Naproxen Sodium

Naproxen Sodium

275mg Tablet

550mg Tablet

Drug Category: Non-steroidal Anti-inflammatory / Analgesic

Brand Name: Flanax

Drug Description:

Naproxen Sodium is a non-steroidal agent developed by Syntex Research. It is non-narcotic analgesic agent with marked anti-inflammatory actions. It has demonstrated these properties in human clinical studies and classical animal test systems. It exhibits its anti-inflammatory effect even in adrenalectomized animals, indicating that its action is not mediated through the pituitary-adrenal axis. It inhibits prostaglandin synthetase, as do no other non-steroidal analgesic/anti-inflammatory agents. As with other agents, however, the exact mechanism of its anti-inflammatory and analgesic actions is not known.

Naproxen Sodium is not a CNS depressant and does not induce metabolizing enzymes.

Naproxen Sodium is freely soluble in water and is rapidly and completely absorbed from the gastrointestinal tract after oral administration. Because of this rapid and complete absorption, significant plasma levels and onset of pain relief are obtained in patients within 20 minutes of administration. It has a mean biological half-life of approximately 13 hours. At therapeutic levels it is greater than 99% bound to serum albumin.

Approximately 95% of a Naproxen Sodium dose is excreted in the urine as unchanged naproxen, 6-0-desmethylnaproxen and their conjugates. The rate of excretion has been found to coincide closely with the rate of drug disappearance from the plasma.

Indications:

Naproxen Sodium is indicated in the relief of mild to moderately severe pain with or without accompanied inflammation, such as musculoskeletal trauma, post-operative pain and post-dental extraction. It is also indicated for the relief of pain associated with post-partum cramping and dysmenorrhea.

Dosage and Administrations:

In the treatment of rheumatic disorders, the usual dose is 550mg to 1100mg (1-2 tablets) as a single dose or in 2 divided doses.

In other painful conditions (such as dysmenorrhea and acute musculoskeletal disorders), the usual initial dose is 550mg (1 tablet) followed by 275mg every 6 to 8 hours, up to a maximum daily dose of 1375mg after the first day.

In acute gout, an initial dose of 825mg followed by 275mg every 8 hours.

For migraine, 825mg is given and may be followed by 275mg to 550mg after at least half an hour, to a maximum daily dose of 1375mg.

Or as prescribed by a physician.

Warning:

Naproxen Sodium is not to be given to patients who have a history of:

• Stroke (Cerebrovascular Accident)
• Heart attack (Myocardial Infarction)
• Coronary artery bypass graft
• Uncontrolled hypertension
• Congestive heart failure (NYHA II-IV)

Other Contraindications:

It is contraindicated in patients with history of hypersensitivity to aspirin of any other NSAIDs. It is also contraindicated in patients with previous or active peptic ulceration. Naproxen Sodium should be used with caution in patients with cardiac, liver, and renal disease. Dose should be adjusted accordingly and renal and liver functions should be constantly monitored when taking the drug.

Use in patients with impaired renal function:

As Naproxen and its metabolites are eliminated to a large extent (95%) by urinary excretion via glomerular filtration, Naproxen Sodium 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.

Naproxen Sodium should not be used chronically in patients having baseline creatinine clearance less than 20ml/minute.

Certain patients, specifically those where renal blood flow is compromised, such as in extracellular volume depletion, cirrhosis of the liver, sodium restriction, congestive heart failure, and pre-existing renal disease. Should have renal function assessed before and during Naproxen Sodium therapy. Some elderly in whom impaired renal function may be expected could also fall within this category. A reduction in daily dosage should be considered to avoid the possibility of excessive accumulation of Naproxen metabolites in these patients.

Use in patients with impaired liver function:

Chronic alcoholic liver disease and probably also other forms of cirrhosis reduce the total plasma concentration of naproxen, but the plasma concentration of unbound naproxen is increased. The implication of this finding for Naproxen Sodium dosing is unknown, but its is prudent to use the lowest effective dose.

Use in the elderly:

Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. The implication of this finding for Naproxen Sodium dosing is unknown. As with other drugs in the elderly, it is prudent to use the lowest effective dose.

Interactions with other drugs:

Due to the high plasma protein binding of naproxen, patients simultaneously receiving hydantoins should be closely monitored for adjustment of dose if required. Interactions have not been observed in clinical studies with Naproxen Sodium and anti-coagulants or sulfonylureas, but caution is advised, nonetheless, since interaction has been seen with other non-steroidal agents of this class.

The natriuretic effect of furosemide has been reported to be inhibited by some drugs of this class. Inhibition of renal lithium clearance leading to an increase in plasma lithium concentration has been reported also.

Naproxen Sodium and other non-steroidal anti-inflammatory drugs can reduce the anti-hypertensive effect of propranolol and other beta-blockers.

Probenecid given concurrently increases naproxen plasma levels and extends its plasma half-life significantly.

Concomitant administration of Naproxen Sodium and methotrexate should be with caution, because Naproxen has been reported among other non-steroidal anti-inflammatory drugs to reduce the tubular secretion of methotrexate in an animal model, and thus possibly enhance its toxicity.

It is suggested that Naproxen Sodium therapy be temporarily discontinued 48 hours before adrenal function tests are performed, because it may artificially interfere with some tests for 17-ketogenic steroids. Similarly it may interfere with some urinary assays of 5-hydroxyindoleacetic acid.

Adverse Reactions:

Most commonly reported adverse events: abdominal discomfort, epigastric distress, headache, nausea, peripheral edema (mild), tinnitus, and vertigo.

The following adverse events are rate but have been reported: alopecia, anaphylactic reactions to naproxen and Naproxen Sodium formulation, angioedema, aplastic and hemolytic anemia, cognitive dysfunction, eosinophilic pneumonitis, epidermal necrolysis, erythema multiforme, fatal hepatitis, gastrointestinal bleeding and/or perforation, granulocytopenia, hearing impairment, hematuria, inability to concentrate, insomnia, jaundice, nephropathy, peptic ulceration, photosensitive dermatitis, skin rash, Stevens-Johnson syndrome, thrombocytopenia, ulcerative stomatitis, vaculitis, and visual disturbances.

Although sodium retention has not been reported in metabolic studies, it is possible that patients with questionable or compromised cardiac function may be at a greater risk when taking Naproxen Sodium.

Use in Pregnancy:

As with other drugs of this type, Naproxen Sodium produces a delay in parturition in animals and also affects the human fetal cardiovascular system (closure of the ductus arteriosus). Therefore it should not be used during pregnancy unless clearly needed. The use of Naproxen Sodium in pregnancy requires cautious of possible benefits against potential risks to the mother and fetus, especially in the first and third trimesters.

Naproxen has been found in the milk of lactating mothers. The use of Naproxen Sodium should therefore be avoided in patients who are breast feeding.

Overdosage:

Significant overdosage of the drug may be characterized by drowsiness, heart burn, indigestion, nausea or vomiting. No evidence of toxicity or late sequelae had been reported 5 – 15 months after ingestion, for three to seven days, of doses up to 3.3g/day. One patient ingested a single dose equivalent to 27.5g of Naproxen Sodium and experienced mild nausea and indigestion. It is not known what dose of the drug would be life threatening.

Should a patient ingest a large quantity of Naproxen Sodium accidentally or purposefully, the stomach may be emptied and usual supportive measures employed. Animal studies indicate that the prompt administration of activated charcoal in adequate amounts would tend to reduce markedly the absorption of the drug.

Storage Condition:

Store at temperature not exceeding 30^oC. Protect from heat.