Schedule H

Oral

• Extended-Release Tablets: 500 mg, 1000 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Chronic Stable Angina Pectoris (Add-on Therapy)

Used when angina remains inadequately controlled despite optimised therapy with beta-blockers, calcium channel blockers, or nitrates.

Parameter Recommendation

Starting dose 500 mg orally twice daily

Titration Increase to 1000 mg twice daily after 2–4 weeks if symptoms persist and drug is tolerated

Usual maintenance dose 500–1000 mg twice daily

Maximum dose 1000 mg twice daily

Clinical Notes:

• Extended-release tablets should be swallowed whole; do not crush, chew, or break

• Does not significantly affect heart rate or blood pressure — suitable for patients with low baseline HR

• Avoid abrupt discontinuation in symptomatic patients

• May be used as first-line add-on when beta-blockers or CCBs are contraindicated or not tolerated

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

Indication Dose Duration Notes

Microvascular Angina (Cardiac Syndrome X) 500–1000 mg twice daily Long-term; adjust to symptoms OFF-LABEL; Specialist only; Based on small RCTs and Indian cardiology practice

Adjunct in Atrial Fibrillation Rate Control 500 mg twice daily Short-term adjunct OFF-LABEL; Limited evidence; Electrophysiology specialist supervision only

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

NOT APPROVED for paediatric use in India.

Age Group Recommendation

< 18 years Not recommended; safety and efficacy not established

• No Indian regulatory approval for paediatric population

• Should not be used in children outside clinical trials or specialist research settings

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

Not applicable.

• No off-label paediatric indications supported by Indian practice or published data

• Pre-existing QT prolongation or congenital long QT syndrome

• Severe hepatic impairment or hepatic cirrhosis

• Concurrent use with strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, nelfinavir)

• Concurrent use with strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, phenobarbital)

• Known hypersensitivity to ranolazine or any formulation component

• History of ventricular arrhythmias or family history of sudden cardiac death

• Moderate renal impairment (eGFR 30–59 mL/min) — dose-related accumulation

• Mild hepatic impairment — monitor LFTs

• Concurrent use of other QT-prolonging drugs (antipsychotics, fluoroquinolones, macrolides, ondansetron)

• Elderly patients — increased risk of dizziness, constipation, falls

• Electrolyte abnormalities (hypokalaemia, hypomagnesaemia) — correct before initiation

• Avoid St. John's Wort (CYP3A4 inducer)

Parameter Details

Risk Category Limited human data; animal studies do not indicate major teratogenicity

Preferred Alternatives Beta-blockers (metoprolol, labetalol) and nitrates preferred for angina in pregnancy as per Indian obstetric practice

When May Be Used Only if potential benefit clearly outweighs risk; requires cardiologist and obstetrician input

Monitoring Maternal ECG (QT interval); fetal growth surveillance

Parameter Details

Compatibility Not adequately studied; safety uncertain

Preferred Alternatives Beta-blockers (metoprolol) preferred when antianginal therapy needed during lactation

Drug Levels in Milk Unknown; likely low based on pharmacokinetic profile

Infant Monitoring If used, monitor for feeding difficulties, sedation, gastrointestinal symptoms

Parameter Recommendation

Starting dose 500 mg twice daily

Titration Slower titration; reassess at 4 weeks before dose escalation

Special Risks Higher incidence of dizziness, constipation, and QT prolongation; increased falls risk

Monitoring Periodic ECG, renal function, and electrolytes; assess for polypharmacy interactions

Interacting Drug Mechanism / Effect Recommendation

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir) Marked increase in ranolazine levels Contraindicated

Strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine) Substantial reduction in ranolazine efficacy Avoid combination

Digoxin P-glycoprotein inhibition by ranolazine increases digoxin levels (up to 1.5-fold) Monitor digoxin levels; consider dose reduction

Simvastatin Increased simvastatin exposure via CYP3A4 inhibition Limit simvastatin to maximum 20 mg/day

QT-prolonging drugs (Class Ia/III antiarrhythmics, haloperidol, thioridazine) Additive QT prolongation; torsades risk Avoid combination or use with extreme caution and ECG monitoring

Interacting Drug Mechanism / Effect Recommendation

Diltiazem / Verapamil Moderate CYP3A4 inhibition; increases ranolazine levels Consider lower ranolazine dose (500 mg BID); monitor QTc

Metformin Ranolazine increases metformin levels via OCT2 inhibition Monitor for metformin-related adverse effects; dose-adjust if eGFR <60

Erythromycin Moderate CYP3A4 inhibition + QT prolongation potential Avoid combination or monitor ECG closely

Atorvastatin Mild increase in atorvastatin levels Monitor for myopathy symptoms

Cyclosporine P-glycoprotein inhibition Monitor cyclosporine levels

Warfarin Potential for increased anticoagulant effect Monitor INR more frequently

• Dizziness

• Constipation

• Nausea

• Headache

• Asthenia / Fatigue

• Dry mouth

• Abdominal pain

Adverse Effect Clinical Action

QT prolongation / Torsades de Pointes Discontinue immediately; ECG monitoring; correct electrolytes; specialist review

Syncope Evaluate for arrhythmia; consider discontinuation

Acute kidney injury (especially in elderly or dehydrated patients) Discontinue; supportive management

Hepatic enzyme elevation Monitor LFTs; discontinue if significant elevation

Angioedema (rare) Discontinue immediately; supportive airway management

2–4 weeks post-initiation or dose change Repeat ECG; assess symptom response and tolerability

Long-term ECG every 6–12 months or if symptoms suggest arrhythmia; renal and hepatic function every 3–6 months in elderly or at-risk patients

• Ranozex (Intas)

• Rancad (USV)

• Ranolaz (Micro Labs)

• Ranexa (Sun Pharma)

• Ranola (Cipla)

• Ranzolol (Torrent)

Note: All formulations are extended-release tablets.

• Not included in NLEM; pricing not NPPA-controlled

• Cost varies across brands and retail outlets

• Reserve ranolazine for angina refractory to first-line agents (beta-blockers, CCBs, nitrates) or when these are contraindicated

• Particularly useful in patients with low resting heart rate where further beta-blockade is undesirable

• Always check baseline QTc and avoid in patients with QTc >500 ms or on other QT-prolonging medications

• Counsel patients about dizziness — advise caution with driving or operating machinery initially

• May provide modest glycaemic benefit in diabetic patients with angina — consider this when choosing antianginal therapy

• Do not use as monotherapy for acute coronary syndromes — it is for chronic stable angina only

Ranolazine; stable angina; antianginal; metabolic modulator; late sodium current inhibitor; QT prolongation; CYP3A4 substrate; add-on therapy; Schedule H

RxIndia v1.0 — 12 Jun 2025

• CDSCO approved product information

• Indian Pharmacopoeia (IP)

• API Textbook of Medicine — Ischaemic Heart Disease chapter

• AIIMS Cardiology Treatment Protocols

• Goodman & Gilman's: The Pharmacological Basis of Therapeutics

• Indian cardiology specialist practice (for off-label indications)

• MERLIN-TIMI 36 trial (supportive evidence for chronic stable angina)