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Ezetimibe and Simvastatin 10 mg; 10 mg Tablet, 90-count — NDC 59651-0835-90 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Ezetimibe and Simvastatin 10 mg; 10 mg Tablet, 90-count — NDC 59651-835-90 (Billing 59651-0835-90)

by Aurobindo Pharma Limited · 90 TABLET in 1 BOTTLE

This is a package of 90 tablets of Ezetimibe and Simvastatin 10 mg; 10 mg Tablet from Aurobindo Pharma Limited, marketed since Mar 2024 and currently FDA-listed.

NDC 59651-0835-90
🏷️ FDA NDC (as labeled) 59651-835-90 billing pads the product segment with a zero
This package
Contains90-count Pack sizes2 compare ↓
Also priced by: Part D plans $0.4456/unit — full pricing hub ↓
Product page 59651-0835-30 Also comes in: 30 tablets 59651-835-30
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Sep 10, 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 Ezetimibe And Simvastatin (different manufacturers) — 1 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class III · May 19, 2025 — Failed Impurities/Degradation Specifications: Out of Specification (OOS) for related substances test for Anhydro Simvastatin at the 06-month time point during long-term stability study. (Glenmark Pharmaceuticals Inc., USA) · FDA recall D-0462-2025
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 59651-835-90
Product NDC 59651-835
11-digit billing NDC 59651083590
RxCUI 476345, 476349, 476350, 476351
UNII AGG2FN16EV, EOR26LQQ24
Application # ANDA200082
SPL Set ID 79dadfde-35c7-4937-9c82-1728fb6be2fb
Established class (EPC) HMG-CoA Reductase Inhibitor; Dietary Cholesterol Absorption Inhibitor
Mechanism of action Hydroxymethylglutaryl-CoA Reductase Inhibitors
Physiologic effect Decreased Cholesterol Absorption
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2024-03-01
Route ORAL
Dosage form TABLET
Substance EZETIMIBE; SIMVASTATIN
TE code (Orange Book) AB · RLD · RS
Quick answers
  • RxCUI (RxNorm): 476345
Why two NDCs? The FDA registers this code as 59651-835-90 — 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 → 59651-0835-90. 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 Dietary Cholesterol Absorption Inhibitor class.

Pharmacologic class Dietary Cholesterol Absorption Inhibitor
Drug family (ATC) Other lipid modifying agents
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.

Clinical

📖 What it is MedlinePlus · NLM

Ezetimibe is used along with diet, alone or in combination with another cholesterol-lowering medications (HMG-CoA reductase inhibitors [statins]) to reduce the amount of low-density lipoprotein (LDL) cholesterol ('bad cholesterol') in the blood in adults and children 10 years of age or older who have familial heterozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). It is also used along with diet, alone or in combination with other cholesterol-lowering medications (HMG-CoA reductase inhibitors [statins] or fenofibrate) in adults...

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It lowers LDL cholesterol when diet alone hasn’t been enough. That includes high cholesterol and inherited forms. Vytorin’s simvastatin is also used to reduce heart attack, stroke...
  • Take one tablet by mouth in the evening, with or without food. If you miss a dose, take it as soon as you remember, but don’t double up the next one. If you take cholestyramine or...
  • Common ones are headache, muscle aches, diarrhea, cold-like symptoms and higher liver enzymes on blood tests. Most people do fine. Tell me or your doctor if anything bothers you.
  • Call promptly for muscle pain, tenderness or weakness you can’t explain, especially with fever or feeling unwell. Also call for yellow skin or eyes, or signs of allergic reaction l...
📖 Read our full Ezetimibe / Simvastatin guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
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.

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 eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $0.4456 $40.10 / 90 tablets
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.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
59651-0835-30 59651-835-30 Main listing 30 TABLET in 1 BOTTLE 2024-03-01 — Active
59651-0835-90 You're viewing this 90 TABLET in 1 BOTTLE 2024-03-01 — Active

You're viewing the largest of 2 pack sizes for this product.

Pack size FAQ

What quantity is in this package?
This is a 90-count package — 90 tablet in 1 bottle.
How does this package differ from NDC 59651-0835-30?
Both are Ezetimibe and Simvastatin 10 mg; 10 mg Tablet — the drug itself is identical. This page's package is the 90-count one, while NDC 59651-0835-30 is the 30 tablets package.
What NDC number is used to bill for this package of Ezetimibe and Simvastatin 10 mg; 10 mg Tablet?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Ezetimibe and Simvastatin 10 mg/1; 10 mg 43598-0742-10 Dr.Reddys 1000 tablets $0.274 AB Availability likely —
ezetimibe and simvastatin 10 mg/1; 10 mg 16714-0778-01 NORTHSTAR 30 tablets $0.383 AB Discontinued —
Ezetimibe and Simvastatin 10 mg/1; 10 mg 69238-1155-03 Amneal 30 tablets $0.383 — Discontinued —
Ezetimibe and Simvastatin 10 mg/1; 10 mg 51407-0190-10 Golden 1000 tablets — AB FDA listed —
Ezetimibe and Simvastatin 10 mg/1; 10 mgthis 59651-0835-90 Aurobindo 90 tablets — AB FDA listed —
Ezetimibe and Simvastatin 10 mg/1; 10 mg 67877-0507-01 Ascend 1000 tablets — AB FDA listed —
ezetimibe and simvastatin 10 mg/1; 10 mg 68462-0321-10 Glenmark 1000 tablets — AB FDA listed —
Vytorin 10 mg/1; 10 mg 78206-0174-01 Organon 30 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

🏛️
2024
On the market since
Mar 2024
📍
2026
Currently FDA-listed
2 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.

What it looks like

Color White
ShapeOval
ImprintTS;4
Size18 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.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII PQ6CK8PD0R
    Ascorbic acid, also known as vitamin C, is a white crystalline powder. It serves as an antioxidant to prevent degradation of other ingredients and may also function as a preservative in the formulation.
  • UNII REK4960K2U
    Butylated hydroxyanisole is a synthetic preservative that prevents oils and fats in medicines from spoiling or becoming rancid. It keeps the medicine stable and extends its shelf life.
  • UNII 2968PHW8QP
    A weak organic acid derived from citrus fruits or made through fermentation. It works as a buffer to control pH, a preservative to extend shelf life, and a flavoring agent in medications.
  • UNII M28OL1HH48
    Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
  • UNII 0VUT3PMY82
    Hypromellose 2910 is a plant-derived thickening agent made from cellulose. In medicines, it forms protective coatings on tablets or capsules, controls how fast the drug releases, and thickens liquid formulations.
  • UNII EWQ57Q8I5X
    Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
  • 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.
  • 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.
  • UNII 368GB5141J
    A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.

9 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — 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?
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.

Manufacturer & labeler

LabelerAurobindo Pharma Limited
Application holderAUROBINDO PHARMA USA INC
FDA applicationANDA200082 (ANDA)
Labeler code59651
First marketedMar 2024
Product typeHuman Prescription Drug
Portfolio1,456 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.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). 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 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE Ezetimibe and simvastatin tablets Ezetimibe and simvastatin tablet is a combination of simvastatin and ezetimibe indicated: As an adjunct to diet to reduce elevated low density lipoprotein cholesterol (LDL-C): In adults with primary hyperlipidemia. In adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH). As an adjunct to other LDL-C-lowering therapies to reduce elevated LDL-C in adults with homozygous familial hypercholesterolemia (HoFH).

Simv a statin Simvastatin, when used as a component of ezetimibe and simvastatin tablets, is indicated to reduce the risk of total mortality by reducing risk of coronary heart disease death, non-fatal myocardial infarction and stroke, and the need for coronary and non-coronary revascularization procedures in adults with established coronary heart disease, cerebrovascular disease, peripheral vascular disease, and/or diabetes, who are at high risk of coronary heart disease events. Ezetimibe and simvastatin tablet is a combination of ezetimibe, a dietary cholesterol absorption inhibitor, and simvastatin, an HMG-CoA reductase inhibitor (statin) indicated: ( 1 ) As an adjunct to diet to reduce elevated low density lipoprotein cholesterol (LDL-C): In adults with primary hyperlipidemia.

In adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH). As an adjunct to other LDL-C lowering therapies to reduce LDL-C in adults with homozygous familial hypercholesterolemia (HoFH). Simvastatin Simvastatin, when used as a component of ezetimibe and simvastatin tablets, is indicated to reduce the risk of total mortality by reducing risk of coronary heart disease death, non-fatal myocardial infarction and stroke, and the need for coronary and non-coronary revascularization procedures in adults with established coronary heart disease, cerebrovascular disease, peripheral vascular disease, and/or diabetes, who are at high risk of coronary heart disease events.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Important Dosage and Administration Information: ( 2.1 ) Take ezetimibe and simvastatin tablets orally once daily in the evening with or without food. Maximum recommended dosage is ezetimibe and simvastatin tablets 10/40 mg once daily. Ezetimibe and simvastatin tablets 10/80 mg daily dosage is restricted to patients who have been taking ezetimibe and simvastatin tablets 10/80 mg daily chronically (e.g., for 12 months or more) without evidence of muscle toxicity.

For patients that require a high-intensity statin or are unable to achieve their LDL-C goal receiving ezetimibe and simvastatin tablets 10/40 mg daily, prescribe alternative LDL-C-lowering treatment. If as dose is missed, take the missed dose as soon as possible. Do not double the next dose.

Assess LDL-C when clinically appropriate, as early as 2 weeks after initiating ezetimibe and simvastatin tablets, and adjust the dosage if necessary. Adults: Recommended dosage range of 10/10 mg to 10/40 mg once daily. ( 2.2 ) See full prescribing information for ezetimibe and simvastatin tablets dosage modifications due to drug interactions.

( 2.3 ) Patients with Renal Impairment: Doses exceeding 10/20 mg should be used with caution and close monitoring in patients with moderate to severe renal impairment. ( 2.4 )

2.1Important Dosage and Administration Information Take ezetimibe and simvastatin tablets orally once daily in the evening with or without food. The maximum recommended dosage is ezetimibe and simvastatin tablets 10/40 mg once daily. The ezetimibe and simvastatin tablets 10/80 mg daily dosage is restricted to adult patients who have been taking ezetimibe and simvastatin tablets 10/80 mg daily chronically (e.g., for 12 months or more) without evidence of muscle toxicity [see Warnings and Precautions (5.1) ] .

For patients that require a high-intensity statin or are unable to achieve their LDL-C goal receiving ezetimibe and simvastatin tablets 10/40 mg daily, prescribe alternative LDL-C-lowering treatment. If as dose is missed, take the missed dose as soon as possible. Do not double the next dose.

Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating ezetimibe and simvastatin tablets, and adjust the dosage if necessary.

2.2Recommended Dosage in Adult Patients The recommended dosage range of ezetimibe and simvastatin tablets 10/10 mg to 10/40 mg once a day.

2.3Recommended Dosage in Pediatric Patients 10 Years of Age and Older with HeFH The recommended dosage range of ezetimibe and simvastatin tablets 10/10 mg to 10/40 mg once a day.

2.4Recommended Dosage in Patients with Renal Impairment Renal impairment is a risk factor for statin-associated myopathy. Doses of ezetimibe and simvastatin tablets exceeding 10/20 mg should be used with caution and close monitoring in patients with moderate to severe renal impairment [see Warnings and Precautions (5.1) and Use in Specific Populations (8.6) ] . There are no dosage adjustment recommendations for patients with mild renal impairment.

2.5Dosage Modifications Due to Drug Interactions Concomitant use of ezetimibe and simvastatin tablets with the following drugs requires dosage modification of ezetimibe and simvastatin tablets [see Warnings and Precautions (5.1) and Drug Interactions (7.1) ]. Patients taking Lomitapide Reduce the dosage of ezetimibe and simvastatin tablets by 50%. Do not exceed ezetimibe and simvastatin tablets 10/20 mg once daily (or 10/40 mg once daily for patients who have previously taken ezetimibe and simvastatin tablets 10/80 mg daily chronically while taking lomitapide) [see Dosage and Administration (2.1) ] .

Patients taking Verapamil, Diltiazem, or Dronedarone Do not exceed ezetimibe and simvastatin tablets 10/10 mg once daily. Patients taking Amiodarone, Amlodipine, or Ranolazine Do not exceed ezetimibe and simvastatin tablets 10/20 mg once daily. Patients taking Bile Acid Sequestrants In patients taking a bile acid sequestrant, administer ezetimibe an… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 159 words ▾

3 DOSAGE FORMS AND STRENGTHS Ezetimibe and Simvastatin Tablets are available containing 10 mg of ezetimibe, USP and 10 mg, 20 mg, 40 mg or 80 mg of simvastatin, USP, providing for the following combinations: 10 mg/10 mg, 10 mg/20 mg, 10 mg/40 mg or 10 mg/80 mg. The 10 mg/10 mg tablets are white, oval, biconvex tablets debossed with “TS” on one side of the tablet and “1” on the other side. The 10 mg/20 mg tablets are white, oval, biconvex tablets debossed with “TS” on one side of the tablet and “2” on the other side.

The 10 mg/40 mg tablets are white, oval, biconvex tablets debossed with “TS” on one side of the tablet and “3” on the other side. The 10 mg/80 mg tablets are white, oval, biconvex tablets debossed with “TS” on one side of the tablet and “4” on the other side. Tablets (ezetimibe mg/simvastatin mg): 10/10, 10/20, 10/40, 10/80 ( 3 )

⛔ Contraindications 140 words ▾

4 CONTRAINDICATIONS Ezetimibe and simvastatin tablets is contraindicated in the following conditions: Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, antiviral medications, and nefazodone) [see Drug Interactions (7.1) ] . Concomitant use of cyclosporine, danazol, or danazol [see Drug Interactions (7.1) ] . Acute liver failure or decompensated cirrhosis [see Warnings and Precautions (5.3) ] .

Hypersensitivity to simvastatin, ezetimibe, or any excipients in ezetimibe and simvastatin tablets. Hypersensitivity reactions, including anaphylaxis, angioedema, and Stevens-Johnson syndrome, have been reported [see Adverse Reactions (6.2) ] . Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications and nefazodone).

( 4 ) Concomitant use of cyclosporine, danazol or gemfibrozil. ( 4 ) Acute liver failure or decompensated cirrhosis. ( 4 ) Hypersensitivity to simvastatin, ezetimibe or any excipient of ezetimibe and simvastatin tablets.

( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Myopathy and Rhabdomyolysis: Risk factors include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs, and higher ezetimibe and simvastatin dosage. Chinese patients may be at higher risk for myopathy. Discontinue ezetimibe and simvastatin if markedly elevated CK levels occur or myopathy is diagnosed or suspected.

Temporarily discontinue ezetimibe and simvastatin in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis. Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing ezetimibe and simvastatin dosage. Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.

( 5.1 ) Immune-Mediated Necrotizing Myopathy (IMNM): Rare reports of IMNM, an autoimmune myopathy, have been reported. Discontinue ezetimibe and simvastatin if IMNM is suspected.( 5.2 ) Hepatic Dysfunction: Increases in serum transaminases have occurred, some persistent. Rare reports of fatal and non-fatal hepatic failure have occurred.

Consider testing liver enzyme before initiating therapy and as clinically indicated thereafter. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue ezetimibe and simvastatin. ( 5.3 )

5.1Myopathy and Rhabdomyolysis Ezetimibe and simvastatin may cause myopathy and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including ezetimibe and simvastatin. In clinical trials of 24,747 simvastatin-treated patients with a median follow-up of 4 years, the incidence of myopathy, defined as unexplained muscle weakness, pain, or tenderness accompanied by creatinine kinase (CK) increases greater than ten times the upper limit of normal (10 X ULN), were approximately 0.03%, 0.08%, and 0.61% in patients treated with simvastatin 20 mg, 40 mg, and 80 mg daily, respectively.

In another clinical trial of 12,064 simvastatin-treated patients (with a history of myocardial infarction) with a mean follow-up of 6.7 years, the incidences of myopathy in patients taking simvastatin 20 mg and 80 mg daily were approximately 0.02% and 0.9%, respectively. The incidences of rhabdomyolysis (defined as myopathy with a CK >40 X ULN) in patients taking simvastatin 20 mg and 80 mg daily were approximately 0% and 0.4%, respectively [see Adverse Reactions (6.1) ] . In the Trial of Heart and Renal Protection (SHARP), 9270 patients with chronic kidney disease were allocated to receive ezetimibe and simvastatin 10/20 mg daily (n=4650) or placebo (n=4620).

During a median follow-up period of 4.9 years, the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum creatine kinase [CK] >10 times upper limit of normal [ULN]) was 0.2% for ezetimibe and simvastatin and 0.1% for placebo: the incidence of rhabdomyolysis (defined as myopathy with a CK > 40 times ULN) was 0.09% for ezetimibe and simvastatin and 0.02% for placebo. In postmarketing experience with ezetimibe, cases of myopathy and rhabdomyolysis have been reported. Most patients who developed rhabdomyolysis were taking a statin prior to initiating ezetimibe.

However, rhabdomyolysis has been reported with ezetimibe monotherapy and with the addition of ezetimibe to agents known to be associated with increased risk of rhabdomyolysis, such as fibric acid derivatives. Ezetimibe and simvastatin and a fenofibrate, if taking concomitantly, should both be immediately discontinued if myopathy is diagnosed or suspected. Risk Factors for Myopathy Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs (including other lipid-lowering therapies), and higher ezetimibe and simvastatin dosage; Chi… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the label: Myopathy and Rhabdomyolysis [see Warnings and Precautions (5.1) ] Immune-Mediated Necrotizing Myopathy [see Warnings and Precautions (5.2) ] Hepatic Dysfunction [see Warnings and Precautions (5.3) ] Increases in HbA1c and Fasting Serum Glucose Levels [see Warnings and Precautions (5.4) ] Common (incidence ≥2% and greater than placebo) adverse reactions in clinical trials: headache, increased ALT, myalgia, upper respiratory tract infection, and diarrhea.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials 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. Ezetimibe and Simvastatin In the ezetimibe and simvastatin placebo-controlled clinical trials database of 1420 patients (age range 20 to 83 years, 52% female, 87% White, 3% Black or African American, 3% Asians, 5% other races identified as Hispanic or Latino ethnicity) with a median treatment duration of 27 weeks, 5% of patients on ezetimibe and simvastatin and 2.2% of patients on placebo discontinued due to adverse reactions.

The most commonly reported adverse reactions (incidence ≥2% and greater than placebo) in controlled clinical trials were: headache (5.8%), increased ALT (3.7%), myalgia (3.6%), upper respiratory tract infection (3.6%), and diarrhea (2.8%). The most common adverse reactions in the group treated with ezetimibe and simvastatin that led to treatment discontinuation and occurred at a rate greater than placebo were: increased ALT (0.9%), myalgia (0.6%), increased AST (0.4%), and back pain (0.4%). Ezetimibe and simvastatin has been evaluated for safety in more than 10,189 patients in clinical trials.

Table 1 summarizes the frequency of clinical adverse reactions reported in ≥2% of patients treated with ezetimibe and simvastatin (n=1420) and at an incidence greater than placebo from four placebo-controlled trials. Table 1*: Adverse Reactions Reported ≥2% of Patients Treated with Ezetimibe and Simvastatin at an Incidence Greater than Placebo Regardless of Causality % Placebo N = 371 % Ezetimibe 10 mg N = 302 % Simvastatin † N = 1234 % Ezetimibe and Simvastatin † N = 1420 Headache 5.4 6.0 5.9

5.8Upper respiratory tract infection 2.7 5.0 5.0

3.6Myalgia 2.4 2.3 2.6

3.6Diarrhea 2.2 5.0 3.7

2.8Pain in extremity 1.3 3.0 2.0

2.3Influenza 0.8 1.0 1.9 2.3 *Includes two placebo-controlled combination studies in which the active ingredients equivalent to ezetimibe and simvastatin were coadministered and two placebo-controlled studies in which ezetimibe and simvastatin was administered. † All doses. Study of Heart and Renal Protection In SHARP, 9270 patients were allocated to ezetimibe and simvastatin 10/20 mg daily (n=4650) or placebo (n=4620) for a median follow-up period of 4.9 years. The proportion of patients who permanently discontinued trial treatment as a result of either an adverse event or abnormal safety blood result was 10.4% vs.

9.8% among patients allocated to ezetimibe and simvastatin and placebo, respectively. Comparing those allocated to ezetimibe and simvastatin vs. placebo, the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum CK >10 times ULN) was 0.2% vs. 0.1% and the incidence of rhabdomyolysis (defined as myopathy with a CK >40 times ULN) was 0.09% vs.

0.02%, respectively. Consecutive elevations of transaminases (>3 X ULN) occurred in 0.7% vs. 0.6%, respectively.

Patients were asked about the occurrence of unexplained muscle pain or weakness at each trial visit: 21.5% vs. 20.9% patients ever reported muscle symptoms in the ezetimibe and simvastatin and place… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Ezetimibe and Simvastatin See full prescribing information for details regarding concomitant use of ezetimibe and simvastatin with other drugs or grapefruit juice that increase the risk of myopathy and rhabdomyolysis. ( 2.3 , 7.1) Cholestyramine: Combination decreases exposure of ezetimibe. ( 2.3 , 7.2 ) Coumarin Anticoagulants: Obtain INR before ezetimibe and simvastatin initiation and monitor INR during ezetimibe and simvastatin dosage initiation or adjustment.

( 7.3 ) Digoxin: During ezetimibe and simvastatin initiation, monitor digoxin levels. ( 7.3 ) Fenofibrates: Combination increases exposure of ezetimibe. If cholelithiasis is suspected in a patient receiving ezetimibe and a fenofibrate, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered.

( 7.3 , 12.3 )

7.1Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Ezetimibe and Simvastatin Ezetimibe and simvastatin is a substrate of CYP3A4 and of the transport protein OATP1B1. Ezetimibe and simvastatin plasma levels can be significantly increased with concomitant administration of inhibitors of CYP3A4 and OATP1B1. Table 2 includes a list of drugs that increase the risk of myopathy and rhabdomyolysis when used concomitantly with ezetimibe and simvastatin and instructions for preventing or managing them [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3) ] .

Table 2: Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Ezetimibe and Simvastatin Strong CYP3A4 inhibitors Clinical Impact: Simvastatin is a substrate of CYP3A4. Concomitant use of strong CYP3A4 inhibitors with ezetimibe and simvastatin increases simvastatin exposure and increases the risk of myopathy and rhabdomyolysis, particularly with higher ezetimibe and simvastatin dosages. Intervention: Concomitant use of strong CYP3A4 inhibitors with ezetimibe and simvastatin is contraindicated [see Contraindications (4) ] .

If treatment with a CYP3A4 inhibitor is unavoidable, suspend ezetimibe and simvastatin during the course of strong CYP3A4 inhibitor treatment. Examples: Select azole anti-fungals (e.g., itraconazole, ketoconazole, posaconazole, and voriconazole), select macrolide antibiotics (e.g., erythromycin and clarithromycin, telithromycin), select HIV protease inhibitors (e.g., nelfinavir, ritonavir, and darunavir/ritonavir), select HCV protease inhibitors (e.g., boceprevir and telaprevir), cobicistat-containing products, and nefazodone.

Cyclosporine, Danazol, or Gemfibrozil Clinical Impact: The risk of myopathy and rhabdomyolysis is increased with concomitant use of cyclosporine, danazol, or gemfibrozil with ezetimibe and simvastatin. Gemfibrozil may cause myopathy when given alone. Intervention: Concomitant use of cyclosporine, danazol, or gemfibrozil with ezetimibe and simvastatin is contraindicated [see Contraindications (4) ] .

Amiodarone, Dronedarone, Ranolazine, or Calcium Channel Blockers Clinical Impact: The risk of myopathy and rhabdomyolysis is increased by concomitant use of amiodarone, dronedarone, ranolazine, or calcium channel blockers with ezetimibe and simvastatin. Intervention: For patients taking verapamil, diltiazem, or dronedarone, do not exceed ezetimibe and simvastatin 10/10 mg daily . For patients taking amiodarone, amlodipine, or ranolazine, do not exceed ezetimibe and simvastatin 10/20 mg daily [see Dosage and Administration (2.3) ] .

Lomitapide Clinical Impact: Simvastatin exposure is approximately doubled with concomitant use of lomitapide and the risk of myopathy and rhabdomyolysis is increased . Intervention: Reduce the dose of ezetimibe and simvastatin by 50% if initiating lomitapide. Do not exceed ezetimibe and simvastatin 10/20 mg daily (or ezetimibe and simvastatin 10/40 mg daily for patients who have previously taken ezetimibe and simvastatin 10/80 mg daily chronically) while taking lomitapide [see Dosage and Administration (2.1 , 2.3) ] .

Daptomycin Clini… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy: May cause fetal harm (8.1) Lactation: Breastfeeding not recommended during treatment with ezetimibe and simvastatin. ( 8.2 )

8.1Pregnancy Ezetimibe and Simvastatin Risk Summary Discontinue ezetimibe and simvastatin when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Ezetimibe and simvastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, ezetimibe and simvastatin may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology (12.1) ] .

In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations.

Published data from prospective and retrospective observational cohort studies with ezetimibe and simvastatin use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see Data) . In animal reproduction studies, no adverse developmental effects were observed in pregnant rats or rabbits orally administered simvastatin during the period of organogenesis at doses that resulted in 2.5 and 2 times, respectively, the human exposure at the maximum recommended human dosage of 80 mg/day, based on body surface area (mg/m 2 ).

In animal reproduction studies, no adverse developmental effects were observed in pregnant rats and rabbits orally administered ezetimibe during the period of organogenesis at doses that resulted in up to 10 and 150 times, respectively, the human exposure at the MRHD, based on AUC (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data Human Data Ezetimibe There are insufficient data on ezetimibe use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Simvastatin A Medicaid cohort linkage trial of 1152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods.

The relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. There were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. In the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified.

Trial limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births. Animal Data Ezetimibe In oral (gavage) embryo-fetal development studies of ezetimibe conducted in rats (gestation days 6 to 15) and rabbits (gestation days 7 to 19), there was no evidence of maternal… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Ezetimibe and Simvastatin Risk Summary Discontinue ezetimibe and simvastatin when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Ezetimibe and simvastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, ezetimibe and simvastatin may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology (12.1) ] .

In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations.

Published data from prospective and retrospective observational cohort studies with ezetimibe and simvastatin use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see Data) . In animal reproduction studies, no adverse developmental effects were observed in pregnant rats or rabbits orally administered simvastatin during the period of organogenesis at doses that resulted in 2.5 and 2 times, respectively, the human exposure at the maximum recommended human dosage of 80 mg/day, based on body surface area (mg/m 2 ).

In animal reproduction studies, no adverse developmental effects were observed in pregnant rats and rabbits orally administered ezetimibe during the period of organogenesis at doses that resulted in up to 10 and 150 times, respectively, the human exposure at the MRHD, based on AUC (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data Human Data Ezetimibe There are insufficient data on ezetimibe use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Simvastatin A Medicaid cohort linkage trial of 1152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods.

The relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. There were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. In the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified.

Trial limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births. Animal Data Ezetimibe In oral (gavage) embryo-fetal development studies of ezetimibe conducted in rats (gestation days 6 to 15) and rabbits (gestation days 7 to 19), there was no evidence of maternal toxicity or embryolethality at any dose tested (250, 500, 1000 mg/kg/day) at exposure equivalent to 10 to 150 times the clinical exposure, based on AUC, in rats and r… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use 136 words ▾

8.4Pediatric Use The safety and effectiveness of ezetimibe in combination with a statin as an adjunct to diet to reduce LDL-C have been established in pediatric patients 10 years of age and older with HeFH. Use of ezetimibe and simvastatin for this indication is based on a double-blind, placebo-controlled clinical trial in 248 pediatric patients (142 males and 106 postmenarchal females) 10 years of age and older with HeFH [see Clinical Studies (14) ] . In this limited controlled trial, there was no significant effect on growth or sexual maturation in the adolescent males or females, or on menstrual cycle length in females.

The safety and effectiveness of ezetimibe and simvastatin have not been established in pediatric patients younger than 10 years of age with HeFH, or in pediatric patients with other types of hyperlipidemia.

🧓 Geriatric Use 142 words ▾

8.5Geriatric Use Advanced age (≥65 years) is a risk factor for ezetimibe and simvastatin-associated myopathy and rhabdomyolysis. Dose selection for an elderly patient should be cautious, recognizing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy. Monitor geriatric patients receiving ezetimibe and simvastatin for the increased risk of myopathy [see Warnings and Precautions (5.1) ] .

Of the 10,189 patients who received ezetimibe and simvastatin in clinical studies, 3242 (32%) were 65 and older (this included 844 (8%) who were 75 and older). No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients but greater sensitivity of some older individuals cannot be ruled out.

🆘 Overdosage 36 words ▾

10 OVERDOSAGE No specific antidotes for ezetimibe and simvastatin are known. In the event of an overdose with ezetimibe and simvastatin, consider contacting the Poison Help Line (1-800-222-1222) or a medical toxicologist for overdosage management recommendations.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Ezetimibe and Simvastatin Plasma cholesterol is derived from intestinal absorption and endogenous synthesis. Ezetimibe and simvastatin contains ezetimibe and simvastatin, two lipid-lowering compounds with complementary mechanisms of action. Ezetimibe Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine.

The molecular target of ezetimibe has been shown to be the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols. Ezetimibe localizes at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood.

Simvastatin Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin acid and its metabolites are inhibitors of HMG-CoA reductase, the rate-limiting enzyme converts HMG-CoA to mevalonate, a precursor of cholesterol.

12.2Pharmacodynamics Ezetimibe and simvastatin reduces total cholesterol (total-C), LDL-C, apolipoprotein (Apo) B, and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with hyperlipidemia. Ezetimibe In a 2-week clinical trial in 18 hypercholesterolemic patients, ezetimibe inhibited intestinal cholesterol absorption by 54%, compared with placebo. Ezetimibe had no clinically meaningful effect on the plasma concentrations of the fat-soluble vitamins A, D, and E and did not impair adrenocortical steroid hormone production.

Simvastatin Inhibition of HMG-CoA reductase by simvastatin acid accelerates the expression of LDL-receptors, followed by the uptake of LDL-C from blood to the liver, leading to a decrease in plasma LDL-C and total cholesterol. Sustained inhibition of cholesterol synthesis in the liver also decreases levels of very-low density lipoproteins. The maximum LDL-C reduction of ZOCOR is usually achieved by 4 weeks and is maintained after that.

12.3Pharmacokinetics The results of a bioequivalence trial in healthy subjects demonstrated that the ezetimibe and simvastatin 10 mg/10 mg to 10 mg/80 mg combination tablets are bioequivalent to coadministration of corresponding doses of ezetimibe (ZETIA ® ) and simvastatin (ZOCOR ® ) as individual tablets. Absorption Ezetimibe After oral administration, ezetimibe is absorbed and extensively conjugated to a pharmacologically active phenolic glucuronide (ezetimibe-glucuronide). Mean maximum plasma concentrations (C max ) occur within 1 to 2 hours for ezetimibe-glucuronide and 4 to 12 hours for ezetimibe.

The absolute bioavailability of ezetimibe cannot be determined as the compound is virtually insoluble in aqueous media suitable for injection. Simvastatin The availability of the β-hydroxyacid to the systemic circulation following an oral dose of simvastatin was found to be less than 5% of the dose, consistent with extensive hepatic first-pass extraction. Effect of Food on Oral Absorption Ezetimibe Concomitant food administration (high-fat or non-fat meals) had no effect on the extent of absorption of ezetimibe when administered as 10-mg tablets.

The C max value of ezetimibe was increased by 38% with consumption of high-fat meals. Simvastatin Relative to the fasting state, the plasma profiles of both active and total inhibitors of HMG-CoA reductase were not affected when simvastatin was administered immediately before an American Heart Association recommended low-fat meal. Distribution Ezetimibe Ezetimibe and ezetimibe-glucuronide are highly bound (>90%) to human plasma proteins.

Simvastatin Both simvastatin and its β-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins. When radiolabeled simvastatin was administered to rats, simvastatin-derived radioactivity crossed the bloo… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 160 words ▾

12.1Mechanism of Action Ezetimibe and Simvastatin Plasma cholesterol is derived from intestinal absorption and endogenous synthesis. Ezetimibe and simvastatin contains ezetimibe and simvastatin, two lipid-lowering compounds with complementary mechanisms of action. Ezetimibe Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine.

The molecular target of ezetimibe has been shown to be the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols. Ezetimibe localizes at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood.

Simvastatin Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin acid and its metabolites are inhibitors of HMG-CoA reductase, the rate-limiting enzyme converts HMG-CoA to mevalonate, a precursor of cholesterol.

📦 How Supplied / Storage and Handling ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Ezetimibe and Simvastatin Tablets are available containing 10 mg of ezetimibe, USP and 10 mg, 20 mg, 40 mg or 80 mg of simvastatin, USP, providing for the following combinations: 10 mg/10 mg, 10 mg/20 mg, 10 mg/40 mg or 10 mg/80 mg. The 10 mg/10 mg tablets are white, oval, biconvex tablets debossed with “TS” on one side of the tablet and “1” on the other side. They are available as follows: Bottles of 30 NDC 59651-835-30 Bottles of 90 NDC 59651-835-90 The 10 mg/20 mg tablets are white, oval, biconvex tablets debossed with “TS” on one side of the tablet and “2” on the other side.

They are available as follows: Bottles of 30 NDC 59651-836-30 Bottles of 90 NDC 59651-836-90 The 10 mg/40 mg tablets are white, oval, biconvex tablets debossed with “TS” on one side of the tablet and “3” on the other side. They are available as follows: Bottles of 30 NDC 59651-837-30 Bottles of 90 NDC 59651-837-90 The 10 mg/80 mg tablets are white, oval, biconvex tablets debossed with “TS” on one side of the tablet and “4” on the other side. They are available as follows: Bottles of 30 NDC 59651-838-30 Bottles of 90 NDC 59651-838-90 Storage Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Keep container tightly closed.

📋 Description ~1 min read ▾

11 DESCRIPTION Ezetimibe and simvastatin tablets contain ezetimibe, a dietary cholesterol absorption inhibitor, and simvastatin, an HMG-CoA reductase inhibitor. The chemical name of ezetimibe is 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone. The molecular formula is C 24 H 21 F 2 NO 3 and its molecular weight is 409.4.

Ezetimibe, USP is a white powder that is freely to very soluble in ethanol, methanol, and acetone and practically insoluble in water. Its structural formula is: Simvastatin, an inactive lactone, is hydrolyzed to the corresponding β-hydroxyacid form, which is an inhibitor of HMG-CoA reductase. Simvastatin is butanoic acid, 2,2-dimethyl-,1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2 H -pyran-2-yl)-ethyl]-1-naphthalenyl ester, [1 S -[1α,3α,7β,8β(2 S *,4 S *),-8aβ]].

The molecular formula of simvastatin is C 25 H 38 O 5 and its molecular weight is 418.57. Simvastatin, USP is a white or almost white powder that is practically insoluble in water and freely soluble in chloroform, methanol and ethanol. Its structural formula is: Ezetimibe and simvastatin are available for oral use as tablets containing 10 mg of ezetimibe USP, and 10 mg, 20 mg, 40 mg or 80 mg of simvastatin USP, providing for the following combinations: 10 mg/10 mg, 10 mg/20 mg, 10 mg/40 mg or 10 mg/80 mg.

Each tablet contains the following inactive ingredients: ascorbic acid, butylated hydroxyanisole, citric acid monohydrate, croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose and sodium lauryl sulfate. Chemical Structure 1 str

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information ). Myopathy and Rhabdomyolysis Advise patients that ezetimibe and simvastatin tablets may cause myopathy and rhabdomyolysis. Inform patients taking the 80 mg daily dose of simvastatin that they are at an increased risk.

Inform patients that the risk is also increased when taking certain types of medication or consuming grapefruit juice and they should discuss all medication, both prescription and over the counter, with their healthcare provider. Instruct patients to inform other healthcare providers prescribing a new medication or increasing the dose of an existing medication that they are taking ezetimibe and simvastatin tablets. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever [see Contraindications (4) , Warnings and Precautions (5.1) , and Drug Interactions (7.1) ] .

Hepatic Dysfunction Inform patients that ezetimibe and simvastatin tablets may cause liver enzyme elevations and possibly liver failure. Advise patients to promptly report fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice [see Warnings and Precautions (5.3) ] . Increases in HbA1c and Fasting Serum Glucose Levels Inform patients that increases in HbA1c and fasting serum glucose levels may occur with ezetimibe and simvastatin tablets.

Encourage patients to optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices [see Warnings and Precautions (5.4) ] . Pregnancy Advise pregnant patients and patients who can become pregnant of the potential risk to a fetus. Advise patients to inform their healthcare provider of a known or suspected pregnancy to discuss if ezetimibe and simvastatin tablets should be discontinued [see Use in Specific Populations (8.1) ] .

Lactation Advise patients that breastfeeding is not recommended during treatment with ezetimibe and simvastatin tablets [see Use in Specific Populations (8.2) ] . Missed Dose Instruct patients to take ezetimibe and simvastatin tablets only as prescribed. If a dose is missed, it should be taken as soon as possible.

Advise patients not to double their next dose. The brands listed are trademarks of their respective owners and are not trademarks of Aurobindo Pharma Limited. Distributed by: Aurobindo Pharma USA, Inc.

279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 032, India Revised: 04/2024

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics The results of a bioequivalence trial in healthy subjects demonstrated that the ezetimibe and simvastatin 10 mg/10 mg to 10 mg/80 mg combination tablets are bioequivalent to coadministration of corresponding doses of ezetimibe (ZETIA ® ) and simvastatin (ZOCOR ® ) as individual tablets. Absorption Ezetimibe After oral administration, ezetimibe is absorbed and extensively conjugated to a pharmacologically active phenolic glucuronide (ezetimibe-glucuronide). Mean maximum plasma concentrations (C max ) occur within 1 to 2 hours for ezetimibe-glucuronide and 4 to 12 hours for ezetimibe.

The absolute bioavailability of ezetimibe cannot be determined as the compound is virtually insoluble in aqueous media suitable for injection. Simvastatin The availability of the β-hydroxyacid to the systemic circulation following an oral dose of simvastatin was found to be less than 5% of the dose, consistent with extensive hepatic first-pass extraction. Effect of Food on Oral Absorption Ezetimibe Concomitant food administration (high-fat or non-fat meals) had no effect on the extent of absorption of ezetimibe when administered as 10-mg tablets.

The C max value of ezetimibe was increased by 38% with consumption of high-fat meals. Simvastatin Relative to the fasting state, the plasma profiles of both active and total inhibitors of HMG-CoA reductase were not affected when simvastatin was administered immediately before an American Heart Association recommended low-fat meal. Distribution Ezetimibe Ezetimibe and ezetimibe-glucuronide are highly bound (>90%) to human plasma proteins.

Simvastatin Both simvastatin and its β-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins. When radiolabeled simvastatin was administered to rats, simvastatin-derived radioactivity crossed the blood-brain barrier. Elimination Metabolism Ezetimibe Ezetimibe is primarily metabolized in the small intestine and liver via glucuronide conjugation with subsequent biliary and renal excretion.

Minimal oxidative metabolism has been observed in all species evaluated. In humans, ezetimibe is rapidly metabolized to ezetimibe-glucuronide. Ezetimibe and ezetimibeglucuronide are the major drug-derived compounds detected in plasma, constituting approximately 10 to 20% and 80 to 90% of the total drug in plasma, respectively.

Both ezetimibe and ezetimibe-glucuronide are eliminated from plasma with a half-life of approximately 22 hours for both ezetimibe and ezetimibeglucuronide. Plasma concentration-time profiles exhibit multiple peaks, suggesting enterohepatic recycling. Simvastatin Simvastatin is a lactone that is readily hydrolyzed in vivo to the corresponding β-hydroxyacid, a potent inhibitor of HMG-CoA reductase.

Inhibition of HMG-CoA reductase is a basis for an assay in pharmacokinetic studies of the β-hydroxyacid metabolites (active inhibitors) and, following base hydrolysis, active plus latent inhibitors (total inhibitors) in plasma following administration of simvastatin. The major active metabolites of simvastatin present in human plasma are the β-hydroxyacid of simvastatin and its 6′-hydroxy, 6′-hydroxymethyl, and 6′-exomethylene derivatives. Excretion Ezetimibe Following oral administration of 14 C-ezetimibe (20 mg) to human subjects, total ezetimibe (ezetimibe + ezetimibe-glucuronide) accounted for approximately 93% of the total radioactivity in plasma.

After 48 hours, there were no detectable levels of radioactivity in the plasma. Approximately 78% and 11% of the administered radioactivity were recovered in the feces and urine, respectively, over a 10-day collection period. Ezetimibe was the major component in feces and accounted for 69% of the administered dose, while ezetimibe-glucuronide was the major component in urine and accounted for 9% of the administered dose.

Simvastatin Following an oral dose of 14 C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces. Plasma concentrations of tota… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 134 words ▾

12.2Pharmacodynamics Ezetimibe and simvastatin reduces total cholesterol (total-C), LDL-C, apolipoprotein (Apo) B, and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with hyperlipidemia. Ezetimibe In a 2-week clinical trial in 18 hypercholesterolemic patients, ezetimibe inhibited intestinal cholesterol absorption by 54%, compared with placebo. Ezetimibe had no clinically meaningful effect on the plasma concentrations of the fat-soluble vitamins A, D, and E and did not impair adrenocortical steroid hormone production.

Simvastatin Inhibition of HMG-CoA reductase by simvastatin acid accelerates the expression of LDL-receptors, followed by the uptake of LDL-C from blood to the liver, leading to a decrease in plasma LDL-C and total cholesterol. Sustained inhibition of cholesterol synthesis in the liver also decreases levels of very-low density lipoproteins. The maximum LDL-C reduction of ZOCOR is usually achieved by 4 weeks and is maintained after that.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES Primary Hyperlipidemia in Adults Ezetimibe and Simvastatin Ezetimibe and simvastatin reduces LDL-C in adult patients with primary hyperlipidemia. Maximal to near maximal response is generally achieved within 2 weeks and maintained during chronic therapy. Ezetimibe and simvastatin is effective in males and females with primary hyperlipidemia.

There were insufficient numbers of patients who self-identified as Black or African American, Asian, or other races to determine if these patients responded differently than White patients. Five multicenter, double-blind trials conducted with either ezetimibe and simvastatin or coadministered ezetimibe and simvastatin equivalent to ezetimibe and simvastatin in patients with primary hyperlipidemia are reported: two were comparisons with simvastatin, two were comparisons with atorvastatin, and one was a comparison with rosuvastatin.

In a multicenter, double-blind, placebo-controlled, 12-week trial, 1528 patients with primary hyperlipidemia were randomized to one of ten treatment groups: placebo, ezetimibe (10 mg), simvastatin (10 mg, 20 mg, 40 mg, or 80 mg), or ezetimibe and simvastatin (10/10, 10/20, 10/40, or 10/80). When patients receiving ezetimibe and simvastatin were compared to those receiving all doses of simvastatin, ezetimibe and simvastatin significantly lowered total-C, LDL-C, Apo B, TG, and non-HDL-C. The effects of ezetimibe and simvastatin on HDL-C were similar to the effects seen with simvastatin.

Further analysis showed ezetimibe and simvastatin significantly increased HDL-C compared with placebo. (See Table 8.) The lipid response to ezetimibe and simvastatin was similar in patients with TG levels greater than or less than 200 mg/dL. Table 8: Response to Ezetimibe and Simvastatin in Patients with Primary Hyperlipidemia (Mean* % Change from Untreated Baseline † ) Treatment (Daily Dose) N Total-C LDL-C Apo B HDL-C TG* Non-HDL-C Pooled data (All ezetimibe and simvastatin doses) ‡ 609 -38 -53 -42 +7 -24 -49 Pooled data (All simvastatin doses) ‡ 622 -28 -39 -32 +7 -21 -36 Ezetimibe 10 mg 149 -13 -19 -15 +5 -11 -18 Placebo 148 -1 -2 0 0 -2 -2 Ezetimibe and simvastatin by dose 10/10 152 -31 -45 -35 +8 -23 -41 10/20 156 -36 -52 -41 +10 -24 -47 10/40 147 -39 -55 -44 +6 -23 -51 10/80 154 -43 -60 -49 +6 -31 -56 Simvastatin by dose 10 mg 158 -23 -33 -26 +5 -17 -30 20 mg 150 -24 -34 -28 +7 -18 -32 40 mg 156 -29 -41 -33 +8 -21 -38 80 mg 158 -35 -49 -39 +7 -27 -45 * For triglycerides, median % change from baseline. † Baseline - on no lipid-lowering drug. ‡ Ezetimibe and simvastatin doses pooled (10/10 to 10/80) significantly reduced total-C, LDL-C, Apo B, TG, and non-HDL-C compared to simvastatin and significantly increased HDL-C compared to placebo.

In a multicenter, double-blind, controlled, 23-week trial, 710 patients with known CHD or CHD risk equivalents, as defined by the NCEP ATP III guidelines, and an LDL-C ≥130 mg/dL were randomized to one of four treatment groups: coadministered ezetimibe and simvastatin equivalent to ezetimibe and simvastatin (10/10, 10/20, and 10/40) or simvastatin 20 mg. Patients not reaching an LDL-C <100 mg/dL had their simvastatin dose titrated at 6-week intervals to a maximal dose of 80 mg. At Week 5, the LDL-C reductions with ezetimibe and simvastatin 10/10, 10/20, or 10/40 were significantly larger than with simvastatin 20 mg (see Table 9).

Table 9: Response to Ezetimibe and Simvastatin after 5 Weeks in Patients with CHD or CHD Risk Equivalents and an LDL-C ≥ 130 mg/dL Simvastatin 20 mg Ezetimibe and simvastatin 10/10 Ezetimibe and simvastatin 10/20 Ezetimibe and simvastatin 10/40 N 253 251 109 97 Mean baseline LDL-C 174 165 167 171 Percent change LDL-C -38 -47 -53 -59 In a multicenter, double-blind, 6-week trial, 1902 patients with primary hyperlipidemia were randomized to one of eight treatment groups: ezetimibe and simvastatin (10/10, 10/20, 10/40, or 10/80) or atorvastatin (10 mg, 20 mg, 40 mg, or 80 mg).

Across the dosage range,… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~3 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Ezetimibe and Simvastatin No animal carcinogenicity or fertility studies have been conducted with the combination of ezetimibe and simvastatin. The combination of ezetimibe with simvastatin did not show evidence of mutagenicity in vitro in a microbial mutagenicity (Ames) test with Salmonella typhimurium and Escherichia coli with or without metabolic activation. No evidence of clastogenicity was observed in vitro in a chromosomal aberration assay in human peripheral blood lymphocytes with ezetimibe and simvastatin with or without metabolic activation.

There was no evidence of genotoxicity at doses up to 600 mg/kg with the combination of ezetimibe and simvastatin (1:1) in the in vivo mouse micronucleus test. Ezetimibe A 104-week dietary carcinogenicity trial with ezetimibe was conducted in rats at doses up to 1500 mg/kg/day (males) and 500 mg/kg/day (females) (~20 times the human exposure at 10 mg daily based on AUC 0-24hr for total ezetimibe). A 104-week dietary carcinogenicity trial with ezetimibe was also conducted in mice at doses up to 500 mg/kg/day (>150 times the human exposure at 10 mg daily based on AUC 0-24hr for total ezetimibe).

There were no statistically significant increases in tumor incidences in drugtreated rats or mice. No evidence of mutagenicity was observed in vitro in a microbial mutagenicity (Ames) test with Salmonella typhimurium and Escherichia coli with or without metabolic activation. No evidence of clastogenicity was observed in vitro in a chromosomal aberration assay in human peripheral blood lymphocytes with or without metabolic activation.

In addition, there was no evidence of genotoxicity in the in vivo mouse micronucleus test. In oral (gavage) fertility studies of ezetimibe conducted in rats, there was no evidence of reproductive toxicity at doses up to 1000 mg/kg/day in male or female rats (~7 times the human exposure at 10 mg daily based on AUC 0-24hr for total ezetimibe). Simvastatin In a 72-week carcinogenicity trial, mice were administered daily doses of simvastatin of 25, 100, and 400 mg/kg body weight, which resulted in mean plasma drug levels approximately 1, 4, and 8 times higher than the mean human plasma drug level, respectively, (as total inhibitory activity based on AUC) after an 80-mg oral dose.

Liver carcinomas were significantly increased in high-dose females and mid- and highdose males with a maximum incidence of 90% in males. The incidence of adenomas of the liver was significantly increased in mid- and high-dose females. Drug treatment also significantly increased the incidence of lung adenomas in mid- and high-dose males and females.

Adenomas of the Harderian gland (a gland of the eye of rodents) were significantly higher in high-dose mice than in controls. No evidence of a tumorigenic effect was observed at 25 mg/kg/day. In a separate 92-week carcinogenicity trial in mice at doses up to 25 mg/kg/day, no evidence of a tumorigenic effect was observed (mean plasma drug levels were 1 times higher than humans given 80 mg simvastatin as measured by AUC).

In a two-year trial in rats at 25 mg/kg/day, there was a statistically significant increase in the incidence of thyroid follicular adenomas in female rats exposed to approximately 11 times higher levels of simvastatin than in humans given 80 mg simvastatin (as measured by AUC). A second two-year rat carcinogenicity trial with doses of 50 and 100 mg/kg/day produced hepatocellular adenomas and carcinomas (in female rats at both doses and in males at 100 mg/kg/day). Thyroid follicular cell adenomas were increased in males and females at both doses; thyroid follicular cell carcinomas were increased in females at 100 mg/kg/day.

The increased incidence of thyroid neoplasms appears to be consistent with findings from other statins. These treatment levels represented plasma drug levels (AUC) of approximately 7 and 15 times (males) and 22 and 25 times (femal… [Excerpted — this section continues on DailyMed.]

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~3 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Ezetimibe and Simvastatin No animal carcinogenicity or fertility studies have been conducted with the combination of ezetimibe and simvastatin. The combination of ezetimibe with simvastatin did not show evidence of mutagenicity in vitro in a microbial mutagenicity (Ames) test with Salmonella typhimurium and Escherichia coli with or without metabolic activation. No evidence of clastogenicity was observed in vitro in a chromosomal aberration assay in human peripheral blood lymphocytes with ezetimibe and simvastatin with or without metabolic activation.

There was no evidence of genotoxicity at doses up to 600 mg/kg with the combination of ezetimibe and simvastatin (1:1) in the in vivo mouse micronucleus test. Ezetimibe A 104-week dietary carcinogenicity trial with ezetimibe was conducted in rats at doses up to 1500 mg/kg/day (males) and 500 mg/kg/day (females) (~20 times the human exposure at 10 mg daily based on AUC 0-24hr for total ezetimibe). A 104-week dietary carcinogenicity trial with ezetimibe was also conducted in mice at doses up to 500 mg/kg/day (>150 times the human exposure at 10 mg daily based on AUC 0-24hr for total ezetimibe).

There were no statistically significant increases in tumor incidences in drugtreated rats or mice. No evidence of mutagenicity was observed in vitro in a microbial mutagenicity (Ames) test with Salmonella typhimurium and Escherichia coli with or without metabolic activation. No evidence of clastogenicity was observed in vitro in a chromosomal aberration assay in human peripheral blood lymphocytes with or without metabolic activation.

In addition, there was no evidence of genotoxicity in the in vivo mouse micronucleus test. In oral (gavage) fertility studies of ezetimibe conducted in rats, there was no evidence of reproductive toxicity at doses up to 1000 mg/kg/day in male or female rats (~7 times the human exposure at 10 mg daily based on AUC 0-24hr for total ezetimibe). Simvastatin In a 72-week carcinogenicity trial, mice were administered daily doses of simvastatin of 25, 100, and 400 mg/kg body weight, which resulted in mean plasma drug levels approximately 1, 4, and 8 times higher than the mean human plasma drug level, respectively, (as total inhibitory activity based on AUC) after an 80-mg oral dose.

Liver carcinomas were significantly increased in high-dose females and mid- and highdose males with a maximum incidence of 90% in males. The incidence of adenomas of the liver was significantly increased in mid- and high-dose females. Drug treatment also significantly increased the incidence of lung adenomas in mid- and high-dose males and females.

Adenomas of the Harderian gland (a gland of the eye of rodents) were significantly higher in high-dose mice than in controls. No evidence of a tumorigenic effect was observed at 25 mg/kg/day. In a separate 92-week carcinogenicity trial in mice at doses up to 25 mg/kg/day, no evidence of a tumorigenic effect was observed (mean plasma drug levels were 1 times higher than humans given 80 mg simvastatin as measured by AUC).

In a two-year trial in rats at 25 mg/kg/day, there was a statistically significant increase in the incidence of thyroid follicular adenomas in female rats exposed to approximately 11 times higher levels of simvastatin than in humans given 80 mg simvastatin (as measured by AUC). A second two-year rat carcinogenicity trial with doses of 50 and 100 mg/kg/day produced hepatocellular adenomas and carcinomas (in female rats at both doses and in males at 100 mg/kg/day). Thyroid follicular cell adenomas were increased in males and females at both doses; thyroid follicular cell carcinomas were increased in females at 100 mg/kg/day.

The increased incidence of thyroid neoplasms appears to be consistent with findings from other statins. These treatment levels represented plasma drug levels (AUC) of approximately 7 and 15 times (males) and 22 and 25 times (females) the mean human plasma… [Excerpted — this section continues on DailyMed.]

📄 Patient Package Insert ~3 min read ▾

PATIENT INFORMATION Ezetimibe and Simvastatin ( e zet′ i mibe and sim″ va stat′ in ) Tablets, for oral use Read this Information carefully before you start taking ezetimibe and simvastatin tablets and each time you get a ezetimibe and simvastatin tablets. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.

If you have any questions about ezetimibe and simvastatin tablets, ask your healthcare provider. Only your healthcare provider can determine if ezetimibe and simvastatin tablets is right for you. What are ezetimibe and simvastatin tablets?

Ezetimibe and simvastatin tablets are a prescription medicine that contains the cholesterol lowering medicines, simvastatin and ezetimibe: Ezetimibe and simvastatin tablets are used along with diet to lower elevated low-density lipoprotein cholesterol (LDL-C) or bad cholesterol in: adults with primary hyperlipidemia (high level of fats in your blood). adults and children 10 years of age and older with heterozygous familial hypercholesterolemia (HeFH). HeFH is an inherited condition that causes high levels of bad cholesterol.

Ezetimibe and simvastatin tablets are also used with other cholesterol lowering treatments to lower elevated LDL-C levels in adults with homozygous familial hypercholesterolemia (HoFH). HoFH is an inherited condition that causes high levels of bad cholesterol. Simvastatin when used as a component of ezetimibe and simvastatin tablets are used to lower: the risk of death by lowering the risk of heart disease death. the risk of heart attacks and strokes. the need for certain types of heart and blood vessel procedures to improve blood flow called arterial revascularization in people with known heart, cerebrovascular disease (conditions that affect blood flow and the blood vessels in the brain), peripheral vascular disease (a blood circulation disorder that causes the blood vessels outside of your heart and brain to narrow, block, or spasm), and diabetes, who are at high risk for heart disease problems.

The safety and effectiveness of ezetimibe and simvastatin tablets have not been established in children younger than 10 years of age with inherited heterozygous familial hypercholesterolemia (HeFH) or other types of hyperlipidemia. Do not take ezetimibe and simvastatin tablets if you: take certain medicines called CYP3A4 inhibitors such as: certain antifungal medicines (such as itraconazole, ketoconazole, posaconazole, voriconazole). certain antibiotics (including erythromycin, clarithromycin, telithromycin). HIV protease inhibitors (such as indinavir, nelfinavir, ritonavir, saquinavir, tipranavir, or atazanavir and cobicistat-containing products such as (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate). certain hepatitis C virus protease inhibitors (such as boceprevir or telaprevir). the antidepressant nefazodone. take medicines called cyclosporine, danazol, or gemfibrozil. have liver problems. are allergic to simvastatin, ezetimibe, or any of the ingredients in ezetimibe and simvastatin tablets.

See the end of this Patient Information leaflet for a complete list of ingredients in ezetimibe and simvastatin tablets. Ask your healthcare provider or pharmacist if you are not sure if your medicine is listed above. Before you take ezetimibe and simvastatin tablets, tell your healthcare provider about all of your medical conditions, including if you: have unexplained muscle aches or weakness. have or have had myasthenia gravis (a disease causing general muscle weakness including in some cases muscles used for breathing), ocular myasthenia (a disease causing eye muscle weakness). have kidney problems. have liver problems or drink more than 2 glasses of alcohol daily. have thyroid problems. are 65 years of age or older. are of Chinese descent. are pregnant or plan to become pregnant.

If you become pregnant while taking ezetimibe and simvastatin tablets, ca… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 40 words ▾

Indications and Usage ( 1 ) 2/2024 Dosage and Administration ( 2.1 , 2.2 , 2.3 , 2.4 , 2.5 ) 2/2024 Contraindications, Pregnancy and Lactation (4) Removed 2/2024 Warnings and Precautions ( 5.1 , 5.2 , 5.3 ) 2/2024

📄 Package Label / Principal Display Panel 144 words ▾

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 10 mg/10 mg (30 Tablets Bottle) NDC 59651-835-30 Rx only Ezetimibe and Simvastatin Tablets 10 mg/10 mg AUROBINDO 30 Tablets PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 10 mg/10 mg (30 Tablets Bottle)

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 10 mg/20 mg (30 Tablets Bottle) NDC 59651-836-30 Rx only Ezetimibe and Simvastatin Tablets 10 mg/20 mg AUROBINDO 30 Tablets PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 10 mg/20 mg (30 Tablets Bottle)

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 10 mg/40 mg (30 Tablets Bottle) NDC 59651-837-30 Rx only Ezetimibe and Simvastatin Tablets 10 mg/40 mg AUROBINDO 30 Tablets PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 10 mg/40 mg (30 Tablets Bottle)

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 10 mg/80 mg (30 Tablets Bottle) NDC 59651-838-30 Rx only Ezetimibe and Simvastatin Tablets 10 mg/80 mg AUROBINDO 30 Tablets PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 10 mg/80 mg (30 Tablets Bottle)

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

About this NDC listing & data coverage

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Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Aurobindo Pharma Limited. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 30 tablets (59651-0835-30). Each has its own NDC and its own page — see the package list near the top of this page.
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Aurobindo Pharma Limited is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
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This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
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Where does this data come from?
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← 59651-0834-60 · Aurobindo 59651-0836-30 · Aurobindo →
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