Ranolazine 500 mg Tablet, Film Coated, Extended Release, 60-count
Other active recalls for Ranolazine (different manufacturers) — 2 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Anti-anginal class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- Ranolazine is specifically for chronic angina — the recurring chest pain or tightness you get when your heart isn't getting enough blood flow. It's not a heart attack treatment or...
- What exactly is ranolazine supposed to do for me?
- If you're taking the extended-release tablet (Ranexa or generic ranolazine), you can take it with or without food — your choice. The important thing is to swallow it whole. Never c...
- Do I have to take this with food? And can I split the tablet?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Ranolazine — tap one for details:
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 1K09F3G675
Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
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UNII EX438O2MRT
Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII NX76LV5T8J
A synthetic plastic polymer made from methacrylic acid and ethyl acrylate. It's used as a coating or binder to control how and where the medicine dissolves in your digestive system.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII 4R4HFI6D95
Polyethylene glycol 4000 is a synthetic polymer derived from petroleum. It serves as a binder, filler, and lubricant in solid dosage forms, and helps control how quickly the medicine dissolves.
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UNII 532B59J990
Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
12 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.161 | $9.65 / 60 tablets |
| Medicaid paysCMS SDUD · 12 mo | $0.2901 | $17.41 / 60 tablets |
| Medicare drug plans payPart D · Q2 2026 | $0.5718 | $34.31 / 60 tablets |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Ranolazine 500 mg 00904-7506-04 | Major | 1 tablet | $0.161 | AB | Availability likely | — |
| Ranolazine 500 mg 27241-0125-02 | Ajanta | 60 tablets | $0.161 | AB | Availability likely | — |
| Ranolazine 500 mg 31722-0668-60 | Camber | 60 tablets | $0.161 | AB | Availability likely | — |
| Ranolazine 500 mg 50268-0722-15 | AvPAK | 1 tablet | $0.161 | AB | Availability likely | — |
| Ranolazine 500 mg 60687-0549-21 | American | 1 tablet | $0.161 | AB | Availability likely | — |
| Ranolazine 500 mgthis 67877-0525-60 | Ascend | 60 tablets | $0.161 | AB | Availability likely | — |
| Ranolazine 500 mg 69367-0293-60 | Westminster | 60 tablets | $0.161 | AB | Availability likely | — |
| Ranolazine 500 mg 70756-0703-60 | Lifestar | 60 tablets | $0.161 | AB | Availability likely | — |
| Ranolazine 500 mg 72319-0021-02 | i3 | 60 tablets | $0.161 | AB | Availability likely | — |
| Ranolazine 500 mg 90096-0151-60 | Zameer | 60 tablets | $0.161 | AB | Availability likely | — |
| Ranolazine 500 mg 00615-8611-39 | NCS | 30 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 13668-0759-60 | Torrent | 60 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 29300-0296-01 | Unichem | 100 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 42291-0773-60 | AvKARE | 60 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 42571-0324-05 | Micro | 500 tablets | — | AB | Discontinued | — |
| Ranolazine 500 mg 50228-0423-05 | ScieGen | 500 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 59651-0009-18 | Aurobindo | 180 tablets | — | — | FDA listed | — |
| Ranolazine 500 mg 63304-0017-05 | Sun | 500 tablets | — | — | FDA listed | — |
| Ranolazine 500 mg 63629-4874-01 | Bryant | 60 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 68462-0319-05 | Glenmark | 500 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 70625-0206-01 | SunGen | 60 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 70771-1499-01 | Zydus | 100 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 71205-0867-00 | Proficient | 100 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 71335-2556-01 | Bryant | 60 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 71610-0518-83 | Aphena | 3600 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 71610-0971-42 | Aphena | 1800 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 72578-0064-01 | Viona | 100 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 73141-0021-02 | A2A | 60 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 77771-0423-60 | Radha | 60 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 82804-0118-60 | Proficient | 60 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 68180-0354-02 | Lupin | 500 tablets | — | AB | FDA listed | — |
| Ranolazine 500 mg 60290-0055-01 | Umedica | 60 tablets | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 67877-0525-10 | 1000 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE (67877-525-10) | — | — | 2020-12-02 | Active |
| 67877-0525-38 | 10 BLISTER PACK in 1 CARTON (67877-525-38) / 10 TABLET, FILM COATED, EXTENDED RELEASE in 1 BLISTER PACK | — | — | 2020-12-02 | Active |
| 67877-0525-60 You're viewing this | 60 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE (67877-525-60) | $0.1609 / ea | $9.65 | 2020-12-02 | Active |
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 67877-0525-60?
What is the difference between NDC 67877-0525-60 and NDC 67877-0525-10?
What NDC number is used to bill for this package of Ranolazine 500 mg Tablet, Film Coated, Extended Release?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS & USAGE Ranolazine extended-release tablets are 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 are an antianginal indicated for the treatment of chronic angina. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE & ADMINISTRATION 500 mg twice daily and increase to 1000 mg twice daily, based on clinical symptoms ( 2.1 )
2.1Dosing Information Initiate ranolazine extended-release tablet dosing at 500 mg twice daily and increase to 1000 mg twice daily, as needed, based on clinical symptoms. Take ranolazine extended-release tablet with or without meals. Swallow ranolazine extended-release tablet whole; do not crush, break, or chew.
The maximum recommended daily dose of ranolazine extended-release tablet is 1000 mg twice daily. If a dose of ranolazine extended-release tablet is missed, take the prescribed dose at the next scheduled time; do not double the next dose.
2.2Dose Modification Dose adjustments may be needed when ranolazine extended-release tablet is taken in combination with certain other drugs [see Drug Interactions (7.1) ] . Limit the maximum dose of ranolazine extended-release tablet to 500 mg twice daily in patients on moderate CYP3A inhibitors such as diltiazem, verapamil, and erythromycin. Use of ranolazine extended-release tablet 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 tablet. Titrate ranolazine extended-release tablet based on clinical response [see Drug Interactions (7.1) ].
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS & STRENGTHS Ranolazine is supplied as extended-release tablets in the following strengths: 500 mg tablets are orange colored, oval shape, biconvex coated tablets, debossed with "500" on one side and "A47" on other side. 1000 mg tablets are yellow colored, oval shape, biconvex coated tablets, debossed with "1000" on one side and A48" on other side. Extended-release tablets: 500 mg, 1000 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Ranolazine 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 Cautions ▾
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 less than 60 mL/min).
If acute renal failure develops, discontinue ranolazine. ( 5.2 )
5.1QT 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 (greater than 1000 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.
5.2Renal Failure Acute renal failure has been observed in some patients with severe renal impairment (creatinine clearance [CrCL] less than 30 mL/min) while taking ranolazine. If acute renal failure develops (e.g., marked increase in serum creatinine associated with an increase in blood urea nitrogen [BUN]), discontinue ranolazine 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 less than 60 mL/min) for increases in serum creatinine accompanied by an increase in BUN.
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Most common adverse reactions (greater than 4% and more common than with placebo) are dizziness, headache, constipation, nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-272-7901 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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, 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 in open-label, long-term studies; 1227 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 (greater than 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 4.0% in patients treated with ranolazine 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 (less than 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, 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, but there was no apparent proarrhythmic effect in these high-risk patients [see Clinical Studies ( 14.2 )] . Laboratory Abnormalities: Ranolazine 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, and is not accompanied by changes in BUN.
In healthy volunteers, ranolazine 1000 mg twice daily had no effect upon the glomerular filtration rate. More marked and progressive increases in serum creatinine, associated with…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin): Limit ranolazine to 500 mg twice daily. ( 7.1 ) P-gp inhibitors (e.g., cyclosporine): Ranolazine exposure increased. Titrate ranolazine based on clinical response.
( 7.1 ) CYP3A substrates: Limit simvastatin to 20 mg when used with ranolazine. 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. ( 7.2 ) OCT2 substrates: Limit the dose of metformin to 1700 mg daily when used with ranolazine 1000 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. ( 7.2 )
7.1Effects of Other Drugs on Ranolazine Strong CYP3A Inhibitors Do not use ranolazine 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 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 and P-gp inhibitors, such as cyclosporine, may result in increases in ranolazine concentrations. Titrate ranolazine 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 with CYP3A inducers such as rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St.
John’s wort [see Contraindications (4) , Clinical Pharmacology ( 12.3 )] .
7.2Effects of Ranolazine on Other Drugs Drugs Metabolized by CYP3A Limit the dose of simvastatin in patients on any dose of ranolazine 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 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, and lower doses of these drugs may be required. Drugs Transported by OCT2 In subjects with type 2 diabetes mellitus, concomitant use of ranolazine 1000 mg twice daily and metformin results in increased plasma levels of metformin.
When ranolazine 1000 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 500 mg twice daily [see Clinical Pharmacology ( 12.3 )].
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary There are no available data on ranolazine 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 to 4% and 15 to 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.
8.2Lactation 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 and any potential adverse effects on the breastfed infant from ranolazine 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.
8.4Pediatric Use Safety and effectiveness have not been established in pediatric patients.
8.5Geriatric 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.
8.6Use in Patients with Hepatic Impairment Ranolazine 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) ] .
8.7Use in Patients with Renal Impairment A pharmacokinetic study of ranolazine in subjects with severe renal impairment (CrCL less than 30 mL/min) was stopped when 2 of 4 subjects developed acute renal failure after receiving ranolazine 500 mg twice daily for 5 days (lead-in phase) followed by 1000 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 wit…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no available data on ranolazine 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 to 4% and 15 to 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 ▾
8.4Pediatric Use Safety and effectiveness have not been established in pediatric patients.
🧓 Geriatric Use ▾
8.5Geriatric 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.
🆘 Overdosage ▾
10 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. In cases of extreme overdose of ranolazine 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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.
12.2Pharmacodynamics Hemodynamic Effects Patients with chronic angina treated with ranolazine in controlled clinical studies had minimal changes in mean heart rate (less than 2 bpm) and systolic blood pressure (less than 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 [see Warnings and Precautions (5.1 )], 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 T max 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 [see Contraindications (4) ] . 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 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.
12.3Pharmacokinetics 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 C max 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, C max and AUC 0-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 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 r…
🧬 Mechanism of Action ▾
12.1Mechanism 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 / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Ranolazine is supplied as extended-release tablets in the following strengths: 500 mg tablets are orange colored, oval shape, biconvex coated tablets, debossed with "500" on one side and "A47" on other side. 1000 mg tablets are yellow colored, oval shape, biconvex coated tablets, debossed with "1000" on one side and A48" on other side. Ranolazine extended-release tablets are available in: Strength NDC Bottle of 60 500 67877-525-60 Bottle of 1000 500 67877-525-10 Carton of 100 (10 X 10 Unit-dose Tablets) 500 67877-525-38 Bottle of 60 1000 67877-526-60 Bottle of 500 1000 67877-526-05 Carton of 100 (10 X 10 Unit-dose Tablets) 1000 67877-526-38 Store ranolazine tablets at 25°C (77°F) with excursions permitted to 15° to 30°C (59° to 86°F).
📋 Description ▾
11 DESCRIPTION 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 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 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 extended-release tablets contain 500 mg or 1000 mg of ranolazine and the following inactive ingredients: colloidal silicon dioxide, hypromellose, iron oxide yellow, magnesium stearate, methacrylic acid copolymer, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, sodium hydroxide, talc, titanium dioxide and additional inactive ingredients for the 500 mg tablet include iron oxide red. ranolazine-structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Inform patients that ranolazine will not abate an acute angina episode. Strong CY3PA Inhibitors, CYP3A Inducers, Liver Cirrhosis Inform patients that ranolazine 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 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 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 [see Drug Interactions (7) ].
QT Interval Prolongation Inform patients that ranolazine 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. Advise patients to inform their physician if they have impaired renal function before or while taking ranolazine [see Warnings and Precautions (5.2)]. Dizziness, Fainting Inform patients that ranolazine may cause dizziness and lightheadedness.
Patients should know how they react to ranolazine 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. Administration Instruct patients to swallow ranolazine 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 tablets higher than 1000 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 tablets, including over-the-counter medications. Manufactured by: Alkem Laboratories Ltd., Mumbai - 400 013, INDIA. Distributed by: Ascend Laboratories, LLC Bedminster, NJ 07921 Revised: March 2025