Pharmacology: Naproxen sodium is a nonsteroidal agent. It is a 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 other nonsteroidal 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 central nervous system depressant and does not induce metabolizing enzymes.
Pharmacokinetics: 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 min of administration. It has a mean biological half-life of approximately 13 hrs. At therapeutic levels, it is >99% bound to serum albumin.
Approximately 95% of a naproxen sodium dose is excreted in the urine as unchanged naproxen, 6-O-desmethylnaproxen and their conjugates. The rate of excretion has been found to coincide closely with the rate of drug disappearance from the plasma.
Relief of mild to moderately severe pain, with or without accompanied inflammation eg, musculoskeletal trauma, postoperative pain and postdental extraction. It is also indicated for the relief of pain associated with postpartum cramping and dysmenorrhea.
Flanax: The recommended starting dose is 2 tablets, followed by 1 tablet every 8 hrs as required. The maximum recommended daily dose is 5 tablets (1375 mg).
Flanax Forte: The recommended dose is 1 tablet twice daily.
Note: As Flanax Forte tablets are intended to be administered whole, they should not be broken.
Symptoms: Significant overdosage of naproxen may be characterized by drowsiness, heartburn, indigestion, nausea or vomiting. No evidence of toxicity or late sequelae have been reported 5-15 months after ingestion, for 3-7 days, of doses up to 3.3 g/day. One patient ingested a single dose equivalent to 27.5 g of naproxen sodium and experienced mild nausea and indigestion. It is not known what dose of the drug would be life-threatening.
Treatment: Should a patient ingest a large quantity of Flanax/Flanax Forte accidentally or purposely, 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.
Hypersensitivity to naproxen or naproxen sodium formulations.
Because the potential exists for cross-sensitivity reactions, Flanax/Flanax Forte should not be given to patients with whom aspirin or other nonsteroidal anti-inflammatory/analgesic drugs induce the syndrome of asthma, rhinitis or urticaria.
Flanax/Flanax Forte should not be given to patients with active peptic ulcer. In other patients with a history of GI disease, it should be given under close supervision.
Flanax/Flanax Forte decreases platelet aggregation and prolongs bleeding time. This effect should be kept in mind when bleeding times are determined.
Elevations of one or more liver function tests have been reported with drugs of this class.
Flanax contains approximately 25 mg (about 1 mEq) of sodium. Flanax Forte contains approximately 50 mg (about 2 mEq) of sodium. This should be considered in patients whose overall intake of sodium must be markedly restricted.
Patients with Impaired Renal Function: As naproxen and its metabolites are eliminated to a large extent (95%) by urinary excretion via glomerular filtration, Flanax/Flanax Forte 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.
Flanax/Flanax Forte should not be used chronically in patients having baseline creatinine clearance >20 mL/min. Certain patients, especially those where renal blood flow is compromised eg, in extracellular volume depletion, cirrhosis of the liver, sodium restriction, congestive heart failure and preexisting renal disease, should have renal function assessed before and during Flanax/Flanax Forte therapy. Some elderly patients 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.
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 Flanax/Flanax Forte dosing is unknown, but it is prudent to use the lowest effective dose.
Use in pregnancy & lactation: As with other drugs of this type, Flanax/Flanax Forte 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 Flanax/Flanax Forte in pregnancy requires cautious balancing 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 Flanax/Flanax Forte should therefore be avoided in patients who are breastfeeding.
Use in children: As safety and efficacy studies are not yet complete, Flanax/Flanax Forte is not recommended for use in children <16 years.
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 Flanax/Flanax Forte dosing is unknown. As with other drugs used in the elderly, it is prudent to use the lowest effective dose.
For the effect of reduced elimination in the elderly, see Patients with Impaired Renal Function.
Most commonly reported adverse reactions: Abdominal discomfort, epigastric distress, headache, nausea, peripheral edema (mild), tinnitus and vertigo.
The following adverse events are rare but have been reported: Alopecia, anaphylactic reactions to naproxen and naproxen sodium formulations, 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, vasculitis 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 Flanax/Flanax Forte.
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 Flanax/Flanax Forte and anticoagulants or sulfonylureas, but caution is advised, since interaction has been seen with other nonsteroidal 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.
Flanax/Flanax Forte and other NSAIDs can reduce the antihypertensive effect of propranolol and other β-blockers.
Probenecid given concurrently increases naproxen plasma levels and extends its plasma half-life significantly.
Concomitant administration of Flanax/Flanax Forte and methotrexate should be done with caution, because naproxen has been reported among other NSAIDs to reduce the tubular secretion of methotrexate in an animal model and thus, possibly enhance its toxicity.
It is suggested that Flanax/Flanax Forte therapy be temporarily discontinued 48 hrs 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-hydroxyindole acetic acid.
Store at temperatures not exceeding 30°C. Protect from heat.
M01AE02 - naproxen ; Belongs to the class of propionic acid derivatives of non-steroidal antiinflammatory and antirheumatic products.
Flanax: Tab 275 mg x 100's, 500's. Flanax Forte: Tab 550 mg x 50's, 250's.