Schedule H

Oral

• Tablets: 2.5 mg, 5 mg

• Controlled-release capsules: 5 mg

Note: Isradipine has LIMITED AVAILABILITY in India. Most Indian pharmacies do not stock this drug routinely. Amlodipine, nifedipine, and cilnidipine are more commonly available alternatives.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Essential Hypertension

Parameter Recommendation

Starting dose: 2.5 mg orally twice daily

Titration: Increase after 2–4 weeks based on BP response

Usual maintenance dose: 5 mg twice daily

Maximum dose: 10 mg twice daily (20 mg/day total)

Clinical notes:

• Short half-life (~8 hours) necessitates twice-daily dosing

• Administer in morning and evening for optimal 24-hour BP control

• Second-generation dihydropyridine: causes less reflex tachycardia than immediate-release nifedipine

• May be used as monotherapy or in combination with other antihypertensives (ACE inhibitors, ARBs, diuretics)

• Not first-line choice in India due to limited availability; amlodipine preferred

• Controlled-release formulation allows once-daily dosing if available

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Raynaud's phenomenon (OFF-LABEL) Starting dose: 2.5 mg twice daily; Usual dose: 5 mg twice daily Seasonal or continuous based on symptoms Specialist only. Evidence: Small RCTs showing benefit; used in select patients unresponsive to nifedipine or amlodipine

Not recommended for:

• Hypertensive emergencies — Sublingual isradipine not safe due to unpredictable absorption and risk of excessive reflex tachycardia; IV agents preferred

• Angina pectoris — Not established for anti-anginal use

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not approved for paediatric use in India.

No standard dosing recommendations available in IAP guidelines, MoHFW protocols, or WHO EML for children.

Secondary Indications — Paediatrics (Off-label)

Indication Dose Notes

Refractory hypertension (OFF-LABEL) Starting dose: 0.05–0.1 mg/kg/dose twice daily; Maximum: 0.8 mg/kg/day or 20 mg/day (whichever lower) Specialist only (Paediatric Nephrology/Cardiology). Evidence: Very limited data; extrapolated from adult dosing

Safety monitoring:

• Blood pressure before and after each dose change

• Heart rate monitoring (reflex tachycardia)

• Signs of hypotension, dizziness

Minimum age statement: Not recommended below 18 years except under specialist supervision in tertiary care settings with no alternative options.

• Hypersensitivity to isradipine or other dihydropyridine calcium channel blockers

• Severe aortic stenosis (haemodynamically significant)

• Cardiogenic shock

• Acute myocardial infarction with haemodynamic instability or pulmonary congestion

• Unstable angina (ongoing ischaemia)

• Heart failure with reduced ejection fraction — may worsen symptoms; use with caution

• Moderate-to-severe hepatic impairment — reduced drug clearance

• Elderly patients — increased sensitivity to hypotensive effects; fall risk

• Sick sinus syndrome (without pacemaker) — though DHPs have minimal nodal effect

• Concurrent use with other antihypertensives — additive BP lowering

• Abrupt discontinuation — may cause rebound hypertension; taper if possible

• Twice-daily dosing — risk of missed doses and inconsistent BP control

Parameter Information

Overall safety: Limited human data; animal studies suggest low teratogenic risk

Risk category: Not formally classified in India

Preferred alternatives: Labetalol, methyldopa, nifedipine (established safety in gestational hypertension per FOGSI/ICMR)

When may be used: Only when preferred agents are contraindicated or unavailable; specialist supervision mandatory

What to monitor: Maternal BP, uteroplacental perfusion (Doppler), fetal growth, fetal heart rate

Parameter Information

Compatible with breastfeeding: Limited human data; likely compatible based on low expected transfer

Drug levels in milk: Expected to be low (lipophilic but high protein binding)

Preferred alternatives: Amlodipine, nifedipine (better studied in lactation)

What to monitor in infant: Feeding adequacy, excessive drowsiness, weight gain, signs of hypotension

Parameter Recommendation

Starting dose: 2.5 mg once daily (not twice daily)

Titration: Slower — increase at 4-week intervals rather than 2 weeks

Extra risks: Orthostatic hypotension, dizziness, falls, peripheral oedema, reduced hepatic/renal reserve affecting drug clearance

Special considerations: Assess BP in both sitting and standing positions; review concurrent medications; ensure adequate hydration

Interacting Drug Effect Recommendation

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin) Significantly increased isradipine plasma levels Avoid combination or reduce isradipine dose substantially; monitor for hypotension

Grapefruit juice Inhibits intestinal CYP3A4; increases bioavailability Avoid grapefruit juice consumption during therapy

Rifampicin Potent CYP3A4 inducer; markedly reduces isradipine levels May lose antihypertensive efficacy; consider alternative CCB or increase isradipine dose with close monitoring

Phenytoin, carbamazepine, phenobarbital CYP3A4 induction; reduced isradipine levels Monitor BP; dose adjustment may be needed

Interacting Drug Effect Recommendation

Beta-blockers Additive BP lowering; beta-blockers counteract reflex tachycardia caused by DHPs Can be beneficial combination; monitor BP and heart rate

Other antihypertensives (ACE inhibitors, ARBs, diuretics) Additive BP-lowering effect Titrate cautiously; monitor BP

Diuretics Enhanced hypotensive effect; volume depletion risk Monitor BP and electrolytes; risk of orthostatic symptoms

NSAIDs (chronic use) May blunt antihypertensive response Monitor BP; consider paracetamol as alternative analgesic

Digoxin Minor increase in digoxin levels possible with some DHPs Monitor for digoxin toxicity if co-administered

Simvastatin CYP3A4 substrate; potential interaction Generally safe; monitor for statin-related adverse effects

• Headache (most common)

• Dizziness and light-headedness

• Peripheral oedema (less than with amlodipine)

• Flushing

• Palpitations and tachycardia

• Fatigue

• Nausea

Adverse Effect Clinical Action

Severe hypotension Supportive care; IV fluids; may require hospitalisation; consider dose reduction or discontinuation

Angina exacerbation May occur with rapid titration or in unstable coronary disease; slow titration; consider alternative

Significant reflex tachycardia Consider adding beta-blocker if persistent; typically less severe than with first-generation DHPs

Hypersensitivity reactions (rash, urticaria, angioedema) Discontinue immediately; supportive care

Severe peripheral oedema Consider dose reduction or switch to alternative CCB

Phase Parameters

Baseline Blood pressure (sitting and standing), heart rate, ECG (if cardiac comorbidity), renal function, hepatic function

After initiation/dose change BP and heart rate at 2–4 weeks; assess for hypotensive symptoms, ankle oedema, palpitations

Long-term BP every 2–3 months; monitor for peripheral oedema, sustained tachycardia; periodic renal/hepatic function if on high doses or with comorbidities

Limited availability in India.

• Dynacirc (Novartis) — may not be currently marketed

• Generic formulations — availability inconsistent

Note: Isradipine is not commonly stocked in Indian pharmacies. Prescribers should verify local availability before initiating therapy. Amlodipine, nifedipine, or cilnidipine are more readily available alternatives.

Strength Approximate Price (per 10 tablets)

2.5 mg ₹50–₹100 (if available)

• NLEM status: Not listed under NLEM 2022

• NPPA control: Not under price control

• Government supply: Not routinely available in public sector

• Private retail: Limited and inconsistent availability

1. Limited availability issue: Isradipine is rarely stocked in Indian pharmacies; confirm availability before prescribing. Amlodipine (once daily, widely available) is the preferred DHP-CCB in most settings.

1. Twice-daily dosing: Short half-life requires BID administration for consistent BP control — may affect compliance. Controlled-release formulation (if available) allows once-daily dosing.

1. Less oedema than amlodipine: May be useful in patients who developed significant ankle swelling on amlodipine and cannot tolerate it.

1. Reflex tachycardia: Though less than immediate-release nifedipine, still occurs — consider combining with beta-blocker in patients with baseline tachycardia.

1. CYP3A4 substrate: Significant interactions with azole antifungals, macrolides, and rifampicin — review concurrent medications carefully.

1. Not for angina: Unlike amlodipine, isradipine is not established for chronic stable angina management.

isradipine; calcium-channel-blocker; CCB; dihydropyridine; hypertension; twice-daily; limited-availability-India; renal-safe; elderly-caution; CYP3A4-substrate

RxIndia v0.4 — 09 Jan 2025

• CDSCO-approved product inserts

• Indian Pharmacopoeia

• NFI (National Formulary of India)

• API Textbook of Medicine, 12th edition

• Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th edition

• ICMR Guidelines: Management of Hypertension in India

• AIIMS and PGIMER internal hypertension protocols (supportive)

• RCTs on Raynaud's phenomenon (for off-label designation)