Naproxen
 Naproxen Delayed Release

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|Naproxen Naproxen Delayed Release

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Naproxen


Generic Name: Naproxen
Dosage Form: Oral suspension usp

Rx only

Naproxen Description

Naproxen is a member of the arylacetic acid group of nonsteroidal anti-inflammatory drugs.

The chemical name for Naproxen is (+)-(S)-6-Methoxy-α-methyl-2-naphthaleneacetic acid. It has the following structure:

C14H14O3 M.W. 230.26

Naproxen is a practically odorless, white to off-white crystalline substance. It is lipid soluble, practically insoluble in water at low pH and freely soluble in water at high pH. The octanol/water partition coefficient of Naproxen at pH 7.4 is 1.6 to 1.8.

Naproxen oral suspension contains 125 mg Naproxen per 5 mL. In addition, the following inactive ingredients are present: FD&C Yellow #6, fumaric acid, imitation orange flavor, imitation pineapple flavor, magnesium aluminum silicate, methylparaben, purified water, sodium chloride, sorbitol solution and sucrose. It has a sodium content of 39.3 mg/5 mL, 1.71 mEq/5 mL, with a pH range of 2.2 to 3.7.

Naproxen - Clinical Pharmacology

Naproxen is a nonsteroidal anti-inflammatory drug with analgesic and antipyretic properties. The Naproxen anion inhibits prostaglandin synthesis but beyond this its mode of action is unknown.

Pharmacokinetics

Naproxen itself is rapidly and completely absorbed from the gastrointestinal tract with an in vivo bioavailability of 95%. The elimination half-life of Naproxen ranges from 12 to 17 hours. Steady-state levels of Naproxen are reached in 4 to 5 days and the degree of Naproxen accumulation is consistent with this half-life.

Absorption

After administration of Naproxen suspension, peak plasma levels are attained in 1 to 4 hours.

Distribution

Naproxen has a volume of distribution of 0.16 L/kg. At therapeutic levels Naproxen is greater than 99% albumin bound. At doses of Naproxen greater than 500 mg/day there is less than proportional increase in plasma levels due to an increase in clearance caused by saturation of plasma protein binding at higher doses (average trough Css 36.5, 49.2, and 56.4 mg/L with 500, 1000, and 1500 mg daily doses of Naproxen). However, the concentration of unbound Naproxen continues to increase proportionally to dose.

Metabolism

Naproxen is extensively metabolized to 6-O-desmethyl Naproxen and both parent and metabolites do not induce metabolizing enzymes.

Elimination

The clearance of Naproxen is 0.13 mL/min/kg. Approximately 95% of the Naproxen from any dose is excreted in the urine, primarily as Naproxen (less than 1%), 6-O-desmethyl Naproxen (less than 1%), or their conjugates (66-92%). The plasma half-life of the Naproxen anion in humans ranges from 12 to 17 hours. The corresponding half-lives of both Naproxen"s metabolites and conjugates are shorter than 12 hours and their rates of excretion have been found to coincide closely with the rate of Naproxen disappearance from the plasma. In patients with renal failure metabolites may accumulate.

Special Populations

Children

In children of 5 to 16 years of age with arthritis, plasma Naproxen levels following a 5 mg/kg single dose of Naproxen suspension (see DOSAGE AND ADMINISTRATION) were found to be similar to those found in normal adults following a 500 mg dose. The terminal half-life appears to be similar in children and adults. Pharmacokinetic studies of Naproxen were not performed in children of less than 5 years of age.

Renal Insufficiency

Naproxen pharmacokinetics has not been determined in subjects with renal insufficiency. Given that Naproxen, its metabolites, and conjugates are primarily excreted by the kidney, the potential exists for Naproxen metabolites to accumulate in the presence of renal insufficiency.

Clinical Studies

General Information

Naproxen has been studied in patients with rheumatoid arthritis, osteoarthritis, juvenile arthritis, ankylosing spondylitis, tendinitis and bursitis, and acute gout. Improvement in patients treated for rheumatoid arthritis has been demonstrated by a reduction in joint swelling, a reduction in duration of morning stiffness, a reduction in disease activity as assessed by both the investigator and patient, and by increased mobility as demonstrated by a reduction in walking time. Generally, response to Naproxen has not been found to be dependent on age, sex, severity or duration of rheumatoid arthritis.

In patients with osteoarthritis, the therapeutic action of Naproxen has been shown by a reduction in joint pain or tenderness, an increase in range of motion in knee joints, increased mobility as demonstrated by a reduction in walking time, and improvement in capacity to perform activities of daily living impaired by the disease.

In a clinical trial comparing standard formulations of Naproxen 375 mg b.i.d. (750 mg a day) versus 750 mg b.i.d. (1500 mg a day), 9 patients in the 750 mg group terminated prematurely because of adverse events. Nineteen patients in the 1500 mg group terminated prematurely because of adverse events. Most of these adverse events were gastrointestinal events.

In clinical studies in patients with rheumatoid arthritis, osteoarthritis, and juvenile arthritis, Naproxen has been shown to be comparable to aspirin and indomethacin in controlling the aforementioned measures of disease activity, but the frequency and severity of the milder gastrointestinal adverse effects (nausea, dyspepsia, heartburn) and nervous system adverse effects (tinnitus, dizziness, lightheadedness) were less in Naproxen treated patients than in those treated with aspirin or indomethacin.

In patients with ankylosing spondylitis, Naproxen has been shown to decrease night pain, morning stiffness and pain at rest. In double-blind studies the drug was shown to be as effective as aspirin, but with fewer side effects.

In patients with acute gout, a favorable response to Naproxen was shown by significant clearing of inflammatory changes (e.g., decrease in swelling, heat) within 24 to 48 hours, as well as by relief of pain and tenderness.

Naproxen has been studied in patients with mild to moderate pain secondary to post-operative, orthopedic, post-partum episiotomy, and uterine contraction pain and dysmenorrhea. Onset of pain relief can begin within one hour in patients taking Naproxen. Analgesic effect was shown by such measures as reduction of pain intensity scores, increase in pain relief scores, decrease in numbers of patients requiring additional analgesic medication, and delay in time to remedication. The analgesic effect has been found to last for up to 12 hours.

Naproxen may be used safely in combination with gold salts and/or corticosteroids; however, in controlled clinical trials, when added to the regimen of patients receiving corticosteroids it did not appear to cause greater improvement over that seen with corticosteroids alone. Whether Naproxen has a “steroid-sparing” effect has not been adequately studied. When added to the regimen of patients receiving gold salts, Naproxen did result in greater improvement. Its use in combination with salicylates is not recommended because there is evidence that aspirin increases the rate of excretion of Naproxen and data are inadequate to demonstrate that Naproxen and aspirin produce greater improvement over that achieved with aspirin alone. In addition, as with other NSAIDS the combination may result in higher frequency of adverse events than demonstrated for either product alone.

In 51Cr blood loss and gastroscopy studies with normal volunteers, daily administration of 1000 mg of Naproxen has been demonstrated to cause statistically significantly less gastric bleeding and erosion than 3250 mg of aspirin.

Individualization of Dosage

Onset of pain relief can begin within one hour in patients taking Naproxen.

The recommended strategy for initiating therapy is to choose a formulation and a starting dose likely to be effective for the patient and then adjust the dosage based on observation of benefit and/or adverse events. A lower dose should be considered in patients with renal or hepatic impairment or in elderly patients (see PRECAUTIONS).

Analgesia/Dysmenorrhea/Bursitis and Tendinitis

Because the sodium salt of Naproxen is more rapidly absorbed, Naproxen sodium is recommended for the management of acute painful conditions when prompt onset of pain relief is desired. Naproxen may also be used for treatment of acute pain and dysmenorrhea. The recommended starting dose of Naproxen is 500 mg followed by 500 mg every 12 hours or 250 mg every 6 to 8 hours, as required. The initial dose should not exceed 1250 mg of Naproxen. Thereafter, the total daily dose should not exceed 1000 mg.

Acute Gout

The recommended starting dose is 750 mg of Naproxen followed by 250 mg every 8 hours until the attack has subsided.

Osteoarthritis/Rheumatoid Arthritis/Ankylosing Spondylitis

The recommended dose of Naproxen is 250 mg, 375 mg, or 500 mg taken twice daily (morning and evening). During long-term administration the dose of Naproxen may be adjusted up or down depending on the clinical response of the patient. A lower daily dose may suffice for long-term administration. In patients who tolerate lower doses well, the dose may be increased to 1500 mg per day when a higher level of anti-inflammatory/analgesic activity is required. When treating patients with Naproxen 1500 mg/day, the physician should observe sufficient increased clinical benefit to offset the potential increased risk. The morning and evening doses do not have to be equal in size and administration of the drug more frequently than twice daily does not generally make a difference in response (see CLINICAL PHARMACOLOGY).

Juvenile Arthritis

The use of Naproxen oral suspension allows for more flexible dose titration. In children, doses of 5 mg/kg/day produced plasma levels of Naproxen similar to those seen in adults taking 500 mg of Naproxen (see CLINICAL PHARMACOLOGY).

The recommended total daily dose is approximately 10 mg/kg given in 2 divided doses (i.e., 5 mg/kg given twice a day). (See DOSAGE AND ADMINISTRATION.)

Indications and Usage for Naproxen

Naproxen oral suspension is indicated for the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and juvenile arthritis.

Naproxen suspension is recommended for juvenile rheumatoid arthritis in order to obtain the maximum dosage flexibility based on the child"s weight.

It is also indicated for the treatment of tendinitis, bursitis, acute gout, and for the management of pain and primary dysmenorrhea.

Contraindications

Naproxen is contraindicated in patients who have had allergic reactions to prescription as well as to over-the-counter products containing Naproxen. It is also contraindicated in patients in whom aspirin or other nonsteroidal anti-inflammatory/analgesic drugs induce the syndrome of asthma, rhinitis, and nasal polyps. Both types of reactions have the potential of being fatal. Anaphylactoid reactions to Naproxen, whether of the true allergic type or the pharmacologic idiosyncratic (e.g., aspirin hypersensitivity syndrome) type, usually but not always occur in patients with a known history of such reactions. Therefore, careful questioning of patients for such things as asthma, nasal polyps, urticaria, and hypotension associated with nonsteroidal anti-inflammatory drugs before starting therapy is important. In addition, if such symptoms occur during therapy, treatment should be discontinued.

Warnings

Risk of GI Ulceration, Bleeding and Perforation with NSAID Therapy

Serious gastrointestinal toxicity such as bleeding, ulceration, and perforation, can occur at any time, with or without warning symptoms, in patients treated chronically with NSAID therapy. Although minor upper gastrointestinal problems, such as dyspepsia, are common, usually developing early in therapy, physicians should remain alert for ulceration and bleeding in patients treated chronically with NSAIDs even in the absence of previous GI tract symptoms. In patients observed in clinical trials of several months to two years’ duration, symptomatic upper GI ulcers, gross bleeding or perforation appear to occur in approximately 1% of patients treated for 3 to 6 months, and in about 2-4% of patients treated for one year.

Physicians should inform patients about the signs and/or symptoms of serious GI toxicity and what steps to take if they occur.

Studies to date with Naproxen have not identified any subset of patients not at risk of developing peptic ulceration and bleeding. Except for a prior history of serious GI events and other risk factors known to be associated with peptic ulcer disease, such as alcoholism, smoking, etc., no risk factors (e.g., age, sex) have been associated with increased risk. Elderly or debilitated patients seem to tolerate ulceration or bleeding less well than other individuals and most spontaneous reports of fatal GI events are in this population. Studies to date are inconclusive concerning the relative risk of various NSAIDs in causing such reactions. High doses of any NSAID probably carry a greater risk of these reactions, although controlled clinical trials showing this do not exist in most cases. In considering the use of relatively large doses (within the recommended dosage range), sufficient benefit should be anticipated to offset the potential increased risk of GI toxicity.

Precautions

General

Naproxen SHOULD NOT BE USED CONCOMITANTLY WITH OTHER Naproxen PRODUCTS (SUCH AS Naproxen SODIUM) SINCE THEY ALL CIRCULATE IN PLASMA AS THE Naproxen ANION.

If the steroid dose is reduced or eliminated during therapy, the steroid dosage should be reduced slowly and the patients should be observed closely for any evidence of adverse effects, including adrenal insufficiency and exacerbation of symptoms of arthritis.

Patients with initial hemoglobin values of 10 grams or less who are to receive long-term therapy should have hemoglobin values determined periodically.

The antipyretic and anti-inflammatory activities of the drug may reduce fever and inflammation, thus diminishing their utility as diagnostic signs in detecting complications of presumed non-infectious, non-inflammatory painful conditions.

Because of adverse eye findings in animal studies with drugs of this class, it is recommended that ophthalmic studies be carried out if any change or disturbance in vision occurs.

Renal Effects

As with other nonsteroidal anti-inflammatory drugs, long-term administration of Naproxen to animals has resulted in renal papillary necrosis and other abnormal renal pathology. In humans, there have been reports of acute interstitial nephritis with hematuria, proteinuria, and occasionally nephrotic syndrome associated with Naproxen containing products and other NSAIDS since they have been marketed.

A second form of renal toxicity has been seen in patients taking Naproxen as well as other nonsteroidal anti-inflammatory drugs. In patients with prerenal conditions leading to the reduction in renal blood flow or blood volume, where the renal prostaglandins have a supportive role in the maintenance of renal perfusion, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics, and the elderly. Discontinuation of nonsteroidal anti-inflammatory therapy is typically followed by recovery to the pretreatment state.

Naproxen and its metabolites are eliminated primarily by the kidneys, therefore, the drug should be used with caution in patients with significantly impaired renal function and the monitoring of serum creatinine and/or creatinine clearance is advised in these patients. Caution should be used if the drug is given to patients with creatinine clearance of less than 20 mL/minute because accumulation of Naproxen metabolites has been seen in such patients.

Chronic alcoholic liver disease and probably other diseases with decreased or abnormal plasma proteins (albumin) reduce the total plasma concentration of Naproxen, but the plasma concentration of unbound Naproxen is increased. Caution is advised when high doses are required and some adjustment of dosage may be required in these patients. It is prudent to use the lowest effective dose.

Studies indicate that, although total plasma concentration of Naproxen is unchanged, the unbound plasma fraction of Naproxen is increased in the elderly. Caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. As with other drugs used in the elderly, it is prudent to use the lowest effective dose.

Hepatic Function

As with other nonsteroidal anti-inflammatory drugs, borderline elevations of one or more liver tests may occur in up to 15% of patients. These abnormalities may progress, may remain essentially unchanged, or may be transient with continued therapy. The SGPT (ALT) test is probably the most sensitive indicator of liver dysfunction. Meaningful (3 times the upper limit of normal) elevations of SGPT or SGOT (AST) occurred in controlled clinical trials in less than 1% of patients. A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of more severe hepatic reaction while on therapy with Naproxen. Severe hepatic reactions, including jaundice and cases of fatal hepatitis, have been reported with Naproxen as with other nonsteroidal anti-inflammatory drugs. Although such reactions are rare, if abnormal liver tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), Naproxen should be discontinued.

Fluid Retention and Edema

Peripheral edema has been observed in some patients receiving Naproxen. Since each teaspoonful of Naproxen suspension contains 39 mg (about 1.5 mEq per each 125 mg of Naproxen) of sodium, this should be considered in patients whose overall intake of sodium must be severely restricted.

Information for Patients

Naproxen, like other drugs of its class, is not free of side effects. The side effects of these drugs can cause discomfort and, rarely, there are more serious side effects, such as gastrointestinal bleeding, which may result in hospitalization and even fatal outcomes.

NSAIDs (Nonsteroid Anti-Inflammatory Drugs) are often essential agents in the management of arthritis and have a major role in the treatment of pain, but they also may be commonly employed for conditions which are less serious.

Physicians may wish to discuss with their patients the potential risks (see WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS sections) and likely benefits of Naproxen treatment, particularly when it is used for less serious conditions where treatment without NSAIDs may represent an acceptable alternative to both the patient and physician.

Caution should be exercised by patients whose activities require alertness if they experience drowsiness, dizziness, vertigo or depression during therapy with Naproxen.

Laboratory Tests

Because serious GI tract ulceration and bleeding can occur without warning symptoms, physicians should follow patients chronically treated with Naproxen for the signs and symptoms of ulceration and bleeding and should inform them of the importance of this follow-up and what they should do if certain signs and symptoms do appear (see WARNINGS - Risk of GI Ulceration, Bleeding and Perforation with NSAID Therapy ).

Drug Interactions

The use of NSAIDS in patients who are receiving ACE inhibitors may potentiate renal disease states (see PRECAUTIONS, Renal Effects).

In vitro studies have shown that Naproxen anion, because of its affinity for protein, may displace from their binding sites other drugs which are also albumin-bound (see CLINICAL PHARMACOLOGY, Pharmacokinetics).

Theoretically, the Naproxen anion itself could likewise be displaced. Short-term controlled studies failed to show that taking the drug significantly affects prothrombin times when administered to individuals on coumarin-type anticoagulants. Caution is advised nonetheless, since interactions have been seen with other nonsteroidal agents of this class. Similarly, patients receiving the drug and a hydantoin, sulfonamide or sulfonylurea should be observed for signs of toxicity to these drugs (see CLINICAL PHARMACOLOGY, Clinical Studies, General Information).

Concomitant administration of Naproxen and aspirin is not recommended because Naproxen is displaced from its binding sites during the concomitant administration of aspirin, resulting in lower plasma concentrations and peak plasma levels.

The natriuretic effect of furosemide has been reported to be inhibited by some drugs of this class. Inhibition of renal lithium clearance leading to increases in plasma lithium concentrations has also been reported. Naproxen and other nonsteroidal anti-inflammatory drugs can reduce the antihypertensive effect of propranolol and other beta-blockers.

Probenecid given concurrently increases Naproxen anion plasma levels and extends its plasma half-life significantly.

Caution should be used if Naproxen is administered concomitantly with methotrexate. Naproxen and other nonsteroidal anti-inflammatory drugs have been reported to reduce the tubular secretion of methotrexate in an animal model, possibly increasing the toxicity of methotrexate.

Drug/Laboratory Test Interactions

Naproxen may decrease platelet aggregation and prolong bleeding time. This effect should be kept in mind when bleeding times are determined.

The administration of Naproxen may result in increased urinary values for 17-ketogenic steroids because of an interaction between the drug and/or its metabolites with m-dinitrobenzene used in this assay. Although 17-hydroxy-corticosteroid measurements (Porter-Silber test) do not appear to be artifactually altered, it is suggested that therapy with Naproxen be temporarily discontinued 72 hours before adrenal function tests are performed if the Porter-Silber test is to be used.

Naproxen may interfere with some urinary assays of 5-hydroxy indoleacetic acid (5HIAA).

Carcinogenesis

A two-year study was performed in rats to evaluate the carcinogenic potential of Naproxen at doses of 8, 16, and 24 mg/kg/day (50, 100, and 150 mg/m2). The maximum dose used was 0.28 times the systemic exposure to humans at the recommended dose. No evidence of tumorigenicity was found.

Pregnancy

Teratogenic Effects

Pregnancy Category B.

Reproduction studies have been performed in rats at 20 mg/kg/day (125 mg/m2/day, 0.23 times the human systemic exposure), rabbits at 20 mg/kg/day (220 mg/m2/day, 0.27 times the human systemic exposure), and mice at 170 mg/kg/day (510 mg/m2/day, 0.28 times the human systemic exposure) with no evidence of impaired fertility or harm to the fetus due to the drug. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Naproxen should not be used during pregnancy unless clearly needed.

Non-Teratogenic Effects

There is some evidence to suggest that when inhibitors of prostaglandin synthesis are used to delay preterm labor, there is an increased risk of neonatal complications such as necrotizing enterocolitis, patent ductus arteriosus, and intracranial hemorrhage. Naproxen treatment given in late pregnancy to delay parturition has been associated with persistent pulmonary hypertension, renal dysfunction, and abnormal prostaglandin E levels in preterm infants. Because of the known effect of drugs of this class on the human fetal cardiovascular system (closure of the ductus arteriosus), use during third trimester should be avoided.

Nursing Mothers

The Naproxen anion has been found in the milk of lactating women at a concentration of approximately 1% of that found in the plasma. Because of the possible adverse effects of prostaglandin-inhibiting drugs on neonates, use in nursing mothers should be avoided.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 2 years have not been established. Pediatric dosing recommendations for juvenile arthritis are based on well-controlled studies. There are no adequate effectiveness or dose-response data for other pediatric conditions, but the experience in juvenile arthritis and other use experience have established that single doses of 2.5 to 5 mg/kg (as Naproxen oral suspension, see DOSAGE AND ADMINISTRATION section) with total daily dose not exceeding 15 mg/kg/day, are well tolerated in pediatric patients over 2 years of age.

Adverse Reactions

The following adverse reactions are divided into 3 parts based on frequency and whether or not the possibility exists of a causal relationship between Naproxen and these adverse events. In those reactions listed as "Probable Causal Relationship" there is at least one case for each adverse reaction where there is evidence to suggest that there is a causal relationship between drug usage and the reported event.

Adverse reactions reported in controlled clinical trials in 960 patients treated for rheumatoid arthritis or osteoarthritis are listed below. In general, reactions in patients treated chronically were reported 2 to 10 times more frequently than they were in short-term studies in the 962 patients treated for mild to moderate pain or for dysmenorrhea. The most frequent complaints reported related to the gastrointestinal tract.

A clinical study found gastrointestinal reactions to be more frequent and more severe in rheumatoid arthritis patients taking 1500 mg Naproxen daily compared to those taking 750 mg daily (see CLINICAL PHARMACOLOGY).

In controlled clinical trials with about 80 children and in well monitored open-label studies with about 400 children with juvenile arthritis, treated with Naproxen, the incidence of rash and prolonged bleeding times were increased, the incidence of gastrointestinal and central nervous system reactions were about the same, and the incidence of other reactions were lower in children than in adults.

The following adverse reactions are divided into three parts based on frequency and causal relationship.

Incidence greater than 1% (Probable Causal Relationship)

Gastrointestinal: Constipation*, heartburn*, abdominal pain*, nausea*, dyspepsia, diarrhea, stomatitis.

Central Nervous System: Headache*, dizziness*, drowsiness*, lightheadedness, vertigo.

Dermatologic: Itching (pruritus)*, skin eruptions*, ecchymoses*, sweating, purpura.

Special Senses: Tinnitus*, hearing disturbances, visual disturbances.

Cardiovascular: Edema*, dyspnea*, palpitations.

General: Thirst.

*Incidence of reported reaction between 3% and 9%. Those reactions occurring in less than 3% of the patients are unmarked.

Incidence less than 1% (Probable Causal Relationship)

The following adverse reactions were reported less frequently than 1% during controlled clinical trials and through voluntary reports since marketing. Those reactions observed through voluntary reporting since marketing are italicized.

Gastrointestinal: Abnormal liver function tests, colitis, gastrointestinal bleeding and/or perforation, hematemesis, jaundice, pancreatitis, melena, vomiting.

Renal: Glomerular nephritis, hematuria, hyperkalemia, interstitial nephritis, nephrotic syndrome, renal disease, renal failure, renal papillary necrosis.

Hematologic: Agranulocytosis, eosinophilia, granulocytopenia, leukopenia, thrombocytopenia.

Central Nervous System: Depression, dream abnormalities, inability to concentrate, insomnia, malaise, myalgia and muscle weakness.

Dermatologic: Alopecia, photosensitive dermatitis, urticaria, skin rashes, photosensitivity reactions resembling porphyria cutanea tarda and epidermolysis bullosa.

Special Senses: Hearing impairment.

Cardiovascular: Congestive heart failure.

Respiratory: Eosinophilic pneumonitis.

General: Anaphylactoid reactions, angioneurotic edema, menstrual disorders, pyrexia (chills and fever).

Incidence Less Than 1% (Causal Relationship Unknown)

These observations are being listed to serve as alerting information to the physicians:

Hematologic: Aplastic anemia, hemolytic anemia.

Central Nervous System: Aseptic meningitis, cognitive dysfunction.

Dermatologic: Epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome.

Gastrointestinal: Non-peptic gastrointestinal ulceration, ulcerative stomatitis.

Cardiovascular: Vasculitis.

General: Hyperglycemia, hypoglycemia.

Overdosage

Significant Naproxen overdosage may be characterized by drowsiness, heartburn, indigestion, nausea or vomiting. A few patients have experienced seizures, but it is not clear whether or not these were drug related. It is not known what dose of the drug would be life threatening. The oral LD50 of the drug is 543 mg/kg in rats, 1234 mg/kg in mice, 4110 mg/kg in hamsters and greater than 1000 mg/kg in dogs.

Should a patient ingest a large volume of suspension, accidentally or purposefully, the stomach may be emptied and usual supportive measures employed. In animals 0.5 g/kg of activated charcoal was effective in reducing plasma levels of Naproxen. Hemodialysis does not decrease the plasma concentration of Naproxen because of the high degree of its protein binding.

Naproxen Dosage and Administration

Rheumatoid Arthritis, Osteoarthritis, and Ankylosing Spondylitis:

The recommended dose of Naproxen in adults is 250 mg (10 mL or 2 teaspoonfuls of suspension), 375 mg (15 mL or 3 teaspoonfuls), or 500 mg (20 mL or 4 teaspoonfuls) twice daily (morning and evening). During long-term administration, the dose may be adjusted up or down depending on the clinical response of the patient. A lower daily dose may suffice for long-term administration. The morning and evening doses do not have to be equal in size and the administration of the drug more frequently than twice daily is not necessary.

In patients who tolerate lower doses well, the dose may be increased to Naproxen 1500 mg per day for limited periods when a higher level of anti-inflammatory/analgesic activity is required. When treating such patients with the Naproxen 1500 mg/day dose, the physician should observe sufficient increased clinical benefits to offset the potential increased risk (see CLINICAL PHARMACOLOGY and Individualization of Dosagee).

Juvenile Arthritis

The recommended total daily dose of Naproxen is approximately 10 mg/kg given in 2 divided doses (i.e., 5 mg/kg given twice a day). The following table may be used as a guide for the suspension:

Child"s Weight:
Dose:
13 kg (29 lb)
2.5 mL (1/2 tsp)
b.i.d.
25 kg (55 lb)
5 mL (1 tsp)
b.i.d.
38 kg (84 lb)
7.5 mL (1 1/2 tsp)
b.i.d.

Management of Pain, Primary Dysmenorrhea and Acute Tendinitis and Bursitis

The recommended starting dose of Naproxen is 500 mg (20 mL or 4 teaspoonfuls) every 12 hours, or is 250 mg (10 mL or 2 teaspoonfuls) every 6 to 8 hours as required. The initial total daily dose should not exceed 1250 mg (50 mL or 10 teaspoonfuls). Thereafter, the total daily dose should not exceed 1000 mg (40 mL or 8 teaspoonfuls) of Naproxen.

Acute Gout: The recommended starting dose of Naproxen is 750 mg (30 mL or 6 teaspoonfuls), followed by 250 mg (10 mL or 2 teaspoonfuls) every 8 hours until the attack has subsided.

How is Naproxen Supplied

Naproxen for oral administration is available as:

Naproxen Oral Suspension USP, 125 mg per 5 mL

Light-orange colored, pineapple-orange flavored opaque suspension. Sodium content: 39.3 mg/5 mL, 1.71 mEq/5 mL.

NDC 0054-3630-63: Bottle of 500 mL.

SHAKE WELL BEFORE USING.

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature].

Avoid excessive heat, above 40°C (104°F).

Dispense in tight, light-resistant container as defined in the USP/NF.

4059100//03

© RLI, 2003


Naproxen (Naproxen)
PRODUCT INFO
Product Code 0054-3630 Dosage Form SUSPENSION
Route Of Administration ORAL DEA Schedule
INGREDIENTS
Name (Active Moiety) Type Strength
Naproxen (Naproxen) Active 125 MILLIGRAM  In 5 MILLILITER
FD&C Yellow #6 Inactive  
fumaric acid Inactive  
imitation orange flavor Inactive  
imitation pineapple flavor Inactive  
magnesium aluminum silicate Inactive  
methylparaben Inactive  
water Inactive  
sodium chloride Inactive  
sorbitol solution Inactive  
sucrose Inactive  
IMPRINT INFORMATION
Characteristic Appearance Characteristic Appearance
Color Score
Shape Symbol
Imprint Code Coating
Size
PACKAGING
# NDC Package Description Multilevel Packaging
1 0054-3630-63 500 MILLILITER In 1 BOTTLE, PLASTIC None

Revised: 06/2006





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