Overview
DESCRIPTION Diflunisal is [1, 1'-Biphenyl]-3-carboxylic acid, 2', 4'-difluoro-4-hydroxy. Its structural formula is: Molecular Formula: C 13 H 8 F 2 O 3 Molecular Weight: 250.20 g/mol 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.
Mechanism of Action
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.
Indications
- INDICATIONS AND USAGE Carefully consider the potential benefits and risks of diflunisal tablets and other treatment options before deciding to use diflunisal tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). Diflunisal tablets are indicated for acute or long-term use for symptomatic treatment of the following: Mild to moderate pain Osteoarthritis Rheumatoid arthritis
Common Doses
- 1000 mg
- 500 mg
- 250 mg
- 1500 mg
Dosage
DOSAGE AND ADMINISTRATION Carefully consider the potential benefits and risks of diflunisal tablets and other treatment options before deciding to use diflunisal 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 diflunisal tablets, the dose and frequency should be adjusted to suit an individual patient's needs.
Black Box Warning
Cardiovascular Thrombotic Events 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 ). Diflunisal tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see CONTRAINDICATION and WARNINGS ).
Contraindications
- CONTRAINDICATIONS Diflunisal tablets are contraindicated in patients with known hypersensitivity to diflunisal or the excipients (see DESCRIPTION ) . Diflunisal tablets should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic/analphylactoid reactions to NSAIDs have been reported in such patients (see WARNINGS , Anaphylactic/Anaphylactoid Reactions and PRECAUTIONS , Preexisting Asthma ). In the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS ) .
Side Effects
- ADVERSE REACTIONS The adverse reactions observed in controlled clinical trials encompass observations in 2,427 patients. Listed below are the adverse reactions reported in the 1,314 of these patients who received treatment in studies of two weeks or longer. Five hundred thirteen patients were treated for at least 24 weeks, 255 patients were treated for at least 48 weeks, and 46 patients were treated for 96 weeks. In general, the adverse reactions listed below were 2 to 14 times less frequent in the 1,113 patients who received short-term treatment for mild to moderate pain.
Interactions
- Drug Interactions ACE-inhibitors and Angiotensin II Anagonists Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors and angiotensin II antagonists. These interactions should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors or angiotensin II antagonists. In some patients with compromised renal function, the coadministration of an NSAID and an ACE-inhibitor or an angiotensin II antagonist may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible.