Advice for healthcare professionals: Use nicorandil for treatment of stable angina only in patients whose angina is inadequately controlled by first line anti-anginal therapies, or who have a contraindication or intolerance to first line anti-anginal therapies such as beta-blockers or calcium antagonists

Nicorandil can cause serious skin, mucosal, and eye ulceration, including gastrointestinal ulcers which may progress to perforation, haemorrhage, fistula, or abscess

Stop nicorandil treatment if ulceration occurs—consider the need for alternative treatment or specialist advice if angina symptoms worsen

Please continue to report suspected adverse drug reactions to nicorandil or any other medicines on a Yellow Card

Ulcers

Nicorandil-induced ulceration has been most frequently reported for the gastrointestinal tract (rarely); very rarely, the skin and mucosa are affected, including the eye.

A review by the UK’s Commission on Human Medicine’s Pharmacovigilance Expert Advisory Group and by EU medicines regulators has led to updated advice for the use of nicorandil.

Risk factors

Patients with diverticular disease may be at risk of fistula formation or bowel perforation. Concomitant use of aspirin, non-steroidal anti-inflammatory drugs, or corticosteroids with nicorandil increases the risk of gastrointestinal ulceration, perforations, or haemorrhage.

Location and time to onset

Ulcers may develop at different sites in the same patient, at the same time or one after another. Ulceration can occur at any time during nicorandil treatment (including years after starting treatment).

Treatment

Almost two-thirds of reported gastrointestinal ulcerations are serious. Ulcers caused by nicorandil do not respond to conventional treatment, including surgery. The only way to cure these ulcers is to stop nicorandil treatment. It may take weeks or months for the ulcers to heal, depending on severity.

Nicorandil is contraindicated in patients with hypovolaemia or acute pulmonary oedema, and it must not be used with soluble guanylate cyclase stimulators such as riociguat (see nicorandil summary of product characteristics for full list of additional warnings and precautions for use)

Use nicorandil with caution in the following situations: in patients with heart failure (New York Heart Association class III or IV) *in patients with glucose 6 phosphate dehydrogenase (G6PD) deficiency (consider the risk of methemoglobinurea) in patients who are taking dapoxetine (consider the risk of reduced orthostatic tolerance) in combination with other medicines that increase potassium levels, especially in patients with moderate to severe renal impairment

Depending on clinical response, patients may now be titrated upwards to a maximum dose of 40 mg twice daily. The usual therapeutic dose range remains 10 to 20 mg twice daily; a lower starting dose of 5 mg twice daily may be used in patients particularly prone to headache

Further information

Letter sent to healthcare professionals 10 November 2015

EMA review of prescribing information for nicorandil containing products

Article citation: Drug Safety Update volume 9 issue 6 January 2016: 1.