Schedule H

Oral

• Tablets: 5 mg, 10 mg, 20 mg

Note: Nicorandil has a dual mechanism of action: (1) activates ATP-sensitive potassium channels (KATP) causing arterial vasodilation, and (2) releases nitric oxide (NO) causing venodilation similar to organic nitrates. This unique dual mechanism provides both preload and afterload reduction.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

1. Chronic Stable Angina Pectoris (Prophylaxis)

Parameter Dose Clinical Notes

Starting dose 5 mg orally twice daily Initiate during daytime to assess for hypotension; take with or after food

Titration Increase to 10 mg twice daily after 1–2 weeks if tolerated and needed Based on symptom control and blood pressure

Usual maintenance dose 10–20 mg twice daily Use lowest effective dose to minimise ulcer risk

Maximum dose 20 mg twice daily (40 mg/day)

Clinical Notes:

• Use for prophylaxis only — NOT effective for acute angina relief

• May be used as monotherapy or add-on to beta-blockers, calcium channel blockers, or nitrates

• Particularly useful when beta-blockers are contraindicated (e.g., asthma, peripheral vascular disease)

• Effective in both effort-induced and vasospastic angina

1. Refractory Angina (Add-on Therapy)

Parameter Dose Clinical Notes

Starting dose 10 mg orally twice daily When added to existing anti-anginal therapy

Titration Increase to 20 mg twice daily after 2 weeks if inadequate control Monitor for hypotension with combination therapy

Usual maintenance dose 10–20 mg twice daily

Maximum dose 20 mg twice daily

Used as adjunct when maximal doses of beta-blockers, CCBs, and/or nitrates provide insufficient angina control.

Secondary Indications — Adults (Off-label, if any)

1. Vasospastic (Prinzmetal's) Angina — OFF-LABEL

Parameter Details

Indication Refractory vasospastic angina unresponsive to calcium channel blockers

Dose 10–20 mg orally twice daily

Duration Long-term prophylaxis

Specialist only Yes — Cardiology

Evidence basis Potassium channel activation causes coronary vasodilation; used in Indian cardiology practice when CCBs inadequate or not tolerated

1. Microvascular Angina (Cardiac Syndrome X) — OFF-LABEL

Parameter Details

Indication Microvascular angina unresponsive to conventional therapy

Dose 10 mg orally twice daily; may increase to 20 mg twice daily

Duration Long-term

Specialist only Yes — Cardiology

Evidence basis Limited RCT data; improves coronary flow reserve; used in Indian tertiary centres

1. Heart Failure with Preserved Ejection Fraction (HFpEF) — OFF-LABEL

Parameter Details

Indication Symptomatic HFpEF with angina or exercise intolerance

Dose 10 mg orally twice daily

Duration Long-term

Specialist only Yes — Cardiology

Evidence basis Limited RCT data suggest symptomatic benefit; not standard of care; used selectively in Indian practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications:

NOT APPROVED for paediatric use in India.

• No paediatric formulations available

• Safety and efficacy not established in children and adolescents

• No paediatric dosing data in Indian or international sources

Secondary Indications — Paediatrics (Off-label, if any)

Not applicable.

Not recommended below 18 years of age. No data available for paediatric populations. Do not use in children unless exceptional circumstances under specialist paediatric cardiology supervision.

Nicorandil is primarily hepatically metabolised; however, renal impairment may increase sensitivity to hypotensive effects.

• Cardiogenic shock

• Acute myocardial infarction with hypotension or low filling pressures

• Severe hypotension (systolic BP <90 mmHg)

• Hypovolaemia

• Left ventricular failure with low filling pressure

• Acute pulmonary oedema

• Concurrent use with phosphodiesterase-5 (PDE5) inhibitors (sildenafil, tadalafil, vardenafil, avanafil) — risk of severe hypotension

• Concurrent use with soluble guanylate cyclase (sGC) stimulators (riociguat)

• Known hypersensitivity to nicorandil or any excipient

• Severe hepatic impairment

• Pre-existing hypotension or systolic BP <100 mmHg — increased risk of symptomatic hypotension

• Active peptic ulcer disease — risk of GI ulceration and perforation

• Diverticular disease — increased risk of GI perforation

• History of GI ulceration or surgery

• History of oral ulceration or anal fissures

• Concurrent use with NSAIDs or corticosteroids — additive GI ulcer risk

• Elderly patients — enhanced sensitivity to hypotensive effects; increased ulcer risk

• Concurrent antihypertensive therapy — additive hypotension

• Volume depletion or dehydration

• Concomitant nitrate therapy — additive vasodilation; use with caution

• G6PD deficiency — nicorandil is a nitrate derivative; theoretical risk of haemolysis (limited data)

Aspect Recommendation

Risk category No formal categorisation in India; limited human data; animal studies inconclusive

Use in pregnancy Avoid unless absolutely necessary and benefit clearly outweighs risk

First trimester Avoid — limited safety data

Second/Third trimester Use only if no alternative available; specialist cardio-obstetric input required

Preferred alternatives Beta-blockers (metoprolol, labetalol); short-acting nitrates if needed for angina

Monitoring Maternal blood pressure; fetal growth and wellbeing

Aspect Recommendation

Compatibility Not well studied; use only if clearly necessary

Drug levels in milk Unknown; presumed moderate based on pharmacokinetic properties

Preferred alternatives Short-acting nitrates; beta-blockers (metoprolol) if anti-anginal therapy required

Recommendations Avoid during breastfeeding if possible; if essential, use lowest effective dose

Infant monitoring Feeding adequacy; signs of hypotension (lethargy, poor feeding); weight gain

Aspect Recommendation

Starting dose 5 mg orally twice daily

Titration Slower titration (every 2–4 weeks); careful BP monitoring

Special considerations Elderly patients have enhanced sensitivity to vasodilatory effects

Extra risks Orthostatic hypotension; falls; syncope; increased GI/mucosal ulceration risk; dehydration

Recommendations Use lowest effective dose; monitor BP (sitting and standing); inquire about oral/anal symptoms at each visit

Drug Interaction Management

PDE5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) Profound, life-threatening hypotension due to synergistic vasodilation Contraindicated; do not use together

Riociguat (sGC stimulator) Severe hypotension Contraindicated

Other nitrates (GTN, ISDN, ISMN) Additive vasodilation and hypotension Avoid concurrent use or use with extreme caution; reduce nicorandil dose if combination essential

Antihypertensives (ACE inhibitors, ARBs, beta-blockers, CCBs, diuretics) Additive hypotensive effect Use with caution; monitor BP closely; dose adjustment may be needed

Drug Interaction Management

Diuretics Additive hypotension; risk of dehydration exacerbating hypotensive effects Monitor BP and hydration status

Tricyclic antidepressants Additive orthostatic hypotension Monitor for postural symptoms

Alpha-blockers (prazosin, terazosin, tamsulosin) Significant additive hypotension Use with caution; start nicorandil at lowest dose

Alcohol Enhanced vasodilatory and hypotensive effects Counsel patients to limit alcohol

NSAIDs Increased risk of GI ulceration and perforation when combined Avoid concurrent use if possible; if essential, monitor closely for GI symptoms

Corticosteroids Additive risk of GI ulceration Use with caution; monitor for GI symptoms

Aspirin (high-dose) May increase GI ulcer risk Use with caution; standard antiplatelet doses generally acceptable

• Headache (most common; ~30–50%; usually diminishes with continued use)

• Dizziness

• Flushing

• Nausea

• Palpitations

• Hypotension

• Weakness and fatigue

• Oral ulceration (stomatitis) — early warning sign

Note: Headache is very common initially but typically improves after 1–2 weeks; paracetamol may be used for symptomatic relief.

Adverse Effect Clinical Notes

Gastrointestinal ulceration Oral, oesophageal, gastric, small bowel, colonic, or rectal ulcers; may cause perforation and bleeding; discontinue immediately if ulcers develop; do not rechallenge

Anal ulceration and fistulae Characteristic of nicorandil; painful perianal ulcers; may be mistaken for malignancy; discontinue immediately; usually heal after discontinuation

Severe hypotension May cause syncope, collapse; more likely with concurrent vasodilators or in volume-depleted patients

Oral/mucosal ulceration May affect tongue, buccal mucosa, gingiva; discontinue if persistent

Skin ulceration Rare; leg ulcers reported

GI perforation Rare but life-threatening; especially in patients with diverticular disease

⚠️ IMPORTANT: Nicorandil-induced ulceration can occur at ANY site in the GI tract and may mimic malignancy. Always consider nicorandil as a cause of unexplained mucosal ulceration. Ulcers typically heal after drug discontinuation but may take weeks to months.

After initiation/dose change Blood pressure at 1–2 weeks; inquire about headache, dizziness, GI symptoms, oral or anal symptoms

Long-term Regular inquiry about oral, GI, or perianal symptoms at every visit; examine oral cavity periodically; monitor for any unexplained ulceration

If symptoms develop Immediate examination of oral cavity, anus; consider endoscopy if GI symptoms

• Nikoran (Torrent) — widely used

• Korandil (Intas)

• Nicostar (Torrent)

• Angedil (Eris)

• Nicodil (Cipla)

• Nicotex K (Glenmark)

• Korcadil (Lupin)

• Multiple generic manufacturers

Note: No significant FDCs available; all formulations are single-agent nicorandil.

• Not listed in NLEM 2022

• Not under NPPA price control

• Available primarily through private retail pharmacies

1. Ulceration is a class-specific risk — nicorandil can cause ulceration anywhere in the GI tract (oral, oesophageal, gastric, small bowel, colonic, anal). Always ask about oral/anal symptoms at each visit. Discontinue immediately if ulcers develop — they typically heal after stopping the drug.

1. Start low, go slow — begin at 5 mg twice daily and titrate gradually to minimise headache and hypotension. Headache is extremely common initially but usually resolves within 1–2 weeks.

1. NOT for acute angina — nicorandil is purely prophylactic; ensure patients have sublingual GTN available for acute attacks.

1. Avoid in diverticular disease — the risk of colonic perforation is significantly increased in patients with diverticular disease; consider alternative anti-anginal agents.

1. PDE5 inhibitor interaction is absolute — nicorandil is contraindicated with sildenafil, tadalafil, etc. Counsel patients and document this in medical records.

1. Ulcers may mimic malignancy — nicorandil-induced ulcers can be deep, chronic, and may histologically appear suspicious; always consider nicorandil as a cause before invasive investigation for suspected malignancy.

1. Dual mechanism advantage — unique combination of potassium channel activation (arterial dilation) and NO release (venodilation) provides both preload and afterload reduction, which may benefit patients who have failed other single-mechanism anti-anginals.

nicorandil; potassium channel opener; anti-anginal; stable angina; vasospastic angina; nitrate-like; GI ulceration; anal ulcer; PDE5 contraindicated; Schedule H

RxIndia v1.0 — 04 May 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia

• API Textbook of Medicine

• AIIMS Pharmacology and Cardiology Guidelines

• Cardiological Society of India (CSI) Practice Recommendations

• MHRA Drug Safety Updates (for ulceration risk alerts)

• IONA Trial (Lancet 2002 — for stable angina efficacy)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (supportive)