Usage
- Nicorandil is prescribed for the symptomatic treatment of chronic stable angina pectoris, particularly in patients who have not responded well to, or cannot tolerate, first-line anti-anginal treatments (such as beta-blockers and/or calcium channel blockers). It can also reduce the risk of acute coronary syndromes in patients with stable angina and additional risk factors such as previous myocardial infarction, coronary artery bypass graft surgery, coronary heart disease diagnosed by angiography or a positive exercise stress test along with left ventricular hypertrophy on ECG, left ventricular dysfunction, age 65 or older, diabetes mellitus (type I or II, excluding those on sulfonylureas), hypertension, or documented vascular disease.
- Pharmacological Classification: Nicorandil is a potassium channel activator with nitrate-like properties. It is classified as an anti-anginal agent and a vasodilator.
- Mechanism of Action: Nicorandil acts via two main mechanisms: 1) Activation of potassium channels in vascular smooth muscle, leading to vasodilation (especially of venous vessels, reducing preload), and 2) Nitric oxide donation, leading to vasodilation of arterial vessels (reducing afterload) and improving myocardial perfusion.
Alternate Names
- No commonly used alternate names.
- Brand Names: Ikorel, Angedil, Dancor, Nikoran, APO-Nicorandil are a few examples. Brand names vary depending on the region.
How It Works
- Pharmacodynamics: Nicorandil reduces myocardial oxygen demand by decreasing preload (through venodilation) and afterload (through arteriodilation). It improves myocardial perfusion by dilating coronary arteries. The potassium channel opening effect also contributes to the anti-anginal action.
- Pharmacokinetics:
- Absorption: Nicorandil is well-absorbed orally, with a bioavailability of about 75%.
- Metabolism: Nicorandil is metabolized in the liver primarily by denitration and glucuronidation. The metabolites Nicotinamide and N-glucuronide are formed.
- Elimination: Nicorandil and its metabolites are primarily excreted in the urine.
- Mode of Action: Nicorandil activates ATP-sensitive potassium channels in vascular smooth muscle, causing hyperpolarization and relaxation. It also donates nitric oxide, which activates guanylate cyclase, leading to increased cyclic GMP, which in turn causes vasodilation.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Nicorandil binds to and opens ATP-sensitive potassium channels. It also releases nitric oxide, which indirectly modulates the activity of guanylate cyclase.
- Elimination Pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
- Initial dose: 10 mg twice daily (morning and evening). A lower starting dose of 5 mg twice daily can be considered for patients prone to headaches.
- Maintenance dose: 10-20 mg twice daily. The dose can be titrated up to a maximum of 40 mg twice daily based on patient response and tolerance.
Children:
- Not recommended for use in children, as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Start with the lowest effective dose and titrate cautiously. No specific dosage adjustments are typically required.
- Patients with Renal Impairment: No specific dosage adjustments are typically required.
- Patients with Hepatic Dysfunction: Use with caution. Dose reduction may be necessary.
- Patients with Comorbid Conditions: Use with caution in patients with hypotension, hypovolemia, acute pulmonary edema, acute myocardial infarction with acute left ventricular failure, and low filling pressures.
Clinical Use Cases
Nicorandil’s clinical use is focused on chronic stable angina. The listed scenarios (Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations) are not typical settings for Nicorandil administration. Other agents are generally preferred in these contexts.
Dosage Adjustments
Dose adjustments should be based on individual patient response and tolerance. Consider lower initial doses for patients prone to headaches. Monitor blood pressure, especially in patients with pre-existing hypotension. In patients with hepatic impairment, dose reduction may be necessary.
Side Effects
Common Side Effects
- Headache (dose-related, often transient)
- Dizziness
- Flushing
- Nausea and vomiting
- Peripheral edema
Rare but Serious Side Effects
- Gastrointestinal ulceration (including mouth, stomach, and intestines), which may lead to perforation, fistula, or hemorrhage.
- Skin and mucosal ulceration (including perianal and genital ulceration).
- Severe hypotension
- Hyperkalemia
Long-Term Effects
Long-term side effects primarily relate to potential for ulceration at various sites.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include severe hypotension, gastrointestinal ulceration/perforation, and hyperkalemia.
Contraindications
- Hypersensitivity to nicorandil or any of its components.
- Cardiogenic shock.
- Acute myocardial infarction with acute left ventricular failure and low filling pressure.
- Severe hypotension.
- Hypovolemia.
- Acute pulmonary edema.
- Left ventricular failure with low filling pressure.
- Concomitant use of phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil).
- Concomitant use of soluble guanylate cyclase stimulators (e.g., riociguat).
Drug Interactions
- Antihypertensives: May potentiate the hypotensive effects of other antihypertensive medications.
- Vasodilators: May potentiate the hypotensive effects of other vasodilators, including alcohol.
- Tricyclic Antidepressants: May enhance the hypotensive effect of nicorandil.
- Phosphodiesterase-5 inhibitors: Contraindicated due to risk of severe hypotension.
- Soluble Guanylate Cyclase Stimulators: Contraindicated due to risk of severe hypotension.
- Potassium supplements: Use with caution in patients with low blood potassium.
- NSAIDs: Use with caution due to potential increased risk of ulceration.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category C (Australian categorization), Category B3 (New Zealand Categorisation). There is insufficient human data to establish safety in pregnancy. Animal studies have shown some adverse effects. Avoid use unless clearly necessary.
- Nicorandil can potentially cross the placental barrier and affect fetal development and is associated with risks like pre-implantation loss and increased fetal mortality in animal studies.
- Breastfeeding: It is unknown if nicorandil is excreted in breast milk, but it is not recommended during breastfeeding due to potential risk to the infant.
Drug Profile Summary
- Mechanism of Action: Potassium channel activation and nitric oxide donation leading to vasodilation and improved myocardial perfusion.
- Side Effects: Headache, dizziness, flushing, nausea, vomiting, hypotension, gastrointestinal ulceration.
- Contraindications: Hypersensitivity, cardiogenic shock, severe hypotension, left ventricular failure, concomitant use of PDE-5 inhibitors or soluble guanylate cyclase stimulators.
- Drug Interactions: Antihypertensives, vasodilators, tricyclic antidepressants.
- Pregnancy & Breastfeeding: Avoid use unless clearly necessary.
- Dosage: Adults: 10-20 mg twice daily (up to 40 mg twice daily). Children: Not recommended.
- Monitoring Parameters: Blood pressure, heart rate, signs of ulceration, potassium levels.
Popular Combinations
Nicorandil can be combined with other anti-anginal medications like beta-blockers and calcium channel blockers if monotherapy is insufficient. However, it is crucial to monitor for hypotension.
Precautions
- Monitor blood pressure, especially during initial therapy and dose titration.
- Monitor for signs and symptoms of gastrointestinal or skin ulceration.
- Assess potassium levels, especially in patients at risk of hyperkalemia.
- Caution is advised in patients with hepatic impairment and renal impairment.
- Advise patients about the potential for dizziness and avoid activities requiring alertness, especially during initial treatment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Nicorandil?
A: The standard adult dose is 10-20 mg twice daily. A starting dose of 5 mg twice daily may be used in patients prone to headaches. The dose can be titrated up to 40 mg twice daily based on response and tolerance. It is not recommended for children.
Q2: What are the common side effects of Nicorandil?
A: Common side effects include headache, dizziness, flushing, nausea, and vomiting.
Q3: How does Nicorandil work in angina?
A: It acts by dilating blood vessels, increasing blood flow to the heart muscle and decreasing cardiac workload, hence improving myocardial perfusion.
Q4: What are the serious side effects of Nicorandil to watch out for?
A: Serious side effects include severe hypotension, gastrointestinal ulceration (potentially with perforation or bleeding), and hyperkalemia. Monitor patients closely.
Q5: Can Nicorandil be used with sildenafil (Viagra)?
A: No, Nicorandil is contraindicated with sildenafil and other phosphodiesterase-5 inhibitors due to the risk of severe hypotension.
Q6: Is Nicorandil safe in pregnancy?
A: Nicorandil should be avoided during pregnancy unless clearly necessary, as its safety has not been established. Discuss risks and benefits with the patient.
Q7: Can Nicorandil be crushed or chewed?
A: No, Nicorandil tablets should be swallowed whole with water. Do not crush or chew them. Tablets can be divided along the score line if needed.
Q8: Should Nicorandil be taken with food?
A: Nicorandil can be taken with or without food. Administration independent of food intake.
Q9: How should I monitor a patient on Nicorandil?
A: Monitor blood pressure, especially during initiation and dose adjustments. Monitor for signs and symptoms of ulceration, such as abdominal pain, rectal bleeding, or skin lesions. Periodically assess potassium levels.
Q10: What are the drug interactions of Nicorandil?
A: Nicorandil may interact with other antihypertensive medications, vasodilators (including alcohol), and tricyclic antidepressants, leading to enhanced hypotensive effects. Concomitant use of phosphodiesterase-5 inhibitors and soluble guanylate cyclase stimulators is contraindicated. Use caution with NSAIDs, aspirin, and potassium supplements.
