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.

A lower starting dose of 5 mg twice daily may be used in patients particularly prone to headache.

Elderly:

There are no special dose requirements for elderly patients, but as with all medicine, 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 Tablets are not recommended in paediatric patients since its safety and efficacy have not been established in this patient group. Method of administration Nicorandil Tablets are administered by oral route. The tablets are to be swallowed in the morning and in the evening with a glass of water.

The tablets should not be crushed or chewed. The tablet can be divided into equal doses. Administration is independent of food intake.

Summary of 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 for 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) Rash, pruritus Angioedema Musculoskeletal and connective tissue disorders Myalgia General disorders and administration site conditions Feeling of weakness *The frequencies were calculated on the basis of the results of the Post Authorisation Safety Study (PASS), which is a retrospective cohort study which was conducted using the UK Clinical Practice Research Datalink (CPRD) database.

Therefore, the frequencies represent those of the UK population. 4). 1). Common Uncommon Very rare Gastrointestinal disorders Rectal bleeding Mouth ulcer Abdominal pain Skin and subcutaneous tissue disorders Angioedema Musculoskeletal & 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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

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- Steroidal Anti-Inflammatory Drugs) concomitantly are at increased risk for severe complications such as gastrointestinal haemorrhage. 5). If advanced, gastrointestinal ulcerations may evolve 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 is considered. Eye ulcerations 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 reported very rarely with nicorandil. 8). Paediatric population Nicorandil Tablets are not recommended in paediatric patients since its safety and efficacy have not been established in this patient group.

1. • Patients with shock (including cardiogenic shock), severe hypotension, or left ventricular dysfunction with low filling pressure or cardiac decompensation. 5). 5). • Hypovolaemia. • Acute pulmonary oedema.