Naproxen Sodium Tablets, USP, Rx only

DESCRIPTION

id: ada05ca6-8ff7-42de-ab4c-aa1e1f96f0f9
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Naproxen, USP is a propionic acid derivative related to the arylacetic acid group of nonsteroidal anti-inflammatory drugs. The chemical name for naproxen sodium, USP is (S)-6-methoxy-α-methyl-2-naphthaleneacetic acid, sodium salt. Naproxen sodium, USP has the following structure: Naproxen sodium, USP has a molecular weight of 252.23 and a molecular formula of C₁₄H₁₃NaO₃. Naproxen sodium, USP is a white to creamy white, crystalline solid, freely soluble in water at neutral pH. Naproxen sodium, USP is available as blue tablets containing 275 mg of naproxen sodium, USP and as blue tablets containing 550 mg of naproxen sodium, USP for oral administration. The inactive ingredients are croscarmellose sodium, macrogol, magnesium stearate, polyvinyl alcohol, povidone, talc, titanium dioxide and FD&C Blue #2.

CLINICAL STUDIES

id: bd0ef607-fe71-4df9-875a-b4b68d643e60
displayName: CLINICAL STUDIES SECTION
FDA Article Code: 34092-7

General Information Naproxen has been studied in patients with rheumatoid arthritis, osteoarthritis, juvenile arthritis, ankylosing spondylitis, tendonitis and bursitis and acute gout. Improvement in patients treated for rheumatoid arthritis was 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 bid (750 mg/day) vs 750 mg bid (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 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 1100 mg of naproxen sodium has been demonstrated to cause statistically significantly less gastric bleeding and erosion than 3250 mg of aspirin. 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.

INDICATIONS AND USAGE

id: 52265dc8-cb81-410e-bfdb-b3b524b3a21b
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Carefully consider the potential benefits and risks of naproxen sodium tablets, USP and other treatment options before deciding to use naproxen sodium tablets, USP. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). Naproxen, USP as naproxen sodium tablets, USP are 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
For relief of the signs and symptoms of tendonitis
For relief of the signs and symptoms of bursitis
For relief of the signs and symptoms of acute gout
For the management of pain
For the management of primary dysmenorrhea

CONTRAINDICATIONS

id: f78b86c3-c5a9-481d-8413-d31d51316cb3
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Naproxen sodium tablets, USP are contraindicated in patients with known hypersensitivity to naproxen, USP and naproxen sodium, USP. Naproxen sodium, USP 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 sodium, USP are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS ).

ADVERSE REACTIONS

id: b56df4ca-3ea6-49a2-ab6f-1e0dd5bf388b
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

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 (GI) Experiences, including: heartburn^*, abdominal pain^*, nausea^*, constipation^*, diarrhea, dyspepsia and 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, erythemia multiforme, erythema nodosum, fixed drug eruption, lichen planus, pustular reaction, systemic lupus erythematosus, 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

OVERDOSAGE

id: 1a70d824-d47a-40c3-8313-b5f6d2fbe2e3
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

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 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. 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.

DOSAGE AND ADMINISTRATION

id: 9108ddc5-842c-4584-8c27-8e92a1540253
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

Carefully consider the potential benefits and risks of naproxen sodium tablets, USP and other treatment options before deciding to use naproxen sodium tablets, USP. 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 sodium tablets, USP, 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. The difference should be taken into consideration when changing formulation. Although naproxen tablets, USP, naproxen suspension, naproxen delayed-release tablets, USP and naproxen sodium tablets, USP all circulate in the plasma as naproxen, USP, they have pharmacokinetic differences that may affect onset of action. Onset of pain relief can begin within 30 minutes in patients taking naproxen sodium, USP and within 1 hour in patients taking naproxen, USP (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, USP 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 sodium tablets, USP	275 mg (naproxen, USP 250 mg with 25 mg sodium)	twice daily
	550 mg (naproxen, USP 500 mg with 50 mg sodium)	twice daily

During long-term administration, the dose of naproxen, USP 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 sodium, USP 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 sodium 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 For the relief of juvenile arthritis, the recommended dose is approximately 10 mg/kg given orally in 2 divided doses (i.e., 5 mg/kg given twice a day). Naproxen sodium tablets, USP are not well suited to this dosage so use of naproxen oral suspension, USP is recommended for this indication. Management of Pain, Primary Dysmenorrhea and Acute Tendonitis and Bursitis: The recommended starting dose is 550 mg of naproxen sodium, USP 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, USP. Thereafter, the total daily dose should not exceed 1100 mg of naproxen sodium. Because the sodium salt of naproxen, USP is more rapidly absorbed, naproxen sodium tablets, USP are recommended for the management of acute painful conditions when prompt onset of pain relief is desired. Acute Gout: The recommended starting dose is 825 mg of naproxen sodium tablets, USP followed by 275 mg every 8 hours until the attack has subsided.

HOW SUPPLIED

id: 8290c4ef-2887-413f-9c3b-3cec64b41390
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Naproxen Sodium Tablets, USP 275 mg, are supplied as blue, oval, biconvex, film coated tablets debossed “IP193” on obverse and plain on reverse. They are available as follows: Bottles of 100:         NDC 65162-193-10
Bottles of 500:         NDC 65162-193-50 Naproxen Sodium Tablets, USP 550 mg, are supplied as blue, oval, biconvex, film coated tablets debossed “IP” bisect “194” on obverse and plain on reverse. They are available as follows: Bottles of 100:         NDC 65162-194-10
Bottles of 500:         NDC 65162-194-50 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) in well-closed containers. Manufactured by:
Amneal Pharmaceuticals
Co. (I) Pvt. Ltd.
Ahmedabad, INDIA  382220 Distributed by:
Amneal Pharmaceuticals
Glasgow, KY 42141 Rev. 09-2013

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

id: 60ff3ae1-1af8-4822-ba0f-2cfb51327a0f
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4