NICORANDIL

Posology The usual therapeutic range is 10 to 20 mg twice daily. The usual starting dose is 10 mg twice daily (bid), in the morning and in the evening preferably. It is recommended that the dose be titrated upwards in accordance with the patient’s needs, response and tolerance up to 40 mg twice daily, if necessary.

Elderly There are no special dose requirements for elderly patients, but as with all medicines, use of the lowest effective dose is recommended. Patients with liver and/or renal impairment There are no special dosage requirements for patients with liver and/or renal impairment.

Paediatric population Nicorandil is not recommended in paediatric patients since its safety and efficacy have not been established in this patient group. Method of administration Nicorandil is administered by oral route. The tablets are to be swallowed in the morning and in the evening as a whole with some liquid.

Administration is independent from food intake.

Summary of the safety profile The most common adverse reaction reported in clinical trials is headache occurring in more than 30% of patients, particularly in the first days of treatment and responsible of most of study withdrawal.

2). 4) were reported during the post marketing surveillance of nicorandil. Tabulated list of adverse reactions The frequencies of adverse reactions reported with nicorandil are summarised in the following table by system organ class (in MedDRA) and by frequency.

Frequencies are defined as:

Very common (≥1/10), Common (≥1/100, <1/10), Uncommon (≥1/1,000, <1/100), Rare (≥1/10,000, <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

4). 1). Common Uncommon Very rare Gastroinstestinal disorders Rectal bleeding Mouth ulcer Abdominal pain Skin and subcutaneous tissue disorders Angioedema Musculoskeletal and connective tissue disorders Myalgia Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard.

8). - Gastrointestinal ulcerations Nicorandil induced ulceration may occur at different locations in the same patient. They are refractory to treatment and most only respond to withdrawal of nicorandil treatment. 8). Healthcare professionals should be aware of the importance of a timely diagnosis of nicorandil-induced ulcerations and of a rapid withdrawal of nicorandil treatment in case of occurrence of such ulcerations.

Based on available information, the time between starting nicorandil use and the onset of ulceration ranges from shortly after initiating nicorandil treatment to several years after starting nicorandil. Gastrointestinal haemorrhage secondary to gastrointestinal ulceration has been reported with nicorandil.

Patients taking acetylsalicylic acid or NSAIDs (Non Steroid Anti Inflammatory Drugs) concomitantly are at increased risk for severe complications such as gastrointestinal haemorrhage. 5). If advanced, ulcers may develop into perforation, fistula, or abscess formation.

Patients with diverticular disease may be at particular risk of fistula formation or bowel perforation during nicorandil treatment. Gastrointestinal perforations in context of concomitant use of nicorandil and corticosteroids have been reported.

Therefore, caution is advised when concomitant use of corticosteroids is considered. - Eye ulcerations Very rare conjunctivitis, conjunctival ulcer and corneal ulcer have been reported with nicorandil. Patients should be advised of the signs and symptoms and monitored closely for corneal ulcerations.

8). 8). Heart failure Due to lack of data, caution is advised to use nicorandil in patients with heart failure class NHYA III or IV. Hyperkalaemia Severe hyperkalaemia has been very rarely reported with nicorandil. 8). Desiccant The tablets are sensitive to moisture; hence the patients should be advised to keep the tablets in their blister until intake.

Besides the nicorandil tablets, each blister contains active substance-free silica gel tablets as desiccant in a separate blister segment which is marked accordingly. The patients should be advised not to take these tablets. Although any accidental intake of this desiccant is usually harmless, it may alter the scheduled intake of the active tablets.

Paediatric population Nicorandil tablets is not recommended in paediatric patients since its safety and efficacy have not been established in this patient group. G6PD deficiency Nicorandil tablets should be used with caution in patients with glucose-6- phosphate-dehydrogenase deficiency.

Nicorandil acts in parts through its organic nitrate moiety. The metabolism of organic nitrates can result in the formation of nitrites which may trigger methemoglobinemia in patients with glucose-6- phosphate dehydrogenase deficiency.

5) • Hypovolaemia • Acute pulmonary oedema