with any abnormal LFT. Severe hepatic reactions (eg, fulminant hepatitis, liver failure) have occurred with NSAID use, rarely; discontinue if signs or symptoms of liver disease develop, or if systemic manifestations occur. Canadian labeling contraindicates use in severe impairment or with active liver disease.
- Hypertension: Use with caution; may cause new-onset hypertension or worsening of existing hypertension. Monitor blood pressure closely with initiation and during therapy.
- Renal impairment: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause renal decompensation. Patients with impaired renal function, dehydration, heart failure, liver dysfunction, those taking diuretics, and ACE inhibitors, and the elderly are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Not recommended for use in patients with advanced renal disease. Canadian labeling contraindicates use in severe renal impairment (Crcl <30 mL/minute) or deteriorating renal disease. Long-term NSAID use may result in renal papillary necrosis.
Special populations:
- Elderly: Use with caution, particularly at higher doses; unbound plasma fraction increased in elderly patients. Dose adjustments may be necessary.
- Pediatric: Not for self-medication (OTC use) in children <12 years. Canadian labeling contraindicates use of certain dosage forms based on age (refer to Contraindications for specific recommendations).
Other warnings/precautions:
- Self-medication (OTC use): Prior to self-medication, patients should contact healthcare provider if they have had recurring stomach pain or upset, ulcers, bleeding problems, asthma, high blood pressure, heart or kidney disease, other serious medical problems, are currently taking a diuretic, anticoagulant, other NSAIDs, or are ≥60 years of age. Recommended dosages and duration should not be exceeded, due to an increased risk of GI bleeding, MI, and stroke. Patients should stop use and consult a healthcare provider if symptoms get worse, newly appear, or continue; if an allergic reaction occurs; if feeling faint, vomit blood or have bloody/black stools; if having difficulty swallowing or heartburn, or if fever lasts for >3 days or pain >10 days. Consuming ≥3 alcoholic beverages/day or taking longer than recommended may increase the risk of GI bleeding.
- Surgical/dental procedures: Withhold for at least 4-6 half-lives prior to surgical or dental procedures.
C
Adverse events were not observed in the initial animal reproduction studies; therefore, the manufacturer classifies naproxen as pregnancy category C. Naproxen crosses the placenta and can be detected in fetal tissue and the serum of newborn infants following in utero exposure. NSAID exposure during the first trimester is not strongly associated with congenital malformations; however, cardiovascular anomalies and cleft palate have been observed following NSAID exposure in some studies. The use of a NSAID close to conception may be associated with an increased risk of miscarriage. Nonteratogenic effects have been observed following NSAID administration during the third trimester including: Myocardial degenerative changes, prenatal constriction of the ductus arteriosus, fetal tricuspid regurgitation, failure of the ductus arteriosus to close postnatally; renal dysfunction or failure, oligohydramnios; gastrointestinal bleeding or perforation, increased risk of necrotizing enterocolitis; intracranial bleeding (including intraventricular hemorrhage), platelet dysfunction with resultant bleeding; pulmonary hypertension. Because they may cause premature closure of the ductus arteriosus, use of NSAIDs late in pregnancy should be avoided (use after 31 or 32 weeks gestation is not recommended by some clinicians). The Canadian labeling contraindicates use during the third trimester of pregnancy. The chronic use of NSAIDs in women of reproductive age may be associated with infertility that is reversible upon discontinuation of the medication. A registry is available for pregnant women exposed to autoimmune medications including naproxen. For additional information contact the Organization of Teratology Information Specialists, OTIS Autoimmune Diseases Study, at (877) 311-8972.
Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties
Other proposed mechanisms not fully elucidated (and possibly contributing to the anti-inflammatory effect to varying degrees), include inhibiting chemotaxis, altering lymphocyte activity, inhibiting neutrophil aggregation/activation, and decreasing proinflammatory cytokine levels.
Oral: Almost 100%
0.16 L/kg
Extensively metabolized in the liver to 6-0-desmethyl naproxen; parent drug and desmethyl metabolite undergo further metabolism to their respective acylglucuronide conjugated metabolites
Urine (95%; primarily as metabolites); feces ( ≤3%)
Analgesic: 30 to 60 minutes
Serum:
Tablets, naproxen: 2 to 4 hours
Tablets, naproxen sodium: 1 to 2 hours
Tablets, delayed-release (empty stomach): 4 to 6 hours; range: 2 to 12 hours
Tablets, delayed-release (with food): 12 hours; range: 4 to 24 hours
Suspension: 1 to 4 hours
Suppository [Canadian product]: 2 to 3 hours
Analgesic: <12 hours
Children: Range: 8 to 17 hours
Children 8 to 14 years: 8 to 10 hours
Adults: Normal renal function: 12 to 17 hours; Moderate-to-severe renal impairment: ~15 to 21 hours (Anttila 1980)
>99% to albumin; increased free fraction in elderly
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience pyrosis, diarrhea, constipation, flatulence, or fatigue. Have patient report immediately to prescriber signs of hepatic impairment, dyspnea, excessive weight gain, edema of extremities, angina, tachycardia, strength differences from one side to another, difficulty speaking or thinking, change in balance, blurred vision, significant headache, severe dizziness, syncope, considerable asthenia, tinnitus, mood changes, depression, intolerable nausea, severe dyspepsia, considerable back pain, melena, hematemesis, ecchymosis, hemorrhaging, urinary retention, oliguria, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.