What is ranexa taken for

Ranexa

Generic Name: ranolazine (ra NOE la zeen)
Brand Names: Ranexa

Medically reviewed by Kaci Durbin, MD Last updated on May 1, 2019.

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What is Ranexa?

Ranexa (ranolazine) is used to treat chronic angina (chest pain). It works by improving blood flow to help the heart work more efficiently.

Ranexa is not for use during an acute (emergency) attack of angina.

Ranexa may also be used for purposes not listed in this medication guide.

Important information

You should not take Ranexa if you have cirrhosis of the liver.

Serious drug interactions can occur when certain medicines are used together with ranolazine. Tell each of your healthcare providers about all medicines you use now, and any medicine you start or stop using.

Ranexa is not for use during an acute (emergency) attack of chest pain. Continue using any other medicines prescribed by your doctor (such as nitroglycerin) to treat acute chest pain.

Before you take Ranexa, tell your doctor about all of your medical conditions, especially if you have a personal or family history of Long QT syndrome.

Chronic angina is often treated with a combination of different drugs. To best treat your condition, use all of your medications as directed by your doctor. Do not change your doses or medication schedule without advice from your doctor.

Before taking this medicine

You should not take Ranexa if you are allergic to ranolazine, or if you have cirrhosis of the liver.

Many other drugs can interact with ranolazine and should not be used at the same time. Your doctor may need to change your treatment plan if you use any of the following drugs:

  • clarithromycin;

  • nefazodone;

  • St. John’s wort;

  • antifungal medicine – itraconazole, ketoconazole;

  • HIV or AIDS medicine – indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, saquinavir;

  • tuberculosis medicine – rifabutin, rifampin, rifapentine; or

  • seizure medicine-carbamazepine, phenobarbital, phenytoin.

To make sure Ranexa is safe for you, tell your doctor if you have:

  • a heart rhythm disorder;

  • liver disease;

  • kidney disease; or

  • a personal or family history of long QT syndrome.

It is not known whether Ranexa will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

It is not known whether ranolazine passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

How should I take Ranexa?

Take Ranexa exactly as prescribed by your doctor. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Ranexa may be taken with or without food.

Do not crush, chew, or break an extended-release tablet. Swallow it whole.

Call your doctor if your symptoms do not improve, or if they get worse while using Ranexa.

Chronic angina is often treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor’s advice.

Store Ranexa at room temperature away from moisture and heat.

Ranexa Dosing Information

Usual Adult Dose of Ranexa for Angina (Chest Pain):

The typical starting dose is: 500 mg orally twice daily. If needed, your doctor may increase to 1000 mg orally twice daily.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose can cause nausea, vomiting, numbness or tingling, dizziness, double vision, confusion, or fainting.

What should I avoid while taking Ranexa?

Ranexa may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Grapefruit and grapefruit juice may interact with Ranexa and lead to unwanted side effects. Discuss the use of grapefruit products with your doctor.

Ranexa side effects

Get emergency medical help if you have any signs of an allergic reaction to Ranexa: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • a light-headed feeling, like you might pass out;

  • headache with chest pain and severe dizziness, fast or pounding heartbeats; or

  • kidney problems – little or no urination; painful or difficult urination, swelling in your feet or ankles; feeling tired or short of breath.

Common Ranexa side effects may include:

  • nausea, constipation;

  • headache; or

  • dizziness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Ranexa?

The following drugs can interact with ranolazine and should not be used at the same time. Your doctor may need to change your treatment plan if you use any of the following drugs:

  • clarithromycin;

  • nefazodone;

  • St. John’s wort;

  • antifungal medicine – itraconazole, ketoconazole;

  • HIV or AIDS medicine – indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, saquinavir;

  • tuberculosis medicine – rifabutin, rifampin, rifapentine; or

  • seizure medicine-carbamazepine, phenobarbital, phenytoin.

Many other drugs can interact with Ranexa. Below is just a partial list. Tell your doctor if you are using:

This list is not complete and here are many other drugs that can interact with Ranexa. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you.

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Ranexa only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2020 Cerner Multum, Inc. Version: 11.01.

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  • Angina

Ranolazine (Ranexa) for Chronic Angina

SAFETY

Ranolazine prolongs the QTc interval in a dose-related manner, particularly in persons with mild, moderate, or severe hepatic dysfunction. It is contraindicated in patients with preexisting QT prolongation, including congenital long QT syndrome, uncorrected hypokalemia, and hepatic impairment. The manufacturer does not state when the drug should be discontinued if QT interval prolongation occurs, only that modest QT prolongation (four to six milliseconds) is associated with torsades de pointes arrhythmia. Ranolazine also has been reported to increase blood pressure by approximately 15 mm Hg in patients with severe renal impairment.1,2

Ranolazine should not be used in patients taking any medication that also prolongs the QT interval or inhibits the CYP3A enzyme system; this includes numerous medications. Potential drug-drug and drug-food interactions should be evaluated before starting ranolazine or when adding any therapy. Ranolazine is a U.S. Food and Drug Administration pregnancy category C drug. It is not known whether it is distributed in breast milk.1,2

TOLERABILITY

In controlled studies of patients with angina, approximately 6 percent of those receiving ranolazine discontinued treatment because of side effects compared with 3 percent of those receiving placebo.2 Dizziness, headache, and constipation were infrequently reported. Small, reversible elevations in serum creatinine and blood urea nitrogen levels have been reported, but no evidence of renal toxicity was observed.1–4

EFFECTIVENESS

Ranolazine primarily has been studied in patients who continue to be symptomatic despite pharmacotherapy with other anti-anginal medications, such as beta blockers or calcium antagonists. Patients with persistent angina who were given ranolazine in addition to another treatment experienced fewer episodes of angina attacks per week compared with patients given placebo (3.3 versus 4.3, respectively) and required fewer nitroglycerin doses per week (2.7 versus 3.6, respectively).2,3 When added to a regimen of maximal dose amlodipine, ranolazine significantly reduced the frequency of angina episodes per week compared with placebo (2.9 versus 3.3, respectively) and weekly nitroglycerine uses (2.0 versus 2.7, respectively).4

Ranolazine therapy increased exercise tolerance, but the average increase was only 30 seconds longer than that seen with placebo (2.0 and 1.5 minutes, respectively).2,5 Increases in exercise duration and decreases in exercise-induced ischemia and angina episodes were similar to those seen with atenolol (Tenormin) but without decreasing blood pressure or heart rate.6 To date, no studies have been conducted to measure the effects of ranolazine on mortality or the progression of coronary heart disease.

PRICE

The addition of ranolazine to beta blockers, calcium antagonists, or nitrates would cost approximately $206 for a one-month supply (60 tablets, 500 mg each).

SIMPLICITY

The recommended starting dosage of ranolazine is one tablet (500 mg) twice daily. It can be increased to two tablets twice daily as needed based on clinical symptoms. Ranolazine can be taken with or without meals and should be swallowed whole and not crushed, broken, or chewed. Grapefruit juice or products should be avoided. If a dose is missed, it should be taken at the next scheduled time; no doses should be doubled. Baseline and follow-up electrocardiography should be performed to evaluate the QTc interval, and blood pressure should be monitored regularly in patients with severe renal failure.1,2

SIDE EFFECTS

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

A total of 2018 patients with chronic angina were treated with ranolazine in controlled clinical trials. Of the patients treated with RANEXA, 1026 were enrolled in three double-blind, placebo-controlled, randomized studies (CARISA, ERICA, MARISA) of up to 12 weeks’ duration. In addition, upon study completion, 1251 patients received treatment with RANEXA in open-label, long-term studies; 1227 patients were exposed to RANEXA for more than 1 year, 613 patients for more than 2 years, 531 patients for more than 3 years, and 326 patients for more than 4 years.

At recommended doses, about 6% of patients discontinued treatment with RANEXA because of an adverse event in controlled studies in angina patients compared to about 3% on placebo. The most common adverse events that led to discontinuation more frequently on RANEXA than placebo were dizziness (1.3% versus 0.1%), nausea (1% versus 0%), asthenia, constipation, and headache (each about 0.5% versus 0%). Doses above 1000 mg twice daily are poorly tolerated.

The following additional adverse reactions occurred at an incidence of 0.5 to 4.0% in patients treated with RANEXA and were more frequent than the incidence observed in placebo-treated patients:

Cardiac Disorders – bradycardia, palpitations

Ear and Labyrinth Disorders – tinnitus, vertigo

Eye Disorders – blurred vision

Gastrointestinal Disorders – abdominal pain, dry mouth, vomiting, dyspepsia

General Disorders and Administrative Site Adverse Events – asthenia, peripheral edema

Metabolism and Nutrition Disorders – anorexia

Nervous System Disorders – syncope (vasovagal)

Psychiatric Disorders – confusional state

Renal and Urinary Disorders – hematuria

Respiratory, Thoracic, and Mediastinal Disorders – dyspnea

Skin and Subcutaneous Tissue Disorders – hyperhidrosis

Vascular Disorders – hypotension, orthostatic hypotension

Other ( < 0.5%) but potentially medically important adverse reactions observed more frequently with RANEXA than placebo treatment in all controlled studies included: angioedema, renal failure, eosinophilia, chromaturia, blood urea increased, hypoesthesia, paresthesia, tremor, pulmonary fibrosis, thrombocytopenia, leukopenia, and pancytopenia.

A large clinical trial in acute coronary syndrome patients was unsuccessful in demonstrating a benefit for RANEXA, but there was no apparent proarrhythmic effect in these high-risk patients .

Laboratory Abnormalities

RANEXA produces small reductions in hemoglobin A1c. RANEXA is not a treatment for diabetes.

RANEXA produces elevations of serum creatinine by 0.1 mg/dL, regardless of previous renal function, likely because of inhibition of creatinine’s tubular secretion. In general, the elevation has a rapid onset, shows no signs of progression during long-term therapy, is reversible after discontinuation of RANEXA, and is not accompanied by changes in BUN. In healthy volunteers, RANEXA 1000 mg twice daily had no effect upon the glomerular filtration rate. More marked and progressive increases in serum creatinine, associated with increases in BUN or potassium, indicating acute renal failure, have been reported after initiation of RANEXA in patients with severe renal impairment .

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of RANEXA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

Nervous System Disorders – Tremor, paresthesia, abnormal coordination, and other serious neurologic adverse events have been reported to occur, sometimes concurrently, in patients taking ranolazine. The onset of events was often associated with an increase in ranolazine dose or exposure. Many patients reported symptom resolution following drug discontinuation or dose decrease.

Psychiatric Disorders – hallucination

Renal and Urinary Disorders – dysuria, urinary retention

Skin and Subcutaneous Tissue Disorders – angioedema, pruritus, rash

Read the entire FDA prescribing information for Ranexa (Ranolazine)

CLINICAL PHARMACOLOGY

Mechanism Of Action

The mechanism of action of ranolazine’s antianginal effects has not been determined. Ranolazine has anti-ischemic and antianginal effects that do not depend upon reductions in heart rate or blood pressure. It does not affect the rate-pressure product, a measure of myocardial work, at maximal exercise. Ranolazine at therapeutic levels can inhibit the cardiac late sodium current (INa). However, the relationship of this inhibition to angina symptoms is uncertain.

The QT prolongation effect of ranolazine on the surface electrocardiogram is the result of inhibition of IKr, which prolongs the ventricular action potential.

Pharmacodynamics

Hemodynamic Effects

Patients with chronic angina treated with RANEXA in controlled clinical studies had minimal changes in mean heart rate ( < 2 bpm) and systolic blood pressure ( < 3 mm Hg). Similar results were observed in subgroups of patients with CHF NYHA Class I or II, diabetes, or reactive airway disease, and in elderly patients.

Electrocardiographic Effects

Dose and plasma concentration-related increases in the QTc interval , reductions in T wave amplitude, and, in some cases, notched T waves, have been observed in patients treated with RANEXA. These effects are believed to be caused by ranolazine and not by its metabolites. The relationship between the change in QTc and ranolazine plasma concentrations is linear, with a slope of about 2.6 msec/1000 ng/mL, through exposures corresponding to doses several-fold higher than the maximum recommended dose of 1000 mg twice daily. The variable blood levels attained after a given dose of ranolazine give a wide range of effects on QTc. At Tmax following repeat dosing at 1000 mg twice daily, the mean change in QTc is about 6 msec, but in the 5% of the population with the highest plasma concentrations, the prolongation of QTc is at least 15 msec. In cirrhotic subjects with mild or moderate hepatic impairment, the relationship between plasma level of ranolazine and QTc is much steeper .

Age, weight, gender, race, heart rate, congestive heart failure, diabetes, and renal impairment did not alter the slope of the QTc-concentration relationship of ranolazine.

No proarrhythmic effects were observed on 7-day Holter recordings in 3162 acute coronary syndrome patients treated with RANEXA. There was a significantly lower incidence of arrhythmias (ventricular tachycardia, bradycardia, supraventricular tachycardia, and new atrial fibrillation) in patients treated with RANEXA (80%) versus placebo (87%), including ventricular tachycardia ≥ 3 beats (52% versus 61%). However, this difference in arrhythmias did not lead to a reduction in mortality, a reduction in arrhythmia hospitalization, or a reduction in arrhythmia symptoms.

Pharmacokinetics

Ranolazine is extensively metabolized in the gut and liver and its absorption is highly variable. For example, at a dose of 1000 mg twice daily, the mean steady-state Cmax was 2600 ng/mL with 95% confidence limits of 400 and 6100 ng/mL. The pharmacokinetics of the (+) R- and (-) S-enantiomers of ranolazine are similar in healthy volunteers. The apparent terminal half-life of ranolazine is 7 hours. Steady state is generally achieved within 3 days of twice-daily dosing with RANEXA. At steady state over the dose range of 500 to 1000 mg twice daily, Cmax and AUC0-τ increase slightly more than proportionally to dose, 2.2- and 2.4-fold, respectively. With twice-daily dosing, the trough:peak ratio of the ranolazine plasma concentration is 0.3 to 0.6. The pharmacokinetics of ranolazine is unaffected by age, gender, or food.

Absorption and Distribution

After oral administration of RANEXA, peak plasma concentrations of ranolazine are reached between 2 and 5 hours. After oral administration of 14C-ranolazine as a solution, 73% of the dose is systemically available as ranolazine or metabolites. The bioavailability of ranolazine from RANEXA tablets relative to that from a solution of ranolazine is 76%. Because ranolazine is a substrate of P-gp, inhibitors of P-gp may increase the absorption of ranolazine.

Food (high-fat breakfast) has no important effect on the Cmax and AUC of ranolazine. Therefore, RANEXA may be taken without regard to meals. Over the concentration range of 0.25 to 10 μg/mL, ranolazine is approximately 62% bound to human plasma proteins.

Metabolism and Excretion

Ranolazine is metabolized mainly by CYP3A and, to a lesser extent, by CYP2D6. Following a single oral dose of ranolazine solution, approximately 75% of the dose is excreted in urine and 25% in feces. Ranolazine is metabolized rapidly and extensively in the liver and intestine; less than 5% is excreted unchanged in urine and feces. The pharmacologic activity of the metabolites has not been well characterized. After dosing to steady state with 500 mg to 1500 mg twice daily, the four most abundant metabolites in plasma have AUC values ranging from about 5 to 33% that of ranolazine, and display apparent half-lives ranging from 6 to 22 hours.

Drug Interactions

Effect of Other Drugs on Ranolazine

In vitro data indicate that ranolazine is a substrate of CYP3A and, to a lesser degree, of CYP2D6. Ranolazine is also a substrate of P-glycoprotein.

Strong CYP3A Inhibitors

Plasma levels of ranolazine with RANEXA 1000 mg twice daily are increased by 220% when co-administered with ketoconazole 200 mg twice daily .

Moderate CYP3A Inhibitors

Plasma levels of ranolazine with RANEXA 1000 mg twice daily are increased by 50 to 130% by diltiazem 180 to 360 mg, respectively. Plasma levels of ranolazine with RANEXA 750 mg twice daily are increased by 100% by verapamil 120 mg three times daily .

Weak CYP3A Inhibitors

The weak CYP3A inhibitors simvastatin (20 mg once daily) and cimetidine (400 mg three times daily) do not increase the exposure to ranolazine in healthy volunteers.

CYP3A Inducers

Rifampin 600 mg once daily decreases the plasma concentrations of ranolazine (1000 mg twice daily) by approximately 95% .

CYP2D6 Inhibitors

Paroxetine 20 mg once daily increased ranolazine concentrations by 20% in healthy volunteers receiving RANEXA 1000 mg twice daily. No dose adjustment of RANEXA is required in patients treated with CYP2D6 inhibitors.

Digoxin

Plasma concentrations of ranolazine are not significantly altered by concomitant digoxin at 0.125 mg once daily.

Effect of Ranolazine on Other Drugs

In vitro ranolazine and its O-demethylated metabolite are weak inhibitors of CYP3A and moderate inhibitors of CYP2D6 and P-gp. in vitro ranolazine is an inhibitor of OCT2.

CYP3A Substrates

The plasma levels of simvastatin, a CYP3A substrate, and its active metabolite are increased by 100% in healthy volunteers receiving 80 mg once daily and RANEXA 1000 mg twice daily . Mean exposure to atorvastatin (80 mg daily) is increased by 40% following co-administration with RANEXA (1000 mg twice daily) in healthy volunteers. However, in one subject the exposure to atorvastatin and metabolites was increased by ~400% in the presence of RANEXA.

Diltiazem

The pharmacokinetics of diltiazem is not affected by ranolazine in healthy volunteers receiving diltiazem 60 mg three times daily and RANEXA 1000 mg twice daily.

P-gp Substrates

Ranolazine increases digoxin concentrations by 50% in healthy volunteers receiving RANEXA 1000 mg twice daily and digoxin 0.125 mg once daily .

CYP2D6 Substrates

RANEXA 750 mg twice daily increases the plasma concentrations of a single dose of immediate release metoprolol (100 mg), a CYP2D6 substrate, by 80% in extensive CYP2D6 metabolizers with no need for dose adjustment of metoprolol. In extensive metabolizers of dextromethorphan, a substrate of CYP2D6, ranolazine inhibits partially the formation of the main metabolite dextrorphan.

OCT2 Substrates

In subjects with type 2 diabetes mellitus, the exposure to metformin is increased by 40% and 80% following administration of ranolazine 500 mg twice daily and 1000 mg twice daily, respectively. If co-administered with RANEXA 1000 mg twice daily, do not exceed metformin doses of 1700 mg/day .

Clinical Studies

Chronic Stable Angina

CARISA (Combination Assessment of Ranolazine In Stable Angina) was a study in 823 chronic angina patients randomized to receive 12 weeks of treatment with twice-daily RANEXA 750 mg, 1000 mg, or placebo, who also continued on daily doses of atenolol 50 mg, amlodipine 5 mg, or diltiazem CD 180 mg. Sublingual nitrates were used in this study as needed.

In this trial, statistically significant (p < 0.05) increases in modified Bruce treadmill exercise duration and time to angina were observed for each RANEXA dose versus placebo, at both trough (12 hours after dosing) and peak (4 hours after dosing) plasma levels, with minimal effects on blood pressure and heart rate. The changes versus placebo in exercise parameters are presented in Table 1. Exercise treadmill results showed no increase in effect on exercise at the 1000 mg dose compared to the 750 mg dose.

Table 1 : Exercise Treadmill Results (CARISA)

Study Mean Difference from Placebo (sec)
CARISA
(N=791)
RANEXA Twice-daily Dose 750 mg 1000 mg
Exercise Duration
Trough 24a 24a
Peak 34b 26a
Time to Angina
Trough 30a 26a
Peak 38b 38b
Time to 1 mm ST-Segment Depression
Trough 20 21
Peak 41b 35b
a p-value ≤ 0.05 b p-value ≤ 0.005

The effects of RANEXA on angina frequency and nitroglycerin use are shown in Table 2.

Table 2 : Angina Frequency and Nitroglycerin Use (CARISA)

Tolerance to RANEXA did not develop after 12 weeks of therapy. Rebound increases in angina, as measured by exercise duration, have not been observed following abrupt discontinuation of RANEXA.

RANEXA has been evaluated in patients with chronic angina who remained symptomatic despite treatment with the maximum dose of an antianginal agent. In the ERICA (Efficacy of Ranolazine In Chronic Angina) trial, 565 patients were randomized to receive an initial dose of RANEXA 500 mg twice daily or placebo for 1 week, followed by 6 weeks of treatment with RANEXA 1000 mg twice daily or placebo, in addition to concomitant treatment with amlodipine 10 mg once daily. In addition, 45% of the study population also received long-acting nitrates. Sublingual nitrates were used as needed to treat angina episodes. Results are shown in Table 3. Statistically significant decreases in angina attack frequency (p=0.028) and nitroglycerin use (p=0.014) were observed with RANEXA compared to placebo. These treatment effects appeared consistent across age and use of long-acting nitrates.

Table 3 : Angina Frequency and Nitroglycerin Use (ERICA)

Gender

Effects on angina frequency and exercise tolerance were considerably smaller in women than in men. In CARISA, the improvement in Exercise Tolerance Test (ETT) in females was about 33% of that in males at the 1000 mg twice-daily dose level. In ERICA, where the primary endpoint was angina attack frequency, the mean reduction in weekly angina attacks was 0.3 for females and 1.3 for males.

Race

There were insufficient numbers of non-Caucasian patients to allow for analyses of efficacy or safety by racial subgroup.

Lack Of Benefit In Acute Coronary Syndrome

In a large (n=6560) placebo-controlled trial (MERLIN-TIMI 36) in patients with acute coronary syndrome, there was no benefit shown on outcome measures. However, the study is somewhat reassuring regarding proarrhythmic risks, as ventricular arrhythmias were less common on ranolazine , and there was no difference between RANEXA and placebo in the risk of all-cause mortality (relative risk ranolazine:placebo 0.99 with an upper 95% confidence limit of 1.22).

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Amisulpride
  • Amitriptyline
  • Amoxapine
  • Amprenavir
  • Atazanavir
  • Bepridil
  • Carbamazepine
  • Cisapride
  • Clarithromycin
  • Clomipramine
  • Cobicistat
  • Colchicine
  • Darunavir
  • Desipramine
  • Doxepin
  • Dronedarone
  • Fosamprenavir
  • Fosphenytoin
  • Idelalisib
  • Imipramine
  • Indinavir
  • Itraconazole
  • Ketoconazole
  • Lopinavir
  • Mesoridazine
  • Nefazodone
  • Nelfinavir
  • Nortriptyline
  • Phenobarbital
  • Phenytoin
  • Pimozide
  • Piperaquine
  • Posaconazole
  • Protriptyline
  • Rifabutin
  • Rifampin
  • Rifapentine
  • Ritonavir
  • Saquinavir
  • Sparfloxacin
  • St John’s Wort
  • Terfenadine
  • Thioridazine
  • Trimipramine
  • Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Acecainide
  • Afatinib
  • Alfentanil
  • Alfuzosin
  • Amiodarone
  • Anagrelide
  • Apomorphine
  • Aprepitant
  • Aripiprazole
  • Aripiprazole Lauroxil
  • Arsenic Trioxide
  • Artemether
  • Asenapine
  • Astemizole
  • Azimilide
  • Azithromycin
  • Bedaquiline
  • Benzhydrocodone
  • Betrixaban
  • Bretylium
  • Buprenorphine
  • Buserelin
  • Ceritinib
  • Chloroquine
  • Chlorpromazine
  • Ciprofloxacin
  • Citalopram
  • Clofazimine
  • Clozapine
  • Codeine
  • Conivaptan
  • Crizotinib
  • Cyclobenzaprine
  • Cyclosporine
  • Dabigatran Etexilate
  • Dabrafenib
  • Dasatinib
  • Degarelix
  • Delamanid
  • Deslorelin
  • Deutetrabenazine
  • Digoxin
  • Dihydrocodeine
  • Dihydroergotamine
  • Diltiazem
  • Dofetilide
  • Dolasetron
  • Domperidone
  • Donepezil
  • Doxorubicin
  • Doxorubicin Hydrochloride Liposome
  • Droperidol
  • Efavirenz
  • Eliglustat
  • Encorafenib
  • Entrectinib
  • Ergotamine
  • Erythromycin
  • Escitalopram
  • Fentanyl
  • Fingolimod
  • Flecainide
  • Fluconazole
  • Fluoxetine
  • Fosaprepitant
  • Foscarnet
  • Fosnetupitant
  • Gatifloxacin
  • Gemifloxacin
  • Glasdegib
  • Gonadorelin
  • Goserelin
  • Granisetron
  • Halofantrine
  • Haloperidol
  • Histrelin
  • Hydrocodone
  • Hydroxychloroquine
  • Hydroxyzine
  • Ibutilide
  • Iloperidone
  • Inotuzumab Ozogamicin
  • Ivabradine
  • Ivosidenib
  • Lapatinib
  • Lefamulin
  • Lenvatinib
  • Leuprolide
  • Levofloxacin
  • Lofexidine
  • Lovastatin
  • Lumefantrine
  • Macimorelin
  • Mefloquine
  • Meperidine
  • Methadone
  • Metronidazole
  • Mifepristone
  • Morphine
  • Morphine Sulfate Liposome
  • Moxifloxacin
  • Nafarelin
  • Netupitant
  • Nilotinib
  • Norfloxacin
  • Octreotide
  • Ofloxacin
  • Ondansetron
  • Osimertinib
  • Oxycodone
  • Paliperidone
  • Panobinostat
  • Pasireotide
  • Pazopanib
  • Pentazocine
  • Pimavanserin
  • Pitolisant
  • Pixantrone
  • Prochlorperazine
  • Promethazine
  • Propafenone
  • Quetiapine
  • Quinidine
  • Quinine
  • Ribociclib
  • Sematilide
  • Sertraline
  • Sevoflurane
  • Simeprevir
  • Simvastatin
  • Siponimod
  • Sodium Phosphate
  • Sodium Phosphate, Dibasic
  • Sodium Phosphate, Monobasic
  • Solifenacin
  • Sorafenib
  • Sotalol
  • Sufentanil
  • Sulpiride
  • Sunitinib
  • Tacrolimus
  • Tedisamil
  • Telithromycin
  • Tetrabenazine
  • Tizanidine
  • Topotecan
  • Toremifene
  • Tramadol
  • Trazodone
  • Triclabendazole
  • Trifluoperazine
  • Triptorelin
  • Vandetanib
  • Vardenafil
  • Vemurafenib
  • Venetoclax
  • Verapamil
  • Vincristine
  • Vincristine Sulfate Liposome
  • Vinflunine
  • Voriconazole
  • Zuclopenthixol

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Metformin

Ranexa is the brand name of ranolazine, a prescription drug used to treat chronic angina – spasmodic attacks of intense chest pain that occur when there’s an insufficient supply of blood to the heart.

“Chronic” is the key word here: The drug should not be used to treat an intense, sudden attack of angina.

Ranexa is one drug in the class of anti-anginal medications, which also include beta-blockers, nitrates, and calcium channel blockers.

Ranexa has also been prescribed “off-label” to treat atrial fibrillation, a rapid, irregular heart rate.

It’s believed that Ranexa works by inhibiting the excess sodium that can flow into the heart during an angina attack — sodium sets off an overload of calcium that causes the heart muscle to contract and stiffen.

Ranexa is thought to improve the flow of blood to the heart so that it beats more efficiently.

The Food and Drug Administration (FDA) approved Ranexa in 2006 as an “add-on” drug to be used with other anti-anginal medications that failed to work on their own.

But in 2008, the FDA revised the drug’s label to allow Ranexa to be taken by itself or with other anti-anginal drugs.

Unlike these other anti-anginal medications, Ranexa, which comes in extended-release tablets, does not lower heart rate or blood pressure.

Gilead Sciences acquired Ranexa when it took over CV Therapeutics (Ranexa’s developer) in 2009, and no generic versions of the drug exist at this time.

Following the settlement of Gilead’s patent-infringement suit against Lupin in 2013, Lupin has been allowed to make and market a generic version of Ranexa starting in 2019.

Ranexa Warnings

The heart rhythm disorder called QT prolongation, or long QT syndrome, which can cause fast, irregular heartbeats, can occur when taking Ranexa.

You need to let your doctor know if you or a family member has a history of QT prolongation.

Ranexa also comes with a warning about possible kidney failure in patients who already have moderate to severe kidney impairment.

Since you will need additional testing, inform your doctor if you have compromised kidney function before you begin treatment.

Your doctor also needs to know if you have liver disease (e.g., cirrhosis), if you have any allergies, and about all the medications you take, whether prescription or over-the-counter, vitamins, illegal or recreational drugs, and dietary or herbal supplements, as they can affect how Ranexa works, and vice-versa.

You must tell your doctor if you are taking St. John’s wort, any medications for fungal infections or any other infections, depression, HIV, tuberculosis (TB), or seizures, as many medications used to treat these conditions should not be used with Ranexa.

Medications you are taking for your heart, cholesterol, diabetes, or for nausea and vomiting brought on by chemotherapy, or any drugs you’re taking to treat mental health problems, also need to be discussed.

Pregnancy and Ranexa

Ranexa might harm a pregnant woman’s fetus. Nonetheless, the drug’s benefits to the mother may outweigh the potential risks to her developing fetus.

You should always tell your doctor if you are pregnant or might become pregnant.

If you are breastfeeding or plan to breastfeed, it’s not known if Ranexa is excreted in breast milk, so you need to decide with your doctor whether to take Ranexa or breastfeed, as you should not do both.

About ranolazine for angina

Type of medicine An anti-anginal medicine
Used for To prevent angina chest pain
Also called Ranexa®
Available as Tablets

Angina is a pain that comes from the heart. It is usually caused by the narrowing of one or more of the arteries that supply blood to your heart. This narrowing reduces the blood supply to parts of your heart muscle. When your heart needs more blood and oxygen than it can get through the narrowed arteries (for example, when you walk fast or climb stairs), you feel angina pain.

Ranolazine is taken in addition to other medicines used to prevent angina pain. You will be prescribed it if the other anti-anginal medicines you are taking are not sufficiently controlling your chest pains.

Before taking ranolazine

Some medicines are not suitable for people with certain conditions, and sometimes a medicine can only be used if extra care is taken. For these reasons, before you start taking ranolazine it is important that your doctor knows:

  • If you are pregnant or breastfeeding.
  • If you know you have an irregular heart rhythm.
  • If you have been told you have heart failure, which is a condition where your heart is not working as well as it should.
  • If you have any problems with the way your liver works, or any problems with the way your kidneys work.
  • If you have ever had an allergic reaction to a medicine.
  • If you are taking or using any other medicines. This includes any medicines you are taking which are available to buy without a prescription, as well as herbal and complementary medicines.

How to take ranolazine

  • Before you start the treatment, read the manufacturer’s printed information leaflet from inside the pack. It will give you more information about ranolazine and will also provide you with a full list of side-effects which you could experience from taking it.
  • Take ranolazine exactly as your doctor tells you to. It is usual to take one tablet two times a day. When starting your treatment your doctor will give you a smaller-strength tablet (375 mg tablet) and may then gradually increase your dose to a 500 mg or a 750 mg strength of tablet. This allows your doctor to make sure that you have the dose that helps your condition but avoids any unwanted symptoms.
  • Try to take your doses at the same times of day each day, as this will help you to remember to take them regularly. You can take ranolazine either before or after a meal. Swallow the tablet whole (without chewing or crushing it) with a drink of water.
  • If you forget to take a dose at your usual time, take it when you remember. However, if it is nearly time to take your next dose when you remember then leave out the forgotten dose and take your next dose when it is due. Do not take two doses together to make up for a missed dose.

Getting the most from your treatment

  • Ranolazine tablets are not suitable to take to relieve pain if you are having an angina attack. Your doctor will also prescribe a nitrate medicine, such as glyceryl trinitrate (GTN), for you to take if this happens. If after using GTN your pain has not eased within a few minutes, call for an ambulance.
  • Try to keep your regular appointments with your doctor. This is so your doctor can check on your progress.
  • Treatment with ranolazine is usually long-term unless you experience an adverse effect. Continue to take the tablets unless you are advised otherwise by your doctor.
  • Do not drink grapefruit juice while you are on ranolazine. This is because a chemical in grapefruit juice increases the amount of ranolazine in your bloodstream. This makes side-effects more likely.
  • It is important if you buy any medicines ‘over the counter’ to check with a pharmacist that they are suitable for you to take. Some medicines and herbal remedies should not be taken with ranolazine.

Can ranolazine cause problems?

Along with their useful effects, most medicines can cause unwanted side-effects although not everyone experiences them. The table below contains some of the most common ones associated with ranolazine. You will find a full list in the manufacturer’s information leaflet supplied with your medicine. The unwanted effects often improve as your body adjusts to the new medicine, but speak with your doctor or pharmacist if any of the following continue or become troublesome.

Common ranolazine side-effects (these affect less than 1 in 10 people) What can I do if I experience this?
Feeling dizzy or weak Do not drive and do not use tools or machines while affected. Please let your doctor know about any dizziness as your dose may need adjusting
Headache Drink plenty of water and ask your pharmacist to recommend a suitable painkiller. If the headaches continue, let your doctor know
Constipation Eat a well-balanced diet and drink plenty of water
Feeling sick (nausea) or being sick (vomiting) Eat simple meals – avoid rich or spicy food. If this continues let your doctor know as your dose may need adjusting

If you experience any other symptoms which you think may be due to the tablets, speak with your doctor or pharmacist for further advice.

How to store ranolazine

  • Keep all medicines out of the reach and sight of children.
  • Store in a cool, dry place, away from direct heat and light.

Important information about all medicines

Never take more than the prescribed dose. If you suspect that you or someone else might have taken an overdose of this medicine go to the accident and emergency department of your local hospital at once. Take the container with you, even if it is empty.

This medicine is for you. Never give it to other people even if their condition appears to be the same as yours.

Do not keep out-of-date or unwanted medicines. Take them to your local pharmacy which will dispose of them for you.

If you have any questions about this medicine ask your pharmacist.

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