gement of pain • for the management of primary dysmenorrhea

sk for an adverse cv event in nsaid-treated patients, use the lowest effective dose for the shortest duration possible. physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous cv symptoms. patients should be informed about the 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, such as naproxen, increases the risk of serious gastrointestinal (gi) events (see warnings; gastrointestinal bleeding, ulceration, and perforation). status post coronary artery bypass graft (cabg) surgery two large, controlled, clinical trials of a cox-2 selective nsaid for the treatment of pain in the first 10 to 14 days following cabg surgery found an increased incidence of myocardial infarction and stroke. nsaids are contraindicated in the setting of cabg (see contraindications). post-mi patients observational studies conducted in the danish national registry have demonstrated that patients treated with nsaids in the post-mi period were at increased risk of reinfarction, cv-related death, and all-cause mortality beginning in the first week of treatment. in this same cohort, the incidence of death in the first year post-mi was 20 per 100 person years in nsaid-treated patients compared to 12 per 100 person years in non-nsaid exposed patients. although the absolute rate of death declined somewhat after the first year post-mi, the increased relative risk of death in nsaid users persisted over at least the next four years of follow-up. avoid the use of naproxen and naproxen sodium in patients with a recent mi unless the benefits are expected to outweigh the risk of recurrent cv thrombotic events. if naproxen or naproxen sodium are used in patients with a recent mi, monitor patients for signs of cardiac ischemia. gastrointestinal bleeding, ulceration, and perforation nsaids, including naproxen cause serious gastrointestinal (gi) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, 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 gi adverse event on nsaid therapy is symptomatic. upper gi ulcers, gross bleeding, or perforation caused by nsaids occurred in approximately 1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients treated for one year. however, even short-term nsaid therapy is not without risk. risk factors for gi bleeding, ulceration, and perforation patients with a prior history of peptic ulcer disease and/or gi bleeding who used nsaids had a greater than 10-fold increased risk for developing a gi bleed compared to patients without these risk factors. other factors that increase the risk of gi bleeding in patients treated with nsaids include longer duration of nsaid therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (ssris); smoking; use of alcohol; older age; and poor general health status. most postmarketing reports of fatal gi events occurred in elderly or debilitated patients. additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for gi bleeding. strategies to minimize the gi risks in nsaid-treated patients: • use the lowest effective dosage for the shortest possible duration. • avoid administration of more than one nsaid at a time. • avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. for such patients, as well as those with active gi bleeding, consider alternate therapies other than nsaids. • remain alert for signs and symptoms of gi ulceration and bleeding during nsaid therapy. • if a serious gi adverse event is suspected, promptly initiate evaluation and treatment, and discontinue naproxen or naproxen sodium until a serious gi adverse event is ruled out. • in the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of gi bleeding (see precautions; drug interactions). hepatotoxicity elevations of alt or ast (three or more times the upper limit of normal [uln]) have been reported in approximately 1% of patients in clinical trials. in addition, rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis and hepatic failure have been reported. elevations of alt or ast (less than three times uln) may occur in up to 15% of patients taking nsaids including naproxen. inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue naproxen or naproxen sodium immediately, and perform a clinical evaluation of the patient. hypertension nsaids, including naproxen and naproxen sodium, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of cv events. patients taking angiotensin converting enzyme (ace) inhibitors, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking nsaids (see precautions; drug interactions). monitor blood pressure (bp) during the initiation of nsaid treatment and throughout the course of therapy. heart failure and edema the coxib and traditional nsaid trialists’ collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalization for heart failure in cox-2 selective-treated patients and nonselective nsaid-treated patients compared to placebo-treated patients. in a danish national registry study of patients with heart failure, nsaid use increased the risk of mi, hospitalization for heart failure, and death. additionally, fluid retention and edema have been observed in some patients treated with nsaids. use of naproxen may blunt the cv effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ace inhibitors, or angiotensin receptor blockers [arbs]) (see precautions; drug interactions). avoid the use of naproxen and naproxen sodium in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. if naproxen or naproxen sodium is used in patients with severe heart failure, monitor patients for signs of worsening heart failure. since each naproxen sodium tablet contains 25 mg or 50 mg of sodium (about 1 meq per each 250 mg of naproxen), this should be considered in patients whose overall intake of sodium must be severely restricted. renal toxicity and hyperkalemia renal toxicity 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 an nsaid 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, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ace inhibitors or arbs, and the elderly. discontinuation of nsaid therapy is usually followed by recovery to the pretreatment state no information is available from controlled clinical studies regarding the use of naproxen or naproxen sodium in patients with advanced renal disease. the renal effects of naproxen or naproxen sodium may hasten the progression of renal dysfunction in patients with preexisting renal disease. correct volume status in dehydrated or hypovolemic patients prior to initiating naproxen or naproxen sodium. monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of naproxen or naproxen sodium (see precautions; drug interactions). avoid the use of naproxen or naproxen sodium in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. if naproxen or naproxen sodium is used in patients with advanced renal disease, monitor patients for signs of worsening renal function. hyperkalemia increases in serum potassium concentration, including hyperkalemia, have been reported with use of nsaids, even in some patients without renal impairment. in patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state. anaphylactic reactions naproxen has been associated with anaphylactic reactions in patients with and without known hypersensitivity to naproxen and in patients with aspirin-sensitive asthma (see contraindications,warnings; exacerbation of asthma related to aspirin sensitivity). exacerbation of asthma related to aspirin sensitivity a subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other nsaids. because cross-reactivity between aspirin and other nsaids has been reported in such aspirin-sensitive patients, naproxen and naproxen sodium are contraindicated in patients with this form of aspirin sensitivity (see contraindications). when naproxen and naproxen sodium are used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma. serious skin reactions nsaids, including naproxen, can cause serious skin adverse reactions such as exfoliative dermatitis, stevens-johnson syndrome (sjs), and toxic epidermal necrolysis (ten), which can be fatal. these serious events may occur without warning. inform patients about the signs and symptoms of serious skin reactions and to discontinue the use of naproxen or naproxen sodium at the first appearance of skin rash or any other sign of hypersensitivity. naproxen and naproxen sodium are contraindicated in patients with previous serious skin reactions to nsaids (see contraindications). premature closure of fetal ductus arteriosus naproxen may cause premature closure of the fetal ductus arteriosus. avoid use of nsaids, including naproxen or naproxen sodium, in pregnant women starting at 30 weeks of gestation (third trimester) (see precautions; pregnancy). hematologic toxicity anemia has occurred in nsaid-treated patients. this may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. if a patient treated with naproxen or naproxen sodium has any signs or symptoms of anemia, monitor hemoglobin or hematocrit. nsaids, including naproxen or naproxen sodium, may increase the risk of bleeding events. co-morbid conditions such as coagulation disorders, or concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (ssris) and serotonin norepinephrine reuptake inhibitors (snris) may increase this risk. monitor these patients for signs of bleeding (see precautions; drug interactions).

ng 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 warnings; hepatotoxicity, and renal toxicity and hyperkalemia, and precautions; geriatric use). 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 (creatinine clearance <30 ml/min) (see warnings: renal effects). rheumatoid arthritis, osteoarthritis and ankylosing spondylitis naproxen tablets 250 mg or 375 mg or 500 mg twice daily twice daily twice daily naproxen sodium tablets 275 mg (naproxen 250 mg with 25 mg sodium) 550 mg (naproxen 500 mg with 50 mg sodium) twice daily 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 antiinflammatory/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 daily does not generally make a difference in response (see clinical pharmacology). juvenile arthritis naproxen tablets may not allow for the flexible dose titration needed in pediatric patients with juvenile arthritis. a liquid formulation may be more appropriate. in pediatric patients, 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 of naproxen is approximately 10 mg/kg given in 2 divided doses. one-half of the 250 mg tablet will be needed for dosing lower-weight children. dosing with naproxen tablets is not appropriate for children weighing less than 25 kilograms. management of pain, primary dysmenorrhea, and acute tendonitis and bursitis the recommended starting dose is 550 mg of naproxen sodium as naproxen sodium followed by 550 mg every 12 hours or 275 mg every 6 to 8 hours as required. the initial total daily dose should not exceed 1375 mg of naproxen sodium. thereafter, the total daily dose should not exceed 1100 mg of naproxen sodium. 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 initial treatment of acute pain. (see clinical pharmacology,indications and usage). acute gout the recommended starting dose is 750 mg of naproxen followed by 250 mg every 8 hours until the attack has subsided. naproxen sodium may also be used at a starting dose of 825 mg followed by 275 mg every 8 hours.

estinal 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 (gi) 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 (gi) experiences, including: flatulence, gross bleeding/perforation, gi 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 postmarketing reports. those adverse reactions observed through postmarketing 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: inflammation, bleeding (sometimes fatal, particularly in the elderly), ulceration, perforation and obstruction of the upper or lower gastrointestinal tract. esophagitis, stomatitis, hematemesis, pancreatitis, vomiting, colitis, exacerbation of inflammatory bowel disease (ulcerative colitis, crohn’s disease). 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 (pseudoporphyria) 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

. the different dosage forms of naproxen are bioequivalent in terms of extent of absorption (auc) and peak concentration (cmax); however, the products do differ in their pattern of absorption. these differences between naproxen products are related to both the chemical form of naproxen used and its formulation. even with the observed differences in pattern of absorption, the elimination half-life of naproxen is unchanged across products ranging 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. this suggests that the differences in pattern of release play only a negligible role in the attainment of steady-state plasma levels. absorption naproxen tablets after administration of naproxen tablets, peak plasma levels are attained in 2 to 4 hours. after oral administration of naproxen sodium, peak plasma levels are attained in 1 to 2 hours. the difference in rates between the two products is due to the increased aqueous solubility of the sodium salt of naproxen used in naproxen sodium. peak plasma levels of naproxen given as naproxen suspension 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, respectively). the naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of maximum naproxen concentration in plasma (see precautions; nursing mothers). elimination metabolism naproxen is extensively metabolized in the liver to 6-0-desmethyl naproxen, and both parent and metabolites do not induce metabolizing enzymes. both naproxen and 6-0-desmethyl naproxen are further metabolized to their respective acylglucuronide conjugated metabolites. excretion 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 (<1%), 6-0-desmethyl naproxen (<1%) or their conjugates (66% to 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. small amounts, 3% or less of the administered dose, are excreted in the feces. in patients with renal failure metabolites may accumulate (see warnings; renal toxicity and hyperkalemia). special populations pediatric patients in pediatric patients aged 5 to 16 years 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 pediatric and adult patients. pharmacokinetic studies of naproxen were not performed in pediatric patients younger than 5 years of age. pharmacokinetic parameters appear to be similar following administration of naproxen suspension or tablets in pediatric patients. geriatric patients studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly, although the unbound fraction is <1% of the total naproxen concentration. unbound trough naproxen concentrations in elderly subjects have been reported to range from 0.12% to 0.19% of total naproxen concentration, compared with 0.05% to 0.075% in younger subjects. the clinical significance of this finding is unclear, although it is possible that the increase in free naproxen concentration could be associated with an increase in the rate of adverse events per a given dosage in some elderly patients. race pharmacokinetic differences due to race have not been studied. hepatic impairment naproxen pharmacokinetics has not been determined in subjects with hepatic insufficiency. 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. renal impairment 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. elimination of naproxen is decreased in patients with severe renal impairment. naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance <30 ml/min) (see warnings; renal toxicity and hyperkalemia). drug interaction studies aspirin: when nsaids were administered with aspirin, the protein binding of nsaids were reduced, although the clearance of free nsaid was not altered. the clinical significance of this interaction is not known. see table 1 for clinically significant drug interactions of nsaids with aspirin (see precautions; drug interactions).

standard formulations of naproxen 375 mg twice a day (750 mg a day) vs 750 mg twice a day (1500 mg/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 postoperative, orthopedic, postpartum episiotomy and uterine contraction pain and dysmenorrhea. onset of pain relief can begin within 1 hour in patients taking naproxen and within 30 minutes in patients taking naproxen sodium. 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 as 1000 mg of naproxen tablets or 1100 mg of naproxen sodium tablets has been demonstrated to cause statistically significantly less gastric bleeding and erosion than 3250 mg of aspirin. three 6-week, double-blind, multicenter studies with naproxen delayed release (375 or 500 mg twice a day, n=385) and naproxen (375 or 500 mg twice a day, n=279) were conducted comparing naproxen delayed release with naproxen, including 355 rheumatoid arthritis and osteoarthritis patients who had a recent history of nsaid-related gi symptoms. these studies indicated that naproxen delayed release and naproxen showed no significant differences in efficacy or safety and had similar prevalence of minor gi complaints. individual patients, however, may find one formulation preferable to the other. geriatric patients the hepatic and renal tolerability of long-term naproxen administration was studied in two double-blind clinical trials involving 586 patients. of the patients studied, 98 patients were age 65 and older and 10 of the 98 patients were age 75 and older. naproxen was administered at doses of 375 mg twice daily or 750 mg twice daily for up to 6 months. transient abnormalities of laboratory tests assessing hepatic and renal function were noted in some patients, although there were no differences noted in the occurrence of abnormal values among different age groups.

€™s (bottle): ndc 68462-190-05 store at 20° to 25°c (68° to 77°f); excursions permitted between 15° to 30°c (59° to 86°f) [see usp controlled room temperature]. dispense in well-closed containers. naproxen sodium tablets usp: 275 mg: blue, oval, film-coated tablets with ‘g 0’ engraved on one side and ‘275’ engraved on the other side. packaged in bottles of 100 and 500 100’s (bottle): ndc 68462-178-01 500’s (bottle): ndc 68462-178-05 550 mg: blue colored, modified capsule shaped, biconvex, film-coated tablets, engraved with ‘g’ and ‘0’ on either side of break line and break line on the other side. packaged in bottles of 100 and 500. 100’s (bottle): ndc 68462-179-01 500’s (bottle): ndc 68462-179-05 store at 20° to 25°c (68° to 77°f); excursions permitted between 15° to 30°c (59° to 86°f) [see usp controlled room temperature]. dispense in well-closed containers. manufactured by: glenmark pharmaceuticals ltd., india manufactured for: glenmark pharmaceuticals inc., usa mahwah, nj 07430 questions? 1 (888)721-7115 www.glenmarkpharma.com/usa may 2016