FLEXIN (Naproxen) TABLET 250MG

      FLEXIN (Naproxen) TABLET 250MG

FLEXIN
(Naproxen)

TABLET 250MG

FLEXIN ® tablets for oral administration each containing 250 mg and 500 mg of 

Naproxen.

Cardiovascular Risk: 

NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, 

myocardial infarction, and stroke, which can be fatal. This risk may increase with 

duration of use. Patients with cardiovascular disease or risk factors for 

cardiovascular disease may be at greater risk (see WARNINGS). Naproxen tablets 

are contraindicated for the treatment of peri-operative pain in the setting of 

coronary artery bypass graft (CABG) surgery (see WARNINGS).

Gastrointestinal Risk: 

NSAIDs cause an increased risk of serious gastrointestinal adverse events including 

bleeding, ulceration, and perforation of the stomach or intestines, which can be 

fatal. These events can occur at any time during use and without warning symptoms. 

Elderly patients are at greater risk for serious gastrointestinal events (see 

WARNINGS).

DESCRIPTION 

Flexin is a proprionic acid derivative related to the arylacetic acid group of 

nonsteroidal anti-inflammatory drugs. 

CLINICAL PHARMACOLOGY 

Flexin tablets for oral administration each containing 250 mg and 500 mg of 

Naproxen.

Pharmacodynamics: 

Naproxen is a non steroidal 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.

Pharmacokinetics: 

Naproxen is rapidly and completely absorbed from the gastrointestinal tract with an 

in vivo bioavailability of 95%. The elimination half-life of naproxen ranges from 12 to 

17 hours.

Absorption: 

After administration of naproxen tablets, peak plasma levels are attained in 2 to 4 

hours.

Distribution: 

Naproxen has a volume of distribution of 0.16 L/kg. At therapeutic levels naproxen 

is greater than 99% albumin-bound. At doses of naproxen greater than 500 mg/day 

there is less than proportional increase in plasma levels due to an increase in 

clearance caused by saturation of plasma protein binding at higher doses (average 

trough Css 36.5, 49.2 and 56.4 mg/L with 500, 1000 and 1500 mg daily doses of 

naproxen, respectively). The naproxen anion has been found in the milk of lactating 

women at a concentration equivalent to approximately 1% of maximum naproxen 

concentration in plasma (see PRECAUTIONS: Nursing Mothers).

Metabolism: 

Naproxen is extensively metabolized in the liver to 6-0-desmethyl naproxen, and 

both parent and metabolites do not induce metabolizing enzymes. Both naproxen 

and 6-0-desmethyl naproxen are further metabolized to their respective 

acylglucuronide conjugated metabolites.

Excretion: 

The clearance of naproxen is 0.13 mL/min/kg. Approximately 95% of the naproxen 

from any dose is excreted in the urine, primarily as naproxen (<1%), 6-0-desmethyl 

naproxen (<1%) or their conjugates (66% to 92%). The plasma half-life of the 

naproxen anion in humans ranges from 12 to 17 hours. The corresponding half-lives 

of both naproxen's metabolites and conjugates are shorter than 12 hours, and their 

rates of excretion have been found to coincide closely with the rate of naproxen 

disappearance from the plasma. Small amounts, 3% or less of the administered dose, 

are excreted in the feces. In patients with renal failure metabolites may accumulate 

(see WARNINGS: Renal Effects).

Special Populations: 

Pediatric Patients 

In pediatric patients aged 5 to 16 years with arthritis, plasma naproxen levels 

following a 5 mg/kg single dose of naproxen suspension (see DOSAGE AND 

ADMINISTRATION) were found to be similar to those found in normal adults 

following a 500 mg dose. The terminal half-life appears to be similar in pediatric and 

adult patients. Pharmacokinetic studies of naproxen were not performed in 

pediatric patients younger than 5 years of age. Pharmacokinetic parameters appear 

to be similar following administration of naproxen tablets in pediatric patients.

Geriatric Patients 

Studies indicate that although total plasma concentration of naproxen is 

unchanged, the unbound plasma fraction of naproxen is increased in the elderly, 

although the unbound fraction is <1% of the total naproxen concentration. Unbound hamsters, and greater than 1000 mg/kg in dogs.
Treatment:
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.

DOSAGE AND ADMINISTRATION 
Carefully consider the potential benefits and risks of naproxen tablets and other
treatment options before deciding to use naproxen tablets. Use the lowest effective
dose for the shortest duration consistent with individual patient treatment goals
(see WARNINGS). After observing the response to initial therapy with naproxen
tablets, the dose and frequency should be adjusted to suit an individual patient's
needs. Different dose strengths and formulations (i.e., tablets, suspension) of the
drug are not necessarily bioequivalent. This difference should be taken into
consideration when changing formulation. Although Flexin Tablets circulates in the
plasma as naproxen, they have pharmacokinetic different that may affect onset of
action. Onset of pain relief can begin within 1 hour in patients taking Flexin.
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 hepatic impairment or in elderly patients (see WARNINGS
and PRECAUTIONS).

Geriatric Patients: 
Studies indicate that although total plasma concentration of naproxen is
unchanged, the unbound plasma fraction of naproxen is increased in the elderly.
Caution is advised when high doses are required and some adjustment of dosage
may be required in elderly patients. As with other drugs used in the elderly, it is
prudent to use the lowest effective dose.
Patients with Moderate to Severe Renal Impairment: 
Naproxen-containing products are not recommended for use in patients with
moderate to severe and severe renal impairment (creatinine clearance <30
mL/min) (see WARNINGS: Renal Effects).
Rheumatoid Arthritis, Osteoarthritis and Ankylosing Spondylitis
Flexin tablets 250 mg twice daily
Flexin tablets 500 mg twice daily
During long-term administration, the dose of naproxen may be adjusted up or down
depending on the clinical response of the patient. A lower daily dose may suffice for
long-term administration. The morning and evening doses do not have to be equal in
size and the administration of the drug more frequently than twice daily is not
necessary. In patients who tolerate lower doses well, the dose may be increased to
naproxen 1500 mg/day for limited periods of up to 6 months when a higher level of
anti-inflammatory/analgesic activity is required. When treating such patients with
naproxen 1500 mg/day, the physician should observe sufficient increased clinical
benefits to offset the potential increased risk. The morning and evening doses do not
have to be equal in size and administration of the drug more frequently than twice
daily does not generally make a difference in response (see CLINICAL
PHARMACOLOGY).

Management of Pain:
Primary Dysmenorrhea, and Acute Tendonitis and Bursitis:
The recommended starting dose of Flexin is 500 mg, followed by 500 mg every 12
hours or 250 mg every 6 to 8 hours as required. The initial total daily dose should not
exceed 1250 mg of naproxen. Thereafter, the total daily dose should not exceed
1000 mg of naproxen.

Acute Gout:
The recommended starting dose is 750 mg of Flexin tablets followed by 250 mg
every 8 hours until the attack has subsided.

STORAGE:
Protect from heat, light & moisture.

HOW SUPPLIED: 
List no. G529,FLEXIN 250 mg tablets in carton of 2x10s
List no. G828,FLEXIN 500 mg scored tablets in carton of 2x10s