DESCRIPTION Naproxen is a proprionic acid derivative related to the arylacetic acid group of nonsteroidal anti-inflammatory drugs. The chemical name for naproxen is (S)-6-methoxy-α-methyl-2-naphthaleneacetic acid. Naproxen has the following structure: Naproxen is an 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. Each tablet, for oral administration, contains 250 mg, 375 mg or 500 mg of naproxen. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, polyvinylpyrrolidone, and sodium starch glycolate. Structure

INDICATIONS AND USAGE Carefully consider the potential benefits and risks of naproxen and other treatment options before deciding to use naproxen tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). Naproxen is indicated: For the relief of the signs and symptoms of rheumatoid arthritis For the relief of the signs and symptoms of osteoarthritis For the relief of the signs and symptoms of ankylosing spondylitis For the relief of the signs and symptoms of juvenile arthritis Naproxen is also indicated: For relief of the signs and symptoms of tendonitis For the relief of the signs and symptoms of bursitis For the relief of the signs and symptoms of acute gout For the management of pain For the management of primary dysmenorrhea

HOW SUPPLIED Naproxen Tablets USP, 250 mg are White, Round, Unscored Tablet; Debossed "West-ward 346" and are available in: Bottles of 30 tablets. Bottles of 100 tablets. Bottles of 500 tablets. Naproxen Tablets USP, 375 mg are White, Oblong, Unscored Tablet; Debossed "West-ward 347" and are available in: Bottles of 30 tablets. Bottles of 100 tablets. Bottles of 500 tablets. Naproxen Tablets USP, 500 mg are White, Oblong, Unscored Tablet; Debossed "West-ward 348" and are available in: Bottles of 30 tablets. Bottles of 100 tablets. Bottles of 500 tablets. Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Manufactured By: West-ward Pharmaceutical Corp. Eatontown, NJ 07724 Revised October 2009

DOSAGE AND ADMINISTRATION: Carefully consider the potential benefits and risks of naproxen and other treatment options before deciding to use naproxen. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). After observing the response to initial therapy with naproxen, the dose and frequency should be adjusted to suit an individual patient's needs. Different dose strengths and formulations (i.e., tablets, suspension) of the drug are not necessarily bioequivalent. This difference should be taken into consideration when changing formulation. Although naproxen circulates in the plasma as naproxen, they have pharmacokinetic differences that may affect onset of action. Onset of pain relief can begin within 1 hour in patients taking naproxen (see CLINICAL PHARMACOLOGY ). 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 WARNINGS and PRECAUTIONS ). Geriatric Patients 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. Patients with Moderate to Severe Renal Impairment Naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment (creatine clearance <30 mL/min) (see WARNINGS: Renal Effects ). Rheumatoid Arthritis, Osteoarthritis and Ankylosing Spondylitis Naproxen 250 mg twice daily or 375 mg twice daily or 500 mg twice daily 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. 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/day for limited periods of up to 6 months when a higher level of anti-inflammatory/analgesic activity is required. When treating such patients with naproxen 1500 mg/day, the physician should observe sufficient increased clinical benefits 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 the daily doses do not generally make a difference in response (See CLINICAL PHARMACOLOGY ). Acute Gout The recommended starting dose is 750 mg of naproxen followed by 250 mg every 8 hours until the attack has subsided.

CONTRAINDICATIONS Naproxen is contraindicated in patients with known hypersensitivity to naproxen and naproxen sodium. Naproxen should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see WARNINGS - Anaphylactoid Reactions, and PRECAUTIONS - Preexisting Asthma ). Naproxen is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS ).

WARNINGS CARDIOVASCULAR EFFECTS Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious Gl events (see Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation ). Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS ). Hypertension NSAIDs, including naproxen, can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including naproxen, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy. Congestive Heart Failure and Edema Fluid retention, edema, and peripheral edema have been observed in some patients taking NSAIDs. Naproxen should be used with caution in patients with fluid retention, hypertension, or heart failure. Gastrointestinal Effects- Risk of Ulceration, Bleeding, and Perforation NSAIDs, including naproxen, can cause serious gastrointestinal (Gl) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper Gl adverse event on NSAID therapy, is symptomatic. Upper Gl ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious Gl event at some time during the course of therapy. However, even short-term therapy is not without risk. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been adequately assessed. Only 1 in 5 patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a Gl bleed compared to patients with neither of these risk factors. Other factors that increase the risk for Gl bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal Gl events are in elderly or debilitated patients and therefore, special care should be taken in treating this population. To minimize the potential risk for an adverse Gl event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of Gl ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious Gl adverse event is suspected. This should include discontinuation of the NSAID until a serious Gl adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered. Epidemiological studies, both of the case-control and cohort design, have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. In two studies, concurrent use of an NSAID or aspirin potentiated the risk of bleeding (see PRECAUTIONS: Drug Interactions ). Although these studies focused on upper gastrointestinal bleeding, there is reason to believe that bleeding at other sites may be similarly potentiated. NSAIDs should be given with care to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn's disease) as their condition may be exacerbated. Renal Effects Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteriodal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, hypovolemia, heart failure, liver dysfunction, salt depletion, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of nonsteroidal anti-inflammatory drug therapy is usually followed by recovery to the pretreatment state (see WARNINGS: Advanced Renal Disease ). Advanced Renal Disease No information is available from controlled clinical studies regarding the use of naproxen in patients with advanced renal disease. Therefore, treatment with naproxen is not recommended in these patients with advanced renal disease. If naproxen therapy must be initiated, close monitoring of the patient's renal function is advisable. Anaphylactoid Reactions As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to naproxen. Naproxen should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS - Preexisting Asthma ). Emergency help should be sought in cases where an anaphylactoid reaction occurs. Anaphylactic reactions, like anaphylaxis, may have a fatal outcome. Skin Reactions NSAIDs, including naproxen, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity. Pregnancy In late pregnancy, as with other NSAIDs, naproxen should be avoided because it may cause premature closure of the ductus arteriosus.

Information for Patients Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed. Naproxen, like other NSAIDs, may cause serious CV side effects, such as Ml or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up (see WARNINGS, Cardiovascular Effects ). Naproxen, like other NSAIDs, can cause Gl discomfort and, rarely, serious Gl side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious Gl tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS, Gastrointestinal Effects: Risk of Ulceration, Bleeding, and Perforation ). Naproxen, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible. Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians. Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy. Patients should be informed of the signs of an anaphylactoid reaction (e.g. difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS ). In late pregnancy, as with other NSAIDs, naproxen should be avoided because it will cause premature closure of the ductus arteriosus. Caution should be exercised by patients whose activities require alertness if they experience drowsiness, dizziness, vertigo or depression during therapy with naproxen.

Drug Interactions ACE-inhibitors Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors. Antacids and Sucralfate Concomitant administration of some antacids (magnesium oxide or aluminum hydroxide) and sucralfate can delay the absorption of naproxen. Aspirin When naproxen is administered with aspirin, its protein binding is reduced, although the clearance of free naproxen is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of naproxen containing products and aspirin is not generally recommended because of the potential of increased adverse effects. Cholestyramine As with other NSAIDs, concomitant administration of cholestyramine can delay the absorption of naproxen. Diuretics Clinical studies as well as postmarketing observations, have shown that naproxen can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAID's the patient should be observed closely for signs of renal failure (see WARNINGS: Renal Effects ), as well as to assure diuretic efficacy. Lithium NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. Methotrexate NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. Naproxen and other nonsteriodal anti-inflammatory drugs have been reported to reduce the tubular secretion of methotrexate in an animal model. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate. Warfarin The effects of warfarin and NSAIDs on Gl bleeding are synergistic, such that users of both drugs together have a risk of serious Gl bleeding higher than users of either drug alone. No significant interactions have been observed in clinical studies with naproxen and coumarin-type anticoagulants. However, caution is advised since interactions have been seen with other nonsteriodal agents of this class. The free fraction of warfarin may increase substantially in some subjects and naproxen interferes with platelet function. Selective Serotonin Reuptake Inhibitors (SSRIs) There is an increased risk of gastrointestinal bleeding when selective serotonin reuptake inhibitors (SSRIs) are combined with NSAIDs. Caution should be used when NSAIDs are administered concomitantly with SSRIs.

Pregnancy Teratogenic Effects. Pregnancy Category C. Reproduction studies have been performed in rats at 20 mg/kg/day (125 mg/m 2 /day, 0.23 times the human systemic exposure), rabbits at 20 mg/kg/day (220 mg/m 2 /day, 0.27 times the human systemic exposure), and mice at 170 mg/kg/day (510 mg/m 2 /day, 0.28 times the human systemic exposure) with no evidence of impaired fertility or harm to the fetus due to the drug. However, animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Naproxen should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Nonteratogenic 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 effects of nonsteriodal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly late pregnancy) 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 (see DOSAGE AND ADMINISTRATION ). 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, with total daily dose not exceeding 15 mg/kg/day, are well tolerated in pediatric patients over 2 years of age.

Geriatric Use 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. Experience indicates that geriatric patients may be particularly sensitive to certain adverse effects of nonsteriodal anti-inflammatory drugs. Elderly or debilitated patients seem to tolerate peptic ulceration or bleeding less well when these events do occur. Most spontaneous reports of fatal Gl events are in the geriatric population (see WARNINGS ). Naproxen is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Geriatric patients may be at a greater risk for the development of a form of renal toxicity precipitated by reduced prostaglandin formation during administration of nonsteroidal anti-inflammatory drugs (see WARNINGS: Renal Effects ).

ADVERSE REACTIONS 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 daily doses of 1500 mg naproxen compared to those taking 750 mg naproxen (see CLINICAL PHARMACOLOGY ). In controlled clinical trials with about 80 pediatric patients and in well-monitored, open-label studies with about 400 pediatric patients 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 pediatric patients than in adults. In patients taking naproxen in clinical trials, the most frequently reported adverse experiences in approximately 1 to 10% of patients are: Gastrointestinal (Gl) Experiences, including: heartburn*, abdominal pain*, nausea*, constipation*, diarrhea, dyspepsia, stomatitis Central Nervous System: headache*, dizziness*, drowsiness*, lightheadedness, vertigo Dermatologic: pruritus (itching)*, skin eruptions*, ecchymoses*, sweating, purpura Special Senses: tinnitus*, visual disturbances, hearing disturbances Cardiovascular: edema*, palpitations General: dyspnea*, thirst *Incidence of reported reaction between 3% and 9%. Those reactions occurring in less than 3% of the patients are unmarked. In patients taking NSAIDs, the following adverse experiences have also been reported in approximately 1 to 10% of patients. Gastrointestinal (Gl) Experiences, including: flatulence, gross bleeding/perforation, Gl ulcers (gastric/duodenal), vomiting General: abnormal renal function, anemia, elevated liver enzymes, increased bleeding time, rashes The following are additional adverse experiences reported in <1% of patients taking naproxen during clinical trials and through post-marketing reports. Those adverse reactions observed through post-marketing reports are italicized. Body as a Whole: anaphylactoid reactions, angioneurotic edema, menstrual disorders, pyrexia (chills and fever) Cardiovascular: congestive heart failure, vasculitis, hypertension, pulmonary edema Gastrointestinal: gastrointestinal bleeding and/or perforation, hematemesis, pancreatitis, vomiting, colitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn's disease), abnormal liver function tests, nonpeptic gastrointestinal ulceration, ulcerative stomatitis Hepatobiliary: jaundice, abnormal liver function tests, hepatitis (some cases have been fatal) Hemic and Lymphatic: eosinophilia, leucopenia, melena , thrombocytopenia, agranulocytosis, granulocytopenia, hemolytic anemia, aplastic anemia Metabolic and Nutritional: hyperglycemia, hypoglycemia Nervous System: inability to concentrate, depression, dream abnormalities, insomnia, malaise, myalgia, muscle weakness, aseptic meningitis, cognitive dysfunction, convulsions Respiratory: eosinophilic pneumonitis, asthma Dermatologic: alopecia, urticaria, skin rashes, toxic epidermal necrolysis, erythema multiforme, erythema nodosum fixed drug eruption, lichen planus pustular reaction, systemic lupus erythematoses, bullous reactions, including Stevens-Johnson syndrome, photosensitive dermatitis, photosensitivity reactions, including rare cases resembling porphyria cutanea tarda (psuedoporphyria) or epidermolysis bullosa. If skin fragility, blistering or other symptoms suggestive of pseudoporphyria occur, treatment should be discontinued and the patient monitored. Special Senses: hearing impairment, corneal opacity, papillitis, retrobulbar optic neuritis, papilledema Urogenital: glomerular nephritis, hematuria, hyperkalemia, interstitial nephritis, nephrotic syndrome, renal disease, renal failure, renal papillary necrosis, raised serum creatinine Reproduction (female): infertility In patients taking NSAIDs, the following adverse experiences have also been reported in <1% of patients. Body as a Whole: fever, infection, sepsis, anaphylactic reactions, appetite changes, death Cardiovascular: hypertension, tachycardia, syncope, arrhythmia, hypotension, myocardial infarction Gastrointestinal: dry mouth, esophagitis, gastric/peptic ulcers, gastritis, glossitis, eructation Hepatobiliary: hepatitis, liver failure Hemic and Lymphatic: rectal bleeding, lymphadenopathy, pancytopenia Metabolic and Nutritional: weight changes Nervous System: anxiety, asthenia, confusion, nervousness, paresthesia, somnolence, tremors, convulsions, coma, hallucinations Respiratory: asthma, respiratory depression, pneumonia Dermatologic: exfoliative dermatitis Special Senses: blurred vision, conjunctivitis Urogenital: cystitis, dysuria, oliguria/polyuria, proteinuria To report SUSPECTED ADVERSE REACTIONS, contact West-ward Pharmaceutical Corp. at 1-877-233-2001, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

OVERDOSAGE Symptoms and Signs Significant naproxen overdosage may be characterized by lethargy, dizziness, drowsiness, epigastric pain, abdominal discomfort, heartburn, indigestion, nausea, transient alterations in liver function, hypoprothrombinemia, renal dysfunction, metabolic acidosis, apnea, disorientation or vomiting. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression, and coma may occur, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose. Because naproxen sodium may be rapidly absorbed, high and early blood levels should be anticipated. A few patients have experienced convulsions, 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 LD 50 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. Treatment Patients should be managed by symptomatic and supportive care following a NSAID overdose. There are no specific antidotes. Hemodialysis does not decrease the plasma concentration of naproxen because of the high degree of its protein binding. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose. Forced diuresis, alkalinization of urine or hemoperfusion may not be useful due to high protein binding.