Safety profile of an anti-anginal agent with potassium channel opening activity: an overview

Safety has been assessed in a total of 1680 subjects who were treated with nicorandil, with 458 patient years of exposure to treatment. Adverse events usually occurred early in the course of treatment. After 30 days of treatment, fewer than 10% of patients reported adverse events. At the recommended doses, the main side effects were limited to headaches. Nearly all episodes of headache were experienced during the first days of nicorandil treatment and were responsible for most of the study withdrawals because of clinical non-acceptability. The incidence can be diminished by a progressive titration. In comparative trials with anti-anginal agents, such as propranolol, diltiazem, nifedipine, ISDN and isosorbide 5 mononitrate, the overall incidence of adverse events was not significantly different between nicorandil and the reference drug. Side-effect distribution was comparable between nicorandil (32%) and diltiazem (30%). Nicorandil can be safely combined with other anti-anginal drugs. Furthermore, due to its favourable pharmacokinetics, nicorandil is less likely to have interactions when combined with another therapeutic agent. Nearly one-third of the patients enrolled in the nicorandil clinical programme were 65 years old or older. Age-specific side-effects were not identified, and overall, the incidence of the most frequent adverse events in the elderly was similar. There is no evidence that nicorandil induces proarrhythmia, exacerbation of myocardial ischaemia or abrupt withdrawal syndrome. With the progressive titration scheme, no symptomatic decrease in blood pressure was recorded when nicorandil was administered in the range of 10-80 mg.day-1. Heart rate was not significantly affected in the same dose range.(ABSTRACT TRUNCATED AT 250 WORDS)