Other Antianginals

High-yield Verified · Oct 2026

Prototype: ranolazine

Other Antianginals are a class of medications used for chronic angina.

Medical view → mechanisms, drug comparisons and Step 1 pharmacology

Ranolazine inhibits the late sodium current in heart muscle. It is added to standard antianginal therapy and does not work by slowing the heart or lowering blood pressure.

How it works in the body

The system involved, what goes wrong, and how the drug and body interact.

01 An antianginal that does not slow the heart or lower blood pressure

Chronic angina is usually treated with beta-blockers, calcium channel blockers and nitrates, and ranolazine can be added to them. Its anti-ischemic and antianginal effects do not depend on reducing heart rate or blood pressure: in clinical studies mean heart rate changed by less than 2 bpm and systolic pressure by less than 3 mm Hg.

Its exact antianginal mechanism is not settled. At therapeutic levels ranolazine inhibits the cardiac late sodium current. In ischemic heart muscle that lowers intracellular sodium, so less calcium enters through the sodium–calcium exchanger; the lower intracellular calcium reduces ventricular wall tension and myocardial oxygen consumption.

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Ranolazine targets the sodium-driven calcium overload of ischemic muscle, not heart rate or blood pressure.

02 QT prolongation and a drug-interaction minefield

Ranolazine also blocks the potassium current IKr, which prolongs the ventricular action potential and the QTc interval in a dose-related way. Clinical experience in acute coronary syndrome did not show more proarrhythmia or sudden death, but there is little experience with high doses, other QT-prolonging drugs, congenital or acquired long QT, or a family history of long QT syndrome.

It is metabolized mainly by CYP3A (less by CYP2D6) and is a P-glycoprotein substrate, so its level swings with other drugs: ketoconazole, a strong CYP3A inhibitor, raised ranolazine levels by 220%, and rifampin, a CYP3A inducer, cut them by about 95%. That is why strong CYP3A inhibitors and CYP3A inducers are both contraindicated. Ranolazine in turn raises the levels of some other drugs — simvastatin, digoxin and metformin among them.

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CYP3A sets the ranolazine level: inhibitors push it up (more QT prolongation), inducers push it far down.

03 Liver and kidneys

Ranolazine is contraindicated in liver cirrhosis: in cirrhotic patients with mild to moderate impairment, QT prolongation was about 3-fold greater, more than the rise in drug level alone explains.

In severe renal impairment (creatinine clearance < 30 mL/min), acute renal failure has occurred. Separately, ranolazine raises serum creatinine by about 0.1 mg/dL in everyone, probably by blocking creatinine’s tubular secretion; that small rise is rapid, does not progress, reverses on stopping and comes without a rise in BUN. A marked, progressive creatinine rise with rising BUN or potassium signals acute renal failure.

Drug names

Generic Brand

ranolazine —

Indications

Chronic angina — added to beta-blockers, nitrates, calcium channel blockers, antiplatelet, lipid-lowering, ACE-inhibitor or ARB therapy

Mechanism of action

Ranolazine has anti-ischemic and antianginal effects that do not depend on reducing heart rate or blood pressure; its exact antianginal mechanism is not established. At therapeutic levels it inhibits the cardiac late sodium current, which in ischemic myocytes lowers intracellular sodium and, through the sodium–calcium exchanger, intracellular calcium, reducing wall tension and oxygen consumption. It also blocks IKr, which prolongs the QT interval.

In plain terms

Ranolazine calms the sodium-and-calcium overload in oxygen-starved heart muscle, easing angina without slowing the heart or lowering blood pressure.

Therapeutic effects — what you'll see working

Success is fewer angina attacks and better exercise tolerance on top of standard therapy. Ranolazine does not relieve an acute attack.

Fewer angina episodes Longer exercise before angina or ischemia Heart rate and blood pressure unchanged

Fewer angina episodes: In trials of patients already on diltiazem, atenolol or amlodipine, adding ranolazine reduced angina episodes and nitroglycerin use.
Longer exercise before angina or ischemia: Exercise duration and the time to angina and to ischemia increased, independently of heart rate, blood pressure and background antianginal therapy.
Heart rate and blood pressure unchanged: Mean heart rate changed by less than 2 bpm and systolic pressure by less than 3 mm Hg.

Adverse effects

Most effects are mild and dose-related (dizziness, nausea, constipation). The serious ones follow from its pharmacology: QT prolongation from IKr block, levels driven up by CYP3A inhibitors, and acute renal failure in severe kidney disease.

Common

Dizziness, headache, constipation and nausea.

These were the most frequent adverse reactions (each above 4%); dizziness may be dose-related, and doses above 1000 mg twice daily are poorly tolerated. Less common: palpitations, tinnitus, vertigo, blurred vision, dry mouth, peripheral edema, and hypotension or orthostatic hypotension. Patients 75 or older had more adverse events.

Serious — QT prolongation Hold & notify

Dose-related QTc prolongation from IKr block.

The QTc rises in proportion to the plasma level; at the maximum dose the mean increase is about 6 msec, but at least 15 msec in the 5% with the highest levels. Risk is greater with other QT-prolonging drugs (class Ia or III antiarrhythmics, erythromycin, some antipsychotics), congenital or acquired long QT, liver cirrhosis, and anything that raises ranolazine levels. Fainting must be reported.

Serious — acute renal failure Hold & notify

Acute renal failure in patients with severe renal impairment (creatinine clearance < 30 mL/min).

A marked rise in serum creatinine together with a rise in BUN (and sometimes potassium) signals acute renal failure; ranolazine is stopped. The small, stable rise of about 0.1 mg/dL in creatinine without a BUN change is expected and benign.

Neurologic toxicity at high exposure Hold & notify

Tremor, myoclonus, abnormal coordination, paresthesia and hallucinations, often after a dose increase or higher exposure.

These postmarketing neurologic events often followed a dose increase or higher exposure, and many resolved after stopping or lowering the dose. Overdose has also caused hypotension, QT prolongation, bradycardia, unsteady gait and, in extreme cases, death; hemodialysis is unlikely to help because ranolazine is about 62% protein-bound.

Interactions

Strong CYP3A inhibitors (ketoconazole, clarithromycin, ritonavir) and CYP3A inducers (rifampin, carbamazepine, St. John’s wort) drug

Contraindicated — inhibitors raise ranolazine levels sharply; inducers lower them drastically.

Moderate CYP3A inhibitors (diltiazem, verapamil, erythromycin, fluconazole) drug

Raise ranolazine levels — its dose is limited to 500 mg twice daily.

P-glycoprotein inhibitors (e.g., cyclosporine) drug

May raise ranolazine levels — the dose is titrated to response.

QT-prolonging drugs (class Ia or III antiarrhythmics such as quinidine, dofetilide, sotalol, amiodarone; erythromycin; thioridazine, ziprasidone) drug

Additive QTc prolongation.

Simvastatin, lovastatin and narrow-range CYP3A substrates (cyclosporine, tacrolimus, sirolimus) drug

Ranolazine raises their levels — simvastatin is limited to 20 mg daily; others may need lower doses.

Digoxin drug

Ranolazine raises digoxin levels (about 50%) through P-glycoprotein — the digoxin dose may need adjusting.

Metformin drug

Ranolazine raises metformin levels (OCT2) — with ranolazine 1000 mg twice daily, metformin is limited to 1700 mg/day; monitor blood glucose.

Grapefruit juice or grapefruit products food

A moderate CYP3A inhibitor — patients limit grapefruit while on ranolazine.

Contraindications

All three label contraindications are about drug level: two kinds of interacting drugs and the cirrhotic liver.

Strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, nefazodone, ritonavir, nelfinavir)

They raise ranolazine levels sharply (ketoconazole by about 220%), increasing QT prolongation and toxicity.

CYP3A inducers (e.g., rifampin, rifabutin, phenobarbital, phenytoin, carbamazepine, St. John’s wort)

They lower ranolazine levels drastically (rifampin by about 95%).

Liver cirrhosis

Drug levels rise, and QT prolongation was about 3-fold greater in cirrhotic patients.

Known QT prolongation, congenital long QT syndrome or a family history of it, or other QT-prolonging drugs use caution

Ranolazine prolongs the QTc, and there is little experience in these patients.

Severe renal impairment (creatinine clearance < 30 mL/min) use caution

Acute renal failure has occurred; renal function is monitored when creatinine clearance is below 60 mL/min.

When to hold

Assess before giving — these findings mean hold the dose and act.

Marked or progressive rise in serum creatinine with rising BUN (acute renal failure)

Hold and notify — the label says to discontinue ranolazine if acute renal failure develops.

Fainting, or a new QT-prolonging drug or strong CYP3A inhibitor ordered

Notify the prescriber before the next dose — QT prolongation is dose- and level-related, and strong CYP3A inhibitors are contraindicated.

Diltiazem, verapamil, erythromycin or another moderate CYP3A inhibitor started

Ranolazine is limited to 500 mg twice daily — confirm the dose with the prescriber.

Nursing considerations

The RN-specific layer — each action paired with the reason it matters.

Before starting & screening

Review every medication (including over-the-counter drugs and St. John’s wort) for strong CYP3A inhibitors, CYP3A inducers, moderate CYP3A inhibitors and QT-prolonging drugs.

Why: Strong inhibitors and inducers are contraindicated, moderate inhibitors cap the dose, and QT-prolonging drugs add to its QT effect.

Obtain a baseline ECG and renal function; ask about liver cirrhosis and any personal or family history of long QT.

Why: Ranolazine prolongs the QT interval, is contraindicated in cirrhosis, and can cause acute renal failure in severe renal impairment.

Administration

Give the extended-release tablet whole — not crushed, broken or chewed — with or without food. A missed dose is skipped, not doubled.

Why: The label says to swallow the extended-release tablet whole; food has no important effect on absorption.

Monitoring

Monitor the QTc when ranolazine is combined with other QT-prolonging drugs, and watch for dizziness, syncope, tremor or confusion.

Why: QTc prolongation is dose- and level-related, and neurologic effects tend to follow higher doses or exposure.

With creatinine clearance below 60 mL/min, check creatinine and BUN after starting and periodically.

Why: A rise in creatinine with a rise in BUN signals acute renal failure, whereas a small isolated creatinine rise of about 0.1 mg/dL is expected.

In patients on metformin or other antidiabetic drugs, monitor blood glucose.

Why: Ranolazine raises metformin levels, and hypoglycemia has been reported in diabetic patients on antidiabetic medication.

Patient teaching

Take it every day as prescribed; it prevents attacks but will not stop one in progress.

Why: Ranolazine does not abate an acute angina episode.

Avoid driving or hazardous tasks until you know how it affects you; report fainting.

Why: Ranolazine can cause dizziness and lightheadedness, and the label asks patients to report fainting spells.

Limit grapefruit juice, and tell every prescriber and pharmacist you take ranolazine before starting any new medicine.

Why: Grapefruit and many drugs change ranolazine levels, and ranolazine changes theirs.

Common questions

What are Other Antianginals used for?

Other Antianginals are used for chronic angina.

How do Other Antianginals work?

Ranolazine calms the sodium-and-calcium overload in oxygen-starved heart muscle, easing angina without slowing the heart or lowering blood pressure.

What are the serious side effects of Other Antianginals?

Watch for dose-related QTc prolongation from IKr block; acute renal failure in patients with severe renal impairment (creatinine clearance < 30 mL/min); tremor, myoclonus, abnormal coordination, paresthesia and hallucinations, often after a dose increase or higher exposure.

When should a nurse hold Other Antianginals, and what safety checks apply?

Marked or progressive rise in serum creatinine with rising BUN (acute renal failure): hold and notify — the label says to discontinue ranolazine if acute renal failure develops. Fainting, or a new QT-prolonging drug or strong CYP3A inhibitor ordered: notify the prescriber before the next dose — QT prolongation is dose- and level-related, and strong CYP3A inhibitors are contraindicated. Diltiazem, verapamil, erythromycin or another moderate CYP3A inhibitor started: ranolazine is limited to 500 mg twice daily — confirm the dose with the prescriber.

Sources

Reviewed by Hae Suk Lee, RN

Educational summary for nursing students. Always verify against current prescribing information and your institution's protocols before administering. Not medical advice.