Naprelan
(naproxen)Dosage & Administration
Naprelan Prescribing Information
Cardiovascular Thrombotic Events
- Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use [see Warnings and Precautions ].
- NAPRELAN is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications and Warnings and Precautions ( 5.1)].
Gastrointestinal Bleeding, Ulceration, and Perforation
- NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events [see Warnings and Precautions ].
NAPRELAN Tablets are indicated for the treatment of:
• rheumatoid arthritis (RA)
• osteoarthritis (OA)
• ankylosing spondylitis (AS)
• tendinitis, bursitis
• acute gout
• primary dysmenorrhea (PD)
• the relief of mild to moderate pain
[see Warnings and Precautions ].
2.5 Dosage Adjustments in Patients with Hepatic Impairment
A lower dose should be considered in patients with renal or hepatic impairment or in elderly patients [see Warnings and Precautions ]. 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.
NAPRELAN (naproxen sodium) Controlled-Release Tablets are available as follows:
NAPRELAN 375: white, capsule-shaped tablet with “N” on one side and “375” on the reverse. Each tablet contains 412.5 mg naproxen sodium equivalent to 375 mg naproxen.
NAPRELAN 500: white, capsule-shaped tablet with “N” on one side and “500” on the reverse. Each tablet contains 550 mg naproxen sodium equivalent to 500 mg naproxen.
NAPRELAN 750: white, capsule-shaped tablet with “N” on one side and “750” on the reverse. Each tablet contains 825 mg naproxen sodium equivalent to 750 mg naproxen.
Females and Males of Reproductive Potential
Infertility
Females
Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including NAPRELAN, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of NSAIDs, including NAPRELAN, in women who have difficulties conceiving or who are undergoing investigation of infertility.
NAPRELAN is contraindicated in the following patients:
- Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen or any components of the drug product [see Warnings and Precautions ]
- History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see Warnings and Precautions ]
- In the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions ]
Laboratory Monitoring
Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically [see Warnings and Precautions ].
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
As with all drugs in this class, the frequency and severity of adverse events depends on several factors: the dose of the drug and duration of treatment; the age, the sex, physical condition of the patient; any concurrent medical diagnoses or individual risk factors. The following adverse reactions are divided into three parts based on frequency and whether or not the possibility exists of a causal relationship between drug usage and these adverse events. In those reactions listed as “Probable Causal Relationship” there is at least one case for each adverse reaction where there is evidence to suggest that there is a causal relationship between drug usage and the reported event. The adverse reactions reported were based on the results from two double-blind controlled clinical trials of three months duration with an additional nine month open-label extension. A total of 542 patients received NAPRELAN Tablets either in the double-blind period or in the nine month open-label extension. Of these 542 patients, 232 received NAPRELAN Tablets, 167 were initially treated with Naprosyn® and 143 were initially treated with placebo. Adverse reactions reported by patients who received NAPRELAN Tablets are shown by body system. Those adverse reactions observed with naproxen but not reported in controlled trials with NAPRELAN Tablets are italicized.
The most frequent adverse events from the double-blind and open-label clinical trials were headache (15%), followed by dyspepsia (14%), and flu syndrome (10%). The incidence of other adverse events occurring in 3% to 9% of the patients are marked with an asterisk.
Those reactions occurring in less than 3% of the patients are unmarked.
Incidence greater than 1% (probable causal relationship)
Body as a Whole—Pain (back)*, pain*, infection*, fever, injury (accident), asthenia, pain chest, headache (15%), flu syndrome (10%).
Gastrointestinal—Nausea*, diarrhea*, constipation*, abdominal pain*, flatulence, gastritis, vomiting, dysphagia, dyspepsia (14%), heartburn*, stomatitis.
Hematologic—Anemia, ecchymosis.
Respiratory—Pharyngitis*, rhinitis*, sinusitis*, bronchitis, cough increased.
Renal—Urinary tract infection*, cystitis.
Dermatologic—Skin rash*, skin eruptions*, ecchymoses*, purpura.
Metabolic and Nutrition—Peripheral edema, hyperglycemia.
Central Nervous System—Dizziness, paresthesia, insomnia, drowsiness*, lightheadedness.
Cardiovascular—Hypertension, edema*, dyspnea*, palpitations.
Musculoskeletal—Cramps (leg), myalgia, arthralgia, joint disorder, tendon disorder.
Special Senses—Tinnitus*, hearing disturbances, visual disturbances.
General—Thirst.
Incidence less than 1% (probable causal relationship)
Body as a Whole—Abscess, monilia, neck rigid, pain neck, abdomen enlarged, carcinoma, cellulitis, edema general, LE syndrome, malaise, mucous membrane disorder, allergic reaction, pain pelvic.
Gastrointestinal—Anorexia, cholecystitis, cholelithiasis, eructation, GI hemorrhage, rectal hemorrhage, stomatitis aphthous, stomatitis ulcer, ulcer mouth, ulcer stomach, periodontal abscess, cardiospasm, colitis, esophagitis, gastroenteritis, GI disorder, rectal disorder, tooth disorder, hepatosplenomegaly, liver function abnormality, melena, ulcer esophagus, hematemesis, jaundice, pancreatitis, necrosis.
Renal—Dysmenorrhea, dysuria, kidney function abnormality, nocturia, prostate disorder, pyelonephritis, carcinoma breast, urinary incontinence, kidney calculus, kidney failure, menorrhagia, metrorrhagia, neoplasm breast, nephrosclerosis, hematuria, pain kidney, pyuria, urine abnormal, urinary frequency, urinary retention, uterine spasm, vaginitis, glomerular nephritis, hyperkalemia, interstitial nephritis, nephrotic syndrome, renal disease, renal failure, renal papillary necrosis.
Hematologic—Leukopenia, bleeding time increased, eosinophilia, abnormal RBC, abnormal WBC, thrombocytopenia, agranulocytosis, granulocytopenia.
Central Nervous System—Depression, anxiety, hypertonia, nervousness, neuralgia, neuritis, vertigo, amnesia, confusion, co-ordination, abnormal diplopia, emotional lability, hematoma subdural, paralysis, dream abnormalities, inability to concentrate, muscle weakness.
Dermatologic: Angiodermatitis, herpes simplex, dry skin, sweating, ulcer skin, acne, alopecia, dermatitis contact, eczema, herpes zoster, nail disorder, skin necrosis, subcutaneous nodule, pruritus, urticaria, neoplasm skin, photosensitive dermatitis, photosensitivity reactions resembling porphyria cutaneous tarda, epidermolysis bullosa.
Special Senses—Amblyopia, scleritis, cataract, conjunctivitis, deaf, ear disorder, keratoconjunctivitis, lacrimation disorder, otitis media, pain eye.
Cardiovascular—Angina pectoris, coronary artery disease, myocardial infarction, deep thrombophlebitis, vasodilation, vascular anomaly, arrhythmia, bundle branch block, abnormal ECG, heart failure right, hemorrhage, migraine, aortic stenosis, syncope, tachycardia, congestive heart failure.
Respiratory—Asthma, dyspnea, lung edema, laryngitis, lung disorder, epistaxis, pneumonia, respiratory distress, respiratory disorder, eosinophilic pneumonitis.
Musculoskeletal—Myasthenia, bone disorder, spontaneous bone fracture, fibrotendinitis, bone pain, ptosis, spasm general, bursitis.
Metabolic and Nutrition—Creatinine increase, glucosuria, hypercholesteremia, albuminuria, alkalosis, BUN increased, dehydration, edema, glucose tolerance decrease, hyperuricemia, hypokalemia, SGOT increase, SGPT increase, weight decrease.
General—Anaphylactoid reactions, angioneurotic edema, menstrual disorders, hypoglycemia, pyrexia (chills and fevers).
Incidence less than 1% (causal relationship unknown)
Other adverse reactions listed in the naproxen package label, but not reported by those who received NAPRELAN Tablets are shown in italics. These observations are being listed as alerting information to the physician.
Hematologic—Aplastic anemia, hemolytic anemia.
Central Nervous System—Aseptic meningitis, cognitive dysfunction.
Dermatologic—Epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome.
Gastrointestinal—Non-peptic GI ulceration, ulcerative stomatitis.
Cardiovascular—Vasculitis.
See Table 1 for clinically significant drug interactions with naproxen.
Table 1: Clinically Significant Drug Interactions with Naproxen
| Drugs That Interfere with Hemostasis | |
| Clinical Impact: |
|
| Intervention: | Monitor patients with concomitant use of NAPRELAN with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding [see Warnings and Precautions ]. |
| Aspirin | |
| Clinical Impact: | A pharmacodynamic (PD) study has demonstrated an interaction in which lower dose naproxen (220 mg/day or 220 mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen [see Clinical Pharmacology ]. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the PD study due to the longer washout period. Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone [see Warnings and Precautions ]. |
| Intervention: | Because there may be an increased risk of cardiovascular events following discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for patients taking low-dose aspirin for cardio protection who require intermittent analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics where appropriate. Concomitant use of NAPRELAN and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [see Warnings and Precautions ]. NAPRELAN is not a substitute for low dose aspirin for cardiovascular protection. |
| ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers | |
| Clinical Impact: |
|
| Intervention: |
|
| Diuretics | |
| Clinical Impact: | Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis. |
| Intervention: | During concomitant use of NAPRELAN with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions ]. |
| Digoxin | |
| Clinical Impact: | The concomitant use of naproxen with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin. |
| Intervention: | During concomitant use of NAPRELAN and digoxin, monitor serum digoxin levels. |
| Lithium | |
| Clinical Impact: | NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis. |
| Intervention: | During concomitant use of NAPRELAN and lithium, monitor patients for signs of lithium toxicity. |
| Methotrexate | |
| Clinical Impact: | Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). |
| Intervention: | During concomitant use of NAPRELAN and methotrexate, monitor patients for methotrexate toxicity. |
| Cyclosporine | |
| Clinical Impact: | Concomitant use of NAPRELAN and cyclosporine may increase cyclosporine’s nephrotoxicity. |
| Intervention: | During concomitant use of NAPRELAN and cyclosporine, monitor patients for signs of worsening renal function. |
| NSAIDs and Salicylates | |
| Clinical Impact: | Concomitant use of naproxen with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy [see Warnings and Precautions ]. |
| Intervention: | The concomitant use of naproxen with other NSAIDs or salicylates is not recommended. |
| Pemetrexed | |
| Clinical Impact: | Concomitant use of NAPRELAN and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information). |
| Intervention: | During concomitant use of NAPRELAN and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and GI toxicity.NSAIDs with short elimination half-lives (e.g., diclofenac, indomethacin) should be avoided for a period of two days before, the day of, and two days following administration of pemetrexed.In the absence of data regarding potential interaction between pemetrexed and NSAIDs with longer half-lives (e.g., meloxicam, nabumetone), patients taking these NSAIDs should interrupt dosing for at least five days before, the day of, and two days following pemetrexed administration. |
| Antacids and Sucralfate | |
| Clinical Impact: | Concomitant administration of some antacids (magnesium oxide or aluminum hydroxide) and sucralfate can delay the absorption of naproxen. |
| Intervention: | Concomitant administration of antacids such as magnesium oxide or aluminum hydroxide, and sucralfate with NAPRELAN is not recommended. |
| Cholestyramine | |
| Clinical Impact: | Concomitant administration of cholestyramine can delay the absorption of naproxen. |
| Intervention: | Concomitant administration of cholestyramine with NAPRELAN is not recommended. |
| Probenecid | |
| Clinical Impact: | Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life significantly. |
| Intervention: | Patients simultaneously receiving NAPRELAN and probenecid should be observed for adjustment of dose if required. |
| Other albumin-bound drugs | |
| Clinical Impact: | 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. |
| Intervention: | Patients simultaneously receiving NAPRELAN and a hydantoin, sulphonamide or sulphonylurea should be observed for adjustment of dose if required. |
Drug/Laboratory Test Interactions
| Bleeding times | |
| Clinical Impact: | Naproxen may decrease platelet aggregation and prolong bleeding time. |
| Intervention: | This effect should be kept in mind when bleeding times are determined. |
| Porter-Silber test | |
| Clinical Impact: | 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. |
| Intervention: | Although 17-hydroxy-corticosteroid measurements (Porter-Silber test) do not appear to be artifactually altered, it is suggested that therapy with NAPRELAN be temporarily discontinued 72 hours before adrenal function tests are performed if the Porter-Silber test is to be used. |
| Urinary assays of 5-hydroxy indoleacetic acid (5HIAA) | |
| Clinical Impact: | Naproxen may interfere with some urinary assays of 5-hydroxy indoleacetic acid (5HIAA). |
| Intervention: | This effect should be kept in mind when urinary 5-hydroxy indoleacetic acid are determined. |
NAPRELAN (naproxen sodium) Controlled-Release Tablets is a nonsteroidal anti-inflammatory drug, available as controlled-release tablets in 375 mg, 500 mg, and 750 mg strengths for oral administration. The chemical name is 2-naphthaleneacetic acid, 6-methoxy-α-methyl-sodium salt, (S)-. The molecular weight is 252.24. Its molecular formula is C14H13NaO3, and it has the following chemical structure.
Naproxen sodium is an odorless crystalline powder, white to creamy in color. It is soluble in methanol and water. NAPRELAN Tablets contain 412.5 mg, 550 mg, or 825 mg of naproxen sodium, equivalent to 375 mg, 500 mg, and 750 mg of naproxen, and 37.5 mg, 50 mg, and 75 mg sodium respectively. Each NAPRELAN Tablet also contains the following inactive ingredients: ammoniomethacrylate copolymer Type A, ammoniomethacrylate copolymer Type B, citric acid, crospovidone, magnesium stearate, methacrylic acid copolymer Type A, microcrystalline cellulose, povidone, and talc. The tablet coating contains hydroxypropyl methylcellulose, polyethylene glycol, and titanium dioxide.
Mechanism of Action
Naproxen has analgesic, anti-inflammatory, and antipyretic properties.
The mechanism of action of NAPRELAN, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).
Naproxen sodium is a potent inhibitor of prostaglandin synthesis in vitro. Naproxen sodium concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because naproxen sodium is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.
Pharmacodynamics
In a healthy volunteer study, 10 days of concomitant administration of naproxen 220 mg once-daily with low-dose immediate-release aspirin (81 mg) showed an interaction with the antiplatelet activity of aspirin as measured by % serum thromboxane B2 inhibition at 24 hours following the day 10 dose [98.7% (aspirin alone) vs 93.1% (naproxen and aspirin)]. The interaction was observed even following discontinuation of naproxen on day 11 (while aspirin dose was continued) but normalized by day 13. In the same study, the interaction was greater when naproxen was administered 30 minutes prior to aspirin [98.7% vs 87.7%] and minimal when aspirin was administered 30 minutes prior to naproxen [98.7% vs 95.4%].
Following administration of naproxen 220 mg twice-daily with low-dose immediate-release aspirin (first naproxen dose given 30 minutes prior to aspirin), the interaction was minimal at 24 h following day 10 dose [98.7% vs 95.7%]. However, the interaction was more prominent after discontinuation of naproxen (washout) on day 11 [98.7% vs 84.3%] and did not normalize completely by day 13 [98.5% vs 90.7%]. [see Drug Interactions ].
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 Drug Interactions ].
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
A two year study was performed in rats to evaluate the carcinogenic potential of naproxen at doses of 8 mg/kg/day, 16 mg/kg/day, and 24 mg/kg/day (0.05, 0.1, and 0.16 times the maximum recommended human daily dose of 1,500 mg/day based on a body surface area comparison). No evidence of tumorigenicity was found.
Mutagenesis
Studies to evaluate the mutagenic potential of Naprosyn Suspension have not been completed.
Impairment of Fertility
Studies to evaluate the impact of naproxen on male or female fertility have not been completed.
Rheumatoid Arthritis
The use of NAPRELAN Tablets for the management of the signs and symptoms of rheumatoid arthritis was assessed in a 12 week double-blind, randomized, placebo, and active-controlled study in 348 patients. Two NAPRELAN 500 mg tablets (1,000 mg) once daily and naproxen 500 mg tablets twice daily (1,000 mg) were more effective than placebo. Clinical effectiveness was demonstrated at one week and continued for the duration of the study.
Osteoarthritis
The use of NAPRELAN Tablets for the management of the signs and symptoms of osteoarthritis of the knee was assessed in a 12 week double-blind, placebo, and active-controlled study in 347 patients. Two NAPRELAN 500 mg tablets (1,000 mg) once daily and naproxen 500 mg tablets twice daily (1,000 mg) were more effective than placebo. Clinical effectiveness was demonstrated at one week and continued for the duration of the study.
Analgesia
The onset of the analgesic effect of NAPRELAN Tablets was seen within 30 minutes in a pharmacokinetic/pharmacodynamic study of patients with pain following oral surgery. In controlled clinical trials, naproxen has been used in combination with gold, D-penicillamine, methotrexate, and corticosteroids. Its use in combination with salicylate 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.
Special Studies
In a double-blind randomized, parallel group study, 19 subjects received either two NAPRELAN 500 mg tablets (1,000 mg) once daily or naproxen 500 mg tablets (1,000 mg) twice daily for 7 days. Mucosal biopsy scores and endoscopic scores were lower in the subjects who received NAPRELAN Tablets. In another double-blind, randomized, crossover study, 23 subjects received two NAPRELAN 500 mg tablets (1,000 mg) once daily, naproxen 500 mg tablets (1,000 mg) twice daily and aspirin 650 mg four times daily (2,600 mg) for 7 days each. There were significantly fewer duodenal erosions seen with NAPRELAN Tablets than with either naproxen or aspirin. There were significantly fewer gastric erosions with both NAPRELAN Tablets and naproxen than with aspirin. The clinical significance of these findings is unknown.
NAPRELAN (naproxen sodium) 375 mg, 500 mg, and 750 mg are controlled-release tablets supplied as:
NAPRELAN 375: white, capsule-shaped tablet with “N” on one side and “375” on the reverse; in bottles of 100; NDC 52427-272-01. Each tablet contains 412.5 mg naproxen sodium equivalent to 375 mg naproxen.
NAPRELAN 500: white, capsule-shaped tablet with “N” on one side and “500” on the reverse; in bottles of 75; NDC 52427-273-75. Each tablet contains 550 mg naproxen sodium equivalent to 500 mg naproxen.
NAPRELAN 750: white, capsule-shaped tablet with “N” on one side and “750” on the reverse; in bottles of 30; NDC 52427-274-30. Each tablet contains 825 mg naproxen sodium equivalent to 750 mg naproxen.
Storage
Store at room temperature, 20°C to 25°C (68°F to 77°F), excursions permitted 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
PHARMACIST: Dispense in a well-closed container.
Mechanism of Action
Naproxen has analgesic, anti-inflammatory, and antipyretic properties.
The mechanism of action of NAPRELAN, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).
Naproxen sodium is a potent inhibitor of prostaglandin synthesis in vitro. Naproxen sodium concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because naproxen sodium is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.