A suspected ADR
Nicorandil has been associated with both mouth ulceration and gastric ulcers. In the Download Drug Analysis Prints or DAPs on the Medicines and Healthcare products Regulatory Agency (MHRA) website (see next section) there were 700 reports of gastrointestinal ADRs for nicorandil from a total of 2033 reports for the period 1994 to 2011. Six patients died. There is no mention of mouth ulcers however, in the MHRA Drug Safety update of June 2008 it did suggest that both mouth ulcers and gastric ulcers were possible ADRs to nicorandil.
The Summary of Product Characteristics (SPC) states while nausea and vomiting are common with nicorandil, gastrointestinal ulcerations such as stomatitis, mouth ulcers, tongue ulcers, intestinal and anal ulcers are rare. Remember that rare in the EU classification is 1:1000 to 1:10,000 .
As the BNF also say that mouth ulcers and gastric ulcers are potential ADRs to nicorandil you should be aware of this.
What might your action be in this case?
In the SPC it goes on to say that these gastric ulcers, if advanced, may develop into perforation, fistula, or abscess formation. Also there is a warning that they are refractory to treatment and most only respond to withdrawal of nicorandil treatment. If ulcerations develop, nicorandil should be discontinued. Reducing the dose may help in some cases.
Therefore the appropriate action is to stop the nicorandil temporarily and check if symptoms clear. The reaction occurs rarely, appears to be dose-related and the time to ulcer onset may be days, weeks or months after starting nicorandil. Treatment should be reconsidered while investigating the ulcers further. However, in the meantime, appropriate alternative anti-anginals should be used (e.g. nitrates, calcium channel blockers etc.).
The MHRA states:
'GPs and other healthcare professionals should consider nicorandil treatment as a possible cause in patients who present with symptoms of gastrointestinal ulceration. Ulcers that result from nicorandil are refractory to treatment; they respond only to withdrawal of nicorandil. Nicorandil withdrawal should take place only under the supervision of a cardiologist.' (MHRA 2008)