Justeen Pharmaceauticals Limited

XENAP^? TABLETS

Naproxen Sodium Tablets 550mg

• Composition

  XENAP? TABLETS (Naproxen Sodium Tablet) 550 mg for oral administration is the sodium salt of naproxen and also is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. The mechanism of action of the naproxen anion, like that of other NSAIDs, is not completely understood but-may be related to prostaglandin synthetase inhibition.

  The chemical name for Naproxen sodium is (S)-6-methoxy-(alpha)-methyl-2-naphthaleneacetic acid, sodium salt, Naproxen sodium has a molecular weight of 252.23 and a molecular formula of C14 Hl3 NaO3.

• INDICATION

  XENAP? TABLETS (naproxen sodium tablet) is indicated for the treatment of rheumatoid arthritis, osteoarthritis, juvenile arthritis, ankylosing spondylitis, tendonitis and bursitis, and acute gout. It is also indicated in the relief of mild to moderate pain and for the treatment of primary dysmenorrheal.

• PHARMACOKINETIC

  After oral administration, it is fully absorbed. It is 99% bound to plasma proteins and crosses placenta. The metabolites of naproxen are almost entirely excreted in urine.

• CLINICAL PHARMACOLOGY

  XENAP? TABLETS (naproxen sodium tablet) is a nonsteroidal anti-inflammatory drug with analgesic and antipyretic properties Naproxen sodium, the sodium salt of Naproxen, has been developed as an analgesic because it is more rapidly absorbed. The naproxen anion inhibits prostaglandin synthesis but beyond this its mode of action is unknown.

  XENAP? TABLETS is rapidly and completely absorbed from the gastrointestinal tract. After administration of naproxen, peak plasma levels of naproxen anion are attained in 2 to 4 hours, with steady-state conditions normally achieved after 4-5 doses. The mean biological half life of the anion in humans is approximately 13 hours and at therapeutic levels it is greater than 995 albumin bound.

  At doses of naproxen greater than 550 mg/day there is a lack of dose proportionality due to an increase in clearance caused by saturation of plasma protein at higher doses. Approximately 95% of the doses is excreted in the urine, primarily as naproxen.6-0-desmethyl naproxen their conjugates. The rate of excretion has been found to coincide closely with the rate of the drug disappearance from the plasma. The drugs does not induce metabolizing enzymes.

• DOSAGE AND USE

  Adults:
  550 mg once daily

  Gout:
  1050 mg initially then 550 mg 8 hourly until attack has passed.

  Acute muskoletal disorders:
  550 initially then 275 mg every 6-8 hours after the first day.

  Dysmenorrhea:
  550 initially then 275 mg every 6-8 hours after the first day.

  Children:
  Not recommended in children less than 2 yrs.

• CONTRAINDICATIONS

  XENAP? TABLETS is contraindicated in patients with known hypersensitivity to naproxen.

  XENAP? TABLETS should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAlDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients.

  XENAP? TABLETS is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.

• ADVERSE REACTIONS

  The following adverse reactions are divided in 3 parts based on frequency and likelihood of causal relationship to naproxen.

  Probable causal Relationship:

  Adverse reactions reported in controlled clinical trials in 960 patients treated for rheumatoid arthritis or osteoarthritis are listed below. In general, these reactions were reported 2 to 10 times more frequently than they were in studies in the 962 patients treated for mild to moderate pain or for dysmenorrheal.

  A clinical study found gastrointestinal reactions to be more frequent and more severe in rheumatoid arthritis patients taking 1,500 mg naproxen daily compared to those taking 825 mg daily.

  In control clinical trials with about 80 children, and in well-monitored open studies with about 400 children with juvenile arthritis, the incidence of rash or 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 children than in adults.

  Gastrointestinal:

  The most frequent complaints reported related to gastrointestinal tracts. They were constipation, hearth burn, abdominal pain, nausea, yspepsia, diarrhea, stomatitis.

  The most frequent adverse events from the double-blind and open-label clinical trials were headache (l5), 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. (15%), flu syndrome (10%).

• WARNINGS

  Gastrointestinal (GI) Effects - Risk of GI Ulceration Bleeding and Perforation

  Serious gastrointestinal toxicity such as bleeding, ulceration and perforation of the stomach, small intestine or large intestine, can occur at any time, with or without warning symptoms, in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs). Minor upper gastrointestinal problems, such as dyspepsia, are common and may also occur at any time during NSAID therapy.

  Therefore, physicians and patients should remain alert for ulceration and bleeding, even in the absence of previous GI tract symptoms (see Patients should be informed about the signs and/or symptoms of serious Gl toxicity and the steps to take if they occur. 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.

  It has been demonstrated that upper GI ulcers, gross bleeding or perforation, caused by NSAIDs, appear to occur in approximately I of patients treated for 3 to 6 months and in about 2 to 4 of patients treated for 1 year. These trends continue, thus 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 patients with a prior history of ulcer disease or gastrointestinal bleeding. 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, the lowest effective dose should be used for the shortest possible duration.

  For high-risk patients, alternate therapies that do not involve NSAIDs should be considered.

  Studies have shown that patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding and who use NSAIDs, have a greater than 10-fold risk for developing a GI bleed than patients with neither of these risk factors. In addition to a past history of ulcer disease, pharmacoepidemiological studies have identified several other co-therapies or co-morbid conditions that may increase the risk for GI bleeding such as: treatment with oral corticosteroids, treatment with anticoagulants, longer duration of NSAID therapy, smoking, alcoholism, older age, and poor general health status.

  Anaphylactoid Reactions

  
  As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to naproxen. Naproxen should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. Emergency help should be sought in cases where an anaphylactoid reaction occurs.

  Advanced Renal Disease

  
  In cases with advanced kidney disease, treatment with naproxen is not recommended. If NSAID therapy, however, must be initiated, close monitoring of the patient's kidney function is advisable.

  Pregnancy

  
  In late pregnancy, as with other NSAIDs, naproxen should be avoided because it may cause premature closure of the ductus arteriosus.

• DRUG INTERACTION

  Aspirin

  Concomitant administration of naproxen 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.

  Methotrexate

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

  ACE-inhibitors

  Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. The use of NSAIDs in patients who are receiving ACE-inhibitors may potentiate renal disease states.

  Furosemide

  Clinical studies, as well as postmarketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis.

  Lithium

  Inhibition of renal lithium clearance leading to increases in plasma lithium concentrations has also been reported. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, patients should be observed carefully for signs of lithium toxicity.

  Warfarin

  The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that patients taking both drugs have a risk of serious GI bleeding that is higher than patients taking either drug alone. No significant interactions have been observed in clinical studies with naproxen and coumarin-type anticoagulants. However, caution is advised since interactions have been seen with other nonsteroidal agents of this class. The free fraction of warfarin may increase substantially in some subjects and naproxen interferes with platelet function.

  Other Interaction

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

  All naproxen products are contraindicated in patients who have had allergic reactions to prescription as well as to over-the-counter products containing naproxen. It is also contraindicated in patients in whom aspirin or other nonsteroidal anti-inflammatory/analgesic drugs induce the syndrome of asthma, rhinitis, and nasal polyps. Both types of reactions have the potential of being fatal. Anaphylactoid reactions to naproxen, whether of the true allergic type or the pharmacologic idiosyncratic (eg, aspirin hypersensitivity syndrome) type, usually but not always occur in patients with a known history of such reactions.

  Therefore, careful questioning of patients for such things as asthma, nasal polyps, urticaria, and hypotension associated with nonsteroidal anti-inflammatory drugs before starting therapy is important. In addition, if such symptoms occur during therapy, treatment should be discontinued.

• SHELF LIFE

  Three years.

• STORAGE

  Store in a cool place and protect from light.
  KEEP OUT OF REACH OF CHILDREN