Ranolazine
Other antianginals
Other antianginals
A chronic angina drug that blocks the late sodium current. It reduces angina without changing heart rate or blood pressure, but it lengthens the QT.
Quick facts
- Group
- Other antianginals
- Target
- Cardiac sodium channel Nav1.5 (late sodium current)
- Used for
- Chronic angina
- Key effects
- Dizziness · Headache · Constipation
- Monitor
- ECG · Kidney function at baseline · Angina frequency
- ATC
- C01EB18
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows ranolazine bound to the rat cardiac sodium channel Nav1.5, very similar to the human channel.
Ranolazine has anti-ischaemic effects that do not depend on heart rate or blood pressure. At therapeutic levels it inhibits the late inward sodium current of cardiac cells; in ischaemia this current loads cells with sodium and then calcium through the sodium-calcium exchanger. The exact link to angina relief is uncertain. It also blocks IKr, which prolongs the QT.
- Ranolazine inhibits the late sodium current in heart cells
- Less sodium loading means less calcium overload in ischaemia
- Diastolic tension falls; heart rate and pressure are unchanged
- IKr block lengthens the QT
Indications
- Chronic angina, usually added to other antianginals Stable angina →
Adverse effects
Common
- Dizziness
- Headache
- Constipation
- Nausea
Contraindications
- Strong CYP3A inhibitors (ketoconazole, clarithromycin, nelfinavir)
- CYP3A inducers (rifampicin, phenobarbital, St John's wort)
- Liver cirrhosis
Key interactions
- Strong CYP3A inhibitors
- Large rise in ranolazine levels; contraindicated
- Diltiazem, verapamil, erythromycin, fluconazole, grapefruit
- Higher ranolazine levels; the ranolazine dose is limited
- Simvastatin and other CYP3A substrates (cyclosporine, tacrolimus)
- Ranolazine raises their levels
- Digoxin (P-glycoprotein)
- Higher digoxin levels
- Metformin (OCT2)
- Higher metformin levels at higher ranolazine doses
What is monitored
- ECG: QT interval
- Kidney function at baseline and periodically when it is reduced
- Angina frequency
Administration and safety
- Extended-release tablets are swallowed whole; not crushed, broken or chewed.
- It does not treat an acute attack: sublingual glyceryl trinitrate is kept for that.
- All medicines are reviewed for CYP3A interactions before starting.
Pregnancy and breastfeeding
Human data are limited; it is used in pregnancy only if the benefit justifies the risk.
Nursing care
- Check the ECG (QT) and report fainting or palpitations.
- Follow creatinine in patients with reduced kidney function.
- Teach the patient to avoid grapefruit and to report new medicines, including antibiotics and antifungals.
Pharmacokinetics
- Absorption
- Extended-release tablet, with or without food
- Metabolism
- Liver, mainly CYP3A and to a lesser extent CYP2D6; substrate of P-glycoprotein
- Elimination
- Mostly as metabolites in urine; exposure rises in kidney impairment
Test yourself
Think of the answer, then tap the question to see it.
Which current does ranolazine inhibit, and why does it help ischaemic cells?
The late inward sodium current; less sodium loading means less calcium overload through the sodium-calcium exchanger.
What are the three contraindications of ranolazine?
Strong CYP3A inhibitors, CYP3A inducers and liver cirrhosis.
Which ECG change does ranolazine cause, and through which current?
QT prolongation, through block of IKr.
Connections
← Back to the class: Other antianginals
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - RANOLAZINE tablet, extended release (DailyMed (U.S. National Library of Medicine), 2026); Ranolazine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); 8F6P: Rat Cardiac Sodium Channel with Ranolazine Bound (RCSB Protein Data Bank, 2023).
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Representative model, for educational purposes only.