Active peptic ulcer, a history of recurrent ulceration, or active inflammatory disease of the GI system. Known or suspected hypersensitivity to the drug or other nonsteroidal anti-inflammatory drugs. The potential for cross-reactivity between different NSAIDs must be kept in mind.

Diflunisal should not be used in patients with the complete or partial syndrome of ASA-intolerance (rhinosinusitis, urticaria/angioedema, nasal polyps, asthma) in whom asthma, anaphylaxis, urticaria/angioedema, rhinitis or other allergic manifestations are precipitated by ASA or other nonsteroidal anti-inflammatory agents. Fatal anaphylactoid reactions have occurred in such individuals. As well, individuals with the above medical problems are at risk of a severe reaction even if they have taken NSAIDs in the past without any adverse effects.

Significant hepatic impairment or active liver disease.

Severely impaired or deteriorating renal function (creatinine clearance < 30 mL/min). Individuals with lesser degrees of renal impairment are at risk of deterioration of their renal function when prescribed NSAIDs and must be monitored.

Diflunisal should not be used in the presence of known hyperkalemia

Diflunisal is not recommended for use with other NSAIDs because of the absence of any evidence demonstrating synergistic benefits and the potential for additive side effects.

Fluid retention and edema have been observed in patients treated with diflunisal. Therefore, as with many other NSAIDs, the possibility of precipitating congestive heart failure in elderly patients or those with compromised cardiac function should be borne in mind. Diflunisal should be used with caution in patients with heart failure, hypertension or other conditions predisposing to fluid retention. Ask patients who are at risk for fluid retention to weigh themselves at regular intervals to assist in monitoring for fluid accumulation. With nonsteroidal anti-inflammatory treatment there is a potential risk of hyperkalemia, particularly in patients with conditions such as diabetes mellitus or renal failure; elderly patients; or in patients receiving concomitant therapy with angiotensin-II receptor antagonists, adrenergic blockers, angiotensin-converting enzyme inhibitors or potassium-sparing diuretics. Patients at risk should be monitored periodically during long-term therapy.