Naprelan

Naprelan Information

Indications:

Naprelan is indicated for the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, tendinitis, bursitis, and acute gout. Naprelan is also indicated in the relief of mild to moderate pain and the treatment of primary dysmenorrhea.

Naprelan Ingredients and Composition

How Does Naprelan Work?

Naprelan 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.

Pharmacokinetics

Although naproxen itself is well absorbed, the sodium salt form is more rapidly absorbed resulting in higher peak plasma levels for a given dose. Approximately 30% of the total naproxen sodium dose in Naprelan is present in the dosage form as an immediate release component. The remaining naproxen sodium is coated as microparticles to provide sustained release properties. After oral administration, plasma levels of naproxen are detected within 30 minutes of dosing, with peak plasma levels occurring approximately 5 hours after dosing. The observed terminal elimination half-life of naproxen from both immediate release naproxen sodium and Naprelan is approximately 15 hours. Steady state levels of naproxen are achieved in 3 days and the degree of naproxen accumulation in the blood is consistent with this.

How To Take Naprelan and Naprelan Dosage and Administration

Rheumatoid Arthritis, Osteoarthritis, And Ankylosing Spondylitis

The usual daily dose of Naprelan is two 375 mg tablets (750 mg) once daily, or two Naprelan 500 mg tablets (1000 mg) once a day. Both larger and smaller doses may be required in individual patients. Regardless of indication, the Naprelan dosage should be individualized to achieve effective dose and minimize adverse events, however the maximum daily dose is three Naprelan 500 mg once daily.

Management Of Pain, Primary Dysmenorrhea, And Acute Tendinitis And Bursitis

The recommended starting dose is two Naprelan 500 mg tablets (1000 mg) once daily. For patients requiring greater analgesic benefit, three Naprelan 500 mg tablets (1500 mg) may be used for a limited period. Thereafter, the total daily dose should not exceed two Naprelan 500 mg tablets (1000 mg).

Acute Gout

The recommended dose on the first day is two to three Naprelan 500 mg tablets (1000 - 1500 mg) once daily, followed by two Naprelan 500 mg tablets (1000 mg) once daily, until the attack has subsided.

If you suspect a Naprelan Overdose

Significant Naprelan (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 LD50 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.

Should a patient ingest a large number of Naprelan tablets, accidentally or purposefully, the stomach may be emptied and usual supportive measures employed. In animals 0.5 g/kg of activated charcoal was effective in reducing plasma levels of naproxen. Hemodialysis does not decrease the plasma concentration of naproxen because of the high degree of its protein binding.

Naprelan Side Effects

Naprelan Precautions and Contraindications

General

Naprelan should not be used concomitantly with other naproxen products since they all circulte in the plasma as the naproxen anion.

The antipyretic and anti-inflammatory activities of the drug may reduce fever and inflammation, thus diminishing their utility as diagnostic signs.

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.

Renal Effects

As with other NSAIDs, long term administration of Naprelan (naproxen) to animals has resulted in renal papillary necrosis and other abnormal renal pathology. In humans, there have been reports of acute interstitial nephritis, hematuria, proteinuria, and occasionally nephrotic syndrome associated with naproxen-containing products and other NSAIDs since they have been marketed.

A second form of renal toxicity has been seen in patients taking Naprelan (naproxen) as well as other NSAIDs. In patients with prerenal conditions with reduction in renal blood flow or blood volume, renal prostaglandins have a supportive role in the maintenance of renal perfusion. Administration of a NSAID may cause a dose-dependent reduction in prostaglandin formation and may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, diuretic use, and the elderly. Discontinuation of NSAID therapy is typically followed by recovery to the pretreatment state.

Naproxen and its metabolites are eliminated primarily by the kidneys, therefore the drug should be used with great caution in patients with significantly impaired renal function and the monitoring of serum creatinine and/or creatinine clearance is advised in these patients. Caution should be used if the drug is given to patients with creatinine clearance of less than 20 mL/minute because accumulation of naproxen has been seen in such patients.

Hepatic Effects

As with other NSAIDs, borderline elevations of one or more liver tests may occur in up to 15% of patients. These abnormalities may progress, may remain essentially unchanged, or may resolve with continued therapy. The ALT (SGPT) is probably the most sensitive indicator of liver dysfunction. Meaningful (3 times the upper limit of normal) elevations of ALT (SGPT) or AST (SGOT) occurred in controlled clinical trials in less than 1% of patients. 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 naproxen. Severe hepatic reactions, including jaundice and cases of fatal hepatitis have been reported with Naprelan (naproxen) as with other NSAIDs. Although such reactions are rare, if abnormal liver tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g. eosinophilia, rash, fever, etc.), naproxen 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.

Fluid Retention and Edema

Peripheral edema has been observed in some patients receiving Naprelan (naproxen). Naprelan (naproxen sodium) tablets contain 37.5 mg or 50 mg of sodium (1.5 mEq or 2.0 mEq respectively). This should be considered in patients whose overall intake of sodium must be severely restricted. For these reasons, Naprelan should be used with caution in patients with fluid retention, hypertension or heart failure.

Contraindications to Naprelan

All naproxen products, such as Naprelan, are contraindicated in patients who have had allergic reactions to prescription as well as to over-the-counter products containing naproxen. Anaphylactoid reactions may occur in patients without previous known exposure or hypersensitivity to aspirin, naproxen, or other NSAIDs, or in individuals with a history of angioedema, urticaria, bronchospastic reactivity (e.g. asthma), and nasal polyps. Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome. Therefore, careful questioning of patients for such things as asthma, nasal polyps, urticaria, and hypotension associated with NSAIDs before starting therapy is important. In addition, if such symptoms occur during therapy, treatment with Naprelan should be discontinued.

Naprelan Warnings

Taking Naprelan during Pregnancy or Breast-feeding

Reproduction studies have been performed in rats at 20 mg/kg/day (125 mg/m2/day, 0.23 times the human systemic exposure) rabbits at 20 mg/kg/day (220 mg/m2/day, 0.27 times the human systemic exposure) and mice at 170 mg/kg/day (510 mg/m2/day, 0.28 times the human systemic exposure) with no evidence of impaired fertility or harm to the fetus due to Naprelan. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Naprelan should be used during pregnancy only if the potential benefits justify the potential risks to the fetus.

The naproxen anion has been found in the milk of lactating women at a concentration of approximately 1% of that found in the plasma. Because of the possible adverse effects of prostaglandin-inhibiting drugs on neonates, use of Naprelan in nursing mothers should be avoided.

Naprelan Drug Interactions

The use of NSAIDs in patients who are receiving ACE inhibitors may potentiate renal disease states.

In vitro studies have shown that naproxen anion, because of its affinity for protein, may displace from their binding sites other drugs which are also albumin-bound.

Theoretically, the naproxen anion itself could likewise be displaced. Short-term controlled studies failed to show that taking the Naprelan significantly affects prothrombin times when administered to individuals on coumarin-type anticoagulants. Caution is advised nonetheless, since interactions have been seen with other nonsteroidal agents of this class. Similarly, patients receiving Naprelan and a hydantoin, sulfonamide or sulfonylurea should be observed for signs of toxicity to these drugs.

Concomitant administration of Naprelan and aspirin is not recommended because naproxen is displaced from its binding sites during the concomitant administration of aspirin, resulting in lower plasma concentrations and peak plasma levels.

The natriuretic effect of furosemide has been reported to be inhibited by some drugs of this class. Inhibition of renal lithium clearance leading to increases in plasma lithium concentrations has also been reported. Naproxen and other NSAIDs 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.

Caution should be used if naproxen is administered concomitantly with methotrexate. Naproxen, naproxen sodium and other NSAIDs have been reported to reduce the tubular secretion of methotrexate in an animal model, possibly increasing the toxicity of methotrexate.

Naprelan Clinical Trials and Studies

Storing Naprelan

Store at controlled room temperature, 20° - 25° C (68° - 77° F).

Articles and information related to Naprelan

Edema