Can diclofenac cause prolonged lower intestinal bleeding?/nA 15-year-old boy has suffered from abdo

Fråga: Can diclofenac cause prolonged lower intestinal bleeding? A 15-year-old boy has suffered from abdominal pain for two years. Investigation revealed fibrotic pancreatitis and the patient has been on pancreatic enzymes (Pankreon) and omeprazole for about a year. He started using diclofenac sporadically 3-4 months ago and has now been using it regularly for six weeks in an oral dose of 50 mg thrice daily. Three weeks ago, he started bleeding per rectum. Although diclofenac was immediately withdrawn, bleeding continued. The patient is scheduled for coloscopy next week.

Sammanfattning: Diclofenac and other NSAID rarely cause a range of pathologies in the large bowel. These can be manifested as blood per rectum. The duration of bleeding depends of course on the severity of the lesions and is not possible to predict in the individual case.

Svar: The role of nonsteroidal anti-inflammatory drugs (NSAID) in inducing peptic ulceration is well-established. However, it is not widely recognized that these drugs may cause "distal" injuries in the intestinal tract. In an extensive review of the literature, Bjarnason and collaborators concluded that ingested NSAID may cause nonspecific colitis, collagenous colitis, large intestinal ulcers with bleeding and perforation (1). These adverse effects are rare in patients with previously "normal" colon but their frequency is increased in those with pre-existing bowel disease (1). NSAID most frequently reported to cause colitis are fenemates (mefenamic and flufenamic acids) which were never approved in Sweden. Other NSAID implicated in colitis are ibuprofen, naproxen and piroxicam. NSAID were found to be used by 19 of 30 patients with collagenous colitis (1). It should be underscored that colitis is still a rare adverse effect of NSAID treatment. Thus, no signs of colonic inflammation were observed in 250 patients on NSAID for rheumatoid arthritis or osteoarthritis (1).

A number of cases of colonic ulceration has been reported in patients on NSAID (1). However, a causal relationship was often difficult to establish, either because the ulcers were difficult to distinguish from idiopathic colonic ulcers or because the patients were concomitantly treated with other gastrointestinal irritants. Colonic ulceration was reported in two patients on diclofenac treatment (2). A 60-year-old woman with osteoarthritis who had been treated with diclofenac (50 mg tid) for four months was found to have anemia and positive stool tests for occult blood. Coloscopy revealed colonic ulcerations which disappeared when sulindac was substituted for diclofenac and sucralfate was added. A confounding factor in this case was the use of ferrous sulfate, a substance with known gastrointestinal adverse effects. Ulcerations of the cecum and ascending colon developed in a 67-year-old woman with rheumatoid arthritis who had been treated with diclofenac (75 mg bid). She tested negative for stool occult blood when diclofenac was stopped and ibuprofen was used instead (2).

In a retrospective study on 268 patients who presented with colonic or small bowel perforation or hemorrhage (1,3), 25 per cent were found to have ingested NSAID. Further, patients with these complications were more than twice as likely to be NSAID users compared to controls (a group of patients, matched for age and sex, with uncomplicated lower bowel disease).

A search in the Swedish Adverse Drug Reactions Advisory Committee (SADRAC):s side effect database, revealed one case of colonic ulceration with perforation and another with bloody diarrhea where the association between the ingestion of diclofenac and the adverse event was judged as probable (4).

NSAID also have adverse effects on the small intestine although severe cases are rare (1). Bleeding occurs but is usually occult (1). It should, however, be remembered that upper intestinal hemorrhage may lead to passage of blood by rectum if massive and associated with rapid intestinal transit (5).

It should be pointed out that the discussion above concerns adverse effects of oral treatment with NSAID. Rectal administration has long been known to be associated with anorectal lesions including erosions, ulcers, bleeding and stenosis (1,4).

We recommend this case be reported to SADRAC.