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Simvastatin 20 mg Tablet, Film Coated, 30-count — NDC 71610-0622-30 package photo

Simvastatin 20 mg Tablet, Film Coated, 30-count

by Aphena Pharma Solutions - Tennessee, LLC · 30 TABLET, FILM COATED in 1 BOTTLE (71610-622-30)
NDC 71610-0622-30
🏷️ FDA NDC (as labeled) 71610-622-30 billing pads the product segment with a zero
This package
Contains30-count Pack sizes4 compare ↓
Also priced by: Part D plans $0.0936/unit — full pricing hub ↓
Also comes in: 15 tablets 71610-0622-15 45 tablets 71610-0622-45 90 tablets 71610-0622-60
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) 71610-622-30
Product NDC 71610-622
11-digit billing NDC 71610062230
NCPDP billing unit EA — each (per item)
RxCUI 198211, 312961
UNII AGG2FN16EV
Application # ANDA078034
SPL Set ID a753846e-4cd5-4ddc-a4f2-c45da571c883
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 2015-12-17
Route ORAL
Dosage form TABLET, FILM COATED
Substance SIMVASTATIN
GPI-14 39400075000330
GPI class Simvastatin
GCN Seq No 016578
GCN 26533
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 20 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 71610-622-30 — 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 → 71610-0622-30. 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

LabelerAphena Pharma Solutions - Tennessee, LLC
Application holderBIOCON PHARMA LTD
FDA applicationANDA078034 (ANDA)
Labeler code71610
First marketedDec 2015
Product typeHuman Prescription Drug
Portfolio794 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 20 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 Orange / Pink
ShapeOval
ImprintB303;40
Size14 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 3K9958V90M
    A liquid solvent derived from fermentation or chemical synthesis. In medicines, alcohol dissolves active ingredients, helps preserve the product, and improves how the body absorbs certain drugs.
  • UNII XF417D3PSL
    Anhydrous citric acid is a sour, crystalline powder derived from citric acid with water removed. In medicines, it acts as a buffer to control pH, adds tartness to improve taste, and helps tablets disintegrate.
  • 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 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 1K09F3G675
    Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
  • 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 3NXW29V3WO
    Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
  • 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 FZ989GH94E
    Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
  • UNII ETJ7Z6XBU4
    Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
  • 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.
  • UNII 8Z96QXD6UM
    Triethyl citrate is a clear liquid derived from citric acid. It acts as a plasticizer and solvent in tablet coatings and film formulations, helping the coating remain flexible and adhere properly to the medicine.

16 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 $2.81 / 30 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 20 mg 16714-0683-01 NorthStar 30 tablets $0.031 AB Availability likely —
Simvastatin 20 mg 68084-0512-01 American 1 tablet $0.031 AB Discontinued —
Simvastatin 20 mg 68180-0479-01 Lupin 30 tablets $0.031 AB Availability likely —
Simvastatin 20 mg 69367-0375-09 Westminster 90 tablets $0.031 AB Availability likely —
Simvastatin 20 mg 70377-0003-12 Biocon 30 tablets $0.031 AB Availability likely —
Simvastatin 20 mg 82009-0014-10 Quallent 1000 tablets $0.031 AB Availability likely —
Zocor 20 mg 78206-0181-01 Organon 30 tablets $9.728 AB Availability likely —
Simvastatin 20 mg 00615-7993-05 NCS 15 tablets — AB FDA listed —
simvastatin 20 mg 16729-0005-10 Accord 30 tablets — AB FDA listed —
Simvastatin 20 mg 31722-0512-01 Camber 100 tablets — AB FDA listed —
Simvastatin 20 mg 42571-0020-05 Micro 500 tablets — AB Discontinued —
simvastatin 20 mg 42708-0148-30 QPharma, 30 tablets — AB FDA listed —
Simvastatin 20 mg 42708-0169-30 QPharma, 30 tablets — AB FDA listed —
Simvastatin 20 mg 50090-4801-00 A-S 1000 tablets — AB FDA listed —
simvastatin 20 mg 50090-4897-00 A-S 90 tablets — AB FDA listed —
Simvastatin 20 mg 50090-5019-00 A-S 90 tablets — AB FDA listed —
Simvastatin 20 mg 50090-6306-01 A-S 30 tablets — AB FDA listed —
Simvastatin 20 mg 50090-6307-00 A-S 90 tablets — AB FDA listed —
Simvastatin 20 mg 50090-6389-01 A-S 30 tablets — AB FDA listed —
Simvastatin 20 mg 50090-6390-00 A-S 90 tablets — AB FDA listed —
Simvastatin 20 mg 50090-7781-00 A-S 45 tablets — AB FDA listed —
Simvastatin 20 mg 51655-0448-26 Northwind 90 tablets — AB FDA listed —
Simvastatin 20 mg 51655-0459-26 Northwind 90 tablets — AB FDA listed —
Simvastatin 20 mg 55154-4782-00 Cardinal 1 tablet — AB FDA listed —
Simvastatin 20 mg 60760-0585-30 St. 30 tablets — AB FDA listed —
simvastatin 20 mg 63187-0075-30 Proficient 30 tablets — AB FDA listed —
simvastatin 20 mg 63629-3393-01 Bryant 30 tablets — AB FDA listed —
Simvastatin 20 mg 65862-0052-00 Aurobindo 100 tablets — AB FDA listed —
Simvastatin 20 mg 67046-0626-03 Coupler 30 tablets — AB FDA listed —
Simvastatin 20 mg 68071-2560-03 NuCare 30 tablets — AB FDA listed —
simvastatin 20 mg 68071-3391-03 NuCare 30 tablets — AB FDA listed —
Simvastatin 20 mg 68071-3530-09 NuCare 90 tablets — AB FDA listed —
simvastatin 20 mg 68071-4996-03 NuCare 30 tablets — AB FDA listed —
Simvastatin 20 mg 68788-8342-01 Preferred 100 tablets — AB FDA listed —
Simvastatin 20 mg 70518-0954-00 REMEDYREPACK 30 tablets — AB FDA listed —
Simvastatin 20 mg 70518-3630-00 REMEDYREPACK 30 tablets — AB FDA listed —
Simvastatin 20 mg 71205-0780-30 Proficient 30 tablets — AB FDA listed —
Simvastatin 20 mg 71205-0809-30 Proficient 30 tablets — AB FDA listed —
Simvastatin 20 mg 71335-1891-01 Bryant 30 tablets — AB FDA listed —
Simvastatin 20 mg 71335-9642-01 Bryant 30 tablets — AB FDA listed —
Simvastatin 20 mg 71610-0609-45 Aphena 45 tablets — AB FDA listed —
Simvastatin 20 mgthis 71610-0622-30 Aphena 30 tablets — AB FDA listed —
Simvastatin 20 mg 72189-0421-30 Direct_Rx 30 tablets — AB FDA listed —
Simvastatin 20 mg 72789-0316-30 PD-Rx 30 tablets — AB FDA listed —
Simvastatin 20 mg 72865-0307-01 XLCare 100 tablets — AB FDA listed —
Simvastatin 20 mg 84677-0016-10 Golden 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

🏛️
2015
On the market since
Dec 2015
📍
2026
Currently FDA-listed
11 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.

📊 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 Marketing startStatus
71610-0622-15 15 TABLET, FILM COATED in 1 BOTTLE (71610-622-15) 2021-12-06 Active
71610-0622-30 You're viewing this 30 TABLET, FILM COATED in 1 BOTTLE (71610-622-30) 2021-12-06 Active
71610-0622-45 45 TABLET, FILM COATED in 1 BOTTLE (71610-622-45) 2021-12-06 Active
71610-0622-60 90 TABLET, FILM COATED in 1 BOTTLE (71610-622-60) 2021-12-06 Active

You're viewing one of 4 pack sizes for this product.

Pack size FAQ

What quantity is in NDC 71610-0622-30?
NDC 71610-0622-30 is a 30-count package — 30 tablet, film coated in 1 bottle.
What is the difference between NDC 71610-0622-30 and NDC 71610-0622-15?
Both are Simvastatin 20 mg Tablet, Film Coated — the drug itself is identical. NDC 71610-0622-30 is the 30-count package, while NDC 71610-0622-15 is the 15 tablets package.
What NDC number is used to bill for this package of Simvastatin 20 mg Tablet, Film Coated?
Bill NDC 71610-0622-30 — the 11-digit billing format is 71610062230. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

🧭 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 71610-622-30, 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: 71610-0622-30, written without dashes as 71610062230. 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 71610-0622-30, the first segment (71610) is the labeler code FDA assigned to Aphena Pharma Solutions - Tennessee, LLC; the middle segment (0622) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (30) 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 Aphena Pharma Solutions - Tennessee, LLC. 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 3 other package presentations of this same product, including 15 tablets (71610-0622-15), 45 tablets (71610-0622-45), 90 tablets (71610-0622-60). 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?
Aphena Pharma Solutions - Tennessee, LLC 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 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🎯 Indications and Usage ~3 min read ▾

1 INDICATIONS AND USAGE Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. In patients with coronary heart disease (CHD) or at high risk of CHD, simvastatin can be started simultaneously with diet.

Simvastatin is an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: • Reduce the risk of total mortality by reducing CHD deaths and reduce the risk of non-fatal myocardial infarction, stroke, and the need for revascularization procedures in patients at high risk of coronary events. ( 1.1 ) • Reduce elevated total-C, LDL-C, Apo B, TG and increase HDL-C in patients with primary hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia. ( 1.2 ) • Reduce elevated TG in patients with hypertriglyceridemia and reduce TG and VLDL-C in patients with primary dysbeta­-lipoproteinemia.

( 1.2 ) • Reduce total-C and LDL-C in adult patients with homozygous familial hypercholesterolemia. ( 1.2 ) • Reduce elevated total-C, LDL-C, and Apo B in boys and postmenarchal girls, 10 to 17 years of age with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy. ( 1.2 , 1.3 ) Limitations of Use Simvastatin has not been studied in Fredrickson Types I and V dyslipidemias.

( 1.4 )

1.1Reductions in Risk of CHD Mortality and Cardiovascular Events In patients at high risk of coronary events because of existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, simvastatin is indicated to: • Reduce the risk of total mortality by reducing CHD deaths. • Reduce the risk of non-fatal myocardial infarction and stroke. • Reduce the need for coronary and non-coronary revascularization procedures.

1.2Hyperlipidemia Simvastatin is indicated to: • Reduce elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary hyperlipidemia (Fredrickson type IIa, heterozygous familial and nonfamilial) or mixed dyslipidemia (Fredrickson type IIb). • Reduce elevated TG in patients with hypertriglyceridemia (Fredrickson type IV hyperlipidemia). • Reduce elevated TG and VLDL-C in patients with primary dysbetalipoproteinemia (Fredrickson type III hyperlipidemia). • Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH) as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.

1.3Adolescent Patients with Heterozygous Familial Hypercholesterolemia (HeFH) Simvastatin is indicated as an adjunct to diet to reduce total-C, LDL-C, and Apo B levels in adolescent boys and girls who are at least one year post-menarche, 10 to 17 years of age, with HeFH, if after an adequate trial of diet therapy the following findings are present: 1. LDL cholesterol remains ≥190 mg/dL; or 2. LDL cholesterol remains ≥160 mg/dL and • There is a positive family history of premature cardiovascular disease (CVD) or • Two or more other CVD risk factors are present in the adolescent patient.

The minimum goal of treatment in pediatric and adolescent patients is to achieve a mean LDL-C <130 mg/dL. The optimal age at which to initiate lipid-lowering therapy to decrease the risk of symptomatic adulthood CAD has not been determined.

1.4Limitations of Use Simvastatin has not been studied in conditions where the major abnormality is elevation of chylomicrons (i.e., hyperlipidemia Fredrickson types I and V).

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION • Dose range is 5 to 40 mg/day. ( 2.1 ) • Recommended usual starting dose is 10 or 20 mg once a day in the evening. ( 2.1 ) • Recommended starting dose for patients at high risk of CHD is 40 mg/day.

( 2.1 ) • Due to the increased risk of myopathy, including rhabdomyolysis, use of the 80-mg dose of simvastatin should be restricted to patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity. ( 2.2 ) • Patients who are currently tolerating the 80-mg dose of simvastatin who need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to an alternative statin with less potential for the drug-drug interaction.

( 2.2 ) • Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 80-mg dose of simvastatin, patients unable to achieve their LDL-C goal utilizing the 40-mg dose of simvastatin should not be titrated to the 80-mg dose, but should be placed on alternative LDL-C-lowering treatment(s) that provides greater LDL-C lowering. ( 2.2 ) • Adolescents (10 to 17 years of age) with HeFH: starting dose is 10 mg/day; maximum recommended dose is 40 mg/day. ( 2.5 )

2.1Recommended Dosing The usual dosage range is 5 to 40 mg/day. In patients with CHD or at high risk of CHD, simvastatin tablets, USP can be started simultaneously with diet. The recommended usual starting dose is 10 or 20 mg once a day in the evening.

For patients at high risk for a CHD event due to existing CHD, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, the recommended starting dose is 40 mg/day. Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter.

2.2Restricted Dosing for 80 mg Due to the increased risk of myopathy, including rhabdomyolysis, particularly during the first year of treatment, use of the 80-mg dose of simvastatin should be restricted to patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity [see Warnings and Precautions (5.1) ]. Patients who are currently tolerating the 80-mg dose of simvastatin who need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to an alternative statin with less potential for the drug-drug interaction.

Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 80-mg dose of simvastatin, patients unable to achieve their LDL-C goal utilizing the 40-mg dose of simvastatin should not be titrated to the 80-mg dose, but should be placed on alternative LDL-C-lowering treatment(s) that provides greater LDL-C lowering.

2.3Coadministration with Other Drugs Patients taking Verapamil, Diltiazem, or Dronedarone · The dose of simvastatin should not exceed 10 mg/day [see Warnings and Precautions (5.1) , Drug Interactions (7.3) , and Clinical Pharmacology (12.3) ]. Patients taking Amiodarone, Amlodipine or Ranolazine · The dose of simvastatin should not exceed 20 mg/day [see Warnings and Precautions (5.1) , Drug Interactions (7.3) , and Clinical Pharmacology (12.3) ].

2.4Patients with Homozygous Familial Hypercholesterolemia The recommended dosage is 40 mg/day in the evening [see Dosage and Administration, Restricted Dosing for 80 mg (2.2 ) ] . Simvastatin should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable. Simvastatin exposure is approximately doubled with concomitant use of lomitapide; therefore, the dose of simvastatin should be reduced by 50% if initiating lomitapide.

Simvastatin dosage should not exceed 20 mg/day (or 40 mg/day for patients who have previously taken simvastatin 80 mg/day chronically, e.g., for 12 months or more, without evidence of muscle toxicity) while taking lomitapide.

2.5 Adolesc…

💊 Dosage Forms and Strengths 157 words ▾

3 DOSAGE FORMS AND STRENGTHS Simvastatin tablets, USP 5 mg are white to off white, oval, biconvex, film-coated tablets with the logo “B300” debossed on one side and “5”on the other side. Simvastatin tablets, USP 10 mg are peach to dark peach, oval, biconvex, film-coated tablets with the logo “B301” debossed on one side and “10” on the other side. Simvastatin tablets, USP 20 mg are orange to dark orange, oval, biconvex, film-coated tablets with the logo “B302” debossed on one side and “20” on the other side.

Simvastatin tablets, USP 40 mg are light pink to pink, oval, biconvex, film-coated tablets with the logo “B303” debossed on one side and “40” on the other side. Simvastatin tablets, USP 80 mg are pink to dark pink, capsule-shaped, film-coated tablets with the logo “B304” debossed on one side and “80” on the other side. Tablets: 5 mg; 10 mg; 20 mg; 40 mg; 80 mg ( 3 )

⛔ Contraindications ~2 min read ▾

4 CONTRAINDICATIONS Simvastatin is contraindicated in the following conditions: Concomitant administration of strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone and cobicistat-containing products) [see Warnings and Precautions (5.1 ) ] Concomitant administration of gemfibrozil, cyclosporine, or danazol [see Warnings and Precautions ( 5.1 ) ] . Hypersensitivity to any component of this medication [see Adverse Reactions (6.2) ] .

Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels [see Warnings and Precautions (5.3) ]. Women who are pregnant or may become pregnant. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development.

Because HMG-CoA reductase inhibitors (statins) decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, simvastatin may cause fetal harm when administered to a pregnant woman. 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 hypercholesterolemia. There are no adequate and well-controlled studies of use with simvastatin during pregnancy; however, in rare reports congenital anomalies were observed following intrauterine exposure to statins.

In rat and rabbit animal reproduction studies, simvastatin revealed no evidence of teratogenicity. Simvastatin tablets should be administered to women of childbearing age only when such patients are highly unlikely to conceive. If the patient becomes pregnant while taking this drug, simvastatin tablets should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1 ) ].

Nursing mothers. It is not known whether simvastatin is excreted into human milk; however, a small amount of another drug in this class does pass into breast milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require treatment with simvastatin tablets should not breastfeed their infants [see Use in Specific Populations (8.3) ] Concomitant administration of strong CYP3A4 inhibitors.

( 4 , 5.1 ) Concomitant administration of gemfibrozil, cyclosporine, or danazol. ( 4 , 5.1 ) Hypersensitivity to any component of this medication. ( 4 , 6.2 ) Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels.

( 4 , 5.3 ) Women who are pregnant or may become pregnant. ( 4 , 8.1 ) Nursing mothers. ( 4 , 8.3 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • Patients should be advised of the increased risk of myopathy including rhabdomyolysis with the 80-mg dose. ( 5.1 ) • Skeletal muscle effects (e.g., myopathy and rhabdomyolysis): Risks increase with higher doses and concomitant use of certain medicines. Predisposing factors include advanced age (≥65), female gender, uncontrolled hypothyroidism, and renal impairment.

Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported. ( 4 , 5.1 , 8.5 , 8.6 ) • Patients should be advised to report promptly any unexplained and/or persistent muscle pain, tenderness, or weakness. Simvastatin therapy should be discontinued immediately if myopathy is diagnosed or suspected.

See Drug Interaction table. ( 5.1 ) • Immune-Mediated Necrotizing Myopathy (IMNM): There have been rare reports of IMNM, an autoimmune myopathy, associated with statin use. IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents.

( 5.2 ) • Liver enzyme abnormalities: Persistent elevations in hepatic transaminases can occur. Check liver enzyme tests before initiating therapy and as clinically indicated thereafter. ( 5.3 )

5.1Myopathy/Rhabdomyolysis Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by elevated plasma levels of simvastatin and simvastatin acid.

Predisposing factors for myopathy include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment. Chinese patients may be at increased risk for myopathy [ see Use in Specific Populations ( 8.8 )]. The risk of myopathy, including rhabdomyolysis, is dose related.

In a clinical trial database in which 41,413 patients were treated with simvastatin, 24,747 (approximately 60%) of whom were enrolled in studies with a median follow-up of at least 4 years, the incidence of myopathy was approximately 0.03% and 0.08% at 20 and 40 mg/day, respectively. The incidence of myopathy with 80 mg (0.61%) was disproportionately higher than that observed at the lower doses. In these trials, patients were carefully monitored and some interacting medicinal products were excluded.

In a clinical trial in which 12,064 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 creatine kinase [CK] >10 times upper limit of normal [ULN]) in patients on 80 mg/day was approximately 0.9% compared with 0.02% for patients on 20 mg/day. The incidence of rhabdomyolysis (defined as myopathy with a CK >40 times ULN) in patients on 80 mg/day was approximately 0.4% compared with 0% for patients on 20 mg/day.

The incidence of myopathy, including rhabdomyolysis, was highest during the first year and then notably decreased during the subsequent years of treatment. In this trial, patients were carefully monitored and some interacting medicinal products were excluded. The risk of myopathy, including rhabdomyolysis, is greater in patients on simvastatin 80 mg compared with other statin therapies with similar or greater LDL-C-lowering efficacy and compared with lower doses of simvastatin.

Therefore, the 80-mg dose of simvastatin should be used only in patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity [see Dosage and Administration, Restricted Dosing for 80 mg (2.2 ) ] . If, however, a patient who is currently tolerating the 80-mg dose of simv…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS Most common adverse reactions (incidence ≥5.0%) are: upper respiratory infection, headache, abdominal pain, constipation, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Biocon Pharma Inc. at 1-866-924-6266 or FDA at 1-800-FDA-1088 or www .fda.gov/medwatch .

6.1Clinical Trials Experience Because clinical ttials 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. In the pre-marketing controlled clinical studies and their open extensions (2,423 patients with median duration of follow-up of approximately 18 months), 1.4% of patients were discontinued due to adverse reactions. The most common adverse reactions that led to treatment discontinuation were: gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia (0.1%).

The most commonly reported adverse reactions (incidence ≥5%) in simvastatin controlled clinical trials were: upper respiratory infections (9.0%), headache (7.4%), abdominal pain (7.3%), constipation (6.6%), and nausea (5.4%). Scandinavian Simvastatin Survival Study In 4S involving 4,444 (age range 35 to 71 years, 19% women, 100% Caucasians) treated with 20 to 40 mg/day of simvastatin (n=2,221) or placebo (n=2,223) over a median of 5.4 years, adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 2.

Heart Protection Study In the Heart Protection Study (HPS), involving 20,536 patients (age range 40 to 80 years, 25% women, 97% Caucasians, 3% other races) treated with simvastatin 40 mg/day (n=10,269) or placebo (n=10,267) over a mean of 5 years, only serious adverse reactions and discontinuations due to any adverse reactions were recorded. Discontinuation rates due to adverse reactions were 4.8% in patients treated with simvastatin compared with 5.1% in patients treated with placebo. The incidence of myopathy/rhabdomyolysis was <0.1% in patients treated with simvastatin.

Other Clinical Studies In a clinical trial in which 12,064 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 creatine kinase [CK] >10 times upper limit of normal [ULN]) in patients on 80 mg/day was approximately 0.9% compared with 0.02% for patients on 20 mg/day. The incidence of rhabdomyolysis (defined as myopathy with a CK >40 times ULN) in patients on 80 mg/day was approximately 0.4% compared with 0% for patients on 20 mg/day.

The incidence of myopathy, including rhabdomyolysis, was highest during the first year and then notably decreased during the subsequent years of treatment. In this trial, patients were carefully monitored and some interacting medicinal products were excluded. Other adverse reactions reported in clinical trials were: diarrhea, rash, dyspepsia, flatulence, and asthenia.

Laboratory Tests Marked persistent increases of hepatic transaminases have been noted [see Warnings and Precautions (5.3) ]. Elevated alkaline phosphatase and γ-glutamyl transpeptidase have also been reported. About 5% of patients had elevations of CK levels of 3 or more times the normal value on one or more occasions.

This was attributable to the noncardiac fraction of CK. [See Warnings and Precautions (5.1). ] Adolescent Patients (ages 10 to17 years) In a 48-week, controlled study in adolescent boys and girls who were at least 1 year post-menarche, 10 to17 years of age (43.4% female, 97.7% Caucasians, 1.7% Hispanics, 0.6% Multiracial) with heterozygous familial hypercholesterolemia (n=175), treated with placebo or simvastatin (10 to 40 mg daily), the most common adverse reactions observed in both groups were upper respiratory infection, headache, abdominal pain, and nausea [see Use in Specific Populations (8.4) and Clinical Studies (14.2 ) ]. tab…

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Drug Interactions Associated with increased Risk of Risk of Myopathy/Rhabdomyolysis ( 2.3 , 2.4 , 4 , 5.1 , 7.1 , 7.2 , 7.3 , 12.3 ) Interacting Agents Prescribing Recommendations Strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole,posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, cobicistat-containing products), gemfibrozil, cyclosporine, danazol Contraindicated with simvastatin Niacin (≥1 g/day) For Chinese patients, notrecommended with simvastatin Verapamil, diltiazem, dronedarone Do not exceed 10 mg simvastatin daily Amiodarone, amlodipine, ranolazine Do not exceed 20 mg simvastatin daily Lomitapide For patients with HoFH, do not exceed 20 mg simvastatin daily* Daptomycin Temporarily suspend simvastatin Grapefruit juice Avoid grapefruit juice *For patients with HoFH who have been taking 80 mg simvastatin chronically (e.g., for 12 months or more) without evidence of muscle toxicity, do not exceed 40 mg simvastatin when taking lomitapide. • Other Lipid-lowering Medications: Use with other fibrate products increases the risk of adverse skeletal muscle effects.

Caution should be used when prescribing with simvastatin. ( 5.1 , 7.2 ) • Coumarin anticoagulants: Concomitant use with simvastatin prolongs INR. Achieve stable INR prior to starting simvastatin.

Monitor INR frequently until stable upon initiation or alteration of simvastatin therapy. ( 7.6 )

7.1Strong CYP3A4 Inhibitors, Cyclosporine, or Danazol Strong CYP3A4 inhibitors: Simvastatin, like several other inhibitors of HMG-CoA reductase, is a substrate of CYP3A4. Simvastatin is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [See Warnings and Precautions (5.1) and Clinical Pharmacology (12.3 ). ] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4 ) ].

If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment. Cyclosporine or Danazol: The risk of myopathy, including rhabdomyolysis is increased by concomitant administration of cyclosporine or danazol. Therefore, concomitant use of these drugs is contraindicated. [see Contraindications (4) , Warnings and Precautions ( 5.1 ) and Clinical Pharmacology (12.3 ) ].

7.2Lipid-Lowering Drugs That Can Cause Myopathy When Given Alone Gemfibrozil: Contraindicated with simvastatin [see Contraindications (4) and Warnings and Precautions (5.1) ]. Other fibrates: Caution should be used when prescribing with simvastatin [see Warnings and Precautions (5.1) ].

7.3Amiodarone, Dronedarone, Ranolazine, or Calcium Channel Blockers The risk of myopathy, including rhabdomyolysis, is increased by concomitant administration of amiodarone, dronedarone, ranolazine, or calcium channel blockers such as verapamil, diltiazem, or amlodipine [see Dosage and Administration (2.3) and Warnings and Precautions (5.1) , and Table 3 in Clinical Pharmacology (12.3) ].

7.4Niacin Cases of myopathy/rhabdomyolysis have been observed with simvastatin coadministered with lipid-modifying doses (≥1 g/day niacin) of niacin-containing products. The risk of myopathy is greater in Chinese patients. In a clinical trial (median follow-up 3.9 years) involving patients at high risk of cardiovascular disease and with well-controlled LDL-C levels on simvastatin 40 mg/day with or without ezetimibe 10 mg/day, there was no incremental benefit on cardiovascular outcomes with the addition of lipid-modifying doses (≥1 g/day) of niacin.

Coadministration of simvastatin tablets with lip…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS • Severe renal impairment: patients should be started at 5 mg/day and be closely monitored. ( 2.6 , 8.6 ) • Chinese patients: May be at higher risk of myopathy; monitor appropriately. ( 5.1 , 8.8 )

8.1Pregnancy Pregnancy Category X [See Contraindications (4). ] Simvastatin is contraindicated in women who are or may become pregnant. Lipid lowering drugs offer no benefit during pregnancy, because cholesterol and cholesterol derivatives are needed for normal fetal development. Atherosclerosis is a chronic process, and discontinuation of lipid-lowering drugs during pregnancy should have little impact on long-term outcomes of primary hypercholesterolemia therapy.

There are no adequate and well-controlled studies of use with simvastatin during pregnancy; however, there are rare reports of congenital anomalies in infants exposed to statins in utero . Animal reproduction studies of simvastatin in rats and rabbits showed no evidence of teratogenicity. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development.

Because statins decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, simvastatin may cause fetal harm when administered to a pregnant woman. If simvastatin is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. There are rare reports of congenital anomalies following intrauterine exposure to statins.

In a review Manson, J.M., Freyssinges, C., Ducrocq, M.B., Stephenson, W.P., Post marketing Surveillance of Lovastatin and Simvastatin Exposure During Pregnancy, Reproductive Toxicology, 10(6):439-446, 1996. of approximately 100 prospectively followed pregnancies in women exposed to simvastatin or another structurally related statin, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed those expected in the general population. However, the study was only able to exclude a 3- to 4-fold increased risk of congenital anomalies over the background rate.

In 89% of these cases, drug treatment was initiated prior to pregnancy and was discontinued during the first trimester when pregnancy was identified. Simvastatin was not teratogenic in rats or rabbits at doses (25, 10 mg/kg/day, respectively) that resulted in 3 times the human exposure based on mg/m 2 surface area. However, in studies with another structurally-related statin, skeletal malformations were observed in rats and mice.

Women of childbearing potential, who require treatment with simvastatin for a lipid disorder, should be advised to use effective contraception. For women trying to conceive, discontinuation of simvastatin should be considered. If pregnancy occurs, simvastatin should be immediately discontinued.

8.3Nursing Mothers It is not known whether simvastatin is excreted in human milk. Because a small amount of another drug in this class is excreted in human milk and because of the potential for serious adverse reactions in nursing infants, women taking simvastatin should not nurse their infants. A decision should be made whether to discontinue nursing or discontinue drug, taking into account the importance of the drug to the mother [see Contraindications (4) ].

8.4Pediatric Use Safety and effectiveness of simvastatin in patients 10 to 17 years of age with heterozygous familial hypercholesterolemia have been evaluated in a controlled clinical trial in adolescent boys and in girls who were at least 1 year post-menarche. Patients treated with simvastatin had an adverse reaction profile similar to that of patients treated with placebo. Doses greater than 40 mg have not been studied in this population.

In this limited controlled study, there was no significant effect on growth or sexual maturation in the adolescent boys or girls, or on mens…

🆘 Overdosage 108 words ▾

10 OVERDOSAGE Significant lethality was observed in mice after a single oral dose of 9 g/m 2 . No evidence of lethality was observed in rats or dogs treated with doses of 30 and 100 g/m 2 , respectively. No specific diagnostic signs were observed in rodents.

At these doses the only signs seen in dogs were emesis and mucoid stools. A few cases of overdosage with simvastatin have been reported; the maximum dose taken was 3.6 g. All patients recovered without sequelae.

Supportive measures should be taken in the event of an overdose. The dialyzability of simvastatin and its metabolites in man is not known at present.

🧬 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 is a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting step in the biosynthetic pathway for cholesterol. In addition, simvastatin reduces VLDL and TG and increases HDL-C.

12.2Pharmacodynamics Epidemiological studies have demonstrated that elevated levels of total-C, LDL-C, as well as decreased levels of HDL-C are associated with the development of atherosclerosis and increased cardiovascular risk. Lowering LDL-C decreases this risk. However, the independent effect of raising HDL-C or lowering TG on the risk of coronary and cardiovascular morbidity and mortality has not been determined.

12.3Pharmacokinetics 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 the 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. 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 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 the drug to the general circulation is low (<5%). Both simvastatin and its β-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins.

Rat studies indicate that when radiolabeled simvastatin was administered, simvastatin­ derived radioactivity crossed the blood-brain barrier. 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. Peak plasma concentrations of both active and total inhibitors were attained within 1.3 to 2.4 hours postdose.

While the recommended therapeutic dose range is 5 to 40 mg/day, there was no substantial deviation from linearity of AUC of inhibitors in the general circulation with an increase in dose to as high as 120 mg. Relative to the fasting state, the plasma profile of inhibitors was not affected when simvastatin was administered immediately before an American Heart Association recommended low-fat meal. In a study including 16 elderly patients between 70 and 78 years of age who received simvastatin 40 mg/day, the mean plasma level of HMG-CoA reductase inhibitory activity was increased approximately 45% compared with 18 patients between 18-30 years of age.

Clinical study experience in the elderly (n=1522), suggests that there were no overall differences in safety between elderly and younger patients [see Use in Specific Populations (8.5 )] . Kinetic studies with another statin, having a similar principal route of elimination, have suggested that for a given dose level higher systemic exposure may be achieved in patients with severe renal insufficiency (as measured by createnine clearance). Simvastatin acid is a substrate of the transport protein OATP1B1.

Concomitant administration of medicinal products that are inhibitors of the transport protein OATP1B1 may lead to increased plasma concentrations of simvastatin acid and an increased risk of myopathy. For example, 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. The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma.

Inhibitors of…

🧬 Mechanism of Action 62 words ▾

12.1Mechanism of Action Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin is a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting step in the biosynthetic pathway for cholesterol. In addition, simvastatin reduces VLDL and TG and increases HDL-C.

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

16 HOW SUPPLIED/STORAGE AND HANDLING Simvastatin Tablets, USP 5 mg are white to off white, oval, biconvex, film-coated tablets with the logo “B300” debossed on one side and “5” on the other side. They are supplied as follows: NDC 70377-001-12 bottles of 30 NDC 70377-001 -13 bottles of 45 NDC 70377-001 -14 bottles of 90 NDC 70377-001 -15 bottles of 1000 Simvastatin Tablets, USP 10 mg are peach to dark peach, oval, biconvex, film-coated tablets with the logo “B301”debossed on one side and “10” on the other side. They are supplied as follows: NDC 70377-002 -12 bottles of 30 NDC 70377-002 -13 bottles of 45 NDC 70377-002 -14 bottles of 90 NDC 70377-002 -15 bottles of 1000.

Simvastatin Tablets, USP 20 mg are orange to dark orange, oval, biconvex, film-coated tablets with the logo “B302” debossed on one side and “20” on the other side. They are supplied as follows: NDC 70377-003 -12 bottles of 30 NDC 70377-003 -13 bottles of 45 NDC 70377-003 -14 bottles of 90. NDC 70377-003 -15 bottles of 1000 Simvastatin Tablets, USP 40 mg are light pink to pink, oval, biconvex, film-coated tablets with the logo “B303” debossed on one side and “40” on the other side.

They are supplied as follows: NDC 70377-004 -12 bottles of 30 NDC 70377-004 -13 bottles of 45 NDC 70377-004 -14 bottles of 90. NDC 70377-004 -15 bottles of 1000 Simvastatin Tablets, USP 80 mg are pink to dark pink, capsule-shaped, film-coated tablets with the logo “B304” debossed on one side and “80” on the other side. They are supplied as follows: NDC 70377-005 -12 bottles of 30 NDC 70377-005 -13 bottles of 45 NDC 70377-005 -14 bottles of 90 NDC 70377-005 -15 bottles of 1000.

Storage Store between 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature]. Dispense in a tightly-closed container as defined in the USP.

📋 Description 192 words ▾

11 DESCRIPTION Simvastatin is a lipid-lowering agent that is derived synthetically from a fermentation product of Aspergillus terreus . After oral ingestion, simvastatin, which is an inactive lactone, is hydrolyzed to the corresponding β-hydroxyacid form. This is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase.

This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate-limiting step in the biosynthesis of cholesterol. Simvastatin is butanoic acid, 2,2-dimethyl-,1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4­hydroxy-6-oxo-2H-pyran-2-yl)-ethyl]-1-naphthalenyl ester, [1S-[1α,3α,7β,8β(2S*,4S*),-8aβ]]. The empirical formula of simvastatin is C 25 H 38 O 5 and its molecular weight is 418.57.

Its structural formula is: Simvastatin 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 for oral administration contain either 5 mg, 10 mg, 20 mg, 40 mg or 80 mg of simvastatin and the following inactive ingredients: ascorbic acid, citric acid, hypromellose, iron oxides, lactose, magnesium stearate, povidone, microcrystalline cellulose, pregelatinized starch (maize), talc,colloidal silicone dioxide and titanium dioxide.

Butylated hydroxyanisole is added as a preservative. Simvastatin 10mg, 20mg, and 40 mg contain red and yellow ferric oxide. Simvastatin 80 mg contains red ferric oxide.

Structure

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Patients should be advised to adhere to their National Cholesterol Education Program (NCEP)­recommended diet, a regular exercise program, and periodic testing of a fasting lipid panel. Patients should be advised about substances they should not take concomitantly with simvastatin [see Contraindications (4) and Warnings and Precautions (5.1) ] . Patients should also be advised to inform other healthcare professionals prescribing a new medication or increasing the dose of an existing medication that they are taking simvastatin.

17.1Muscle Pain All patients starting therapy with simvastatin tablets should be advised of the risk of myopathy, including rhabdomyolysis, and told to report promptly any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever or if these muscle signs or symptoms persist after discontinuing simvastatin. Patients using the 80-mg dose should be informed that the risk of myopathy, including rhabdomyolysis, is increased with use of the 80-mg dose. The risk of myopathy, including rhabdomyolysis, occurring with use of simvastatin is increased when taking certain types of medication or consuming grapefruit juice.

Patients should discuss all medication, both prescription and over the counter, with their healthcare professional.

17.2Liver Enzymes It is recommended that liver function tests be performed before the initiation of simvastatin, and thereafter when clinically indicated. All patients treated with simvastatin should be advised to report promptly any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.

17.3Pregnancy Women of childbearing age should be advised to use an effective method of birth control to prevent pregnancy while using simvastatin tablets. Discuss future pregnancy plans with your patients, and discuss when to stop taking simvastatin tablets if they are trying to conceive. Patients should be advised that if they become pregnant they should stop taking simvastatin tablets and call their healthcare professional.

17.4Breastfeeding Women who are breastfeeding should not use simvastatin tablets. Patients who have a lipid disorder and are breastfeeding should be advised to discuss the options with their healthcare professional. Manufactured for: Biocon Pharma Inc, Iselin, NJ 08830-3009 USA Manufactured by: PuraCap Caribe Dorado, PR 00646 USA Rev. 10-2020 BP0141 BPCM0017/07

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