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Simvastatin 5 mg Tablet, Film Coated, 1,000-count — NDC 65862-0050-99 package photo

Simvastatin 5 mg Tablet, Film Coated, 1,000-count

by Aurobindo Pharma Limited · 1000 TABLET, FILM COATED in 1 BOTTLE (65862-050-99)
NDC 65862-0050-99
🏷️ FDA NDC (as labeled) 65862-050-99 billing pads the product segment with a zero
This package
Contains1,000-count Pack sizes8 compare ↓
Also priced by: Part D plans $0.0936/unit — full pricing hub ↓
Also comes in: 30 tablets 65862-0050-30 45 tablets 65862-0050-45 90 tablets 65862-0050-90 100 tablets 65862-0050-00 100 tablets 65862-0050-01 2500 tablets 65862-0050-26 11000 tablets 65862-0050-11
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

🆔 Identity & classification

FDA NDC (as labeled) 65862-050-99
Product NDC 65862-050
11-digit billing NDC 65862005099
NCPDP billing unit EA — each (per item)
RxCUI 198211, 200345, 312961, 312962, 314231
UNII AGG2FN16EV
Application # ANDA077691
SPL Set ID 4724dbb4-3613-4e6a-948f-a43d34f97f06
Established class (EPC) HMG-CoA Reductase Inhibitor
Mechanism of action Hydroxymethylglutaryl-CoA Reductase Inhibitors
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2006-12-20
Route ORAL
Dosage form TABLET, FILM COATED
Substance SIMVASTATIN
GPI-14 39400075000310
GPI class Simvastatin
GCN Seq No 016576
GCN 26531
HICL code 006312
Ingredient (HICL) Simvastatin
HIC1 code M
Therapeutic class — broad (HIC1) Blood
HIC2 code M4
Therapeutic class — intermediate (HIC2) Affect Blood Lipids/Sugar/Amino Acids
HIC3 code M4D
Therapeutic class — specific (HIC3) Antihyperlipidemic-Hmgcoa Reductase Inhib(Statins)
AHFS code 24:06.08.00
AHFS class Hmg-Coa Reductase Inhibitors
FDB label name SIMVASTATIN 5 MG TABLET
FDB brand name Simvastatin
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 65862-050-99 — 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 → 65862-0050-99. 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 HMG-CoA Reductase Inhibitor class.

Pharmacologic class HMG-CoA Reductase Inhibitor
Drug family (ATC) Dipeptidyl peptidase 4 (DPP-4) inhibitors, HMG CoA reductase inhibitors
How it works Hydroxymethylglutaryl-CoA Reductase 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

LabelerAurobindo Pharma Limited
Application holderAUROBINDO PHARMA LTD
FDA applicationANDA077691 (ANDA)
Labeler code65862
First marketedDec 2006
Product typeHuman Prescription Drug
Portfolio1,449 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 SIMVASTATIN 5 MG TABLET Ingredient Simvastatin
📖 What it is MedlinePlus · NLM

Simvastatin is used to reduce the risk of heart attack and stroke in patients at high risk of these developing decrease the amount of cholesterol (a fat-like substance) Simvastatin is in a class of medications called HMG-CoA reductase inhibitors (statins). It works by slowing how much cholesterol your body makes. This lowers the amount of cholesterol that can build up on the walls of the arteries and block blood flow to the heart, brain, and other parts of the body.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Simvastatin does two main things. First, it lowers your LDL (bad) cholesterol and triglycerides while nudging up your HDL (good) cholesterol. Second — and this is the big one for p...
  • What exactly is simvastatin supposed to do for me?
  • Take simvastatin once a day in the evening — the timing matters because your body makes most of its cholesterol at night, so an evening dose is most effective. You can take it with...
  • When should I take it, and does it matter if I take it with food?
📖 Read our full Simvastatin guide →
2
Nutrient depletion considerations

Simvastatin may be associated with lower levels of 2 nutrients — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Simvastatin nutrient depletion report →
An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
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 Yellow / Pink
ShapeCapsule
ImprintA;04
Size19 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 EX438O2MRT
    Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
  • UNII RFW2ET671P
    Hydroxypropyl cellulose is a plant-derived thickening agent made from cellulose. It acts as a binder to hold tablet ingredients together and as a film-former to coat tablets or control how fast the medicine releases.
  • UNII 0WZ8WG20P6
    Hypromellose 2910 is a plant-based cellulose derivative that acts as a thickener, binder, and film-coating agent. It helps control how quickly the medicine dissolves and protects the tablet or capsule from moisture and light.
  • UNII ND2M416302
    Isopropyl alcohol is a clear liquid solvent derived from petroleum. In medicines, it dissolves active ingredients and other components, helps the product flow smoothly, and aids in sterilization during manufacturing.
  • 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 O8232NY3SJ
    A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
  • UNII 7SEV7J4R1U
    A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
  • UNII 15FIX9V2JP
    Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.

13 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.

💲 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 $0.0936 $93.60 / 1000 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.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Simvastatin 5 mg 16714-0681-01 NorthStar 30 tablets $0.031 AB Availability likely —
Simvastatin 5 mg 70377-0001-12 Biocon 30 tablets $0.031 AB Availability likely —
Simvastatin 5 mg 82009-0012-10 Quallent 1000 tablets $0.031 AB Availability likely —
simvastatin 5 mg 16729-0156-10 Accord 30 tablets — AB FDA listed —
Simvastatin 5 mg 31722-0510-01 Camber 100 tablets — AB FDA listed —
Simvastatin 5 mg 42571-0005-05 Micro 500 tablets — AB Discontinued —
Simvastatin 5 mg 50090-6459-00 A-S 30 tablets — AB FDA listed —
Simvastatin 5 mg 50090-7776-00 A-S 30 tablets — AB FDA listed —
Simvastatin 5 mg 50090-7777-00 A-S 90 tablets — AB FDA listed —
simvastatin 5 mg 63629-7421-01 Bryant 30 tablets — AB Discontinued —
Simvastatin 5 mgthis 65862-0050-99 Aurobindo 1000 tablets — AB FDA listed —
Simvastatin 5 mg 70518-4102-00 REMEDYREPACK 30 tablets — AB FDA listed —
Simvastatin 5 mg 71335-2262-01 Bryant 30 tablets — AB FDA listed —
Simvastatin 5 mg 72865-0305-01 XLCare 100 tablets — AB FDA listed —
Simvastatin 5 mg 84677-0014-10 Golden 1000 tablets — AB FDA listed —
Simvastatin 5 mg 68180-0482-03 Lupin 1000 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

🏛️
2006
On the market since
Dec 2006
📍
2026
Currently FDA-listed
20 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 by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
90 tablets65862-0050-90 20,838 Rx · $199,371
100 tablets65862-0050-00 No Medicaid data
100 tablets65862-0050-01 No Medicaid data
2500 tablets65862-0050-26 No Medicaid data
30 tablets65862-0050-30 No Medicaid data
45 tablets65862-0050-45 No Medicaid data
1000 tablets this page65862-0050-99 No Medicaid data
11000 tablets65862-0050-11 No Medicaid data
Drug total (last 4 qtrs): 20,838 Rx · 1,086,336 units · $199,371 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

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

Medicare Part D (outpatient prescription) spending for Simvastatin — the program that covers self-administered drugs. 11 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 Simvastatin. 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
$28.9M
Claims incl. refills
3.2M
Beneficiaries
2.6M
Spend / beneficiary
$11.12
Spend / claim
$9.08
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 SIMVASTATIN — the ingredient across all brands.

Top reported reactions

Fatigue14,524
Nausea14,119
Dyspnoea13,226
Diarrhoea12,591
Dizziness11,830
Pain9,871
Asthenia9,793

Age at onset

Neonate94
Infant26
Child39
Adolescent20
Adult9,678
Elderly19,530

Reporter sex

263,006 reports
Male · 48%
Female · 51%
Unknown · 0%

Serious outcomes

Hospitalization100,178
Death22,974
Life-threatening14,164
Disabling13,111
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 17,092 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 Per unit Per pack Marketing startStatus
65862-0050-00 100 TABLET, FILM COATED in 1 BOTTLE (65862-050-00) — — 2006-12-20 Active
65862-0050-01 100 TABLET, FILM COATED in 1 BOTTLE (65862-050-01) — — 2006-12-20 Active
65862-0050-26 2500 TABLET, FILM COATED in 1 BOTTLE (65862-050-26) — — 2006-12-20 Active
65862-0050-30 30 TABLET, FILM COATED in 1 BOTTLE (65862-050-30) — — 2006-12-20 Active
65862-0050-45 45 TABLET, FILM COATED in 1 BOTTLE (65862-050-45) — — 2006-12-20 Active
65862-0050-90 90 TABLET, FILM COATED in 1 BOTTLE (65862-050-90) $0.0314 / ea $2.83 2006-12-20 Active
65862-0050-99 You're viewing this 1000 TABLET, FILM COATED in 1 BOTTLE (65862-050-99) — — 2006-12-20 Active
65862-0050-11 11000 TABLET, FILM COATED in 1 BAG (65862-050-11) — — — Active

This pack shows little to no recent Medicaid volume — the 90 tablets pack carries most fills. See all packs ↓

Pack size FAQ

What quantity is in NDC 65862-0050-99?
NDC 65862-0050-99 is a 1,000-count package — 1000 tablet, film coated in 1 bottle.
What is the difference between NDC 65862-0050-99 and NDC 65862-0050-30?
Both are Simvastatin 5 mg Tablet, Film Coated — the drug itself is identical. NDC 65862-0050-99 is the 1,000-count package, while NDC 65862-0050-30 is the 30 tablets package.
What NDC number is used to bill for this package of Simvastatin 5 mg Tablet, Film Coated?
Bill NDC 65862-0050-99 — the 11-digit billing format is 65862005099. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

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 FDA registers it as 65862-050-99, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 65862-0050-99, written without dashes as 65862005099. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 65862-0050-99, the first segment (65862) is the labeler code FDA assigned to Aurobindo Pharma Limited; the middle segment (0050) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (99) identifies this exact package size and type. Together they name one specific package of one specific product.
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 7 other package presentations of this same product, including 30 tablets (65862-0050-30), 45 tablets (65862-0050-45), 90 tablets (65862-0050-90). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
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.
Do I need a prescription for this product?
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.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 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 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE Simvastatin tablets are 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. As an adjunct to diet to reduce 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). As an adjunct to diet for the treatment of adults with: Primary dysbetalipoproteinemia.

Hypertriglyceridemia. Simvastatin tablets are an HMG-CoA reductase inhibitor indicated: ( 1 ) 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. As an adjunct to diet to reduce 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). As an adjunct to diet for the treatment of adults with: Primary dysbetalipoproteinemia.

Hypertriglyceridemia.

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND ADMINISTRATION Important Dosage and Administration Information: ( 2.1 ) Take simvastatin tablets orally once daily in the evening. Maximum recommended dosage is simvastatin tablets 40 mg once daily. An 80 mg daily dosage of simvastatin tablets are restricted to patients who have been taking simvastatin tablets 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 simvastatin tablets 40 mg daily, prescribe alternative LDL-C lowering treatment. Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating, and adjust the dosage if necessary. Adults : Recommended dosage is 20 mg to 40 mg once daily.

( 2.2 ) Pediatric Patients Aged 10 Years and Older with HeFH : Recommended dosage is 10 mg to 40 mg once daily. ( 2.3 ) Patients with Severe Renal Impairment : Recommended starting dosage is simvastatin 5 mg once daily. ( 2.4 , 8.6 ) See full prescribing information for simvastatin tablets dosage modifications due to drug interactions.

( 2.5 )

2.1Important Dosage and Administration Information Take simvastatin tablets orally once daily in the evening. The maximum recommended dosage is simvastatin tablets 40 mg once daily [see Dosage and Administration (2.2 , 2.3) ] . An 80 mg daily dosage of simvastatin tablets are restricted to patients who have been taking simvastatin 80 mg daily chronically (e.g., for 12 months or more) without evidence of muscle toxicity [see Warnings and Precautions (5.1) ] .

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

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

2.2Recommended Dosage in Adult Patients The recommended dosage range of simvastatin tablets are 20 mg to 40 mg once daily.

2.3Recommended Dosage in Pediatric Patients 10 Years of Age and Older with HeFH The recommended dosage range of simvastatin tablets are 10 mg to 40 mg daily.

2.4Recommended Dosage in Patients with Renal Impairment For patients with severe renal impairment [creatinine clearance (CLcr) 15 to 29 mL/min], the recommended starting dosage of simvastatin is 5 mg once daily [see Warnings and Precautions (5.1) and Use in Specific Populations (8.6) ]. There are no dosage adjustment recommendations for patients with mild or moderate renal impairment.

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

Patients taking Verapamil, Diltiazem, or Dronedarone Do not exceed simvastatin tablets 10 mg once daily. Patients taking Amiodarone, Amlodipine, or Ranolazine Do not exceed simvastatin tablets 20 mg once daily.

💊 Dosage Forms and Strengths 132 words ▾

3 DOSAGE FORMS AND STRENGTHS Simvastatin tablets: 5 mg: yellow colored, round shaped, biconvex, film coated tablets, debossed with ‘A’ on one side and ‘15’ on the other side. 10 mg: light pink colored, round shaped, biconvex, film coated tablets, debossed with ‘A’ on one side and ‘01’ on the other side. 20 mg: light pink colored, round shaped, biconvex, film coated tablets, debossed with ‘A’ on one side and ‘02’ on the other side.

40 mg: pink colored, round shaped, biconvex, film coated tablets, debossed with ‘A’ on one side and ‘03’ on the other side. 80 mg: pink colored, capsule shaped, biconvex, film coated tablets, debossed with ‘A’ on one side and ‘04’ on the other side. Tablets : 5 mg; 10 mg; 20 mg; 40 mg; 80 mg (3)

⛔ Contraindications 137 words ▾

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

Hypersensitivity to simvastatin or any excipients in 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 , 7.1 ) Concomitant use of cyclosporine, danazol or gemfibrozil ( 4 , 7.1 ) Acute liver failure or decompensated cirrhosis ( 4 , 5.3 ) Hypersensitivity to simvastatin or any excipient in simvastatin tablets ( 4 , 6.2 )

⚠️ 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 simvastatin dosage. Chinese patients may be at higher risk for myopathy. Discontinue simvastatin if markedly elevated CK levels occur or myopathy is diagnosed or suspected.

Temporarily discontinue 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 simvastatin dosage. Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.

( 5.1 , 7.1 , 8.5 , 8.6 , 8.8 ) Immune-Mediated Necrotizing Myopathy (IMNM): Rare reports of IMNM, an autoimmune myopathy, have been reported. Discontinue 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 simvastatin.

( 4 , 5.3 , 8.7 )

5.1Myopathy and Rhabdomyolysis 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 simvastatin. In clinical studies 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 (10xULN), 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 study 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 >40xULN) in patients taking simvastatin 20 mg and 80 mg daily were approximately 0% and 0.4%, respectively [see Adverse Reactions (6.1) ]. 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 simvastatin dosage; Chinese patients on simvastatin may be at higher risk for myopathy [see Contraindications (4) , Drug Interactions (7.1) , and Use in Specific Populations (8.8) ] .

The risk of myopathy is increased by elevated plasma levels of simvastatin and simvastatin acid. The risk is also greater in patients taking an 80 mg daily dosage of simvastatin compared with patients taking lower simvastatin dosages and compared with patients using other statins with similar or greater LDL-C-lowering efficacy [see Adverse Reactions (6.1) ]. Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis The concomitant use of strong CYP3A4 inhibitors with simvastatin is contraindicated.

If short-term treatment with strong CYP3A4 inhibitors is required, temporarily suspend simvastatin during the duration of strong CYP3A4 inhibitor treatment. The concomitant use of simvastatin with gemfibrozil, cyclosporine, or danazol is also contraindicated [see Contraindications (4) and Drug Interactions (7.1) ]. Simvastatin dosage modifications are recommended for patients taking lomitapide, verapamil, diltiazem, dronedarone, amiodarone, amlodipine or ranolazine [see Dosage and Administration (2.5) ].

Simvastatin use should be temporarily suspended in pa…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following important adverse reactions are described below and elsewhere in the labeling: 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) ] Most common adverse reactions (incidence ≥5%) are upper respiratory infection, headache, abdominal pain, constipation, and nausea.

(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 studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. In clinical studies, 2,423 adult patients were exposed to simvastatin with a median duration of follow-up of approximately 18 months. The most commonly reported adverse reactions (incidence ≥5%) in these simvastatin clinical studies were: upper respiratory infections (9%), headache (7%), abdominal pain (7%), constipation (7%), and nausea (5%).

Overall, 1.4% of patients discontinued simvastatin due to adverse reactions. The most common adverse reactions that led to discontinuation were: gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia (0.1%). In a Cardiovascular Outcomes Study (the Scandinavian Simvastatin Survival Study [Study 4S]), adult patients (age range 35 to 71 years, 19% women, 100% Caucasians) were treated with 20 to 40 mg per day of simvastatin or placebo over a median of 5.4 years [see Clinical Studies (14) ] ; adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 1.

Table 1: Adverse Reactions Reported ≥2% of Patients Treated with Simvastatin and Greater than Placebo in Study 4S % Placebo (N = 2,223) % Simvastatin (N = 2,221) Bronchitis 6.3

6.6Abdominal pain 5.8

5.9Atrial fibrillation 5.1

5.7Gastritis 3.9

4.9Eczema 3.0

4.5Vertigo 4.2

4.5Diabetes mellitus 3.6

4.2Insomnia 3.8

4.0Myalgia 3.2

3.7Urinary tract infection 3.1

3.2Edema/swelling 2.3

2.7Headache 2.1

2.5Sinusitis 1.8

2.3Constipation 1.6

2.2Myopathy/Rhabdomyolysis In clinical studies with a median follow-up of at least 4 years, in which 24,747 patients received simvastatin, the incidence of myopathy (defined as unexplained muscle weakness, pain, or tenderness accompanied by CK increases greater than 10xULN) was approximately 0.03%, 0.08%, and 0.61% for the simvastatin 20 mg, 40 mg, and 80 mg daily groups, respectively. In a clinical outcomes study in which 12,064 adult patients with a history of myocardial infarction were treated with simvastatin (mean follow-up 6.7 years), the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum CK >10x [1200 U/L] ULN) in patients taking simvastatin 20 mg and 80 mg daily was approximately 0.02% and 0.9%, respectively.

The incidence of rhabdomyolysis (defined as myopathy with a CK >40xULN) in patients on simvastatin 20 mg and 80 mg daily was approximately 0% and 0.4%, respectively. The incidence of myopathy and rhabdomyolysis were highest during the first year and then decreased during the subsequent years of treatment. In another clinical outcomes study in which 10,269 adult patients were treated with simvastatin 40 mg per day (mean follow-up of 5 years), the incidence of myopathy/rhabdomyolysis was <0.1% in patients treated with simvastatin.

Elevations in Liver Enzyme Tests Moderate (less than 3xULN) elevations of serum transaminases have been reported with use of simvastatin. Persistent increases to more than 3xULN in serum transaminases have occurred in approximately 1% of patients receiving simvastatin in clinical studies. Marked persistent increases of hepat…

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS See full prescribing information for details regarding concomitant use of simvastatin with other drugs or grapefruit juice that increase the risk of myopathy and rhabdomyolysis. ( 2.5 , 7.1 ) Coumarin Anticoagulants : Obtain INR before simvastatin initiation and monitor INR during simvastatin dosage initiation or adjustment. ( 7.2 ) Digoxin : During simvastatin initiation, monitor digoxin levels. ( 7.2 )

7.1Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Simvastatin Simvastatin is a substrate of CYP3A4 and of the transport protein OATP1B1. Simvastatin exposure 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 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 Simvastatin Strong CYP3A4 inhibitors Clinical Impact: Simvastatin is a substrate of CYP3A4. Concomitant use of strong CYP3A4 inhibitors with simvastatin increases simvastatin exposure and increases the risk of myopathy and rhabdomyolysis, particularly with higher simvastatin dosages. Intervention: Concomitant use of strong CYP3A4 inhibitors with simvastatin is contraindicated [see Contraindications (4) ].

If treatment with a CYP3A4 inhibitor is unavoidable, suspend 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), 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 simvastatin.

Gemfibrozil may cause myopathy when given alone. Intervention: Concomitant use of cyclosporine, danazol, or gemfibrozil with 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 simvastatin.

Intervention: For patients taking verapamil, diltiazem, or dronedarone, do not exceed simvastatin 10 mg daily. For patients taking amiodarone, amlodipine, or ranolazine, do not exceed simvastatin 20 mg daily [see Dosage and Administration (2.5) ]. 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 simvastatin by 50% if initiating lomitapide. Do not exceed simvastatin 20 mg daily (or simvastatin 40 mg daily for patients who have previously taken an 80 mg daily dosage of simvastatin chronically) while taking lomitapide [see Dosage and Administration (2.1 , 2.5) ]. Daptomycin Clinical Impact: Cases of rhabdomyolysis have been reported with simvastatin administered with daptomycin.

Both simvastatin and daptomycin can cause myopathy and rhabdomyolysis when given alone and the risk of myopathy and rhabdomyolysis may be increased by coadministration. Intervention: If treatment with daptomycin is required, consider temporarily suspending simvastatin during the course of daptomycin treatment. Niacin Clinical Impact: Cases of myopathy and rhabdomyolysis have been observed with concomitant use of lipid modifying dosages of niacin-containing products (≥1 gram/day niacin) with simvastatin.

The risk of myopathy is greater in Chinese patients. In a clinical study (me…

👥 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 simvastatin. ( 8.2 )

8.1Pregnancy Risk Summary Discontinue simvastatin when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Simvastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, 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 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 ) (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 A Medicaid cohort linkage study 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.

Study 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 Simvastatin was given to pregnant rats at doses of 6.25, 12.5 and 25 mg/kg/day (0.6 times, 1.3 times, and 2.5 times, respectively, the maximum recommended dosage of 80 mg/day when normalized to body surface area) from gestation days 6 to 17 and to pregnant rabbits from gestation days 6 to 18 at doses of 2.5, 5, and 10 mg/kg/day (0.5 times, 1 times, and 2 times, respectively, the maximum recommended dosage of 80 mg/day when normalized to body surface area).

For both species, there was no evidence of maternal toxicity or embryolethality. In rats, mean fetal body weights in the 25 mg/kg/day group were decreased 5.4%. Similar fetal body weight effects were not observed in rabbits.

Simvastatin doses of 6.25, 12.5 and 25 mg/kg/day (0.6 times, 1.3 times, and…

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary Discontinue simvastatin when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Simvastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, 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 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 ) (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 A Medicaid cohort linkage study 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.

Study 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 Simvastatin was given to pregnant rats at doses of 6.25, 12.5 and 25 mg/kg/day (0.6 times, 1.3 times, and 2.5 times, respectively, the maximum recommended dosage of 80 mg/day when normalized to body surface area) from gestation days 6 to 17 and to pregnant rabbits from gestation days 6 to 18 at doses of 2.5, 5, and 10 mg/kg/day (0.5 times, 1 times, and 2 times, respectively, the maximum recommended dosage of 80 mg/day when normalized to body surface area).

For both species, there was no evidence of maternal toxicity or embryolethality. In rats, mean fetal body weights in the 25 mg/kg/day group were decreased 5.4%. Similar fetal body weight effects were not observed in rabbits.

Simvastatin doses of 6.25, 12.5 and 25 mg/kg/day (0.6 times, 1.3 times, and 2.5 times, respectively, the maximum recommended dosage of 80 mg/day when normalized to body surface area) were given to pregnant rats from gestation day 1…

🧒 Pediatric Use 127 words ▾

8.4Pediatric Use The safety and effectiveness of simvastatin 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 simvastatin for this indication is based on a double-blind, placebo-controlled clinical study in 175 pediatric patients (99 boys and 76 girls at least 1 year post-menarche) 10 years of age and older with HeFH. In this limited controlled study, there was no significant effect on growth or sexual maturation in the boys or girls, or on menstrual cycle length in girls.

The safety and effectiveness of 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 (other than HeFH).

🧓 Geriatric Use 184 words ▾

8.5Geriatric Use Of the total number of simvastatin-treated patients in clinical studies 1,021 (23%) patients, 5,366 (52%) patients, and 363 (15%) patients were ≥65 years old, respectively. In Study HPS, 615 (6%) patients were ≥75 years old [see Clinical Studies (14) ]. In a clinical study of patients treated with simvastatin 80 mg daily, patients ≥65 years of age had an increased risk of myopathy, including rhabdomyolysis, compared to patients <65 years of age.

A pharmacokinetic study with simvastatin use showed the mean plasma level of total inhibitors to be approximately 45% higher in geriatric patients between 70 to 78 years of age compared with patients between 18 to 30 years of age [see Clinical Pharmacology (12.3) ] . Advanced age (≥65 years) is a risk factor for 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 simvastatin for the increased risk of myopathy [see Warnings and Precautions (5.1) ].

🆘 Overdosage 16 words ▾

10 OVERDOSAGE No specific antidotes for simvastatin are known. Contact Poison Control (1-800-222-1222) for latest recommendations.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action 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 that converts HMG-CoA to mevalonate, a precursor of cholesterol.

12.2Pharmacodynamics 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 simvastatin is usually achieved by 4 weeks and is maintained after that.

12.3Pharmacokinetics Simvastatin is a lactone that is readily hydrolyzed in vivo to the corresponding β-hydroxyacid. Pharmacokinetics (PK) of simvastatin and its metabolites was originally characterized using inhibition of HMG-CoA reductase activity following base hydrolysis of plasma samples, as specific bioanalytical methods were not available. Inhibition of the enzyme activity (equivalent to the level of total inhibitors) represented the combination of activities in plasma following administration of simvastatin from both active (simvastatin acid and its metabolites) and latent forms (simvastatin and its metabolites) after conversion to the active forms in the presence of base.

Absorption Following an oral dose of 14 C-labeled simvastatin, plasma concentrations of total radioactivity (simvastatin plus 14 C-metabolites) peaked at 4 hours and declined rapidly to about 10% of peak by 12 hours postdose. Since simvastatin undergoes extensive first-pass extraction in the liver, the availability of simvastatin to the general circulation is low (<5%). PK, assessed as area under the concentrations of total inhibitors – time curve, was apparently linear with doses up to 120 mg.

Effect of Food The plasma profile of total inhibitors concentration was not affected when simvastatin was administered with low fat meal. Distribution Both simvastatin and its β-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins. Elimination Metabolism Simvastatin is metabolized by CYP3A4.

The major active metabolites of simvastatin present in human plasma are simvastatin acid and its 6′-hydroxy, 6′-hydroxymethyl, and 6′-exomethylene derivatives. Peak plasma concentrations of both active and total inhibitors were attained within 1.3 to 2.4 hours postdose. Excretion Following an oral dose of 14 C-labeled simvastatin, 13% of the dose was excreted in urine and 60% in feces.

Specific Populations Geriatric Patients In a study including 16 geriatric patients between 70 and 78 years of age who received simvastatin 40 mg/day, the mean plasma level of total inhibitors was increased approximately 45% compared with 18 patients between 18 to 30 years of age [see Use in Specific Populations (8.5) ] . Drug Interaction Studies Simvastatin acid is a substrate of the transport protein OATP1B1. Concomitant administration of inhibitors of the transport protein OATP1B1 and/or CYP3A4 may lead to increased exposure of simvastatin acid.

Cyclosporine has been shown to increase the AUC of statins; although the mechanism is not fully understood, the increase in AUC for simvastatin acid is presumably due, in part, to inhibition of CYP3A4 and/or OATP1B1 [see Drug Interactions (7) ] . Table 4 displays the effect of coadministered drugs or grapefruit juice on simvastatin systemic exposure [see Drug Interactions (7) ]. Table 4: Effect of Coadministered Drugs or Grapefruit Juice on Simvastatin Systemic Exposure Coadministered Drug or Grapefruit Juice Dosing of Coadministered Drug or Grapefruit Juice Dosing of Simvastatin Geometric Mean Ratio (Ratio* with / without coadministered drug) No Effect = 1 AUC C max * Results based on a chemical assay except results with propranolol as indicat…

🧬 Mechanism of Action 42 words ▾

12.1Mechanism of Action 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 that converts HMG-CoA to mevalonate, a precursor of cholesterol.

📦 How Supplied / Storage and Handling ~2 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Simvastatin Tablets USP, 5 mg are yellow colored, round shaped, biconvex, film coated tablets, debossed with ‘A’ on one side and ‘15’ on the other side. They are supplied as follows: Bottles of 30 NDC 65862-050-30 (Child Resistant Closure) Bottles of 45 NDC 65862-050-45 (Child Resistant Closure) Bottles of 90 NDC 65862-050-90 (Child Resistant Closure) Bottles of 100 NDC 65862-050-01 (Child Resistant Closure) Bottles of 100 NDC 65862-050-00 (Non-Child Resistant Closure) Bottles of 1,000 NDC 65862-050-99 (Non-Child Resistant Closure) Bottles of 2,500 NDC 65862-050-26 (Non-Child Resistant Closure) Simvastatin Tablets USP, 10 mg are light pink colored, round shaped, biconvex, film coated tablets, debossed with ‘A’ on one side and ‘01’ on the other side.

They are supplied as follows: Bottles of 30 NDC 65862-051-30 (Child Resistant Closure) Bottles of 45 NDC 65862-051-45 (Child Resistant Closure) Bottles of 90 NDC 65862-051-90 (Child Resistant Closure) Bottles of 100 NDC 65862-051-01 (Child Resistant Closure) Bottles of 100 NDC 65862-051-00 (Non-Child Resistant Closure) Bottles of 1,000 NDC 65862-051-99 (Non-Child Resistant Closure) Bottles of 2,500 NDC 65862-051-26 (Non-Child Resistant Closure) Simvastatin Tablets USP, 20 mg are light pink colored, round shaped, biconvex, film coated tablets, debossed with ‘A’ on one side and ‘02’ on the other side.

They are supplied as follows: Bottles of 30 NDC 65862-052-30 (Child Resistant Closure) Bottles of 45 NDC 65862-052-45 (Child Resistant Closure) Bottles of 90 NDC 65862-052-90 (Child Resistant Closure) Bottles of 100 NDC 65862-052-01 (Child Resistant Closure) Bottles of 100 NDC 65862-052-00 (Non-Child Resistant Closure) Bottles of 1,000 NDC 65862-052-99 (Non-Child Resistant Closure) Bottles of 2,500 NDC 65862-052-26 (Non-Child Resistant Closure) Simvastatin Tablets USP, 40 mg are pink colored, round shaped, biconvex, film coated tablets, debossed with ‘A’ on one side and ‘03’ on the other side.

They are supplied as follows: Bottles of 30 NDC 65862-053-30 (Child Resistant Closure) Bottles of 45 NDC 65862-053-45 (Child Resistant Closure) Bottles of 90 NDC 65862-053-90 (Child Resistant Closure) Bottles of 100 NDC 65862-053-01 (Child Resistant Closure) Bottles of 100 NDC 65862-053-00 (Non-Child Resistant Closure) Bottles of 1,000 NDC 65862-053-99 (Non-Child Resistant Closure) Bottles of 2,000 NDC 65862-053-22 (Non-Child Resistant Closure) Simvastatin Tablets USP, 80 mg are pink colored, capsule shaped, biconvex, film coated tablets, debossed with ‘A’ on one side and ‘04’ on the other side.

They are supplied as follows: Bottles of 30 NDC 65862-054-30 (Child Resistant Closure) Bottles of 45 NDC 65862-054-45 (Child Resistant Closure) Bottles of 90 NDC 65862-054-90 (Child Resistant Closure) Bottles of 100 NDC 65862-054-00 (Non-Child Resistant Closure) Bottles of 1,000 NDC 65862-054-99 (Non-Child Resistant Closure) Bottles of 3,000 NDC 65862-054-39 (Non-Child Resistant Closure) Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

📋 Description 178 words ▾

11 DESCRIPTION Simvastatin is a prodrug of 3-hydoroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that is derived synthetically from a fermentation product of Aspergillus terreus . 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.

Its structural formula is: Simvastatin USP is a white to off-white, nonhygroscopic, crystalline powder that is practically insoluble in water, and freely soluble in chloroform, methanol and ethanol. Simvastatin tablets USP are available for oral administration in strength of 5 mg, 10 mg, 20 mg, 40 mg or 80 mg. Each tablet contains following inactive ingredients: ascorbic acid, lactose monohydrate, microcrystalline cellulose, pregelatinized starch (maize), hydroxypropyl cellulose, hypromellose, titanium dioxide, talc, citric acid monohydrate, isopropyl alcohol, magnesium stearate and butylated hydroxyanisole.

Simvastatin 5 mg also contains ferric oxide yellow, simvastatin 10 mg and simvastatin 20 mg also contains ferric oxide red and ferric oxide yellow, simvastatin 40 mg and simvastatin 80 mg also contains ferric oxide red. Chemical Structure

💬 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 simvastatin may cause myopathy and rhabdomyolysis. Inform patients taking an 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 simvastatin. 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 simvastatin 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 simvastatin.

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 simvastatin should be discontinued [see Use in Specific Populations (8.1) ].

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

Advise patients not to double their next dose. Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 032, India Revised: 09/2023

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