Home › NDC Lookup › Ingredients › Ranolazine › 72319-0022-02
⚪image loading
(from DailyMed)

RANOLAZINE 1000 mg Tablet, Film Coated, Extended Release, 60-count

by i3 Pharmaceuticals, LLC · 60 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (72319-022-02)
NDC 72319-0022-02
🏷️ FDA NDC (as labeled) 72319-022-02 billing pads the product segment with a zero
Rx only Generic On market Non-controlled
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

⚠️
Other active recalls for Ranolazine (different manufacturers) — 2 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Mar 13, 2025 — CGMP Deviations (Glenmark Pharmaceuticals Inc., USA) · FDA recall D-0335-2025
Class II · Oct 23, 2023 — Failed Dissolution Specifications: Out of specification for dissolution. (Glenmark Pharmaceuticals Inc., USA) · FDA recall D-0092-2024
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

🆔 Identity & classification

FDA NDC (as labeled) 72319-022-02
Product NDC 72319-022
11-digit billing NDC 72319002202
NCPDP billing unit EA — each (per item)
RxCUI 616749, 728231
UNII A6IEZ5M406
Application # ANDA213517
SPL Set ID de3185bf-448a-15f7-e053-2995a90a9a2e
Established class (EPC) Anti-anginal
Mechanism of action Cytochrome P450 3A Inhibitors; P-Glycoprotein Inhibitors; Cytochrome P450 2D6 Inhibitors; Organic Cation Transporter 2 Inhibitors
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2022-06-15
Route ORAL
Dosage form TABLET, FILM COATED, EXTENDED RELEASE
Substance RANOLAZINE
GPI-14 32200040007430
GCN Seq No 062973
GCN 98733
HICL code 033446
Ingredient (HICL) Ranolazine
HIC1 code A
Therapeutic class — broad (HIC1) Cardiovascular System
HIC2 code A2
Therapeutic class — intermediate (HIC2) Cardiac Depressants
HIC3 code A2C
Therapeutic class — specific (HIC3) Antianginal, Anti-Ischemic Agents,Non-Hemodynamic
AHFS code 24:04.92.00
AHFS class Cardiac Drugs, Miscellaneous
FDB label name RANOLAZINE ER 1,000 MG TABLET
FDB brand name Ranolazine Er
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AB · RLD · RS
Why two NDCs? The FDA registers this code as 72319-022-02 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 72319-0022-02. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Anti-anginal class.

Pharmacologic class Anti-anginal
Drug family (ATC) Other cardiac preparations
How it works Cytochrome P450 2D6 Inhibitors, P-Glycoprotein Inhibitors, Organic Cation Transporter 2 Inhibitors, Cytochrome P450 3A Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

Labeleri3 Pharmaceuticals, LLC
Application holderI3 PHARMACEUTICALS LLC
FDA applicationANDA213517 (ANDA)
Labeler code72319
First marketedJun 2022
Product typeHuman Prescription Drug
Portfolio19 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name RANOLAZINE ER 1,000 MG TABLET Ingredient Ranolazine
📖 What it is MedlinePlus · NLM

Ranolazine is used alone or with other medications to treat chronic angina (ongoing 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.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • 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?
📖 Read our full Ranolazine guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

💊 What it looks like

Color orange / yellow
ShapeOval
ImprintI3;22
Size21 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

🧪 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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 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 systemPer eaPer package
Retail pharmacies payNADAC · weekly $0.279 $16.72 / 60 tablets
Medicaid paysCMS SDUD · 12 mo $0.4586 $27.52 / 60 tablets
Medicare drug plans payPart D · Q2 2026 $0.5718 $34.31 / 60 tablets
NADAC price history (per ea) — tap or hover for the price & month
Dec 2023 Dec 2025 Apr 2026 Aug 2026 $0.365 $0.273
▼ Down 12% over the last 12 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Ranolazine 1000 mg 27241-0126-02 Ajanta 60 tablets $0.279 AB Availability likely —
Ranolazine 1000 mg 31722-0669-60 Camber 60 tablets $0.279 AB Availability likely —
Ranolazine 1000 mg 50268-0723-13 AvPAK 1 tablet $0.279 AB Availability likely —
Ranolazine 1000 mg 69367-0294-60 Westminster 60 tablets $0.279 AB Availability likely —
Ranolazine 1000 mg 70756-0704-60 Lifestar 60 tablets $0.279 AB Availability likely —
Ranolazine 1000 mgthis 72319-0022-02 i3 60 tablets $0.279 AB Availability likely —
Ranolazine 1000 mg 90096-0152-60 Zameer 60 tablets $0.279 AB Availability likely —
Ranolazine 1000 mg 13668-0760-60 Torrent 60 tablets — AB FDA listed —
Ranolazine 1000 mg 29300-0297-01 Unichem 100 tablets — AB FDA listed —
Ranolazine 1000 mg 42291-0774-60 AvKARE 60 tablets — AB FDA listed —
Ranolazine 1000 mg 42571-0325-11 Micro 10 tablets — AB Discontinued —
Ranolazine 1000 mg 50228-0424-05 ScieGen 500 tablets — AB FDA listed —
Ranolazine 1000 mg 59651-0010-18 Aurobindo 180 tablets — — FDA listed —
Ranolazine 1000 mg 63304-0018-05 Sun 500 tablets — — FDA listed —
Ranolazine 1000 mg 67877-0526-05 Ascend 500 tablets — AB FDA listed —
Ranolazine 1000 mg 68462-0320-05 Glenmark 500 tablets — AB FDA listed —
Ranolazine 1000 mg 70625-0207-01 SunGen 60 tablets — AB FDA listed —
Ranolazine 1000 mg 70771-1500-01 Zydus 100 tablets — AB FDA listed —
Ranolazine 1000 mg 71205-0868-00 Proficient 100 tablets — AB FDA listed —
Ranolazine 1000 mg 72578-0065-01 Viona 100 tablets — AB FDA listed —
Ranolazine 1000 mg 73141-0022-02 A2A 60 tablets — AB FDA listed —
Ranolazine 1000 mg 77771-0424-60 Radha 60 tablets — AB FDA listed —
Ranolazine 1000 mg 68180-0355-02 Lupin 500 tablets — AB FDA listed —
Ranolazine 1000 mg 60290-0056-01 Umedica 60 tablets — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

⏳ Availability & generic status

🏛️
2022
On the market since
Jun 2022
📍
2026
Currently FDA-listed
4 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

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?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

🗺️ Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for 72319-0022-02, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q4 2025 · 4 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
1.8K
Units reimbursed last 4 qtrs
132.2K
Gross reimbursed last 4 qtrs
$60.6K
Avg / prescription
$33.28
Avg / unit
$0.4586
Latest quarter Q4 2025
379Rx
Medicaid pays / ea
$0.4586
gross reimbursed
vs
NADAC / ea
$0.2787
acquisition cost
=
Spread
+$0.1799
+65% vs cost
What Medicaid paid per ea (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care ⓘ
33% FFS 67% MCO
Fee-for-service · 608 Rx Managed care · 1,213 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: 2,820 units · 28.1 per 100k residents MI New York: 17,760 units · 90.7 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: 27,056 units · 230 per 100k residents OH Pennsylvania: 11,850 units · 91.4 per 100k residents PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: 10,920 units · 28.0 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: 7,800 units · 172 per 100k residents KY West Virginia: 5,130 units · 290 per 100k residents WV Virginia: 4,500 units · 51.6 per 100k residents VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: 2,760 units · 38.7 per 100k residents TN North Carolina: 8,106 units · 74.8 per 100k residents NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: 14,672 units · 321 per 100k residents LA Mississippi: no data reported MS Alabama: 3,000 units · 58.7 per 100k residents AL Georgia: 2,190 units · 19.9 per 100k residents GA D.C.: no data reported DC Hawaii: no data reported HI Texas: 716 units · 2.3 per 100k residents TX Florida: 12,880 units · 57.0 per 100k residents FL
Units reimbursed · per 100k residents
2.3321
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Louisiana 321 /100k
2 West Virginia 290 /100k
3 Ohio 230 /100k
4 Kentucky 172 /100k
5 Pennsylvania 91.4 /100k
6 New York 90.7 /100k
7 North Carolina 74.8 /100k
8 Alabama 58.7 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

📊 Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Ranolazine ER (matched by generic name) — the program that covers self-administered drugs. 16 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Ranolazine ER. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$22.88M
Claims incl. refills
332.4K
Beneficiaries
221.5K
Spend / beneficiary
$103.31
Spend / claim
$68.83
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for RANOLAZINE — the ingredient across all brands.

Top reported reactions

Death826
Myocardial Infarction646
Chest Pain614
Angina Pectoris595
Stent Placement582
Dyspnoea439
Dizziness427

Age at onset

Neonate3
Infant16
Child1
Adolescent2
Adult1,878
Elderly4,639

Reporter sex

10,376 reports
Male · 59%
Female · 41%
Unknown · 0%

Serious outcomes

Hospitalization4,453
Death1,337
Disabling347
Life-threatening268
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 983 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
72319-0022-02 You're viewing this 60 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE, PLASTIC (72319-022-02) 2022-06-15 Active

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🆘 Overdosage 🧬 Clinical Pharmacology 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🎯 Indications and Usage 54 words ▾

1 INDICATIONS AND 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 is an antianginal indicated for the treatment of chronic angina. ( 1 )

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND 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 Tablets dosing at 500 mg twice daily and increase to 1000 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 1000 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.

2.2Dose 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) ].

2.1Dosing Information Initiate Ranolazine Extended-Release Tablets dosing at 500 mg twice daily and increase to 1000 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 1000 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.

2.2Dose 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 62 words ▾

3 DOSAGE FORMS AND STRENGTHS Ranolazine Extended-Release Tablets is supplied as film-coated, oval-shaped, extended-release tablets in the following strengths: • 500 mg tablets are orange, with I3 on one side and 21 on the other side • 1000 mg tablets are yellow, with I3 on one side and 22 on the other side Extended-release tablets: 500 mg, 1000 mg ( 3 )

⛔ Contraindications 79 words ▾

4 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 Cautions ~2 min read ▾

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<60mL/min).

If acute renal failure develops, discontinue Ranolazine Extended-Release Tablets. ( 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 (>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] <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.

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 (>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] <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.

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS Most common adverse reactions (>4% and more common than with placebo) are dizziness, headache, constipation, nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact i3 Pharmaceuticals, LLC at 1-844-874-7353 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 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 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 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-Re…

🔄 Drug Interactions ~2 min read ▾

7 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 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 Extended-Release Tablets. ( 7.2 ) See 17 for PATIENT COUNSELING INFORMATION and FDA-Approved Patient Labeling

7.1Effects 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) ].

7.2Effects 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 1000 mg twice daily and metformin results in increased plasma levels of metformin. When Ranolazine Extended-Release Tablets 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 Extended-Release Tablets 500 mg twice daily [see Clinical Pharmacology (12.3) ].

7.1 Effects of Other Drugs on Ranolazine Strong CYP3A Inhibitor…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy 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.

8.2Lactation 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 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.

8.4Pediatric Use Safety and effectiveness have not been established in pediatric patients.

8.5Geriatric 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.

8.6Use 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) ].

8.7Use 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 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 su…

🆘 Overdosage 92 words ▾

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 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.

🧬 Clinical Pharmacology ~3 min read ▾

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 Extended-Release Tablets 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 [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 Extended-Release Tablets.

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 Extended-Release Tablets. There was a significantly lower incidence of arrhythmias (ventricular tachycardia, bradycardia, supraventricular tachycardia, and new atrial fibrillation) in patients treated with Ranolazine Extended-Release Tablets (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 Extended-Release Tablets. 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 Extended-Release Tablets, peak plasma concentrations of ranolazine are reache…

📦 How Supplied / Storage and Handling 100 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Ranolazine Extended-Release Tablets is supplied as film-coated, oval-shaped, extended-release tablets in the following strengths: • 500 mg tablets are orange, with I3 on one side and 21 on the other side • 1000 mg tablets are yellow, with I3 on one side and 22 on the other side Ranolazine Extended-Release Tablets are available in: Strength NDC Unit-of-Use Bottle (60 Tablets) 500 mg 72319-021-02 Unit-of-Use Bottle (60 Tablets) 1000 mg 72319-022-02 Store Ranolazine Extended-Release Tablets at 25°C (77°F) with excursions permitted to 15° to 30°C (59° to 86°F).

Ranolazine Extended-Release Tablets come in a child-resistant package.

📋 Description 166 words ▾

11 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 C24H33N3O4, 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: microcrystalline cellulose, hydroxypropyl methylcellulose, methacrylic acid and ethyl acrylate copolymer, sodium lauryl sulfate, polysorbate 80, sodium hydroxide and magnesium stearate.

Additional inactive ingredients for the 500 mg tablet include polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, iron oxide yellow and iron oxide red; additional inactive ingredients for the 1000 mg tablet include hypromellose, polydextrose, titanium dioxide, talc, maltodextrin, medium chain triglycerides and iron oxide yellow. chemicalstructure

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING 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 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 Extended-Release Tablets, including over-the-counter medications. Manufactured and Distributed by: i3 Pharmaceuticals, LLC 200 Park Avenue, Warminster, PA 18974 OS022-02 Rev.0720 Revised: 07/2020

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
← 72319-0021-02 · i3 72319-0023-02 · i3 →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.