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ENTRESTO Sacubitril and Valsartan 49 mg; 51 mg Tablet, Film Coated, 780-count — NDC 71610-0806-32 package photo

ENTRESTO Sacubitril and Valsartan 49 mg; 51 mg Tablet, Film Coated, 780-count

by Aphena Pharma Solutions - Tennessee, LLC · 780 TABLET, FILM COATED in 1 BOTTLE (71610-806-32)
NDC 71610-0806-32
🏷️ FDA NDC (as labeled) 71610-806-32 billing pads the product segment with a zero
Rx only Brand 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) 71610-806-32
Product NDC 71610-806
11-digit billing NDC 71610080632
NCPDP billing unit EA — each (per item)
RxCUI 1656349, 1656351
UNII 17ERJ0MKGI, 80M03YXJ7I
Application # NDA207620
SPL Set ID 14bf8041-0b7f-9acb-e063-6294a90a8256
Established class (EPC) Angiotensin 2 Receptor Blocker
Mechanism of action Angiotensin 2 Receptor Antagonists
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2015-07-07
Route ORAL
Dosage form TABLET, FILM COATED
Substance SACUBITRIL; VALSARTAN
GCN Seq No 074409
GCN 39047
HICL code 042256
Ingredient (HICL) Sacubitril/Valsartan
HIC1 code A
Therapeutic class — broad (HIC1) Cardiovascular System
HIC2 code A4
Therapeutic class — intermediate (HIC2) Antihypertensives
HIC3 code A4L
Therapeutic class — specific (HIC3) Angiotensin Recept-Neprilysin Inhibitor Comb(Arni)
AHFS code 24:32.12.00
AHFS class Angiotensin Ii Recep Antagonist/Neprolys
FDB label name ENTRESTO 49 MG-51 MG TABLET
FDB brand name Entresto
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 71610-806-32 — 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 → 71610-0806-32. 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 Angiotensin II receptor blockers (ARBs), other combinations class.

Drug family (ATC) Angiotensin II receptor blockers (ARBs), other combinations
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 holderNOVARTIS PHARMACEUTICALS CORP
FDA applicationNDA207620 (NDA)
Labeler code71610
First marketedJul 2015
Product typeHuman Prescription Drug
Portfolio788 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 ENTRESTO 49 MG-51 MG TABLET Ingredient Sacubitril/Valsartan
📗 Our plain-language guide HelloPharmacist
  • Sacubitril and valsartan works on two fronts at once. One part (sacubitril) helps your body's own protective heart hormones stick around longer, which helps your kidneys get rid of...
  • What exactly is this medication supposed to do for my heart failure?
  • That's a really important question. A few combinations need to be avoided or watched carefully. You should never take this with an ACE inhibitor like lisinopril or enalapril at the...
  • Can I take it with my other medications? I'm also on ibuprofen sometimes for pain.
📖 Read our full Valsartan and Sacubitril guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

🧪 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 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 68401960MK
    Crospovidone is a synthetic polymer made from polyvinylpyrrolidone. It acts as a disintegrant, helping tablets break apart quickly in the stomach so the medicine dissolves and absorbs into the body.
  • 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 2165RE0K14
    A plant-based thickener made from cellulose that helps control how quickly the medicine dissolves and releases its active ingredient. It also binds ingredients together and improves the tablet's texture and handling during manufacturing.
  • 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 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 4R4HFI6D95
    Polyethylene glycol 4000 is a synthetic polymer derived from petroleum. It serves as a binder, filler, and lubricant in solid dosage forms, and helps control how quickly the medicine dissolves.
  • 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 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.

11 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 $1.23 $958.78 / 780 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
Sacubitril and Valsartan 49 mg/1; 51 mg 00904-7582-04 Major 1 tablet $0.529 AB Availability likely —
Sacubitril and valsartan 49 mg/1; 51 mg 31722-0674-18 Camber 180 tablets $0.529 AB Availability likely —
Sacubitril and Valsartan 49 mg/1; 51 mg 33342-0571-09 Macleods 60 tablets $0.529 AB Availability likely —
Sacubitril and Valsartan Sacubitril and Valsartan 49 mg/1; 51 mg 43598-0644-18 Dr. 180 tablets $0.529 AB Availability likely —
Sacubitril and Valsartan 49 mg/1; 51 mg 50268-0607-15 AvPAK 1 tablet $0.529 AB Availability likely —
Sacubitril and Valsartan 49 mg/1; 51 mg 60687-0966-57 American 1 tablet $0.529 AB Availability likely —
Sacubitril and Valsartan 49 mg/1; 51 mg 69238-2732-01 Amneal 60 tablets $0.529 AB Availability likely —
sacubitril and valsartan 49 mg/1; 51 mg 70748-0196-07 Lupin 60 tablets $0.529 AB Availability likely —
Sacubitril and Valsartan 49 mg/1; 51 mg 70954-0976-20 ANI 60 tablets $0.529 AB Availability likely —
Sacubitril and Valsartan 49 mg/1; 51 mg 72205-0281-18 Novadoz 180 tablets $0.529 AB Availability likely —
Sacubitril and Valsartan 49 mg/1; 51 mg 82293-0028-10 Novugen 60 tablets $0.529 AB Availability likely —
Entresto 49 mg/1; 51 mg 00078-0777-20 Novartis 60 tablets $11.557 AB Availability likely —
Entresto 49 mg/1; 51 mg 00078-9777-50 Novartis 28 tablets — AB FDA listed —
sacubitril and valsartan 49 mg/1; 51 mg 13668-0635-05 Torrent 500 tablets — AB FDA listed —
sacubitril and valsartan 49 mg/1; 51 mg 13668-0746-05 Torrent 500 tablets — AB FDA listed —
Sacubitril and Valsartan 49 mg/1; 51 mg 42385-0931-18 Laurus 180 tablets — AB FDA listed —
sacubitril and valsartan 49 mg/1; 51 mg 46708-0557-10 Alembic 10 tablets — AB FDA listed —
sacubitril and valsartan 49 mg/1; 51 mg 51407-0936-10 Golden 1000 tablets — AB FDA listed —
sacubitril and valsartan 49 mg/1; 51 mg 62332-0557-10 Alembic 10 tablets — AB FDA listed —
Sacubitril and Valsartan 49 mg/1; 51 mg 67877-0708-51 Ascend 180 tablets — AB FDA listed —
Sacubitril and Valsartan 49 mg/1; 51 mg 67877-0949-33 Ascend 10 tablets — AB FDA listed —
Sacubitril and Valsartan 49 mg/1; 51 mg 70069-0854-60 Somerset 60 tablets — AB FDA listed —
Sacubitril and Valsartan 49 mg/1; 51 mg 70377-0032-11 Biocon 30 tablets — AB FDA listed —
sacubitril and valsartan 49 mg/1; 51 mg 70710-1273-04 Zydus 100 tablets — AB FDA listed —
sacubitril and valsartan 49 mg/1; 51 mg 70771-1922-04 Zydus 100 tablets — AB FDA listed —
Entresto 49 mg/1; 51 mgthis 71610-0806-32 Aphena 780 tablets — AB FDA listed —
Sacubitril and Valsartan 49 mg/1; 51 mg 71610-0939-32 Aphena 780 tablets — AB FDA listed —
Sacubitril and Valsartan 49 mg/1; 51 mg 71610-0982-89 Aphena 720 tablets — AB FDA listed —
Sacubitril and Valsartan 49 mg/1; 51 mg 72865-0311-10 XLCare 1000 tablets — AB FDA listed —
Sacubitril and Valsartan 49 mg/1; 51 mg 73190-0006-10 AvKARE 1000 tablets — AB FDA listed —
Sacubitril and Valsartan 49 mg/1; 51 mg 73190-0018-18 AvKARE 180 tablets — AB FDA listed —
Sacubitril and Valsartan 49 mg/1; 51 mg 72603-0881-01 NorthStar 60 tablets — AB FDA listed —
Sacubitril and Valsartan 49 mg/1; 51 mg 60290-0086-01 Umedica 60 tablets — — FDA listed —
About this product: this is the brand-name version. FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available.
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
First FDA approval
Jul 2015
📍
2026
Currently FDA-listed
11 years listed
🛡️
2036
Latest patent/protection listed
not a guaranteed launch date
✅Generic appears available

FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through May 2036. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Jul 7, 2015 AB TE-rated RLD RS ⏳ ~9.7 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 9388134 — method of use (U-1723)
US 9388134 — method of use (U-1723)
US 11135192 — method of use (U-3084)
US 11135192 — method of use (U-3084)
US 11135192 — method of use (U-3084)
US 9517226 — method of use (U-3084)
US 9937143 — method of use (U-3084)
US 9517226 — method of use (U-3084)
US 9937143 — method of use (U-3084)
US 9517226 — method of use (U-3084)
US 9937143 — method of use (U-3084)
US 9388134 — method of use (U-1723)
US 11058667 — method of use (U-3170)
US 11058667 — method of use (U-3170)
US 11058667 — method of use (U-3170)
US 8877938 — drug substance
US 8877938 — drug substance
US 8877938 — drug substance
US 8877938*PED — drug product
US 8877938*PED — drug product
US 8877938*PED — drug product
US 9388134*PED — drug product
US 9388134*PED — drug product
US 9388134*PED — drug product
2015 2017 2019 2021 2023 2025 2027 2029 2031 2033 2035
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (24)
PatentTypeUse codeExpires
US 9388134 ↗ Method of use U-1723 Nov 8, 2026
US 9388134 ↗ Method of use U-1723 Nov 8, 2026
US 11135192 ↗ Method of use U-3084 Aug 22, 2033
US 11135192 ↗ Method of use U-3084 Aug 22, 2033
US 11135192 ↗ Method of use U-3084 Aug 22, 2033
US 9517226 ↗ Method of use U-3084 Aug 22, 2033
US 9937143 ↗ Method of use U-3084 Aug 22, 2033
US 9517226 ↗ Method of use U-3084 Aug 22, 2033
US 9937143 ↗ Method of use U-3084 Aug 22, 2033
US 9517226 ↗ Method of use U-3084 Aug 22, 2033
US 9937143 ↗ Method of use U-3084 Aug 22, 2033
US 9388134 ↗ Method of use U-1723 Nov 8, 2026
US 11058667 ↗ Method of use U-3170 May 9, 2036
US 11058667 ↗ Method of use U-3170 May 9, 2036
US 11058667 ↗ Method of use U-3170 May 9, 2036
US 8877938 ↗ Drug substance — May 27, 2027
US 8877938 ↗ Drug substance — May 27, 2027
US 8877938 ↗ Drug substance — May 27, 2027
US 8877938*PED ↗ Drug product — Nov 27, 2027
US 8877938*PED ↗ Drug product — Nov 27, 2027
US 8877938*PED ↗ Drug product — Nov 27, 2027
US 9388134*PED ↗ Drug product — May 8, 2027
US 9388134*PED ↗ Drug product — May 8, 2027
US 9388134*PED ↗ Drug product — May 8, 2027
Common questions
Is there a generic version of ENTRESTO 49 MG-51 MG TABLET?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for ENTRESTO 49 MG-51 MG TABLET. See the alternatives section for substitutable, lower-cost products.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
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 Entresto — the program that covers self-administered drugs. 1 manufacturer.
⚠️ 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 Entresto. 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
$39.74M
Claims incl. refills
122.1K
Beneficiaries
103.7K
Spend / beneficiary
$383.36
Spend / claim
$325.48
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.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
71610-0806-32 You're viewing this 780 TABLET, FILM COATED in 1 BOTTLE (71610-806-32) 2024-03-22 Active

🧭 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 71610-806-32, 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: 71610-0806-32, written without dashes as 71610080632. 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 71610-0806-32, the first segment (71610) is the labeler code FDA assigned to Aphena Pharma Solutions - Tennessee, LLC; the middle segment (0806) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (32) 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.
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.
🚨 Boxed Warning 🎯 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 📦 Storage and Handling 📋 Description 💬 Information for Patients
🚨 Boxed Warning 76 words ▾

WARNING: FETAL TOXICITY When pregnancy is detected, discontinue ENTRESTO as soon as possible (5.1) Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus (5.1) WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning. When pregnancy is detected, discontinue ENTRESTO as soon as possible. ( 5.1 ) Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

( 5.1 )

🎯 Indications and Usage 176 words ▾

1 INDICATIONS AND USAGE ENTRESTO is indicated: to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal. ( 1.1 ) for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older.

ENTRESTO reduces NT-proBNP and is expected to improve cardiovascular outcomes. ( 1.2 )

1.1Adult Heart Failure ENTRESTO is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal. LVEF is a variable measure, so use clinical judgment in deciding whom to treat [see Clinical Studies (14.1)] .

1.2Pediatric Heart Failure ENTRESTO is indicated for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older. ENTRESTO reduces NT-proBNP and is expected to improve cardiovascular outcomes.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Indication Titration Step Dose (twice daily) Starting Second Final Adult Heart Failure 49/51 mg 97/103 mg Pediatric Heart Failure Patients less than 40 kg 1.6 mg/kg 2.3 mg/kg 3.1 mg/kg Pediatric Heart Failure Patients at least 40 kg, less than 50 kg 24/26 mg 49/51 mg 72/78 mg Pediatric Heart Failure Patients at least 50 kg 49/51 mg 72/78 mg 97/103 mg Adjust adult doses every 2 to 4 weeks and pediatric doses every 2 weeks to the target maintenance dose, as tolerated by the patient. ( 2.2 , 2.3 ) Reduce starting dose to half the usually recommended starting dosage for: - patients not currently taking an ACE inhibitor or ARB or previously taking a low dose of these agents ( 2.5 ) - patients with severe renal impairment ( 2.6 ) - patients with moderate hepatic impairment ( 2.7 )

2.1General Considerations ENTRESTO is contraindicated with concomitant use of an angiotensin-converting enzyme (ACE) inhibitor. If switching from an ACE inhibitor to ENTRESTO allow a washout period of 36 hours between administration of the two drugs [see Contraindications (4) and Drug Interactions (7.1)] .

2.2Adult Heart Failure The recommended starting dose of ENTRESTO is 49/51 mg orally twice-daily. Double the dose of ENTRESTO after 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.

2.3Pediatric Heart Failure Refer to Table 1 for the recommended dose for pediatric patients aged one year and older. Take the recommended dose orally twice daily. Adjust pediatric patient doses every 2 weeks, as tolerated by the patient.

Table 1: Recommended Dose Titration † Use of the Oral Suspension recommended in these patients. Recommended mg/kg doses are of the combined amount of both sacubitril and valsartan [see Dosage and Administration (2.4)] . ‡ Doses of 72/78 mg can be achieved using three 24/26 mg tablets [see Dosage Forms and Strengths (3)] . Titration Step Dose (twice daily) Starting Second Final Pediatric Patients Less than 40 kg † 1.6 mg/kg 2.3 mg/kg 3.1 mg/kg Pediatric Patients At least 40 kg, less than 50 kg 24/26 mg 49/51 mg 72/78 mg ‡ Pediatric Patients At least 50 kg 49/51 mg 72/78 mg ‡ 97/103 mg

2.4Preparation of Oral Suspension ENTRESTO oral suspension can be substituted at the recommended tablet dosage in patients unable to swallow tablets. ENTRESTO 800 mg/200 mL oral suspension can be prepared in a concentration of 4 mg/mL (sacubitril/valsartan 1.96/2.04 mg/mL). Use ENTRESTO 49/51 mg tablets in the preparation of the suspension.

To make an 800 mg/200 mL (4 mg/mL) oral suspension, transfer eight tablets of ENTRESTO 49/51 mg film-coated tablets into a mortar. Crush the tablets into a fine powder using a pestle. Add 60 mL of Ora-Plus ® into the mortar and triturate gently with pestle for 10 minutes, to form a uniform suspension.

Add 140 mL of Ora-Sweet ® SF into mortar and triturate with pestle for another 10 minutes, to form a uniform suspension. Transfer the entire contents from the mortar into a clean 200 mL amber colored PET or glass bottle. Place a press-in bottle adapter and close the bottle with a child resistant cap.

The oral suspension can be stored for up to 15 days. Do not store above 25°C (77°F) and do not refrigerate. Shake before each use. * Ora-Sweet SF ® and Ora-Plus ® are registered trademarks of Paddock Laboratories, Inc.

2.5Dose Adjustment for Patients Not Taking an ACE inhibitor or ARB or Previously Taking Low Doses of These Agents In patients not currently taking an ACE inhibitor or an angiotensin II receptor blocker (ARB) and for patients previously taking low doses of these agents, start ENTRESTO at half the usually recommended starting dose. After initiation, increase the dose every 2 to 4 weeks in adults and every 2 weeks in pediatric patients to follow the recommended dose escalation thereafter [see Dosage and Administration (2.2, 2.3)] .

Note: Initiate pediatric patients weighing 40 to 50 kg who meet this criterion at 0.8 mg/kg twice daily using th…

💊 Dosage Forms and Strengths 106 words ▾

3 DOSAGE FORMS AND STRENGTHS ENTRESTO is supplied as unscored, ovaloid, film-coated tablets in the following strengths: ENTRESTO 24/26 mg, (sacubitril 24 mg and valsartan 26 mg) are violet white and debossed with “NVR” on one side and “LZ” on the other side. ENTRESTO 49/51 mg, (sacubitril 49 mg and valsartan 51 mg) are pale yellow and debossed with “NVR” on one side and “L1” on the other side. ENTRESTO 97/103 mg, (sacubitril 97 mg and valsartan 103 mg) are light pink and debossed with “NVR” on one side and “L11” on the other side.

Film-coated tablets: 24/26 mg; 49/51 mg; 97/103 mg ( 3 )

⛔ Contraindications 112 words ▾

4 CONTRAINDICATIONS ENTRESTO is contraindicated: in patients with hypersensitivity to any component in patients with a history of angioedema related to previous ACE inhibitor or ARB therapy [see Warnings and Precautions (5.2)] with concomitant use of ACE inhibitors. Do not administer within 36 hours of switching from or to an ACE inhibitor [see Drug Interactions (7.1)] with concomitant use of aliskiren in patients with diabetes [see Drug Interactions (7.1)] Hypersensitivity to any component. ( 4 ) History of angioedema related to previous ACEi or ARB therapy.

( 4 ) Concomitant use with ACE inhibitors. ( 4 , 7.1 ) Concomitant use with aliskiren in patients with diabetes. ( 4 , 7.1 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Observe for signs and symptoms of angioedema and hypotension. ( 5.2 , 5.3 ) Monitor renal function and potassium in susceptible patients. ( 5.4 , 5.5 )

5.1Fetal Toxicity ENTRESTO can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. When pregnancy is detected, consider alternative drug treatment and discontinue ENTRESTO.

However, if there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system, and if the drug is considered lifesaving for the mother, advise a pregnant woman of the potential risk to the fetus [see Use in Specific Populations (8.1)] .

5.2Angioedema ENTRESTO may cause angioedema [see Adverse Reactions (6.1)] . If angioedema occurs, discontinue ENTRESTO immediately, provide appropriate therapy, and monitor for airway compromise. ENTRESTO must not be re-administered.

In cases of confirmed angioedema where swelling has been confined to the face and lips, the condition has generally resolved without treatment, although antihistamines have been useful in relieving symptoms. Angioedema associated with laryngeal edema may be fatal. Where there is involvement of the tongue, glottis or larynx, likely to cause airway obstruction, administer appropriate therapy, e.g., subcutaneous epinephrine/adrenaline solution 1:1000 (0.3 mL to 0.5 mL) and take measures necessary to ensure maintenance of a patent airway.

ENTRESTO has been associated with a higher rate of angioedema in Black than in non-Black patients. Patients with a prior history of angioedema may be at increased risk of angioedema with ENTRESTO [see Adverse Reactions (6.1)] . ENTRESTO must not be used in patients with a known history of angioedema related to previous ACE inhibitor or ARB therapy [see Contraindications (4)] .

ENTRESTO should not be used in patients with hereditary angioedema.

5.3Hypotension ENTRESTO lowers blood pressure and may cause symptomatic hypotension [see Adverse Reactions (6.1)] . Patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients (e.g., those being treated with high doses of diuretics), are at greater risk. Correct volume or salt depletion prior to administration of ENTRESTO or start at a lower dose.

If hypotension occurs, consider dose adjustment of diuretics, concomitant antihypertensive drugs, and treatment of other causes of hypotension (e.g., hypovolemia). If hypotension persists despite such measures, reduce the dosage or temporarily discontinue ENTRESTO. Permanent discontinuation of therapy is usually not required.

5.4Impaired Renal Function As a consequence of inhibiting the renin-angiotensin-aldosterone system (RAAS), decreases in renal function may be anticipated in susceptible individuals treated with ENTRESTO [see Adverse Reactions (6.1)] . In patients whose renal function depends upon the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure), treatment with ACE inhibitors and angiotensin receptor antagonists has been associated with oliguria, progressive azotemia and, rarely, acute renal failure and death.

Closely monitor serum creatinine, and down-titrate or interrupt ENTRESTO in patients who develop a clinically significant decrease in renal function [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)] . As with all drugs that affect the RAAS, ENTRESTO may increase blood urea and serum creatinine levels in patients with bilateral or unilateral renal artery stenosis. In patients with renal artery stenosis, monitor renal function.

5.5Hyperkalemia Through its actions on the RAAS, hyperkalemia may occur with ENTRESTO [see Adverse Reactions (6.1)] . Monitor serum potassium periodically and treat appropriately, especially in patients with risk factors for hype…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS Clinically significant adverse reactions that appear in other sections of the labeling include: Angioedema [see Warnings and Precautions (5.2)] Hypotension [see Warnings and Precautions (5.3)] Impaired Renal Function [see Warnings and Precautions (5.4)] Hyperkalemia [see Warnings and Precautions (5.5)] Adverse reactions occurring ≥ 5% are hypotension, hyperkalemia, cough, dizziness, and renal failure. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 6,622 heart failure patients were treated with ENTRESTO in the PARADIGM-HF (vs. enalapril) and PARAGON-HF (vs. valsartan) clinical trials. Of these, 5,085 were exposed for at least 1 year.

Adult Heart Failure In PARADIGM-HF, patients were required to complete sequential enalapril and ENTRESTO run-in periods of (median) 15 and 29 days, respectively, prior to entering the randomized double-blind period comparing ENTRESTO and enalapril. During the enalapril run-in period, 1,102 patients (10.5%) were permanently discontinued from the study, 5.6% because of an adverse event, most commonly renal dysfunction (1.7%), hyperkalemia (1.7%) and hypotension (1.4%). During the ENTRESTO run-in period, an additional 10.4% of patients permanently discontinued treatment, 5.9% because of an adverse event, most commonly renal dysfunction (1.8%), hypotension (1.7%) and hyperkalemia (1.3%).

Because of this run-in design, the adverse reaction rates described below are lower than expected in practice. In the double-blind period, safety was evaluated in 4,203 patients treated with ENTRESTO and 4,229 treated with enalapril. In PARADIGM-HF, patients randomized to ENTRESTO received treatment for up to 4.3 years, with a median duration of exposure of 24 months; 3,271 patients were treated for more than one year.

Discontinuation of therapy because of an adverse event during the double-blind period occurred in 450 (10.7%) of ENTRESTO treated patients and 516 (12.2%) of patients receiving enalapril. Adverse reactions occurring at an incidence of ≥ 5% in patients who were treated with ENTRESTO in the double-blind period of PARADIGM-HF are shown in Table 2. In PARADIGM-HF, the incidence of angioedema was 0.1% in both the enalapril and ENTRESTO run-in periods.

In the double-blind period, the incidence of angioedema was higher in patients treated with ENTRESTO than enalapril (0.5% and 0.2%, respectively). The incidence of angioedema in Black patients was 2.4% with ENTRESTO and 0.5% with enalapril [see Warnings and Precautions (5.2)] . Orthostasis was reported in 2.1% of patients treated with ENTRESTO compared to 1.1% of patients treated with enalapril during the double-blind period of PARADIGM-HF.

Falls were reported in 1.9% of patients treated with ENTRESTO compared to 1.3% of patients treated with enalapril. Table 2: Adverse Reactions Reported in ≥ 5% of Patients Treated with ENTRESTO in the Double-Blind Period of PARADIGM-HF ENTRESTO (n = 4,203) % Enalapril (n = 4,229) % Hypotension 18 12 Hyperkalemia 12 14 Cough 9 13 Dizziness 6 5 Renal failure/acute renal failure 5 5 In PARAGON-HF, no new adverse reactions were identified. Pediatric Heart Failure The adverse reactions observed in pediatric patients 1 to < 18 years old who received treatment with ENTRESTO were consistent with those observed in adult patients.

Laboratory Abnormalities Hemoglobin and Hematocrit Decreases in hemoglobin/hematocrit of > 20% were observed in approximately 5% of both ENTRESTO- and enalapril-treated patients in the double-blind period in PARADIGM-HF. Decreases in hemoglobin/hematocrit of >20% were observed i…

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS Avoid concomitant use with aliskiren in patients with eGFR < 60. ( 7.1 ) Potassium-sparing diuretics: May lead to increased serum potassium. ( 7.2 ) NSAIDs: May lead to increased risk of renal impairment. ( 7.3 ) Lithium: Increased risk of lithium toxicity. ( 7.4 )

7.1Dual Blockade of the Renin-Angiotensin-Aldosterone System Concomitant use of ENTRESTO with an ACE inhibitor is contraindicated because of the increased risk of angioedema [see Contraindications (4)] . Avoid use of ENTRESTO with an ARB, because ENTRESTO contains the angiotensin II receptor blocker valsartan. The concomitant use of ENTRESTO with aliskiren is contraindicated in patients with diabetes [see Contraindications (4)] .

Avoid use with aliskiren in patients with renal impairment (eGFR < 60 mL/min/1.73 m 2 ).

7.2Potassium-Sparing Diuretics As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium [see Warnings and Precautions (5.5)] .

7.3Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, concomitant use of NSAIDs, including COX-2 inhibitors, with ENTRESTO may result in worsening of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically.

7.4Lithium Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists. Monitor serum lithium levels during concomitant use with ENTRESTO.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Breastfeeding or drug should be discontinued. ( 8.2 ) Severe Hepatic Impairment: Use not recommended. ( 2.7 , 8.6 )

8.1Pregnancy Risk Summary ENTRESTO can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents.

In animal reproduction studies, ENTRESTO treatment during organogenesis resulted in increased embryo-fetal lethality in rats and rabbits and teratogenicity in rabbits. When pregnancy is detected, consider alternative drug treatment and discontinue ENTRESTO. However, if there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system, and if the drug is considered lifesaving for the mother, advise a pregnant woman of the potential risk to the fetus.

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 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death.

Perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.

If oligohydramnios is observed, consider alternative drug treatment. Closely observe neonates with histories of in utero exposure to ENTRESTO for hypotension, oliguria, and hyperkalemia. In neonates with a history of in utero exposure to ENTRESTO, if oliguria or hypotension occurs, support blood pressure and renal perfusion.

Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function. Data Animal Data ENTRESTO treatment during organogenesis resulted in increased embryo-fetal lethality in rats at doses ≥ 49 mg sacubitril/51 mg valsartan/kg/day (≤ 0.06 [LBQ657, the active metabolite] and 0.72 [valsartan]-fold the maximum recommended human dose [MRHD] of 97/103 mg twice-daily on the basis of the area under the plasma drug concentration-time curve [AUC]) and rabbits at doses ≥ 5 mg sacubitril/5 mg valsartan/kg/day (2-fold and 0.03-fold the MRHD on the basis of valsartan and LBQ657 AUC, respectively).

ENTRESTO is teratogenic based on a low incidence of fetal hydrocephaly, associated with maternally toxic doses, which was observed in rabbits at an ENTRESTO dose of ≥ 5 mg sacubitril/5 mg valsartan/kg/day. The adverse embryo-fetal effects of ENTRESTO are attributed to the angiotensin receptor antagonist activity. Pre- and postnatal development studies in rats at sacubitril doses up to 750 mg/kg/day (2.2-fold the MRHD on the basis of LBQ657 AUC) and valsartan at doses up to 600 mg/kg/day (0.86-fold the MRHD on the basis of AUC) indicate that treatment with ENTRESTO during organogenesis, gestation and lactation may affect pup development and survival.

8.2Lactation Risk Summary There is no information regarding the presence of sacubitril/valsartan in human milk, the effects on the breastfed infant, or the effects on milk production. Sacubitril/valsartan is present in rat milk. Because of the potential for serious adv…

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary ENTRESTO can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents.

In animal reproduction studies, ENTRESTO treatment during organogenesis resulted in increased embryo-fetal lethality in rats and rabbits and teratogenicity in rabbits. When pregnancy is detected, consider alternative drug treatment and discontinue ENTRESTO. However, if there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system, and if the drug is considered lifesaving for the mother, advise a pregnant woman of the potential risk to the fetus.

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 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death.

Perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.

If oligohydramnios is observed, consider alternative drug treatment. Closely observe neonates with histories of in utero exposure to ENTRESTO for hypotension, oliguria, and hyperkalemia. In neonates with a history of in utero exposure to ENTRESTO, if oliguria or hypotension occurs, support blood pressure and renal perfusion.

Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function. Data Animal Data ENTRESTO treatment during organogenesis resulted in increased embryo-fetal lethality in rats at doses ≥ 49 mg sacubitril/51 mg valsartan/kg/day (≤ 0.06 [LBQ657, the active metabolite] and 0.72 [valsartan]-fold the maximum recommended human dose [MRHD] of 97/103 mg twice-daily on the basis of the area under the plasma drug concentration-time curve [AUC]) and rabbits at doses ≥ 5 mg sacubitril/5 mg valsartan/kg/day (2-fold and 0.03-fold the MRHD on the basis of valsartan and LBQ657 AUC, respectively).

ENTRESTO is teratogenic based on a low incidence of fetal hydrocephaly, associated with maternally toxic doses, which was observed in rabbits at an ENTRESTO dose of ≥ 5 mg sacubitril/5 mg valsartan/kg/day. The adverse embryo-fetal effects of ENTRESTO are attributed to the angiotensin receptor antagonist activity. Pre- and postnatal development studies in rats at sacubitril doses up to 750 mg/kg/day (2.2-fold the MRHD on the basis of LBQ657 AUC) and valsartan at doses up to 600 mg/kg/day (0.86-fold the MRHD on the basis of AUC) indicate that treatment with ENTRESTO during organogenesis, gestation and lactation may affect pup development and survival.

🧒 Pediatric Use ~1 min read ▾

8.4Pediatric Use The safety and effectiveness of ENTRESTO in pediatric heart failure patients 1 to < 18 years old are supported by the reduction from baseline to 12 weeks in NT-proBNP in a randomized, double-blind clinical study [see Clinical Studies (14.2)] . The analysis of NT-proBNP included 90 patients age 6 to 18 years and 20 patients age 1 to 6 years. Safety and effectiveness have not been established in pediatric patients less than 1 year of age.

Animal Data Sacubitril given orally to juvenile rats from postnatal day (PND) 7 to PND 35 or PND 70 (an age approximately equivalent to neonatal through pre-pubertal development or adulthood in humans) at doses ≥ 400 mg/kg/day (approximately 2-fold the AUC exposure to the active metabolite of sacubitril, LBQ657, at an ENTRESTO pediatric clinical dose of 3.1 mg/kg twice daily) resulted in decreases in body weight, bone length, and bone mass. The decrease in body weight was transient from PND 10 to PND 20 and the effects for most bone parameters were reversible after treatment stopped.

Exposure at the No-Observed-Adverse-Effect-Level (NOAEL) of 100 mg/kg/day was approximately 0.5-fold the AUC exposure to LBQ657 at the 3.1 mg/kg twice daily dose of ENTRESTO. The mechanism underlying bone effects in rats and the translatability to pediatric patients are unknown. Valsartan given orally to juvenile rats from PND 7 to PND 70 (an age approximately equivalent to neonatal through adulthood in humans) produced persistent, irreversible kidney damage at all dose levels.

Exposure at the lowest tested dose of 1 mg/kg/day was approximately 0.2-fold the exposure at 3.1 mg/kg twice daily dose of ENTRESTO based on AUC. These kidney effects in neonatal rats represent expected exaggerated pharmacological effects that are observed if rats are treated during the first 13 days of life.

🧓 Geriatric Use 32 words ▾

8.5Geriatric Use No relevant pharmacokinetic differences have been observed in elderly (≥ 65 years) or very elderly (≥ 75 years) patients compared to the overall population [see Clinical Pharmacology (12.3)] .

🆘 Overdosage 81 words ▾

10 OVERDOSAGE Limited data are available with regard to overdosage in human subjects with ENTRESTO. In healthy volunteers, a single dose of ENTRESTO 583 mg sacubitril/617 mg valsartan, and multiple doses of 437 mg sacubitril/463 mg valsartan (14 days) have been studied and were well tolerated. Hypotension is the most likely result of overdosage due to the blood pressure lowering effects of ENTRESTO.

Symptomatic treatment should be provided. ENTRESTO is unlikely to be removed by hemodialysis because of high protein binding.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action ENTRESTO contains a neprilysin inhibitor, sacubitril, and an angiotensin receptor blocker, valsartan. ENTRESTO inhibits neprilysin (neutral endopeptidase; NEP) via LBQ657, the active metabolite of the prodrug sacubitril, and blocks the angiotensin II type-1 (AT 1 ) receptor via valsartan. The cardiovascular and renal effects of ENTRESTO in heart failure patients are attributed to the increased levels of peptides that are degraded by neprilysin, such as natriuretic peptides, by LBQ657, and the simultaneous inhibition of the effects of angiotensin II by valsartan.

Valsartan inhibits the effects of angiotensin II by selectively blocking the AT 1 receptor, and also inhibits angiotensin II-dependent aldosterone release.

12.2Pharmacodynamics The pharmacodynamic effects of ENTRESTO were evaluated after single and multiple dose administrations in healthy subjects and in patients with heart failure, and are consistent with simultaneous neprilysin inhibition and renin-angiotensin system blockade. In a 7-day valsartan-controlled study in patients with reduced ejection fraction (HFrEF), administration of ENTRESTO resulted in a significant non-sustained increase in natriuresis, increased urine cGMP, and decreased plasma MR-proANP and NT-proBNP compared to valsartan.

In a 21-day study in HFrEF patients, ENTRESTO significantly increased urine ANP and cGMP and plasma cGMP, and decreased plasma NT-proBNP, aldosterone and endothelin-1. ENTRESTO also blocked the AT 1 -receptor as evidenced by increased plasma renin activity and plasma renin concentrations. In PARADIGM-HF, ENTRESTO decreased plasma NT-proBNP (not a neprilysin substrate) and increased plasma BNP (a neprilysin substrate) and urine cGMP compared with enalapril.

In PARAMOUNT, a randomized, double-blind, 36-week study in patients with heart failure with LVEF ≥ 45% comparing 97/103 mg of ENTRESTO (n=149) to 160 mg of valsartan (n =152) twice-daily, ENTRESTO decreased NT-proBNP by 17% while valsartan increased NT-proBNP by 8% at Week 12 (p = 0.005). In PARAGON-HF, ENTRESTO decreased NT-proBNP by 24% (Week 16) and 19% (Week 48) compared to 6% and 3% reductions on valsartan, respectively. QT Prolongation: In a thorough QTc clinical study in healthy male subjects, single doses of ENTRESTO 194 mg sacubitril/206 mg valsartan and 583 mg sacubitril/617 mg valsartan had no effect on cardiac repolarization.

Amyloid-β: Neprilysin is one of multiple enzymes involved in the clearance of amyloid-β (Aβ) from the brain and cerebrospinal fluid (CSF). Administration of ENTRESTO 194 mg sacubitril/206 mg valsartan once-daily for 2 weeks to healthy subjects was associated with an increase in CSF Aβ 1-38 compared to placebo; there were no changes in concentrations of CSF Aβ 1-40 or CSF Aβ 1-42 . The clinical relevance of this finding is unknown [see Nonclinical Toxicology (13)] .

Blood Pressure: Addition of a 50 mg single dose of sildenafil to ENTRESTO at steady state (194 mg sacubitril/206 mg valsartan once daily for 5 days) in patients with hypertension was associated with additional blood pressure (BP) reduction (~ 5/4 mmHg, systolic/diastolic BP) compared to administration of ENTRESTO alone. Co-administration of ENTRESTO did not significantly alter the BP effect of intravenous nitroglycerin.

12.3Pharmacokinetics Absorption Following oral administration, ENTRESTO dissociates into sacubitril and valsartan. Sacubitril is further metabolized to LBQ657. The peak plasma concentrations of sacubitril, LBQ657, and valsartan are reached in 0.5 hours, 2 hours, and 1.5 hours, respectively.

The oral absolute bioavailability of sacubitril is estimated to be ≥ 60%. The valsartan in ENTRESTO is more bioavailable than the valsartan in other marketed tablet formulations; 26 mg, 51 mg, and 103 mg of valsartan in ENTRESTO is equivalent to 40 mg, 80 mg, and 160 mg of valsartan in other marketed tablet formulations, respectively. Following twice-daily dosing of ENTRESTO, st…

🧬 Mechanism of Action 106 words ▾

12.1Mechanism of Action ENTRESTO contains a neprilysin inhibitor, sacubitril, and an angiotensin receptor blocker, valsartan. ENTRESTO inhibits neprilysin (neutral endopeptidase; NEP) via LBQ657, the active metabolite of the prodrug sacubitril, and blocks the angiotensin II type-1 (AT 1 ) receptor via valsartan. The cardiovascular and renal effects of ENTRESTO in heart failure patients are attributed to the increased levels of peptides that are degraded by neprilysin, such as natriuretic peptides, by LBQ657, and the simultaneous inhibition of the effects of angiotensin II by valsartan.

Valsartan inhibits the effects of angiotensin II by selectively blocking the AT 1 receptor, and also inhibits angiotensin II-dependent aldosterone release.

📦 How Supplied / Storage and Handling 117 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING ENTRESTO (sacubitril/valsartan) is available as unscored, ovaloid, biconvex, film-coated tablets, containing 24 mg of sacubitril and 26 mg of valsartan; 49 mg of sacubitril and 51 mg of valsartan; and 97 mg of sacubitril and 103 mg of valsartan. All strengths are packaged in bottles as described below. Tablet Color Debossment NDC # 0078-XXXX-XX Sacubitril/Valsartan “NVR” and Bottle of 60 Bottle of 180 24 mg/26 mg Violet white LZ 0659-20 0659-67 49 mg/51 mg Pale yellow L1 0777-20 0777-67 97 mg/103 mg Light pink L11 0696-20 0696-67 Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

Protect from moisture.

📦 Storage and Handling 25 words ▾

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Protect from moisture.

📋 Description ~1 min read ▾

11 DESCRIPTION ENTRESTO (sacubitril and valsartan) is a combination of a neprilysin inhibitor and an angiotensin II receptor blocker. ENTRESTO contains a complex comprised of anionic forms of sacubitril and valsartan, sodium cations, and water molecules in the molar ratio of 1:1:3:2.5, respectively. Following oral administration, the complex dissociates into sacubitril (which is further metabolized to LBQ657) and valsartan.

The complex is chemically described as Octadecasodiumhexakis(4-{[(1S,3R)-1-([1,1´-biphenyl]-4-ylmethyl)-4-ethoxy-3-methyl-4-oxobutyl]amino}-4-oxobutanoate)hexakis(N-pentanoyl-N-{[2´-(1H-tetrazol-1-id-5-yl)[1,1´-biphenyl]-4-yl]methyl}-L-valinate)—water (1/15). Its empirical formula (hemipentahydrate) is C 48 H 55 N 6 O 8 Na 3

2.5H 2 O. Its molecular mass is 957.99 and its schematic structural formula is: ENTRESTO is available as film-coated tablets for oral administration, containing 24 mg of sacubitril and 26 mg of valsartan; 49 mg of sacubitril and 51 mg of valsartan; and 97 mg of sacubitril and 103 mg of valsartan. The tablet inactive ingredients are microcrystalline cellulose, low-substituted hydroxypropylcellulose, crospovidone, magnesium stearate (vegetable origin), talc, and colloidal silicon dioxide.

The film-coat inactive ingredients are hypromellose, titanium dioxide (E 171), Macrogol 4000, talc, and iron oxide red (E 172). The film-coat for the 24 mg of sacubitril and 26 mg of valsartan tablet and the 97 mg of sacubitril and 103 mg of valsartan tablet also contains iron oxide black (E 172). The film-coat for the 49 mg of sacubitril and 51 mg of valsartan tablet contains iron oxide yellow (E 172).

Valsartan structural formula

💬 Information for Patients 103 words ▾

17 PATIENT COUNSELING INFORMATION Advise patients to read the FDA-approved patient labeling (Patient Information). Pregnancy: Advise female patients of childbearing age about the consequences of exposure to ENTRESTO during pregnancy. Discuss treatment options with women planning to become pregnant.

Ask patients to report pregnancies to their physicians as soon as possible [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)] . Angioedema: Advise patients to discontinue use of their previous ACE inhibitor or ARB. Advise patients to allow a 36 hour wash-out period if switching from or to an ACE inhibitor [see Contraindications (4) and Warnings and Precautions (5.2)] .

T2021-08

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
← 71610-0805-34 · Aphena 71610-0807-37 · Aphena →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.