CLINICAL PHARMACOLOGY:

Ibuprofen tablets contain Ibuprofen which possesses analgesic and antipyretic activities. Its mode of action, like that of other nonsteroidal anti-inflammatory agents, is not completely understood, but may be related to prostaglandin synthetase inhibition.

Pharmacokinetics: Ibuprofen is rapidly absorbed. Peak serum Ibuprofen levels are generally attained one to two hours after administration. The bioavailability of the drug is minimally altered by the presence of food. Studies have shown that following ingestion of the drug, 45% to 79% of the dose was recovered in the urine within 24 hours as metabolite A (25%), and metabolite B (37%),; the percentages of free and conjugated Ibuprofen were approximately 1% and 14%, respectively. The serum half-life is 1.8 to 2.0 hours.

CLINICAL STUDIES: In clinical studies in patients with rheumatoid arthritis and osteoarthritis, the relief of episiotomy pain, pain following dental extraction procedures, and primary dysmenorrhea. Ibuprofen has been shown to be comparable to aspirin in controlling pain and inflammation and to be associated with a statistically significant reduction in the milder gastrointestinal side effects.Ibuprofen may be used in combination with gold salts and/or corticosteroids.

WARNINGS:

Risk of GI ulceration, Bleeding and Perforation with Nonsteroidal Anti-inflammatory Therapy: In patients observed in clinical trials of several months to two years duration, symptomatic upper GI ulcers, gross bleeding or perforation appear to occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year.

Pregnancy: Administration of Ibuprofen is not recommended during pregnancy.

Nursing Mothers: Ibuprofen is not recommended for use in nursing mothers.

PRECAUTIONS:

General: Blurred and/or diminished vision, Fluid retention and edema,.

Liver effects: borderline elevations of one or more liver function tests may occur in up to 15% of patients. Severe hepatic reactions, including jaundice and cases of fatal hepatitis, have been reported.

Hemoglobin levels: in cross-study comparisons with doses ranging from 1200 mg to 3200 mg daily for several weeks, a slight dose-response decrease in hemoglobin/hematocrit was noted.

Aseptic meningitis: aseptic meningitis with fever and coma has been observed on rare occasions.

Renal effects: there have been reports of acute interstitial nephritis with hematuria, proteinuria, and occasionally nephrotic syndrome.

Since Ibuprofen is eliminated primarily by the kidneys, patients with significantly impaired renal function should be closely monitored; and a reduction in dosage should be anticipated to avoid drug accumulation.

Drug Interactions:

Coumarin-Type Anticoagulants, Aspirin, Methotrexate, H-2 Antagonists, Furosemide, Lithium.

SIDE EFFECTS:

Incidence greater than 1% (but less than 3%):

Gastrointestinal: nausea, epigastric pain, heartburn, diarrhea, abdominal distress, nausea and vomiting, indigestion, constipation, abdominal cramps or pain, fullness of GI tract (bloating and flatulence).

Central nervous system:  dizziness, headache, nervousness

Dermatologic: rash (including maculopapular type), pruritus

Special Senses: tinnitus

Metabolic/Endocrine: decreased appetite

Cardiovascular: edema, fluid retention (generally responds promptly to drug discontinuation)

OVERDOSAGE:

In cases of acute overdosage, the stomach should be emptied by vomiting or lavage, though little drug will likely be recovered if more than an hour has elapsed since ingestion. Because the drug is acidic and is excreted in the urine, it is theoretically beneficial to administer alkali and induce diuresis. In addition to supportive measures, the use of oral activated charcoal may help to reduce the absorption and reabsorption of Ibuprofen.

DOSAGE AND ADMINISTRATION:

Do not exceed 3600 mg total daily dose. If gastrointestinal complaints occur, administer Ibuprofen tablets with meals or milk.

Rheumatoid arthritis and osteoarthritis, including flare-ups of chronic disease

Suggested dosage: 1200 mg-3200 mg daily (400 mg, 600 mg t.i.d. or q.i.d.). Individual patients may show a better response to 3200 mg daily, sufficient increased clinical benefits to offset potential increased risk.

In chronic conditions: a therapeutic response to therapy with Ibuprofen is sometimes seen in a few days to a week but most often is observed by two weeks. After a satisfactory response has been achieved, the patient's dose should be reviewed and adjusted as required.

Juvenile arthritis: The usual dose is 30 to 40 mg/kg/day divided into 3 or 4 doses. Patients with milder disease may be adequately treated with 20 mg/kg/day. Doses above 50 mg/kg/day are not recommended.

Fever reduction in adults: 400 mg every 4-6 hours as necessary.

Mild to moderate pain: 400 mg every 4 to 6 hours as necessary for the relief of pain in adults.

Dysmenorrhea: For the treatment of dysmenorrhea, beginning with the earliest onset of such pain, Ibuprofen children's suspension should be given in a dose of 400 mg every 4 hours as necessary for the relief of pain.

How Supplied: Each Pack of Ruz-Ibuprofen 200 or 400 mg tablets contain 100 film coated tablets in 10 Blisters.

storage: Store at controlled room temperature to 30°C. Protect from light and moisture.

Reference: PDR 2000, page 1684-6

                  USPDI for Professional Health Care, 2004, Page 374-95

                  Martindale 2005, Page 45-7