General Information

Naprelan (naproxen sodium) is a nonsteroidal anti-inflammatory drug.

Naprelan is specifically indicated for the following:

• osteoarthritis
• rheumatoid arthritis
• ankylosing spondylitis
• tendinitis
• bursitis
• acute gout
• primary dysmenorrhea
• relief of mild to moderate pain

Naprelan is supplied as Controlled-Release Tablets, for oral use. Carefully consider the potential benefits and risks of Naprelan and other treatment options before deciding to use Naprelan. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. After observing the response to initial therapy with Naprelan, the dose and frequency should be adjusted to suit an individual patient’s needs.

The recommended dosing/administration is as follows:

Rheumatoid Arthritis, Osteoarthritis, and Ankylosing Spondylitis

The recommended starting dose of Naprelan Tablets in adults is two 375 mg tablets (750 mg) once daily, one Naprelan 750 mg (750 mg) once daily, or two Naprelan 500 mg tablets (1,000 mg) once daily. Patients already taking naproxen 250 mg, 375 mg, or 500 mg twice daily (morning and evening) may have their total daily dose replaced with Naprelan Tablets as a single daily dose.

During long-term administration, the dose of Naprelan Tablets may be adjusted up or down depending on the clinical response of the patient. In patients who tolerate lower doses of Naprelan Tablets well, the dose may be increased to two Naprelan 750 mg tablets (1,500 mg), or three Naprelan 500 mg tablets (1,500 mg) once daily for limited periods when a higher level of anti-inflammatory/analgesic

Management of Pain, Primary Dysmenorrhea, and Acute Tendinitis and Bursitis

The recommended starting dose is two Naprelan 500 mg tablets (1,000 mg) once daily. For patients requiring greater analgesic benefit, two Naprelan 750 mg tablets (1,500 mg) or three Naprelan 500 mg tablets (1,500 mg) may be used for a limited period. Thereafter, the total daily dose should not exceed two Naprelan500 mg tablets (1,000 mg). 

Acute Gout

The recommended dose on the first day is two to three NAPRELAN 500 mg tablets (1,000 to 1,500 mg) once daily, followed by two NAPRELAN 500 mg tablets (1,000 mg) once daily, until the attack has subsided.

Mechanism of Action

Naprelan (naproxen sodium) is a nonsteroidal anti-inflammatory drug. 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.

Side Effects

The most frequent complaints relate to the gastrointestinal tract. In subjects treated chronically with Naprelan, a non-steroidal anti-inflammatory drug, serious gastrointestinal toxicity such as perforation, ulceration, and bleeding can occur.

The Naprelan drug label comes with the following Black Box Warning: 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. Naprelan is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. 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. When treating patients, especially at the higher dose levels, the physician should observe sufficient increased clinical benefit to offset the potential increased risk. The lowest effective dose should be sought and used in every patient. Symptomatic improvement in arthritis usually begins within one week; however, treatment for two weeks may be required to achieve a therapeutic benefit.

Clinical Trial Results

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 (1000 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.