Diflunisal Dosage

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Usual Adult Dose for:

Additional dosage information:

Usual Adult Dose for Pain

Initial: 1000 mg orally one time.

Maintenance: 500 mg orally every 12 hours. Some patients may require 500 mg every 8 hours.

Usual Adult Dose for Osteoarthritis

250 to 500 mg orally twice a day.
The dosage may be increased or decreased according to patient response. Maintenance doses higher than 1500 mg/day are not recommended

Usual Adult Dose for Rheumatoid Arthritis

250 to 500 mg orally twice a day.
The dosage may be increased or decreased according to patient response. Maintenance doses higher than 1500 mg/day are not recommended

Renal Dose Adjustments

CrCl less than 50 mL/min: The dose should be reduced by 50%.

Liver Dose Adjustments

Data not available

Dose Adjustments

Some patients may receive an initial dose of 500 mg, followed by 250 mg every 8 to 12 hours, depending on such factors as pain severity, patient response, weight, or advanced age.

Precautions

NSAIDs may cause an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of administration. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with NSAIDs, the lowest effective dose should be used for the shortest duration possible. Prescribers and patients should remain vigilant for the development of such events, even in the absence of previous CV symptoms. Patients should be advised about the signs and/or symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID therapy.

NSAIDs, including diflunisal, can cause serious gastrointestinal (GI) adverse events including inflammation, ulceration, bleeding, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These events can occur at any time during administration and without warning symptoms. Only one in five patients, who develop a serious upper GI adverse event while on NSAID therapy, is symptomatic. It has been shown that the incidence of upper GI ulcers, gross bleeding, or perforation, caused by NSAIDs, increases with duration of use. However, even short-term therapy has risk. NSAIDs should be prescribed with extreme caution in patients with prior history of ulcer disease or GI bleeding. Patients with a prior history of peptic ulcer disease and/or GI bleeding who use NSAIDs have a greater than 10-fold increased risk of developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients on NSAIDs therapy include longer duration of NSAID therapy, older age, and poor general health status. Most spontaneous reports of fatal GI adverse events are in elderly or debilitated patients and therefore special care should be taken in treating this population. To minimize the potential risk for an adverse GI event in patients on NSAID therapy, the lowest effective dose should be used for the shortest possible duration. For high risk patients, alternate therapies that do not involve NSAID therapy should be considered. Physicians and patients should remain vigilant for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of NSAID therapy until a serious GI adverse event is ruled out. Clinicians prescribing diflunisal must weigh the benefits of diflunisal therapy against the possible hazards, particularly in patients with an active ulcer, or active gastrointestinal bleeding. Before taking diflunisal, all patients should be fully informed about the adverse effects, and the signs and/or symptoms of GI toxicity and the steps to take if they occur.

Diflunisal is contraindicated for the treatment of perioperative pain in the setting or coronary artery bypass graft (CABG) surgery. Patients with a hypersensitivity (angioedema, bronchospasm, urticaria, or rhinitis) to aspirin or other NSAIDs may be cross sensitive to diflunisal. Patients with the "triad" of asthma, nasal polyps, and aspirin or other NSAID hypersensitivity are at particular risk. The use of diflunisal is considered contraindicated in these patients.

As with all NSAIDs, diflunisal can lead to the onset of new hypertension or worsening or preexisting hypertension, either of which may contribute to an increased incidence of CV events. NSAIDs, including diflunisal, should be administered with caution in patients with hypertension. Blood pressure should be closely monitored during the initiation of diflunisal therapy and throughout the course of therapy.

In some patients taking NSAIDs, fluid retention and edema have been reported. Diflunisal should be administered with caution in these patients.

Long-term NSAIDs treatment has resulted in renal papillary necrosis and other renal injury. Renal function may be further compromised by the use of diflunisal in patients with renal dysfunction, heart failure, hypovolemia, cirrhosis, nephrotic syndrome, or hypoalbuminemia. Renal blood flow in patients with renal dysfunction, edematous disorders, or hypovolemic states is dependent upon renal prostaglandin synthesis. No information is available from studies regarding the use of diflunisal in patients with advanced renal disease. Therefore, diflunisal therapy is not recommended in these patients with advanced renal disease. Since diflunisal is eliminated primarily by the kidneys, close monitoring of renal function is advisable if diflunisal must be initiated. A lower daily dosage should be anticipated to avoid excessive drug accumulation.

Borderline elevations of one or more liver tests have been reported in patients taking NSAIDs, including diflunisal. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continued therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in patients in clinical trials with NSAIDs. Rarely, cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported. A patient with signs and/or symptoms suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with diflunisal. If signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), diflunisal should be discontinued.

Anemia is sometimes seen in patients receiving NSAIDs therapy, including diflunisal. This adverse event may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term therapy with NSAIDs, including diflunisal, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.

NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving diflunisal who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be closely monitored.

Because of reports of adverse eye events with agents of this class, it is recommended that patients who develop eye complaints during treatment with diflunisal have ophthalmologic studies.

Reye's syndrome has been reported with acetylsalicylic acid. Since diflunisal is a derivative of salicylic acid, the possibility of its association with Reye's syndrome cannot be excluded. NSAIDs, including diflunisal, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious adverse events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and administration of the drug should be discontinued at first appearance of skin rash or any other sign of hypersensitivity.

A potentially life-threatening, apparently hypersensitivity syndrome has been reported with treatment with NSAIDs. This multisystem syndrome includes constitutional symptoms (fever, chills), and cutaneous findings. It may also include involvement of major organs (changes in liver function, jaundice, leucopenia, thrombocytopenia, eosinophilia, disseminated intravascular coagulation, renal impairment, including renal failure) and less specific findings (adenitis, myalgia, arthralgia, arthritis, malaise, anorexia, disorientation). If evidence of hypersensitivity occurs, diflunisal therapy should be discontinued.

Patients on long-term therapy with NSAIDs should have their CBC and a chemistry profile checked periodically. Safety and effectiveness of diflunisal in pediatric patients below the age of 12 have not been determined. Diflunisal is not recommended in pediatric patients below the age of 12.

Dialysis

Diflunisal is not significantly dialyzable.

Other Comments

Tablets should be swallowed whole, not crushed or chewed.

Diflunisal is not recommended for use as an antipyretic drug, however, in some patients receiving chronic or high doses consider the possibility that it may mask fever.

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