Adult: For patients who are inadequately controlled or have a contraindication or intolerance to the 1st-line treatment: Initially, 10 mg bid, may be increased if needed up to 40 mg bid based on individual response and tolerance. Usual dose range: 10-20 mg bid. In patients who are susceptible to headache: Initially, 5 mg bid. Elderly: Initiate at the lowest effective dose.
Administration
May be taken with or without food.
Contraindications
Acute pulmonary oedema, severe hypotension, cardiogenic shock, cardiac decompensation, hypovolaemia, left ventricular failure with low filling pressure. Coadministration with phosphodiesterase 5 (PDE-5) inhibitors and soluble guanylate cyclase stimulators (e.g. riociguat).
Special Precautions
Patient with heart failure (NYHA class III and IV), hypertrophic obstructive cardiomyopathy, aortic stenosis, low systolic blood pressure, diverticular disease, G6PD deficiency, glaucoma, hyperkalaemia. Renal and hepatic impairment. Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Gastrointestinal ulceration which may lead to perforation, fistula, abscess formation, and haemorrhage; skin or mucosal ulceration (e.g. perianal, genital or parastomal ulceration), severe hypotension, dose-related headache (particularly during initial dosing). Rarely, severe hyperkalaemia, ocular effects (e.g. conjunctivitis, conjunctival and corneal ulcers). Cardiac disorders: Chest pain, palpitation. Gastrointestinal disorders: Nausea, vomiting, abdominal pain, rectal bleeding, dyspepsia. General disorders and administration site conditions: Weakness, lethargy. Infections and infestations: Skin abscess. Investigations: Increased heart rate. Musculoskeletal and connective tissue disorders: Myalgia, back pain. Nervous system disorders: Dizziness, vertigo. Respiratory, thoracic and mediastinal disorders: Dyspnoea, bronchitis, respiratory tract disease. Skin and subcutaneous tissue disorders: Rash, angioedema. Vascular disorders: Cutaneous vasodilation, flushing.
Patient Counseling Information
This drug may cause dizziness, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor blood pressure and heart rate.
Overdosage
Symptoms: Reflex tachycardia, peripheral vasodilation with a fall in blood pressure. Management: Supportive treatment. Monitor cardiac function. May consider substitution of fluid to increase circulating plasma volume. Consider administering vasopressors in life-threatening situations.
Drug Interactions
Increased risk of gastrointestinal ulceration and haemorrhage with NSAIDs and aspirin. Increased risk of gastrointestinal perforation with corticosteroids. Hypotensive effects may be increased with antihypertensive drugs, other vasodilators, and TCAs. May increase the risk of hyperkalaemia with other agents that elevate serum K levels. Enhanced orthostatic hypotensive effect with dapoxetine. Potentially Fatal: Significantly enhanced hypotensive effects with PDE-5 inhibitors (e.g. sildenafil, vardenafil, tadalafil) and soluble guanylate cyclase stimulators (e.g. riociguat).
Food Interaction
Hypotensive effect may be increased with alcohol.
Action
Description: Mechanism of Action: Nicorandil, a nitrate derivative of nicotinamide, is an antianginal agent with a dual mechanism of action. It acts as a vasodilator by activating the K channels which cause vascular membrane hyperpolarisation, thereby dilating the arterioles and large coronary arteries and decreasing cardiac afterload. Additionally, its nitrate component relaxes the venous vascular smooth muscle by increasing cyclic guanosine monophosphate (cGMP) resulting in reduced preload. Pharmacokinetics: Absorption: Rapidly and completely absorbed from the gastrointestinal tract. Absolute bioavailability: 75%. Time to peak plasma concentration: 30-60 minutes. Distribution: Plasma protein binding: 25-41.5%. Metabolism: Metabolised in the liver via denitration into N-(2-hydroxyethyl)-nicotinamide (major metabolite), nicotinuric acid, nicotinamide, N-methylnicotinamide and nicotinic acid. Excretion: Via urine (approx 20% mainly as metabolites, approx 1% as unchanged drug). Elimination half-life: Approx 1 hour.