Naprosyn Information
Naprosyn () Description
Naproxen is a proprionic acid derivative related to the arylacetic acid group of nonsteroidal anti-inflammatory drugs.
The chemical names for naproxen and naproxen sodium are (S)-6-methoxy-α-methyl-2-naphthaleneacetic acid and (S)-6-methoxy-α-methyl-2-naphthaleneacetic acid, sodium salt, respectively. Naproxen and naproxen sodium have the following structures, respectively:
Naproxen has a molecular weight of 230.26 and a molecular formula of CHO. Naproxen sodium has a molecular weight of 252.23 and a molecular formula of CHNaO.
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. Naproxen sodium is a white to creamy white, crystalline solid, freely soluble in water at neutral pH.
Naprosyn () (naproxen tablets) is available as yellow tablets containing 250 mg of naproxen, pink tablets containing 375 mg of naproxen and yellow tablets containing 500 mg of naproxen for oral administration. The inactive ingredients are croscarmellose sodium, iron oxides, povidone and magnesium stearate.
EC-Naprosyn () (naproxen delayed-release tablets) is available as enteric-coated white tablets containing 375 mg of naproxen and 500 mg of naproxen for oral administration. The inactive ingredients are croscarmellose sodium, povidone and magnesium stearate. The enteric coating dispersion contains methacrylic acid copolymer, talc, triethyl citrate, sodium hydroxide and purified water. The dissolution of this enteric-coated naproxen tablet is pH dependent with rapid dissolution above pH 6. There is no dissolution below pH 4.
ANAPROX (naproxen sodium tablets) is available as blue tablets containing 275 mg of naproxen sodium and ANAPROX DS (naproxen sodium tablets) is available as dark blue tablets containing 550 mg of naproxen sodium for oral administration. The inactive ingredients are magnesium stearate, microcrystalline cellulose, povidone and talc. The coating suspension for the ANAPROX 275 mg tablet may contain hydroxypropyl methylcellulose 2910, Opaspray K-1-4210A, polyethylene glycol 8000 or Opadry YS-1-4215. The coating suspension for the ANAPROX DS 550 mg tablet may contain hydroxypropyl methylcellulose 2910, Opaspray K-1-4227, polyethylene glycol 8000 or Opadry YS-1-4216.
Naprosyn () (naproxen suspension) is available as a light orange-colored opaque oral suspension containing 125 mg/5 mL of naproxen in a vehicle containing sucrose, magnesium aluminum silicate, sorbitol solution and sodium chloride (39 mg/5 mL, 1.5 mEq), methylparaben, fumaric acid, FD&C Yellow No. 6, imitation pineapple flavor, imitation orange flavor and purified water. The pH of the suspension ranges from 2.2 to 3.7.
Naprosyn () Clinical Studies
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 a 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 (eg, 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 Cr blood loss and gastroscopy studies with normal volunteers, daily administration of 1000 mg of naproxen as 1000 mg of Naprosyn () (naproxen) or 1100 mg of ANAPROX (naproxen sodium) 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 EC-Naprosyn () (naproxen) (375 or 500 mg bid, n=385) and Naprosyn () (375 or 500 mg bid, n=279) were conducted comparing EC-Naprosyn () with Naprosyn () , including 355 rheumatoid arthritis and osteoarthritis patients who had a recent history of NSAID-related GI symptoms. These studies indicated that EC-Naprosyn () and Naprosyn () 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.
Five hundred and fifty-three patients received EC-Naprosyn () during long-term open-label trials (mean length of treatment was 159 days). The rates for clinically-diagnosed peptic ulcers and GI bleeds were similar to what has been historically reported for long-term NSAID use.
Naprosyn () Indications And Usage
Carefully consider the potential benefits and risks of Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS or Naprosyn () Suspension and other treatment options before deciding to use Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS or Naprosyn () Suspension. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see ).
Naproxen as Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS or Naprosyn () Suspension is indicated:
Naproxen as Naprosyn () Suspension is recommended for juvenile rheumatoid arthritis in order to obtain the maximum dosage flexibility based on the patient's weight.
Naproxen as Naprosyn () , ANAPROX, ANAPROX DS and Naprosyn () Suspension is also indicated:
EC-Naprosyn () is not recommended for initial treatment of acute pain because the absorption of naproxen is delayed compared to absorption from other naproxen-containing products (see and ).
Naprosyn () Contraindications
Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS and Naprosyn () Suspension are contraindicated in patients with known hypersensitivity to naproxen and naproxen sodium.
Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS and Naprosyn () Suspension 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 and ).
Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS and Naprosyn () Suspension are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see ).
Naprosyn () Warnings
NSAIDs, including Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS and Naprosyn () Suspension, 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 3-6 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 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 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 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 ). 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.
Naprosyn () Precautions
Naproxen-containing products such as Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS, Naprosyn () SUSPENSION, ALEVE, and other naproxen products should not be used concomitantly since they all circulate in the plasma as the naproxen anion.
Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS and Naprosyn () Suspension cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids and the patient should be observed closely for any evidence of adverse effects, including adrenal insufficiency and exacerbation of symptoms of arthritis.
Patients with initial hemoglobin values of 10 g or less who are to receive long-term therapy should have hemoglobin values determined periodically.
The pharmacological activity of Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS and Naprosyn () Suspension in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, noninflammatory painful conditions.
Because of adverse eye findings in animal studies with drugs of this class, it is recommended that ophthalmic studies be carried out if any change or disturbance in vision occurs.
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS and Naprosyn () Suspension. Hepatic abnormalities may be the result of hypersensitivity rather than direct toxicity. These laboratory abnormalities may progress, may remain essentially unchanged, or may be transient with continued therapy. The SGPT (ALT) test is probably the most sensitive indicator of liver dysfunction. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.
A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of more severe hepatic reaction while on therapy with Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS or Naprosyn () Suspension.
If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash, etc.), Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS or Naprosyn () Suspension should be discontinued.
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.
Anemia is sometimes seen in patients receiving NSAIDs, including Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS and Naprosyn () Suspension. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS and Naprosyn () Suspension, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.
NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving either Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS or Naprosyn () Suspension who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.
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 is highly bound to plasma albumin; it thus has a theoretical potential for interaction with other albumin-bound drugs such as coumarin-type anticoagulants, sulphonylureas, hydantoins, other NSAIDs, and aspirin. Patients simultaneously receiving naproxen and a hydantoin, sulphonamide or sulphonylurea should be observed for adjustment of dose if required.
Naproxen and other nonsteroidal anti-inflammatory drugs can reduce the antihypertensive effect of propranolol and other beta-blockers.
Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life significantly.
Due to the gastric pH elevating effects of H-blockers, sucralfate and intensive antacid therapy, concomitant administration of EC-Naprosyn () is not recommended.
Naproxen may decrease platelet aggregation and prolong bleeding time. This effect should be kept in mind when bleeding times are determined.
The administration of naproxen may result in increased urinary values for 17-ketogenic steroids because of an interaction between the drug and/or its metabolites with m-di-nitrobenzene used in this assay. Although 17-hydroxy-corticosteroid measurements (Porter-Silber test) do not appear to be artifactually altered, it is suggested that therapy with naproxen be temporarily discontinued 72 hours before adrenal function tests are performed if the Porter-Silber test is to be used.
Naproxen may interfere with some urinary assays of 5-hydroxy indoleacetic acid (5HIAA).
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 nonsteroidal 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 GI events are in the geriatric population (see ).
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 ).
Naprosyn () 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 ).
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:
In patients taking NSAIDs, the following adverse experiences have also been reported in approximately 1% to 10% of patients.
The following are additional adverse experiences reported in
In patients taking NSAIDs, the following adverse experiences have also been reported in
Naprosyn () Dosage And Administration
Carefully consider the potential benefits and risks of Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS and Naprosyn () Suspension and other treatment options before deciding to use Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS and Naprosyn () Suspension. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see ).
After observing the response to initial therapy with Naprosyn () , EC-Naprosyn () , ANAPROX, ANAPROX DS or Naprosyn () Suspension, the dose and frequency should be adjusted to suit an individual patient's needs.
Although Naprosyn () , Naprosyn () Suspension, EC-Naprosyn () , ANAPROX and ANAPROX DS all circulate in the plasma as naproxen, they have pharmacokinetic differences that may affect onset of action. Onset of pain relief can begin within 30 minutes in patients taking naproxen sodium and within 1 hour in patients taking naproxen. Because EC-Naprosyn () dissolves in the small intestine rather than in the stomach, the absorption of the drug is delayed compared to the other naproxen formulations (see ).
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 and ).
Naprosyn () How Supplied
100's (bottle): NDC 0004-6313-01.
375 mg: pink, biconvex oval, engraved with NPR LE 375 on one side. Packaged in light-resistant bottles of 100.
100's (bottle): NDC 0004-6314-01.
500 mg: yellow, capsule-shaped, engraved with NPR LE 500 on one side and scored on the other. Packaged in light-resistant bottles of 100.
100's (bottle): NDC 0004-6316-01.
Store at 15° to 30°C (59° to 86°F) in well-closed containers; dispense in light-resistant containers.
Store at 15° to 30°C (59° to 86°F); avoid excessive heat, above 40°C (104°F). Dispense in light-resistant containers. Shake gently before use.
100's (bottle): NDC 0004-6415-01.
500 mg: white, oblong coated tablets imprinted with NPR EC 500 on one side. Packaged in light-resistant bottles of 100.
100's (bottle): NDC 0004-6416-01.
Store at 15° to 30°C (59° to 86°F) in well-closed containers; dispense in light-resistant containers.
100's (bottle): NDC 0004-6202-01.
Store at 15° to 30°C (59° to 86°F) in well-closed containers.
100's (bottle): NDC 0004-6203-01.
Store at 15° to 30°C (59° to 86°F) in well-closed containers.
Revised: October 2010
Naprosyn () Medication Guide For Non-steroidal Anti-inflammatory Drugs (nsaids)
NSAID medicines are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as:
These are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or Genentech at 1-888-835-2555.
*Vicoprofen contains the same dose of ibuprofen as over-the-counter (OTC) NSAID, and is usually used for less than 10 days to treat pain. The OTC NSAID label warns that long term continuous use may increase the risk of heart attack or stroke.
Naprosyn ()
Naprosyn ()
Naprosyn () Principal Display Panel - Mg Tablet Bottle Label
NDC 0004-6313-01
Each tablet contains250 mg naproxen.
100 tablets
Naprosyn () Principal Display Panel - Mg Tablet Bottle Label
NDC 0004-6314-01
Each tablet contains375 mg naproxen.
100 tablets
Naprosyn () Principal Display Panel - Mg Tablet Bottle Label
NDC 0004-6316-01
Each tablet contains500 mg naproxen.
100 tablets
Naprosyn () Principal Display Panel - Mg Enteric Coated Tablet Bottle Label
NDC 0004-6415-01
Each tablet contains 375 mg naproxen.
100 tablets
Naprosyn () Principal Display Panel - Mg Enteric Coated Tablet Bottle Label
NDC 0004-6416-01
Each tablet contains500 mg naproxen.
100 tablets
Naprosyn () Principal Display Panel - Ml Bottle Carton
NDC 0004-0028-28
1 Pint (473 mL)
Naprosyn () Principal Display Panel - Mg Tablet Bottle Label
NDC 0004-6202-01
Each tablet contains275 mg naproxen sodium.
100 tablets
Naprosyn () Principal Display Panel - Mg Tablet Bottle Label
NDC 0004-6203-01
Each tablet contains550 mg naproxen sodium.
100 tablets
