APO-NICORANDIL

What it is

APO-NICORANDIL contains nicorandil 10 mg or 20 mg per tablet. Nicorandil is a potassium channel opener with nitrate moiety, an antianginal agent with a dual mechanism of action. It opens ATP-dependent potassium channels in vascular smooth muscle, causing hyperpolarisation of the smooth muscle cells and arterial dilatation with afterload reduction. Due to its nitrate moiety, nicorandil also relaxes vascular smooth muscle via an increase in intracellular cyclic GMP, resulting in increased pooling in capacitance vessels with a decrease in preload.

Approved indications

— Treatment of chronic stable angina pectoris.

Dosing overview

The recommended therapeutic dose for nicorandil is 10 to 20 mg twice daily. The usual starting dose is 10 mg twice daily, preferably in the morning and in the evening. A lower starting dose of 5 mg twice daily may be used in patients who are prone to headache or other adverse reactions. Dosage should be titrated to the minimum effective dose. There are no dosage adjustments required for elderly patients; however, the lowest effective dose should be used. Nicorandil is not recommended for use in children as safety and efficacy have not been established.

Key safety warnings

Gastrointestinal, skin and mucosal ulcerations have been reported with nicorandil, and gastrointestinal haemorrhage secondary to gastrointestinal ulceration has also been reported. The onset of ulceration may vary from shortly after initiation of nicorandil treatment to several years after starting nicorandil. Occurrence of persisting ulcers should lead to permanent drug discontinuation because the ulcers may be refractory to treatment while taking nicorandil and most only respond to withdrawal of nicorandil treatment. Patients with diverticular disease may be at particular risk of fistula formation or bowel perforation during nicorandil treatment. Gastrointestinal perforations in the context of concomitant use of nicorandil and corticosteroids have been reported, and caution is advised when concomitant use is considered. Gastrointestinal ulcerations and haemorrhage in the context of concomitant use of acetylsalicylic acid or NSAIDs with nicorandil have also been reported, and caution is advised when concomitant use is considered. Conjunctivitis, conjunctival ulcer and corneal ulcer have been reported with nicorandil, and patients should be advised of the signs and symptoms and monitored closely for corneal ulcerations. If mouth ulceration, stomatitis or persistent or severe buccal ulcerations appear, this drug should be discontinued and appropriate measures taken. Headache is very common, usually transient in nature and dose-related, especially when treatment is initiated, and usually occurs during the first week of treatment and tends to diminish with time. Careful dose titration, using low starting dose of 5 mg twice daily for even two days, has significantly reduced the incidence of headache and number of patients discontinuing treatment due to headache. Nicorandil should be used with caution in patients who may have blood volume depletion or in those who present low systolic blood pressure (below 100 mm Hg). Nicorandil may lower the blood pressure of hypertensive patients and therefore should be used with care when prescribed with antihypertensive drugs.

Contraindications

APO-NICORANDIL is contraindicated in patients with known or idiosyncratic hypersensitivity to nicorandil, nicotinamide, nicotinic acid or any of the excipients in this product, cardiogenic shock, hypotension, severe hypotension or with a risk of developing severe hypotension including acute myocardial infarction with acute left ventricular failure and low filling pressures, hypovolaemia, cardiac decompensation, and acute pulmonary oedema. It is also contraindicated in patients receiving any soluble guanylate cyclase stimulators since it can lead to a serious fall in blood pressure. Due to the risk of severe hypotension, the concomitant use of nicorandil and phosphodiesterase 5 inhibitors such as sildenafil, tadalafil or vardenafil is contraindicated.

Regulatory history

APO-NICORANDIL 10 mg and 20 mg were first listed on the ARTG on 3 October 2017.