Naproxen
Generic: NAPROXEN
Basic Information
Manufacturer
Proficient Rx LP
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
fc3ee94a-adb7-411e-a662-2f2c6ddbabaf
Indications & Usage
INDICATIONS AND USAGE Carefully consider the potential benefits and risks of naproxen tablets, USP and other treatment options before deciding to use naproxen tablets, USP.
Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ).
Naproxen, USP as naproxen tablets, USP 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 • 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
Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ).
Naproxen, USP as naproxen tablets, USP 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 • 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
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 GI events (see WARNINGS: 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 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS ).
Hypertension NSAIDs, including naproxen tablets, 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 tablets, 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 tablets 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 tablets, can cause serious gastrointestinal (GI) 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 GI adverse event on NSAID therapy, is symptomatic.
Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients treated for one year.
These trends continue with longer duration of use, increasing the likelihood of developing a serious GI 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 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 GI bleed compared to patients with neither of these risk factors.
Other factors that increase the risk for GI 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 GI 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 GI 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 GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected.
This should include discontinuation of the NSAID until a serious GI 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 no 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, Chrohn’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 nonsteroidal 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 angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), 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 tablets in patients with advanced renal disease.
Therefore, treatment with naproxen tablets is not recommended in these patients with advanced renal disease.
If naproxen tablets therapy must be initiated, close monitoring of the patient’s renal function is advisable and patients should be adequately hydrated.
Anaphylactoid Reactions As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to naproxen tablets.
Naproxen tablets 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.
Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome.
Skin Reactions NSAIDs, including naproxen tablets, 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 tablets should be avoided because it may cause premature closure of the ductus arteriosus.
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 GI events (see WARNINGS: 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 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS ).
Hypertension NSAIDs, including naproxen tablets, 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 tablets, 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 tablets 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 tablets, can cause serious gastrointestinal (GI) 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 GI adverse event on NSAID therapy, is symptomatic.
Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients treated for one year.
These trends continue with longer duration of use, increasing the likelihood of developing a serious GI 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 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 GI bleed compared to patients with neither of these risk factors.
Other factors that increase the risk for GI 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 GI 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 GI 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 GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected.
This should include discontinuation of the NSAID until a serious GI 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 no 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, Chrohn’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 nonsteroidal 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 angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), 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 tablets in patients with advanced renal disease.
Therefore, treatment with naproxen tablets is not recommended in these patients with advanced renal disease.
If naproxen tablets therapy must be initiated, close monitoring of the patient’s renal function is advisable and patients should be adequately hydrated.
Anaphylactoid Reactions As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to naproxen tablets.
Naproxen tablets 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.
Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome.
Skin Reactions NSAIDs, including naproxen tablets, 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 tablets should be avoided because it may cause premature closure of the ductus arteriosus.
Adverse Reactions
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 (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 and lower gastrointestinal tract.
Esophagitis, stomatitis, hematemesis, pancreatitis, vomiting, colitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Chrohn’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
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, 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 and lower gastrointestinal tract.
Esophagitis, stomatitis, hematemesis, pancreatitis, vomiting, colitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Chrohn’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