Nicorandil associated anal ulcers: an estimate of incidence

Abstract

INTRODUCTION Nicorandil is a commonly prescribed antianginal medication that has been found to be associated with painful anal ulceration. The incidence of this complication is unknown. We have used the best data available to us to make an estimate of this figure in a health district with a remarkably stable population of approximately 200,000 people. METHODS Using an electronic search of all letters generated from colorectal and gastroenterology clinics as well as endoscopy reports from January 2004 to November 2010, patients with anal ulceration who were taking nicorandil were identified. Other causes of ulceration were excluded by biopsy in the majority of cases. The central hospital and community pharmacy database was interrogated to estimate the number of patients who were prescribed nicorandil over a six-year period (2004)(2005)(2006)(2007)(2008)(2009)(2010). RESULTS A total of 30 patients (24 men, 6 women) with a median age of 79.5 years were identified who fulfilled the criteria of: taking nicorandil; having no other identified cause for anal ulceration; and achieving eventual healing after withdrawal of nicorandil. In the six-year period an estimated mean of 1,379 patients were prescribed nicorandil each year. The mean annual incidence of anal ulcers among nicorandil users is therefore calculated to be in the region of 0.37%. CONCLUSIONS Anal ulceration appears to occur in approximately four in every thousand patients prescribed nicorandil each year. Prescribing physicians should explain the risk of this unpleasant complication to their patients.

Nicorandil, Gastrointestinal Adverse Drug Reactions and Ulcerations: A Systematic Review

“…While no anal ulceration was formally mentioned in the IONA, it has been suggested that the overall incidence might be around 0.07% [18]. A higher rate was estimated by Colvin et al (0.37%) [19] in their retrospective cohort study, where the number of exposed was calculated from prescriptions in general practices. The main features are gradual onset, pain, failure to heal and resolution on withdrawal of the drug.…”

“…The occurrence of gastrointestinal ADR in the form of ulcerative and fistulating disease, is underestimated [17][18][19][20][21] and the awareness of the problem is still suboptimal among physicians. No systematic review has ever been conducted, published or registered and such a study would assess the extent of the problem from a broader perspective.…”

“…The literature reports the involvement of the ileum in the context of surgical stomata as well [19,20,101,102]; apart from rare cases of cutaneous manifestation of Crohn's disease, peristomal ulcerations in clinical practice usually recognize a mechanical cause [103]. The drug is considered in fact the commonest cause of stoma ulceration in patients not affected by inflammatory bowel disease.…”

“…Perianal fistulating disease whilst taking nicorandil appears more rare, constituting 1.9% and 1.2% of the MHRA and WHO gastrointestinal reaction reports, respectively. Data from the literature regarding 165 patients with ulcerations of the distal gastrointestinal tract [18][19][20]93,96,101,102, is presented in table 3.…”

Is research declining amongst gastroenterology trainees in the United Kingdom?

“…A recent survey estimated 1 in 250 patients get anal ulcers, which requires discontinuing treatment. 2 In more serious cases, ulcers progress to fistulae into adjacent organs. 3 The mechanism is, as yet, unclear but may involve the effects of nicotinic acid on causing ulceration in the epithelium of healing wounds.…”