Naproxen (Page 6 of 8)

OVERDOSAGE

Symptoms and Signs

Significant naproxen overdosage may be characterized by lethargy, dizziness, drowsiness, epigastric pain, abdominal discomfort, heartburn, indigestion, nausea, transient alterations in liver function, hypoprothrombinemia, renal dysfunction, metabolic acidosis, apnea, disorientation or vomiting. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression, and coma may occur, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose. Because naproxen sodium may be rapidly absorbed, high and early blood levels should be anticipated. A few patients have experienced convulsions, 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 543 mg/kg in rats, 1234 mg/kg in mice, 4110 mg/kg in 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, naproxen sodium and other treatment options before deciding to use naproxen and naproxen sodium 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 or naproxen sodium the dose and frequency should be adjusted to suit an individual patient’s needs.

Different dose strengths and formulations (ie, tablets, suspension) of the drug are not necessarily bioequivalent. This difference should be taken into consideration when changing formulation.

Although naproxen and naproxen sodium circulate in the plasma as naproxen, they have pharmacokinetic differences that may affect onset of action. Onset of pain relief can begin within 30 minutes in patients taking naproxen sodium and within 1 hour in patients taking naproxen.

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

Naproxen	250 mg or 375 mg	twice daily twice daily
Naproxen sodium	275 mg (naproxen 250 mg with 25 mg sodium)	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).

Juvenile Arthritis

The recommended total daily dose of naproxen is approximately 10 mg/kg given in 2 divided doses (ie, 5 mg/kg given twice a day).

Management of Pain, Primary Dysmenorrhea, and Acute Tendonitis and Bursitis

The recommended starting dose is 550 mg of naproxen sodium as naproxen sodium tablet followed by 550 mg every 12 hours or 275 mg every 6 to 8 hours as required. The initial total daily dose should not exceed 1375 mg of naproxen sodium. Thereafter, the total daily dose should not exceed 1100 mg of naproxen sodium. Because the sodium salt of naproxen is more rapidly absorbed, naproxen sodium tablets are recommended for the management of acute painful conditions when prompt onset of pain relief is desired. Naproxen may also be used for initial treatment of acute pain (see CLINICAL PHARMACOLOGY, INDICATIONS AND USAGE).

Acute Gout

The recommended starting dose is 750 mg of naproxen followed by 250 mg every 8 hours until the attack has subsided. Naproxen sodium may also be used at a starting dose of 825 mg followed by 275 mg every 8 hours.

HOW SUPPLIED

Naproxen tablets USP:

250 mg: circular, light orange colored, flat, uncoated tablets, engraved with ‘G’ and ‘32’ on either side of break line on one side and ‘250’ on the other side. Packaged in light-resistant bottles of 100 and 500.

100’s (bottle): NDC 68462-188-01

500’s (bottle): NDC 68462-188-05

375 mg: oval, light orange colored, biconvex, uncoated tablets, engraved with ‘G 32” on one side and ‘375” on the other side. Packaged in light-resistant bottles of 60, 100 and 500.

60’s (bottle): NDC 68462-189-60

100’s (bottle): NDC 68462-189-01

500’s (bottle): NDC 68462-189-05

500 mg: capsule shaped, light orange colored, uncoated tablets, having debossed with ‘G’ and ‘32’ on either side of break line on one side and ‘500’ on the other side. Packaged in light-resistant bottles of 30, 50, 60, 100 and 500.

30’s (bottle): NDC 68462-190-30

50’s (bottle): NDC 68462-190-50

60’s (bottle): NDC 68462-190-60

100’s (bottle): NDC 68462-190-01

500’s (bottle): NDC 68462-190-05

Store at 15° to 30°C (59° to 86°F) in well-closed containers; dispense in light-resistant containers.

Naproxen sodium tablets USP:

275 mg: blue, oval, film-coated tablets with ‘G 0’ engraved on one side and ‘275’ engraved on the other side. Packaged in bottles of 100 and 500

100’s (bottle): NDC 68462-178-01

500’s (bottle): NDC 68462-178-05

550 mg: blue colored, modified capsule shaped, biconvex, film-coated tablets with ‘G breakline 0’ engraved on one side and breakline on the other side. Packaged in bottles of 100 and 500.

100’s (bottle): NDC 68462-179-01

500’s (bottle): NDC 68462-179-05

Store at 15° to 30°C (59° to 86°F) in well-closed containers.

Manufactured by:
Glenmark Generics Ltd
Colvale-Bardez, Goa 403 513
India

Manufactured for:

Glenmark Generics Inc., USA
Mahwah, NJ 07430

January 2009