Naprelan Information
Naprelan (Naproxen)
Naprelan (Naproxen) Description
Naprelan (Naproxen) Tablets contain naproxen sodium, a member of the arylacetic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). Naprelan (Naproxen) Tablets use the proprietary IPDAS (Intestinal Protective Drug Absorption System) technology. It is a rapidly disintegrating tablet system combining an immediate release component and a sustained release component of microparticles that are widely dispersed, allowing absorption of the active ingredient throughout the gastrointestinal (GI) tract, maintaining blood levels over 24 hours. The chemical name for naproxen sodium is 2-naphthaleneacetic acid, 6-methoxy-a-methyl-sodium salt, (S)- with the following structural formula:
Naproxen sodium is an odorless crystalline powder, white to creamy in color. It is soluble in methanol and water. Naprelan (Naproxen) 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 (Naproxen) 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.
Naprelan (Naproxen) Clinical Pharmacology
Naproxen is a nonsteroidal anti-inflammatory drug (NSAID), with analgesic and antipyretic properties. As with other NSAIDs, its mode of action is not fully understood; however, its ability to inhibit prostaglandin synthesis may be involved in the anti-inflammatory effect.
Naprelan (Naproxen) Indications And Usage
Carefully consider the potential benefits and risks of Naprelan (Naproxen) Tablets and other treatment options before deciding to use Naprelan (Naproxen) Tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see ).
Naprelan (Naproxen) Tablets are indicated for the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, tendinitis, bursitis and acute gout. It is also indicated in the relief of mild to moderate pain and the treatment of primary dysmenorrhea.
Naprelan (Naproxen) Contraindications
Naprelan (Naproxen) is contraindicated in patients with known hypersensitivity to naproxen.
Naprelan (Naproxen) 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 ).
Naprelan (Naproxen) is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see ).
Naprelan (Naproxen) Warnings
NSAIDs, including Naprelan (Naproxen) , 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.
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.
Naprelan (Naproxen) Precautions
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including Naprelan (Naproxen) . These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. 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 a more severe hepatic reaction while on therapy with Naprelan (Naproxen) . If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), Naprelan (Naproxen) should be discontinued.
Anemia is sometimes seen in patients receiving NSAIDs, including Naprelan (Naproxen) . 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 Naprelan (Naproxen) , 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 Naprelan (Naproxen) ® who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.
Naprelan (Naproxen) Information For Patients
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.
Naprelan (Naproxen) Drug/laboratory Test Interactions
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-dinitrobenzene used in this assay. Although 17-hydroxy-corticosteroid measurements (Porter-Silber test) do not appear to be artificially 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).
Naprelan (Naproxen) Carcinogenesis, Mutagenesis, Impairment Of Fertility
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 (50 mg/m, 100 mg/m, and 150 mg/m). The maximum dose used was 0.28 times the systemic exposure to humans at the recommended dose. No evidence of tumorigenicity was found.
Naprelan (Naproxen) Pediatric Use
No pediatric studies have performed with Naprelan (Naproxen) Tablets, thus safety of Naprelan (Naproxen) Tablets in pediatric populations has not been established.
Naprelan (Naproxen) Geriatric Use
Clinical studies of Naprelan (Naproxen) Tablets did not include a sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for the elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Aging may affect the pharmacokinetics of naproxen. 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. Elderly or debilitated patients seem to tolerate GI ulcerations and bleeding less well than other individuals taking NSAIDs (see ). Additionally, elderly patients may be more sensitive to dose-dependent reduction in renal prostaglandin formation while taking NSAIDs (see ).
Naprelan (Naproxen) Adverse Reactions
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 (Naproxen) Tablets either in the double-blind period or in the nine month open-label extension. Of these 542 patients, 232 received Naprelan (Naproxen) Tablets, 167 were initially treated with Naprosyn and 143 were initially treated with placebo. Adverse reactions reported by patients who received Naprelan (Naproxen) Tablets are shown by body system. Those adverse reactions observed with naproxen but not reported in controlled trials with Naprelan (Naproxen) Tablets are .
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% - 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)
INCIDENCE LESS THAN 1% (PROBABLE CAUSAL RELATIONSHIP)
INCIDENCE LESS THAN 1% (CAUSAL RELATIONSHIP UNKNOWN)
Other adverse reactions listed in the naproxen package label, but not reported by those who received Naprelan (Naproxen) Tablets are shown in italics. These observations are being listed as alerting information to the physician.
Naprelan (Naproxen) Overdosage
Significant naproxen overdosage may be characterized by drowsiness, heartburn, indigestion, nausea or vomiting. Because naproxen sodium may be rapidly absorbed, high and early blood levels should be anticipated. A few patients have experienced seizures, 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 LD of the drug is 500 mg/kg in rats, 1200 mg/kg in mice, 4000 mg/kg in hamsters and greater than 1000 mg/kg in dogs. In animals 0.5 g/kg of activated charcoal was effective in reducing plasma levels of naproxen.
Patients should be managed by symptomatic and supportive care following an 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 carthartic 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.
Naprelan (Naproxen) Dosage And Administration
Carefully consider the potential benefits and risks of Naprelan (Naproxen) and other treatment options before deciding to use Naprelan (Naproxen) . Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see ).
After observing the response to initial therapy with Naprelan (Naproxen) , the dose and frequency should be adjusted to suit an individual patient's needs.
The recommended starting dose of Naprelan (Naproxen) Tablets in adults is two Naprelan (Naproxen) 375 mg tablets (750 mg) once daily, one Naprelan (Naproxen) 750 mg (750 mg) once daily, or two Naprelan (Naproxen) 500 mg tablets (1000 mg) once a daily. Patients already taking naproxen 250 mg, 375 mg, or 500mg twice daily (morning and evening) may have their total daily dose replaced with Naprelan (Naproxen) Tablets as a single daily dose.
During long-term administration, the dose of Naprelan (Naproxen) Tablets may be adjusted up or down depending on the clinical response of the patient. In patients who tolerate lower doses of Naprelan (Naproxen) Tablets well, the dose may be increased to two Naprelan (Naproxen) 750 mg tablets (1500 mg), or three Naprelan (Naproxen) 500 mg tablets (1500 mg) once daily for limited periods when a higher level of anti-inflammatory/analgesic activity is required. When treating patients, especially at the higher dose levels, the physician should observe sufficient increased clinical benefit to offset the potential increased risk (see ). 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.
A lower dose should be considered in patients with renal or hepatic impairment or in elderly patients (see ). Studies indicate that although total plasma contcentration 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) How Supplied
Naprelan (Naproxen) (naproxen sodium) Controlled-Release Tablets are available as follows:
Rx Only
US Patent 5,637,320
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Manufactured for: Victory Pharma, Inc., San Diego, CA 92130
Manufactured by: Elan Pharma International Ltd., Athlone, Ireland
PI3750107
Rev 8/09
Naprelan (Naproxen)
Naprelan (Naproxen) Principal Display Panel
Naprelan (Naproxen) Principal Display Panel
