Ranolazine

(ra noe' la zeen)

Molecule Info

 |  See TERMINOLOGY & ABBREVIATIONS |
Content & Description

Tablet, Film Coated, Extended Release ranolazine 500mg & 1000mg.

Ranolazine is available as a film-coated, non-scored, extended-release tablet for oral administration.

Ranolazine is a racemic mixture, chemically described as 1-piperazineacetamide, N-(2,6-dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-, (±)-. It has an empirical formula of C24H33N3O4, a molecular weight of 427.54 g/mole. 

Ranolazine is a white to off-white solid. Ranolazine is soluble in dichloromethane and methanol; sparingly soluble in tetrahydrofuran, ethanol, acetonitrile, and acetone; slightly soluble in ethyl acetate, isopropanol, toluene, and ethyl ether; and very slightly soluble in water. 

Ranolazine tablet may contain 500mg or 1000mg of ranolazine and the following inactive ingredients: carnauba wax, hypromellose, magnesium stearate, methacrylic acid copolymer (Type C), microcrystalline cellulose, polyethylene glycol, sodium hydroxide, and titanium dioxide. Additional inactive ingredients for the 500 mg tablet include polysorbate 80 and FD&C Yellow No. 6 Lake; additional inactive ingredients for the 1000 mg tablet include lactose monohydrate, triacetin, and Iron Oxide Yellow.

Indication(s) & Dosage

Ranolazine is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled or intolerant to first-line antianginal therapies (such as beta-blockers and/or calcium antagonists).

Dosing Information

Initiate Ranolazine dosing at 500 mg twice daily and increase to 1000 mg twice daily, as needed, based on clinical symptoms. Take Ranolazine with or without meals. Swallow Ranolazine tablets whole; do not crush, break, or chew.

The maximum recommended daily dose of Ranolazine is 1000 mg twice daily. 

If a dose of Ranolazine is missed, take the prescribed dose at the next scheduled time; do not double the next dose. 

Dose Modification
Dose adjustments may be needed when Ranolazine is taken in combination with certain other drugs. Limit the maximum dose of Ranolazine to 500 mg twice daily in patients on diltiazem, verapamil, and other moderate CYP3A inhibitors. Down-titrate Ranolazine based on clinical response in patients concomitantly treated with P-gp inhibitors, such as cyclosporine. 

Ranolazine may be supplied as film-coated, oblong-shaped, extended-release tablets in 500 & 1000mg strengths.

Overdosage

In an oral high-dose tolerability study in angina patients, the incidence of dizziness, nausea, and vomiting increased in a dose-dependent manner. In addition to these adverse events, diplopia, lethargy, and syncope were observed in an intravenous overdose study in healthy volunteers. In the event of overdose, the patient should be closely monitored and the treatment should be symptomatic and supportive.

Approximately 62% of ranolazine is bound to plasma proteins, and therefore, complete clearance by haemodialysis is unlikely.

Contraindications Ranolazine is contraindicated in patients:
  • Taking strong inhibitors of CYP3A 
  • Taking inducers of CYP3A
  • With clinically significant hepatic impairment
Warnings & Precautions

• QT interval prolongation: Can occur with ranolazine. Little data available on high doses, long exposure, use with QT interval-prolonging drugs, potassium channel variants causing prolonged QT interval, in patients with a family history of (or congenital) long QT syndrome, or in patients with known acquired QT interval prolongation.


Pregnancy Category (FDA) and use in Specific Population

USE IN SPECIFIC POPULATIONS

Pregnancy: Pregnancy Category C
In animal studies, ranolazine at exposures 1.5 (rabbit) to 2 (rat) times the usual human exposure caused maternal toxicity and misshapen sternebrae and reduced ossification in offspring. These doses in rats and rabbits were associated with an increased maternal mortality rate. There are no adequate well-controlled studies in pregnant women. Ranolazine should be used during pregnancy only when the potential benefit to the patient justifies the potential risk to the fetus. 

Nursing Mothers
It is not known whether ranolazine is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions from ranolazine in nursing infants, decide whether to discontinue nursing or to discontinue Ranolazine, taking into account the importance of the drug to the mother. 

Pediatric Use
Safety and effectiveness have not been established in pediatric patients. 

Geriatric Use
Of the chronic angina patients treated with Ranolazine in controlled studies, 496 (48%) were ≥ 65 years of age, and 114 (11%) were ≥ 75 years of age. No overall differences in efficacy were observed between older and younger patients. There were no differences in safety for patients ≥ 65 years compared to younger patients, but patients ≥ 75 years of age on ranolazine, compared to placebo, had a higher incidence of adverse events, serious adverse events, and drug discontinuations due to adverse events. In general, dose selection for an elderly patient should usually start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease, or other drug therapy.

Use in Patients with Hepatic Impairment 
Ranolazine is contraindicated in patients with clinically significant hepatic impairment. Plasma concentrations of ranolazine were increased by 30% in patients with mild (Child-Pugh Class A) and by 60% in patients with moderate (Child-Pugh Class B) hepatic impairment. This was not enough to account for the 3-fold increase in QT prolongation seen in patients with mild to severe hepatic impairment.

Use in Patients with Renal Impairment 
In patients with varying degrees of renal impairment, ranolazine plasma levels increased up to 50%. The pharmacokinetics of ranolazine has not been assessed in patients on dialysis. 

Use in Patients with Heart Failure 
Heart failure (NYHA Class I to IV) had no significant effect on ranolazine pharmacokinetics. Ranolazine had minimal effects on heart rate and blood pressure in patients with angina and heart failure NYHA Class I to IV. No dose adjustment of Ranolazine is required in patients with heart failure.

Use in Patients with Diabetes Mellitus 
A population pharmacokinetic evaluation of data from angina patients and healthy subjects showed no effect of diabetes on ranolazine pharmacokinetics. No dose adjustment is required in patients with diabetes. 

Ranolazine produces small reductions in HbA1c in patients with diabetes, the clinical significance of which is unknown. Ranolazine should not be considered a treatment for diabetes. 

NONCLINICAL TOXICOLOGY

Carcinogenesis, Mutagenesis, Impairment of Fertility
Ranolazine tested negative for genotoxic potential in the following assays: Ames bacterial mutation assay, Saccharomyces assay for mitotic gene conversion, chromosomal aberrations assay in Chinese hamster ovary (CHO) cells, mammalian CHO/HGPRT gene mutation assay, and mouse and rat bone marrow micronucleus assays. 

There was no evidence of carcinogenic potential in mice or rats. The highest oral doses used in the carcinogenicity studies were 150 mg/kg/day for 21 months in rats (900 mg/m2/day) and 50 mg/kg/day for 24 months in mice (150 mg/m2/day). These maximally tolerated doses are 0.8 and 0.1 times, respectively, the maximum recommended human dose (MRHD) of 2 grams on a surface area basis. A published study reported that ranolazine promoted tumor formation and progression to malignancy when given to transgenic APC (min/+) mice at a dose of 30 mg/kg twice daily. The clinical significance of this finding is unclear.

Reproductive Toxicology Studies
Animal reproduction studies with ranolazine were conducted in rats and rabbits.
There was an increased incidence of misshapen sternebrae and reduced ossification of pelvic and cranial bones in fetuses of pregnant rats dosed at 400 mg/kg/day (2 times the MRHD on a surface area basis). Reduced ossification of sternebrae was observed in fetuses of pregnant rabbits dosed at 150 mg/kg/day (1.5 times the MRHD on a surface area basis). These doses in rats and rabbits were associated with an increased maternal mortality rate.

Adverse Drug Reaction(s)
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 2,018 patients with chronic angina were treated with ranolazine in controlled clinical trials. Of the patients treated with Ranolazine, 1,026 were enrolled in three double-blind, placebo-controlled, randomized studies (CARISA, ERICA, MARISA) of up to 12 weeks duration. In addition, upon study completion, 1,251 patients received treatment with Ranolazine in open-label, long-term studies; 1,227 patients were exposed to Ranolazine 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 Ranolazine 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 Ranolazine 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.

In controlled clinical trials of angina patients, the most frequently reported treatment-emergent adverse reactions (> 4% and more common on Ranolazine than on placebo) were dizziness (6.2%), headache (5.5%), constipation (4.5%), and nausea (4.4%). Dizziness may be dose-related. In open-label, long-term treatment studies, a similar adverse reaction profile was observed. 

The following additional adverse reactions occurred at an incidence of 0.5 to 2.0% in patients treated with Ranolazine and were more frequent than the incidence observed in placebo-treated patients:

Cardiac Disorders â€“ bradycardia, palpitations

Ear and Labyrinth Disorders â€“ tinnitus, vertigo 

Gastrointestinal Disorders â€“ abdominal pain, dry mouth, vomiting

General Disorders and Administrative Site Adverse Events â€“ peripheral edema

RespiratoryThoracic, and Mediastinal Disorders â€“ dyspnea

Vascular Disorders â€“ hypotension, orthostatic hypotension

Other (< 0.5%) but potentially medically important adverse reactions observed more frequently with Ranolazine than placebo treatment in all controlled studies included: angioedema, renal failure, eosinophilia, blurred vision, confusional state, hematuria, 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 Ranolazine, but there was no apparent proarrhythmic effect in these high-risk patients

Laboratory Abnormalities
Ranolazine produces small reductions in hemoglobin A1c. Ranolazine is not a treatment for diabetes. 

Ranolazine produces elevations of serum creatinine by 0.1 mg/dL, regardless of previous renal function. The elevation has a rapid onset, shows no signs of progression during long-term therapy, is reversible after discontinuation of Ranolazine, and is not accompanied by changes in BUN. In healthy volunteers, Ranolazine 1000 mg twice daily had no effect upon the glomerular filtration rate. The elevated creatinine levels are likely due to a blockage of creatinine's tubular secretion by ranolazine or one of its metabolites.
Drug Interactions

Effects of Other Drugs on Ranolazine
Ranolazine is primarily metabolized by CYP3A and is a substrate of P-glycoprotein (P-gp).

CYP3A Inhibitors 
Do not use Ranolazine with strong CYP3A inhibitors, including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir. Ketoconazole (200 mg twice daily) increases average steady-state plasma concentrations of ranolazine 3.2-fold [see Contraindications].

Limit the dose of Ranolazine to 500 mg twice daily in patients on moderate CYP3A inhibitors, including diltiazem, verapamil, aprepitant, erythromycin, fluconazole, and grapefruit juice or grapefruit-containing products. Diltiazem (180–360 mg daily) and verapamil (120 mg three times daily) increase ranolazine steady-state plasma concentrations about 2-fold

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

P-gp Inhibitors 
Down-titrate Ranolazine based on clinical response in patients concomitantly treated with P-gp inhibitors, such as cyclosporine

CYP3A and P-gp Inducers
Avoid co-administration of Ranolazine and CYP3A inducers such as rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, and St. John's wort. Rifampin (600 mg once daily) decreases the plasma concentration of ranolazine (1000 mg twice daily) by approximately 95% by induction of CYP3A and, probably, P-gp. 

CYP2D6 Inhibitors
The potent CYP2D6 inhibitor, paroxetine (20 mg once daily), increases ranolazine concentrations 1.2-fold. No dose adjustment of Ranolazine is required in patients treated with CYP2D6 inhibitors.

Digoxin 
Digoxin (0.125 mg) does not significantly alter ranolazine levels.

Effects of Ranolazine on Other Drugs
In vitro studies indicate that ranolazine and its O-demethylated metabolite are weak inhibitors of CYP3A, moderate inhibitors of CYP2D6 and moderate P-gp inhibitors. Ranolazine and its most abundant metabolites are not known to inhibit the metabolism of substrates for CYP 1A2, 2C8, 2C9, 2C19, or 2E1 in human liver microsomes, suggesting that ranolazine is unlikely to alter the pharmacokinetics of drugs metabolized by these enzymes. 

Drugs Metabolized by CYP3A 
The plasma levels of simvastatin, a CYP3A substrate, and its active metabolite are each increased about 2-fold in healthy subjects receiving simvastatin (80 mg once daily) and Ranolazine (1000 mg twice daily). Dose adjustments of simvastatin are not required when Ranolazine is co-administered with simvastatin. 

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

Drugs Transported by P-gp
Ranolazine (1000 mg twice daily) causes a 1.5-fold elevation of digoxin plasma concentrations. The dose of digoxin may have to be adjusted. 

Drugs Metabolized by CYP2D6
Ranolazine or its metabolites partially inhibit CYP2D6. There are no studies of concomitant use of Ranolazine with other drugs metabolized by CYP2D6, such as tricyclic antidepressants and antipsychotics, but lower doses of CYP2D6 substrates may be required.

Storage Store Ranolazine tablets at 25°C (77°F) with excursion permitted to 15° to 30°C (59° to 86°F).
Pharmacology

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 Ranolazine 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 Ranolazine. 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 subjects with mild or moderate hepatic impairment, the relationship between plasma level of ranolazine and QTc is much steeper [see Contraindications]

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 3,162 acute coronary syndrome patients treated with Ranolazine. There was a significantly lower incidence of arrhythmias (ventricular tachycardia, bradycardia, supraventricular tachycardia, and new atrial fibrillation) in patients treated with Ranolazine (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 Ranolazine. At steady state over the dose range of 500 to 1000 mg twice daily, Cmax and AUC0-Ï„ 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 Ranolazine, 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 Ranolazine 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, Ranolazine 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. 

CLINICAL STUDIES
(Reference Brand: 
Ranexa®)

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 Ranolazine 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 Ranolazine 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. 

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

Table 2 Angina Frequency and Nitroglycerin Use (CARISA)
  Placebo Ranolazine
750 mg
Ranolazine
1000 mg#
#Twice daily
Angina Frequency
(attacks/week)
N 258 272 261
Mean 3.3 2.5 2.1
p-value vs placebo — 0.006 < 0.001
Nitroglycerin Use
(doses/week)
N 252 262 244
Mean 3.1 2.1 1.8
p-value vs placebo — 0.016 < 0.001

Tolerance to Ranolazine 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 Ranolazine.

Ranolazine 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 Ranolazine 500 mg twice daily or placebo for 1 week, followed by 6 weeks of treatment with Ranolazine 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 Ranolazine compared to placebo. These treatment effects appeared consistent across age and use of long-acting nitrates.

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 = 6,560) 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 Ranolazine and placebo in the risk of all-cause mortality (relative risk ranolazine:placebo 0.99 with an upper 95% confidence limit of 1.22).

 

Brand/Product Info


Total Products : 4    
Brand Name Manufacturer/Marketer Composition Dosage Form Pack Size & Price
Ralozine SR Incepta Pharmaceuticals Limited Ranolazine INN 500 mg Film Coated Tablet 20's:MRP 320 Tk
RANOLA ER General Pharmaceuticals Ltd Ranolazine INN 500mg Tablet (extended release) 500mg x 20's: 280.00 MRP
RANOLIN XR Square Pharmaceuticals Ltd. Ranolazine 500mg Tablet 2x10's: 321.00 MRP
RANOLIN XR 500mg Square Pharmaceuticals Ltd. Ranolazine 500mg Tablet 20's: 320.00 MRP

Gen. MedInfo

Why is this medication prescribed?

Ranolazine is used alone or with other medications to treat ongoing angina (chest pain or pressure that is felt when the heart does not get enough oxygen). Ranolazine is in a class of medications called anti-anginals. The exact way that ranolazine works is not known at this time.

How should this medicine be used?

Ranolazine comes as an extended-release (long-acting) tablet to take by mouth. It is usually taken with or without food two times a day. Take ranolazine at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor to explain any part you do not understand. Take ranolazine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the tablets whole; do not break, chew, or crush them.

Your doctor will probably start you on a low dose of ranolazine and gradually increase your dose.

Do not take ranolazine to treat a sudden attack of angina. Your doctor will tell you what you should do if you experience an attack of angina. Make sure that you understand these directions.

Ranolazine may help control your condition but will not cure it. Continue to take ranolazine even if you feel well. Do not stop taking ranolazine without talking to your doctor.

Other uses for this medicine

This medication may be prescribed for other uses; ask your doctor for more information.

What special precautions should I follow?

Before taking ranolazine,

  • tell your doctor if you are allergic to ranolazine or any other medications.
  • tell your doctor if you are taking any of the following medications: clarithromycin; certain antifungals such as itraconazole and ketoconazole (Nizoral); certain medications to treat human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) such as indinavir, nelfinavir, ritonavir, and saquinavir; nefazodone; certain medications for seizures such as carbamazepine, phenobarbital, and phenytoin; rifabutin; rifampin; and rifapentin . Also tell your doctor if you are taking St. John's wort. Your doctor may tell you not to take ranolazine if you are taking one or more of these medications or herbal products.
  • tell your doctor what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: amiodarone; certain antidepressants such as amitriptyline, clomipramine, desipramine, and imipramine; aprepitant; cisapride ; cyclosporine; digoxin; diltiazem; disopyramide; dofetilide; erythromycin; fluconazole; certain medications for mental illness such as haloperidol, risperidone, thioridazine, and ziprasidone; moxifloxacin; pimozide; procainamide; quinidine; sotalol; sparfloxacin ; and verapamil . Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with ranolazine, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list or the list above.
  • tell your doctor if you have or have ever had liver disease. Your doctor may tell you that you should not take ranolazine.
  • tell your doctor if you or anyone in your family has or has ever had a prolonged QT interval (a rare heart problem that may cause fainting or irregular heartbeat) or a fast, slow, or irregular heartbeat. Also tell your doctor if you have or have ever had an abnormal electrocardiogram (EKG: heart rhythm test), low levels of potassium in the blood, or kidney disease.
  • tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking ranolazine, call your doctor.
  • you should know that ranolazine may make you dizzy and lightheaded. Do not drive a car, operate machinery, or participate in activities requiring mental alertness and coordination until you know how this medication affects you.

What special dietary instructions should I follow?

Do not drink grapefruit juice or eat grapefruit products while taking this medication.

What should I do if I forget a dose?

Skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What side effects can this medication cause?

Ranolazine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

  • nausea

  • constipation

  • headache

  • dizziness

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

  • fast, pounding, or irregular heartbeat

  • difficulty breathing

  • fainting

Ranolazine may cause other side effects. Call your doctor if you have any unusual problems while you are taking this medication.

What should I know about storage and disposal of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

In case of emergency/overdose

In case of overdose, consult your doctor. If the victim has collapsed or is not breathing, consult local medical emergency services.

Symptoms of overdose may include:

  • nausea

  • vomiting

  • dizziness

  • confusion

  • double vision

  • pain, burning, numbness, or tingling in any part of the body

  • fainting

What other information should I know?

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your response to this medicine.

Do not let anyone else use your medication. If you still have symptoms and need further treatment, consult your doctor.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Ref:  U.S. National Library of Medicine.


This information is provided for reference only and not a replacement for and should only be used in conjunction with full consultation with a registered medical practitioner. It may not contain all the available information you require and cannot substitute professional medical care, nor does it take into account all individual circumstances. Although great effort has been made to ensure content accuracy, mph-bd shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise.

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