Naproxen Information
Naproxen ()
Naproxen () Description
Naproxen () sodium is a member of the arylacetic acid group of nonsteroidal anti-inflammatory drugs.
The chemical name for Naproxen () sodium is (-)-Sodium 6-methoxy-α-methyl-2-naphthaleneacetate. It has the following structural formula:
Naproxen () sodium is a white to creamy, crystalline solid, freely soluble in water at neutral pH.
Each film coated tablet, for oral administration, contains 275 mg or 550 mg Naproxen () sodium, equivalent to 250 mg or 500 mg Naproxen () with 25 mg (about 1 mEq) or 50 mg (about 2 mEq) of sodium respectively. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hydrogenated vegetable oil, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone (K-30) and sodium lauryl sulfate.
The film coating contains: hydroxypropyl methylcellulose 2910, methacrylic acid copolymer, povidone (K-30), simethicone emulsion, talc and titanium dioxide.
Naproxen () Clinical Pharmacology
Pharmacodynamics:
Pharmacokinetics:
in vivo
Absorption:
Distribution:
ss
PRECAUTIONS: Nursing Mothers
Metabolism:
Excretion:
WARNINGS: Renal Effects
Naproxen () Indications And Usage
Carefully consider the potential benefits and risks of Naproxen () sodium tablets and other treatment options before deciding to use Naproxen () sodium tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see ).
Naproxen () sodium tablets are indicated:
Naproxen () sodium tablets are also indicated:
Naproxen () Contraindications
Naproxen () sodium is contraindicated in patients with known hypersensitivity to Naproxen () and Naproxen () sodium.
Naproxen () sodium 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 ).
Naproxen () sodium is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see
Naproxen () Warnings
NSAIDs, including Naproxen () sodium, 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.
Naproxen () Precautions
Naproxen () SODIUM SHOULD NOT BE USED CONCOMITANTLY WITH OTHER Naproxen () PRODUCTS SINCE THEY ALL CIRCULATE IN THE PLASMA AS THE Naproxen () ANION.
Naproxen () sodium 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 helmoglobin values of 10 grams or less who are to receive long-term therapy should have hemoglobin values determined periodically.
The pharmacological activity of Naproxen () sodium 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.
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.
Laboratory Tests:
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.
Probenacid given concurrently increases Naproxen () anion plasma levels and extends its plasma half-life significantly.
Drug/Laboratory Test Interactions:
The administration of Naproxen () sodium 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 () sodium be temporarily discontinued 72 hours before adrenal function tests are performed if the Porter-Silber test is to be used.
Naproxen () sodium may interfere with some urinary assays of 5-hydroxy indoleacetic acid (5HIAA).
Carcinogenesis:
2
Reproductive studies have been performed in rats at 20 mg/kg/day (125 mg/m/day, 0.23 times the human systemic exposure), rabbits at 20 mg/kg/day (220 mg/m/day, 0.27 times the human systemic exposure), and mice at 170 mg/kg/day (510 mg/m/day), 0.28 times the human systemic exposure) with no evidence of impaired fertility or harm to the fetus due to the drug. However, animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Naproxen () sodium should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.
Labor and Delivery:
Nursing Mothers:
Pediatric Use:
Geriatric Use:
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 ).
Naproxen () 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 () daily (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 incidences 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:
*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.
The following are additional adverse experiences reported in
In patients taking NSAIDs, the following adverse experiences have also been reported in
Naproxen () Overdosage
Significant Naproxen () overdosage may be characterized by lethargy, dizziness, drowsiness, epigastric pain, abdominal discomfort, heartburn, indigestion, nausea, transient alterations in liver function, hypoprothrombinemia, renal dysfunction, metabolic acidosis, apnea, disorientation or vomiting. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression, and coma may occur, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose. Because Naproxen () sodium may be rapidly absorbed, high and early blood levels should be anticipated. A few patients have experienced convulsions, 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 543 mg/kg in rats, 1234 mg/kg in mice, 4110 mg/kg in hamsters, and greater than 1000 mg/kg in dogs.
Patients should be managed by symptomatic and supportive care following a 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 cathartic 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.
Naproxen () Dosage And Administration
Carefully consider the potential benefits and risks of Naproxen () sodium and other treatment options before deciding to use Naproxen () sodium. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see ).
After observing the response to initial therapy with Naproxen () sodium, the dose and frequency should be adjusted to suit an individual patient's needs.
Although Naproxen () sodium circulates in the plasma as Naproxen () , it has 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 () .
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 hapatic impairment or in elderly patients (see and ).
Naproxen () How Supplied
Naproxen () Sodium Tablets USP, 275 mg is available as white, unscored, capsule shaped, film coated tablets imprinted "H 1"
Naproxen () Sodium Tablets USP, 550 mg is available as white, unscored, capsule shaped, film coated tablets imprinted "H 2".
Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.
Dispense in well-closed containers as defined in the USP using a child-resistant closure.
Manufactured by:P. O. Box 182400AMMAN 11118 - JORDAN
Revised: June 2006
