Ranolazine
Tablet, Film Coated, Extended Release · Oral
Uses
Ranolazine extended-release tablets is indicated for the treatment of chronic angina. Ranolazine extended-release tablets may be used with beta-blockers, nitrates, calcium channel blockers, anti- platelet therapy, lipid-lowering therapy, ACE inhibitors, and angiotensin receptor blockers. Ranolazine extended-release tablets is an antianginal indicated for the treatment of chronic angina.
Dosage and administration
500 mg twice daily and increase to 1,000 mg twice daily, based on clinical symptoms. ( 2.1 ) 2.1 Dosing Information Initiate ranolazine extended-release tablets dosing at 500 mg twice daily and increase to 1,000 mg twice daily, as needed, based on clinical symptoms. Take ranolazine extended-release tablets with or without meals. Swallow ranolazine extended-release tablets whole; do not crush, break, or chew. The maximum recommended daily dose of ranolazine extended-release tablets is 1,000 mg twice daily. If a dose of ranolazine extended-release tablets is missed, take the prescribed dose at the next scheduled time; do not double the next dose. 2.2 Dose Modification Dose adjustments may be needed when ranolazine extended-release tablets is taken in combination with certain other drugs [see Drug Interactions (7.1) ]. Limit the maximum dose of ranolazine extended-release tablets to 500 mg twice daily in patients on moderate CYP3A inhibitors such as diltiazem, verapamil, and erythromycin. Use of ranolazine extended-release tablets with strong CYP3A inhibitors is contraindicated [see Contraindications (4) , Drug Interactions (7.1) ]. Use of P-gp inhibitors, such as cyclosporine, may increase exposure to ranolazine extended-release tablets. Titrate ranolazine extended-release tablets based on clinical response [see Drug Interactions (7.1) ].
Dosage forms and strengths
Ranolazine extended-release tablets is supplied as film-coated, oblong-shaped, extended-release tablets in the following strengths: 500 mg tablets are Yellow color, with RAN500 on one side and plain on other side 1,000 mg tablets are Yellow color, with RAN1000 on one side and plain on other side Extended-release tablets: 500 mg, 1,000 mg.
Contraindications
Ranolazine extended-release tablets is contraindicated in patients: Taking strong inhibitors of CYP3A [see Drug Interactions (7.1) ] Taking inducers of CYP3A [see Drug Interactions (7.1) ] With liver cirrhosis [see Use in Specific Populations (8.6) ] Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin, nelfinavir) ( 4 , 7.1 ) CYP3A inducers (e.g., rifampin, phenobarbital, St. John's wort) ( 4 , 7.1 ) Liver cirrhosis ( 4 , 8.6 )
Warnings and precautions
5 WARNINGS AND 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. ( 5.1 ) Renal failure: Monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (CrCL<60 mL/min). If acute renal failure develops, discontinue ranolazine extended-release tablets. ( 5.2 ) 5.1 QT Interval Prolongation Ranolazine blocks I Kr and prolongs the QTc interval in a dose-related manner. Clinical experience in an acute coronary syndrome population did not show an increased risk of proarrhythmia or sudden death [see Clinical Studies (14.2) ]. However, there is little experience with high doses (>1,000 mg twice daily) or exposure, other QT- prolonging drugs, potassium channel variants resulting in a long QT interval, in patients with a family history of (or congenital) long QT syndrome, or in patients with known acquired QT interval prolongation. 5.2 Renal Failure Acute renal failure has been observed in some patients with severe renal impairment (creatinine clearance [CrCL] <30 mL/min) while taking ranolazine extended-release tablets. If acute renal failure develops (e.g., marked increase in serum creatinine associated with an increase in blood urea nitrogen [BUN]), discontinue ranolazine extended-release tablets and treat appropriately [see Use in Specific Populations (8.7) ]. Monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (CrCL <60 mL/min) for increases in serum creatinine accompanied by an increase in BUN.
Side effects
Most common adverse reactions (>4% and more common than with placebo) are dizziness, headache, constipation, nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Umedica Laboratories USA Inc. at 1-855-288-5777 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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 ranolazine extended-release tablets, 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 ranolazine extended-release tablets in open-label, long-term studies; 1227 patients were exposed to ranolazine extended-release tablets 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 extended-release tablets 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 extended-release tablets 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 ,1,000 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 extended-release tablets 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 4.0% in patients treated with ranolazine extended-release tablets 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 ranolazine extended-release tablets 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 ranolazine extended-release tablets, but there was no apparent proarrhythmic effect in these high-risk patients [see Clinical Studies (14.2) ]. Laboratory Abnormalities: Ranolazine extended-release tablets 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 ranolazine extended-release tablets, and is not accompanied by changes in BUN. In healthy volunteers, ranolazine extended-release tablets 1,000 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 ranolazine extended-release tablets in patients with severe renal impairment [see Warnings and Precautions (5.2), Use in Specific Populations (8.7) ]. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of ranolazine extended-release tablets. 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 - Abnormal coordination, myoclonus, paresthesia, tremor, 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. Metabolism and Nutrition Disorders - Cases of hypoglycemia have been reported in diabetic patients on antidiabetic medication. Psychiatric Disorders - hallucination Renal and Urinary Disorders - dysuria, urinary retention Skin and Subcutaneous Tissue Disorders - angioedema, pruritus, rash
Drug interactions
Moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin): Limit ranolazine extended-release tablets to 500 mg twice daily. ( 7.1 ) P-gp inhibitors (e.g., cyclosporine): Ranolazine exposure increased. Titrate ranolazine extended-release tablets based on clinical response. ( 7.1 ) CYP3A substrates: Limit simvastatin to 20 mg when used with ranolazine extended-release tablets. Doses of other sensitive CYP3A substrates (e.g., lovastatin) and CYP3A substrates with narrow therapeutic range (e.g., cyclosporine, tacrolimus, sirolimus) may need to be reduced with ranolazine extended-release tablets. ( 7.2 ) OCT2 substrates: Limit the dose of metformin to 1700 mg daily when used with ranolazine extended-release tablets 1,000 mg twice daily. Doses of other OCT2 substrates may require adjusted doses. ( 7.2 ) Drugs transported by P-gp (e.g., digoxin), or drugs metabolized by CYP2D6 (e.g., tricyclic antidepressants) may need reduced doses when used with ranolazine extended-release tablets. ( 7.2 ) 7.1 Effects of Other Drugs on Ranolazine Strong CYP3A Inhibitors Do not use ranolazine extended-release tablets with strong CYP3A inhibitors, including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir [see Contraindications (4), Clinical Pharmacology (12.3) ]. Moderate CYP3A Inhibitors Limit the dose of ranolazine extended-release tablets to 500 mg twice daily in patients on moderate CYP3A inhibitors, including diltiazem, verapamil, erythromycin, fluconazole, and grapefruit juice or grapefruit-containing products [see Dosage and Administration (2.2) , Clinical Pharmacology (12.3) ]. P-gp Inhibitors Concomitant use of ranolazine extended-release tablets and P-gp inhibitors, such as cyclosporine, may result in increases in ranolazine concentrations. Titrate ranolazine extended-release tablets based on clinical response in patients concomitantly treated with predominant P-gp inhibitors such as cyclosporine [see Dosage and Administration (2.2) ]. CYP3A Inducers Do not use ranolazine extended-release tablets with CYP3A inducers such as rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John's wort [see Contraindications (4) , Clinical Pharmacology (12.3) ]. 7.2 Effects of Ranolazine on Other Drugs Drugs Metabolized by CYP3A Limit the dose of simvastatin in patients on any dose of ranolazine extended-release tablets to 20 mg once daily, when ranolazine is co-administered. Dose adjustment of other sensitive CYP3A substrates (e.g., lovastatin) and CYP3A substrates with a narrow therapeutic range (e.g., cyclosporine, tacrolimus, sirolimus) may be required as ranolazine extended-release tablets may increase plasma concentrations of these drugs [see Clinical Pharmacology (12.3) ]. Drugs Transported by P-gp Concomitant use of ranolazine and digoxin results in increased exposure to digoxin. The dose of digoxin may have to be adjusted [see Clinical Pharmacology (12.3) ]. Drugs Metabolized by CYP2D6 The exposure to CYP2D6 substrates, such as tricyclic antidepressants and antipsychotics, may be increased during co-administration with ranolazine extended-release tablets, and lower doses of these drugs may be required. Drugs Transported by OCT2 In subjects with type 2 diabetes mellitus, concomitant use of ranolazine extended-release tablets 1,000 mg twice daily and metformin results in increased plasma levels of metformin. When ranolazine extended-release tablets 1,000 mg twice daily is co-administered with metformin, metformin dose should not exceed 1700 mg/day. Monitor blood glucose levels and risks associated with high exposures of metformin. Metformin exposure was not significantly increased when given with ranolazine extended-release tablets 500 mg twice daily [see Clinical Pharmacology (12.3) ].
Use in specific populations
8.1 Pregnancy Risk Summary There are no available data on ranolazine extended-release tablets use in pregnant women to inform any drug- associated risks. Studies in rats and rabbits showed no evidence of fetal harm at exposures 4 times the maximum recommended human dose (MRHD) (see Data). In the U.S. general population, the estimated background risk of major birth defects and of miscarriage of clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Embryofetal toxicity studies were conducted in rats and rabbits orally administered ranolazine during organogenesis. In rats, decreased fetal weight and reduced ossification were observed at doses (corresponding to 4-fold the AUC for the MRHD) that caused maternal weight loss. No adverse fetal effects were observed in either species exposed (AUC) to ranolazine at exposures (AUC) equal to the MRHD. 8.2 Lactation Risk Summary There are no data on the presence of ranolazine in human milk, the effects on the breastfed infant, or the effects on milk production. However, ranolazine is present in rat milk [see Use in Specific Populations (8.1)]. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ranolazine extended-release tablets and any potential adverse effects on the breastfed infant from ranolazine extended-release tablets or from the underlying maternal condition. Adult female rats were administered ranolazine orally from gestation day 6 through postnatal day 20. No adverse effects on pup development, behavior, or reproduction parameters were observed at a maternal dosage level of 60 mg/kg/day (equal to the MHRD based on AUC). At maternally toxic doses, male and female pups exhibited increased mortality and decreased body weight, and female pups showed increased motor activity. The pups were potentially exposed to low amounts of ranolazine via the maternal milk. 8.4 Pediatric Use Safety and effectiveness have not been established in pediatric patients. 8.5 Geriatric Use Of the chronic angina patients treated with ranolazine extended-release tablets 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 extended-release tablets, 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. 8.6 Use in Patients with Hepatic Impairment Ranolazine extended-release tablets is contraindicated in patients with liver cirrhosis. In a study of cirrhotic patients, the C max of ranolazine was increased 30% in cirrhotic patients with mild (Child- Pugh Class A) hepatic impairment, but increased 80% in cirrhotic patients with moderate (Child-Pugh Class B) hepatic impairment compared to patients without hepatic impairment. This increase was not enough to account for the 3-fold increase in QT prolongation seen in cirrhotic patients with mild to moderate hepatic impairment [see Clinical Pharmacology (12.2) ]. 8.7 Use in Patients with Renal Impairment A pharmacokinetic study of ranolazine extended-release tablets in subjects with severe renal impairment (CrCL<30 mL/min) was stopped when 2 of 4 subjects developed acute renal failure after receiving ranolazine extended-release tablets 500 mg twice daily for 5 days (lead-in phase) followed by 1,000 mg twice a day (1 dose in one subject and 11 doses in the other). Increases in creatinine, BUN, and potassium were observed in 3 subjects during the 500 mg lead-in phase. One subject required hemodialysis, while the other 2 subjects improved upon drug discontinuation [see Warnings and Precautions (5.2) ]. Monitor renal function periodically in patients with moderate to severe renal impairment. Discontinue ranolazine extended-release tablets if acute renal failure develops. In a separate study, C max was increased between 40% and 50% in patients with mild, moderate, or severe renal impairment compared to patients with no renal impairment, suggesting a similar increase in exposure in patients with renal failure independent of the degree of impairment. The pharmacokinetics of ranolazine has not been assessed in patients on dialysis. 8.8 Use in Patients with Heart Failure Heart failure (NYHA Class I to IV) had no significant effect on ranolazine pharmacokinetics. ranolazine extended-release tablets 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 extended-release tablets is required in patients with heart failure. 8.9 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 extended-release tablets produces small reductions in HbA1c in patients with diabetes, the clinical significance of which is unknown. Ranolazine extended-release tablets should not be considered a treatment for diabetes.
Pregnancy
8.1 Pregnancy Risk Summary There are no available data on ranolazine extended-release tablets use in pregnant women to inform any drug- associated risks. Studies in rats and rabbits showed no evidence of fetal harm at exposures 4 times the maximum recommended human dose (MRHD) (see Data). In the U.S. general population, the estimated background risk of major birth defects and of miscarriage of clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Embryofetal toxicity studies were conducted in rats and rabbits orally administered ranolazine during organogenesis. In rats, decreased fetal weight and reduced ossification were observed at doses (corresponding to 4-fold the AUC for the MRHD) that caused maternal weight loss. No adverse fetal effects were observed in either species exposed (AUC) to ranolazine at exposures (AUC) equal to the MRHD.
Pediatric use
8.4 Pediatric Use Safety and effectiveness have not been established in pediatric patients.
Geriatric use
8.5 Geriatric Use Of the chronic angina patients treated with ranolazine extended-release tablets 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 extended-release tablets, 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.
Overdosage
Hypotension, QT prolongation, bradycardia, myoclonic activity, severe tremor, unsteady gait/incoordination, dizziness, nausea, vomiting, dysphasia, and hallucinations have been seen in cases of oral overdose of ranolazine extended-release tablets. In cases of extreme overdose of ranolazine extended-release tablets fatal outcomes have been reported. In clinical studies, high intravenous exposure resulted in diplopia, paresthesia, confusion, and syncope. In addition to general supportive measures, continuous ECG monitoring may be warranted in the event of overdose. Since ranolazine is about 62% bound to plasma proteins, hemodialysis is unlikely to be effective in clearing ranolazine.
Description
Ranolazine extended-release tablets 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 C 24 H 33 N 3 O 4 , a molecular weight of 427.54 g/mole, and the following structural formula: Ranolazine is a white to off-white colored powder. Ranolazine is soluble in dichloromethane and soluble in methanol. Ranolazine extended-release tablets contain 500 mg or 1,000 mg of ranolazine and the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, methacrylic acid–ethyl acrylate copolymer, sodium hydroxide pellets, hydroxypropyl methylcellulose, magnesium stearate, hypromellose, titanium dioxide, macrogol, triacetin, iron oxide yellow. Methacrylic acid–ethyl acrylate copolymer contains 0.7%, Sodium Lauryl sulfate Ph. Eur. / NF and 2.3% Polysorbate 80 Ph. Eur. / NF on solid substance. ranolazine-strecture
Mechanism of action
12.1 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 (I Na ). 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 I Kr , which prolongs the ventricular action potential.
How supplied
Ranolazine extended-release tablets is supplied as film-coated, oblong-shaped, extended-release tablets in the following strengths: 500 mg tablets are Yellow color, with RAN500 on one side and plain on other side 1,000 mg tablets are Yellow color, with RAN1000 on one side and plain on other side Ranolazine extended-release tablets are available in: Strength NDC Unit-of-Use Bottle (60 Tablets) 500 mg 60290-055-01 Carton of 60 tablets (6 blister cards of 10 tablets) 500 mg 60290-055-03 Unit-of-Use Bottle (60 Tablets) 1,000 mg 60290-056-01 Carton of 60 tablets (6 blister cards of 10 tablets) 1,000 mg 60290-056-03 Store at 20° to 25°C (68° to 77°F), excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information). Inform patients that ranolazine extended-release tablets will not abate an acute angina episode. Strong CY3PA Inhibitors, CYP3A Inducers, Liver Cirrhosis Inform patients that ranolazine extended-release tablets should not be used with drugs that are strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin, nefazodone, ritonavir) [see Contraindications (4) , Drug Interactions (7.1) ]. Inform patients that ranolazine extended-release tablets should not be used with drugs that are inducers of CYP3A (e.g., rifampin, rifabutin, rifapentine, barbiturates, carbamazepine, phenytoin, St. John's wort) [see Contraindications (4) , Drug Interactions (7.1) ]. Inform patients that ranolazine extended-release tablets should not be used in patients with liver cirrhosis [(see Contraindications (4) , Use in Specific Populations (8.6) ]. Moderate CYP3A Inhibitors, P-gp Inhibitors, Grapefruit Products Advise patients to inform their physician if they are receiving drugs that are moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin) [see Drug Interactions (7) ]. Advise patients to inform their physician if they are receiving drugs that are P-gp inhibitors (e.g., cyclosporine) [see Drug Interactions (7) ]. Advise patients to limit grapefruit juice or grapefruit products when taking ranolazine extended-release tablets [see Drug Interactions (7) ]. QT Interval Prolongation Inform patients that ranolazine extended-release tablets may produce changes in the electrocardiogram (QTc interval prolongation) [see Warnings and Precautions (5.1) ]. Advise patients to inform their physician of any personal or family history of QTc prolongation, congenital long QT syndrome, or if they are receiving drugs that prolong the QTc interval such as Class Ia (e.g., quinidine) or Class III (e.g., dofetilide, sotalol, amiodarone) antiarrhythmic agents, erythromycin, and certain antipsychotics (e.g., thioridazine, ziprasidone) [see Warnings and Precautions (5.1) ]. Use in Patients with Renal Impairment Patients with severe renal impairment may be at risk of renal failure while on ranolazine extended-release tablets. Advise patients to inform their physician if they have impaired renal function before or while taking ranolazine extended-release tablets [see Warnings and Precautions (5.2) ]. Dizziness, Fainting Inform patients that ranolazine extended-release tablets may cause dizziness and lightheadedness. Patients should know how they react to ranolazine extended-release tablets before they operate an automobile or machinery, or engage in activities requiring mental alertness or coordination [see Adverse Reactions (6.1) ]. Advise patients to contact their physician if they experience fainting spells while taking ranolazine extended-release tablets. Administration Instruct patients to swallow ranolazine extended-release tablets whole, with or without meals, and not to crush, break, or chew tablets. Inform patients that if a dose is missed, to take the usual dose at the next scheduled time. The next dose should not be doubled. Inform patients that doses of ranolazine extended-release tablets higher than 1,000 mg twice daily should not be used [see Dosage and Administration (2) ]. Advise patients to inform their physician of any other medications taken concurrently with ranolazine extended-release tablets, including over-the-counter medications. Manufactured by: Umedica Laboratories Pvt. Ltd. Vapi, Gujarat 396195, India. Distributed by: Umedica Laboratories USA Inc. Parsippany, NJ, 07054. Product of India Revised: July 2026 ; V-00 Patient Information Ranolazine (ra noeʹ la zeen) Extended-Release Tablets Dosing Strengths: 500 mg tablets 1,000 mg tablets Read this Patient Information before you start taking ranolazine extended-release tablets and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or treatment. What is ranolazine extended-release tablets? Ranolazine extended-release tablets is a prescription medicine used to treat angina that keeps coming back (chronic angina). Ranolazine extended-release tablets may be used with other medicines that are used for heart problems and blood pressure control. It is not known if ranolazine extended-release tablets is safe and effective in children. Who should not take ranolazine extended-release tablets? Do not take ranolazine extended-release tablets if: you take any of the following medicines: for fungus infection: ketoconazole (Nizoral ® ), itraconazole (Sporanox ® , Onmel TM ) for infection: clarithromycin (Biaxin ® ) for depression: nefazodone for HIV: nelfinavir (Viracept ® ), ritonavir (Norvir ® ), lopinavir and ritonavir (Kaletra ® ), indinavir (Crixivan ® ), saquinavir (Invirase ® ) for tuberculosis (TB): rifampin (Rifadin ® ), rifabutin (Mycobutin ® ), rifapentine (Priftin ® ) for seizures: phenobarbital, phenytoin (Phenytek ® , Dilantin ® , Dilantin- 125 ® ), carbamazepine (Tegretol ® ) St. John’s wort (Hypericum perforatum) you have scarring (cirrhosis) of your liver What should I tell my doctor before taking ranolazine extended-release tablets? Before you take ranolazine extended-release tablets,tell your doctor if you: have or have a family history of a heart problem, called ‘QT prolongation’ or ‘long QT syndrome’. have liver problems. have kidney problems. are pregnant or plan to become pregnant. It is not known if ranolazine extended-release tablets will harm your unborn baby. are breast-feeding or plan to breast-feed. It is not known if ranolazine extended-release tablets passes into your breast milk. You and your doctor should decide if you will breast-feed. Tell your doctor about all the medicines you take, including all prescription and nonprescription medicines, vitamins, and herbal supplements.
Label text from the FDA structured product label by Umedica Laboratories USA Inc. (revised Aug 7, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Ranolazine in 54 products
Ranolazine NDC products (54)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 73141-022 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | A2A Integrated Pharmaceuticals | ANDA |
| 73141-021 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | A2A Integrated Pharmaceuticals | ANDA |
| 27241-125 | Ranolazine 500 mg/1 Tablet, Extended Release | Ajanta Pharma USA Inc. | ANDA |
| 27241-126 | Ranolazine 1000 mg/1 Tablet, Extended Release | Ajanta Pharma USA Inc. | ANDA |
| 60687-549 | Ranolazine 500 mg/1 Tablet, Extended Release | American Health Packaging | ANDA |
| 71610-971 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Aphena Pharma Solutions - Tennessee, LLC | ANDA |
| 71610-518 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Aphena Pharma Solutions - Tennessee, LLC | ANDA |
| 67877-526 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | Ascend Laboratories, LLC | ANDA |
| 67877-525 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Ascend Laboratories, LLC | ANDA |
| 59651-010 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | Aurobindo Pharma Limited | ANDA |
| 59651-009 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Aurobindo Pharma Limited | ANDA |
| 42291-773 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | AvKARE | ANDA |
| 42291-774 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | AvKARE | ANDA |
| 50268-722 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | AvPAK | ANDA |
| 50268-723 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | AvPAK | ANDA |
| 71335-2556 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Bryant Ranch Prepack | ANDA |
| 63629-4874 | Ranolazine 500 mg/1 Tablet, Extended Release | Bryant Ranch Prepack | ANDA |
| 31722-669 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-668 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Camber Pharmaceuticals, Inc. | ANDA |
| 68462-320 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | Glenmark Pharmaceuticals Inc., USA | ANDA |
| 68462-319 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Glenmark Pharmaceuticals Inc., USA | ANDA |
| 72319-021 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | i3 Pharmaceuticals, LLC | ANDA |
| 72319-022 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | i3 Pharmaceuticals, LLC | ANDA |
| 70756-704 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | Lifestar Pharma LLC | ANDA |
| 70756-703 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Lifestar Pharma LLC | ANDA |
| 68180-354 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Lupin Pharmaceuticals, Inc. | ANDA |
| 68180-355 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | Lupin Pharmaceuticals, Inc. | ANDA |
| 0904-7506 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Major Pharmaceuticals | ANDA |
| 0615-8611 | Ranolazine 500 mg/1 Tablet, Extended Release | NCS HealthCare of KY, LLC dba Vangard Labs | ANDA |
| 82804-118 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Proficient Rx LP | ANDA |
| 71205-868 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | Proficient Rx LP | ANDA |
| 71205-867 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Proficient Rx LP | ANDA |
| 77771-424 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | Radha Pharmaceuticals, Inc | ANDA |
| 77771-423 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Radha Pharmaceuticals, Inc | ANDA |
| 50228-423 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | ScieGen Pharmaceuticals, Inc | ANDA |
| 50228-424 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | ScieGen Pharmaceuticals, Inc | ANDA |
| 63304-017 | Ranolazine 500 mg/1 Tablet, Extended Release | Sun Pharmaceutical Industries, Inc. | ANDA |
| 63304-018 | Ranolazine 1000 mg/1 Tablet, Extended Release | Sun Pharmaceutical Industries, Inc. | ANDA |
| 70625-207 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | SunGen Pharma LLC | ANDA |
| 70625-206 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | SunGen Pharma LLC | ANDA |
| 13668-760 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | Torrent Pharma, Inc. | ANDA |
| 13668-759 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Torrent Pharma, Inc. | ANDA |
| 60290-055 | Ranolazine 500 mg/1 Tablet, Extended Release | Umedica Laboratories USA Inc. | ANDA |
| 60290-056 | Ranolazine 1000 mg/1 Tablet, Extended Release | Umedica Laboratories USA Inc. | ANDA |
| 29300-297 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | Unichem Pharmaceuticals (USA), Inc. | ANDA |
| 29300-296 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Unichem Pharmaceuticals (USA), Inc. | ANDA |
| 72578-064 | Ranolazine 500 mg/1 Tablet, Extended Release | Viona Pharmaceuticals Inc | ANDA |
| 72578-065 | Ranolazine 1000 mg/1 Tablet, Extended Release | Viona Pharmaceuticals Inc | ANDA |
| 69367-294 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | Westminster Pharmaceuticals, LLC | ANDA |
| 69367-293 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Westminster Pharmaceuticals, LLC | ANDA |
| 90096-152 | Ranolazine 1000 mg/1 Tablet, Film Coated, Extended Release | Zameer Pharmaceuticals LLC | ANDA |
| 90096-151 | Ranolazine 500 mg/1 Tablet, Film Coated, Extended Release | Zameer Pharmaceuticals LLC | ANDA |
| 70771-1499 | Ranolazine 500 mg/1 Tablet, Extended Release | Zydus Lifesciences Limited | ANDA |
| 70771-1500 | Ranolazine 1000 mg/1 Tablet, Extended Release | Zydus Lifesciences Limited | ANDA |
Ranolazine recalls
- D-0335-2025 Apr 16, 2025 · Class II · Ongoing
CGMP Deviations - D-0092-2024 Nov 15, 2023 · Class II · Ongoing
Failed Dissolution Specifications: Out of specification for dissolution.
Frequently asked questions
What is Ranolazine used for?
Ranolazine extended-release tablets is indicated for the treatment of chronic angina. Ranolazine extended-release tablets may be used with beta-blockers, nitrates, calcium channel blockers, anti- platelet therapy, lipid-lowering therapy, ACE inhibitors, and angiotensin receptor blockers. Ranolazine extended-release tablets is an antianginal indicated for the treatment of chronic angina.
What are the side effects of Ranolazine?
Most common adverse reactions (>4% and more common than with placebo) are dizziness, headache, constipation, nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Umedica Laboratories USA Inc. at 1-855-288-5777 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates… See the full label for the complete list.
Who makes Ranolazine?
Ranolazine is listed by 28 labelers in the FDA NDC directory, including A2A Integrated Pharmaceuticals, Ajanta Pharma USA Inc., American Health Packaging, Aphena Pharma Solutions - Tennessee, LLC.
Has Ranolazine been recalled?
The FDA enforcement database lists 2 recalls for Ranolazine, most recently D-0335-2025 (class ii): CGMP Deviations