DIFLUNISAL- diflunisal tablet, film coated
Teva Pharmaceuticals USA, Inc.
Cardiovascular Thrombotic Events
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Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use (see WARNINGS and PRECAUTIONS).
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Diflunisal tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see CONTRAINDICATIONS and WARNINGS).
Gastrointestinal Risk
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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
Diflunisal is 2?,4?-difluoro-4-hydroxy-3-biphenylcarboxylic acid. Its structural formula is:
Chemical structure for diflunisal
C13 H8 F2 O3 M.W. 250.20
Diflunisal is a stable, white, crystalline compound with a melting point of 211� to 213�C. It is practically insoluble in water at neutral or acidic pH. Because it is an organic acid, it dissolves readily in dilute alkali to give a moderately stable solution at room temperature. It is soluble in most organic solvents including ethanol, methanol, and acetone.
Each tablet, for oral administration, contains 500 mg diflunisal, USP. In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, FD&C Blue #2 aluminum lake, hypromellose, microcrystalline cellulose, pregelatinized starch, propylene glycol, sodium stearyl fumarate, and titanium dioxide.
CLINICAL PHARMACOLOGY
Action
Diflunisal is a non-steroidal drug with analgesic, anti-inflammatory and antipyretic properties. It is a peripherally-acting non-narcotic analgesic drug. Habituation, tolerance, and addiction have not been reported.
Diflunisal is a difluorophenyl derivative of salicylic acid. Chemically, diflunisal differs from aspirin (acetylsalicylic acid) in two respects. The first of these two is the presence of a difluorophenyl substituent at carbon 1. The second difference is the removal of the O -acetyl group from the carbon 4 position. Diflunisal is not metabolized to salicylic acid, and the fluorine atoms are not displaced from the difluorophenyl ring structure.
The precise mechanism of the analgesic and anti-inflammatory actions of diflunisal is not known. Diflunisal is a prostaglandin synthetase inhibitor. In animals, prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain. Since prostaglandins are known to be among the mediators of pain and inflammation, the mode of action of diflunisal may be due to a decrease of prostaglandins in peripheral tissues.
