Diflunisal adverse effects

Diflunisal is a fluorinated salicyhc acid derivative, which is absorbed unchanged from the gastrointestinal tract, reaching peak concentrations after about 2 hours, and is metabolized by glucuronidation (1). Its adverse effects and other characteristics are those of aspirin, although gastrointestinal haemorrhage may be less common (2). 

Widespread use of naproxen, sulindac, diclofenac, and diflunisal probably explains why they were the most frequently rmphcated, rather than because they have a greater tendency to cause these adverse effects. NSAIDs differ in their ability to cause adverse skin reactions in terms of both frequency and severity pyrazolones, butazones, and oxicams are most often blamed, and among the arylalkanoic acid derivatives fenbufen and carprofen are most often incriminated. 

One pharmaeodynamic study in healthy subjeets found that gastric instillation of a solution of diflunisal before an indometacin solution prevented the fall in transmucosal potential difference seen with indometacin alone. This was interpreted as evidence that diflnnisal protects the human gastric mucosa against the damaging effects of indometacin. However, the relevance of this test to the adverse effects of NSAIDs used clinically is unknown. Note that fatal gastrointestinal haemorrhage has been reported in a patient taking diflnnisal and indometacin. ... 

A study in 16 healthy subjects showed that diflunisal 500 mg twice daily raised the steady-state plasma levels and the AUC of indometacin 50 mg twice daily about twofold. Combined use was associated with more gastrointestinal and CNS adverse effects, but there was no clear effect on blood loss in the faeces. Another study produced similar findings. ... 

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