NICORIL 10MG TABLETS

Indications

• Chronic stable angina
• Acute coronary syndromes
• Angina pectoris

Dosage

Children: Dosage recommendations for paediatric patients are not established; refer to the BNF for Children for guidance.

Adults: The usual adult starting dose is 10 mg taken twice daily, which may be increased to a maximum of 20 mg twice daily based on clinical response. Doses should be adjusted according to individual tolerance and effectiveness.

Mechanism of action

Nicorandil activates ATP-sensitive potassium channels (KATP channels) composed of Kir6.x-type subunits and sulfonylurea receptor (SUR) subunits, particularly SUR2. This activation results in hyperpolarization of smooth muscle cells, leading to vasodilation. Additionally, the drug contains a nitrate moiety, which contributes to its vasodilatory effects by releasing nitric oxide, enhancing coronary blood flow while preventing intracellular calcium overload and cellular injury.

Pharmacodynamics

As a potassium channel opener and nitrovasodilator, nicorandil causes sustained arterial and venous dilation. It enhances coronary blood flow without causing coronary steal phenomenon, reduces myocardial oxygen demand by lowering preload and afterload, and ultimately helps in reducing infarct size. The drug is effective in alleviating symptoms of angina pectoris through improved hemodynamics.

Pharmacokinetics

Nicorandil is absorbed rapidly following oral administration and undergoes extensive first-pass metabolism. Its half-life is typically around 1 hour. The drug is primarily metabolized in the liver, and its metabolites are excreted via the kidneys. Caution is advised in patients with hepatic or renal impairment as this may affect drug clearance.

Contra-indications

• Severe hepatic impairment
• Severe renal impairment
• Hypersensitivity to nicorandil or any component of the formulation

Adverse effects

• Asthenia
• Dizziness
• Headache
• Nausea
• Vomiting
• Constipation
• Diarrhoea
• Abdominal pain
• Muscle cramps
• Skin reactions
• Angioedema
• Hyperuricaemia
• Hypotension
• QT interval prolongation
• Bradycardia
• Genital ulceration
• Mucosal ulceration
• Gastrointestinal ulcers
• Skin ulceration
• Eosinophilia
• Diplopia

Interactions

• Severe interaction with phosphodiesterase type 5 inhibitors (increases risk of hypotension)
• Unknown interaction with aspirin (increases risk of gastrointestinal perforation)

Precautions

• Caution in patients with moderate hepatic impairment
• Monitor for bradycardia, especially after dose increases
• Consider benefits and risks of continued treatment in patients with atrial fibrillation
• Patients should be warned not to drive or operate machinery until it is established that their performance is unimpaired

Pregnancy

Manufacturer advises use only if potential benefit outweighs risk; no information available.

Breast-feeding

Present in milk in animal studies; manufacturer advises avoid.

Storage

Store below 25°C. Protect from light.

Formulations

• Nicorandil 10 mg tablets
• Nicorandil 20 mg tablets
• Ikorel 10 mg tablets
• Ikorel 20 mg tablets

Mechanism of action

Nicorandil mediates its therapeutic efficacy via two main mechanisms. Nicorandil is an activator and opener of ATP-sensitive (ATP-dependent) potassium channels (KATP channels) that are composed of Kir6.x-type subunits and sulfonylurea receptor (SUR) subunits. Nicorandil binding sites are located in the sulfonylurea receptor 2 (SUR2) in the ATP-sensitive potassium channel, which are regulatory subunits of the channel that exhibit an ATPase activitiy. There are 2 types of SUR2 subunits (2A/2B) that have identical nucleotide binding domains (NBD), where SUR2A is more predominantly expressed in skeletal and cardiac myocytes and SUR2B in smooth muscle cells. Nicorandil more potently activates SUR2B/Kir6.2 than SUR2A/Kir6.2 channels to cause hyperpolarization. ATP-NBD1 interaction influences the channel signalling by nicorandil, and the response of the channel to nicorandil is also facilitated and heightened by the interaction of ATP or ADP with NBD2. Potentiated activity of ATP-sensitive channels have cardioprotective role by limiting the duration of action potentials and preventing intraceullar calcium overload. This attenuates cellular injury by preserving cellular energetics and ultimately cell survival. KATP channel-dependent membrane hyperpolarization can also lead to vasodilation via reduction in Ca2+ influx through the voltage-gated Ca2+ channels and regulation of intracellular Ca2+ mobilization in smooth muscle cells. Nicorandil contain a nitrate moiety in its structure, making it a good dilator of vascular smooth muscle like other nitroglycerin esters. Direct relaxation of venous vascular system arises from NO-donor mediated stimulation of guanylyl cyclase and increased levels of intracellular cyclic GMP (cGMP). Elevated levels of cGMP contributes to the total relaxing effect of nicorandil at higher concentrations of the drug.

Pharmacodynamics

Nicorandil is a potassium channel opener with nitrovasodilator (NO donor) actions, making it both an arterial and a venous dilator. It causes sustained dilation of both the arterial resistance and conductive vessels that increases coronary blood flow, however the effect of the drug on coronary arteries does not involve the coronary steal phenomenon. Activation of potassium channels lead to hyperpolarization of the smooth muscle cells, followed by arterial dilation and afterload reduction. Nicorandil is shown to increase pooling in the capacitance vessels with a decrease in preload through relaxing the venous vascular system. Overall, improved blood flow and reduced infarct size are achieved through reduction of end-diastolix pressure and decreased extravascular component of vascular resistance. Open studies showed the effectiveness of nicorandil treatment on various types of angina pectoris.