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BREZTRI budesonide, glycopyrrolate, and formoterol fumarate 160 ug; 9 ug; 4.8 ug Aerosol, Metered, 28-count — NDC 00310-4616-28 package photo

BREZTRI budesonide, glycopyrrolate, and formoterol fumarate 160 ug; 9 ug; 4.8 ug Aerosol, Metered, 28-count

by AstraZeneca Pharmaceuticals LP · 28 AEROSOL, METERED in 1 INHALER (0310-4616-28)
NDC 00310-4616-28
🏷️ FDA NDC (as labeled) 0310-4616-28 billing pads the labeler segment with a zero
This package
Contains28-count Pack sizes3 compare ↓
Also priced by: Part D plans $61.59/unit — full pricing hub ↓
Also comes in: 28 aerosols 00310-4616-39 120 aerosols 00310-4616-12
Rx only Brand On market Non-controlled
🗂️ Data synced Sep 17, 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) 0310-4616-28
Product NDC 0310-4616
11-digit billing NDC 00310461628
NCPDP billing unit GM — per gram (weight)
RxCUI 2387326, 2387328, 2387329, 2387331, 2741705, 2741708, 2741710, 2741711
UNII Q3OKS62Q6X, 5ZZ84GCW8B, V92SO9WP2I
Application # NDA212122
SPL Set ID 715433dc-cb2b-43ea-b6df-c5b4177adc6c
Established class (EPC) Corticosteroid; beta2-Adrenergic Agonist
Mechanism of action Corticosteroid Hormone Receptor Agonists; Adrenergic beta2-Agonists
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2020-07-23
Route RESPIRATORY (INHALATION)
Dosage form AEROSOL, METERED
Substance BUDESONIDE; GLYCOPYRROLATE; FORMOTEROL
GPI-14 44209903303220
GPI class Breztri Aerosphere
GCN Seq No 081351
GCN 48435
HICL code 046753
Ingredient (HICL) Budesonide/Glycopyr/Formoterol
HIC1 code B
Therapeutic class — broad (HIC1) Respiratory System
HIC2 code B6
Therapeutic class — intermediate (HIC2) Drugs Affecting The Trachea And Bronchi (Cont3)
HIC3 code B64
Therapeutic class — specific (HIC3) Beta-Adrenergic-Anticholinergic-Glucocort, Inhaled
AHFS code 48:12.04.12
AHFS class Select.beta-2-Adrenergic Agonist(Respir)
FDB label name BREZTRI AEROSPHR 160-9-4.8 MCG
FDB brand name Breztri Aerosphere
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 0310-4616-28 — a 4-4-2 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 labeler segment → 00310-4616-28. 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 Anticholinergic class.

Pharmacologic class Anticholinergic, Cholinergic Muscarinic Antagonist
Drug family (ATC) Antihidrotics
How it works Cholinergic Muscarinic Antagonists, Cholinergic Antagonists
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

LabelerAstraZeneca Pharmaceuticals LP
Application holderASTRAZENECA AB
FDA applicationNDA212122 (NDA)
Labeler code00310
First marketedJul 2020
Product typeHuman Prescription Drug
Portfolio113 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 BREZTRI AEROSPHR 160-9-4.8 MCG Ingredient Budesonide/Glycopyr/Formoterol

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 043IPI2M0K
    A phospholipid derived from natural sources, commonly used as an emulsifier and surfactant in medicines. It helps mix oil and water-based ingredients together and is often used in injectable formulations and lipid-based drug delivery systems.
  • UNII M4I0D6VV5M
    Calcium chloride is a salt compound that acts as a firming agent and source of calcium ions in medications. It's used in formulations to help maintain tablet structure, improve texture, or serve as a buffering agent.
  • UNII DH9E53K1Y8
    A synthetic fluorinated hydrocarbon used primarily as a propellant or aerosol dispersant in pressurized inhaler formulations to help deliver medication to the lungs.

3 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 $61.59 $1,724.56 / 28 aerosols
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
Breztri 160 ug/1; 9 ug/1; 4.8 ugthis 00310-4616-28 AstraZeneca 28 aerosols — — FDA listed —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
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

🏛️
2020
First FDA approval
Jul 2020
📍
2026
Currently FDA-listed
6 years listed
🛡️
2038
Latest patent/protection listed
not a guaranteed launch date
🔒No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Oct 2038. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Jul 23, 2020 RLD RS ⏳ ~12 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 8815258 — method of use (U-2889)
US 8703806 — method of use (U-2889)
US 8808713 — method of use (U-2889)
US 8324266 — method of use (U-2889)
US 9415009 — method of use (U-2889)
US 10716753 — method of use (U-2889)
US 9463161 — method of use (U-2889)
US 8324266 — method of use (U-4503)
US 8703806 — method of use (U-4503)
US 8808713 — method of use (U-4503)
US 8815258 — method of use (U-4503)
US 9415009 — method of use (U-4503)
US 9463161 — method of use (U-4503)
US 10716753 — method of use (U-4503)
US 11331442 — drug product
US 11833292 — drug product
US 11833292 — drug product
US 11331442 — drug product
Exclusivity NS
2020 2022 2024 2026 2028 2030 2032 2034 2036 2038
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 (18)
PatentTypeUse codeExpires
US 8815258 ↗ Method of use U-2889 Mar 17, 2031
US 8703806 ↗ Method of use U-2889 May 28, 2030
US 8808713 ↗ Method of use U-2889 May 28, 2030
US 8324266 ↗ Method of use U-2889 May 28, 2030
US 9415009 ↗ Method of use U-2889 May 28, 2030
US 10716753 ↗ Method of use U-2889 May 28, 2030
US 9463161 ↗ Method of use U-2889 May 28, 2030
US 8324266 ↗ Method of use U-4503 May 28, 2030
US 8703806 ↗ Method of use U-4503 May 28, 2030
US 8808713 ↗ Method of use U-4503 May 28, 2030
US 8815258 ↗ Method of use U-4503 Mar 17, 2031
US 9415009 ↗ Method of use U-4503 May 28, 2030
US 9463161 ↗ Method of use U-4503 May 28, 2030
US 10716753 ↗ Method of use U-4503 May 28, 2030
US 11331442 ↗ Drug product — Oct 5, 2038
US 11833292 ↗ Drug product — Oct 5, 2038
US 11833292 ↗ Drug product — Oct 5, 2038
US 11331442 ↗ Drug product — Oct 5, 2038
FDA exclusivity
CodeWhat it grantsExpires
NSNew StrengthApr 27, 2029
Common questions
Is there a generic version of BREZTRI AEROSPHR 160-9-4.8 MCG?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for BREZTRI AEROSPHR 160-9-4.8 MCG. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Oct 2038 — an estimate, not a guaranteed launch date.
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.

💊 Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
120 aerosols00310-4616-12 155,917 Rx · $104,957,270
28 aerosols00310-4616-39 116 Rx · $38,585
28 aerosols this page00310-4616-28 No Medicaid data
Drug total (last 4 qtrs): 156,033 Rx · 1,752,698 units · $104,995,855 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

🔬 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 BREZTRI (this brand).

Top reported reactions

Dyspnoea2,012
Device Delivery System Issue1,579
Wrong Technique In Device Usage Process1,166
Death1,140
Device Use Issue1,089
Cough839
Device Malfunction822

Age at onset

Child1
Adolescent2
Adult927
Elderly1,783

Reporter sex

10,386 reports
Male · 41%
Female · 59%

Serious outcomes

Death1,280
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 1,838 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Per unit Per pack Marketing startStatus
00310-4616-12 120 AEROSOL, METERED in 1 INHALER (0310-4616-12) $61.28 / g — 2020-07-23 Active
00310-4616-28 You're viewing this 28 AEROSOL, METERED in 1 INHALER (0310-4616-28) — — 2020-07-23 Active
00310-4616-39 28 AEROSOL, METERED in 1 INHALER (0310-4616-39) $61.39 / g — 2020-07-23 Active

This pack shows little to no recent Medicaid volume — the 120 aerosols pack carries most fills. See all packs ↓

Pack size FAQ

What quantity is in NDC 00310-4616-28?
NDC 00310-4616-28 is a 28-count package — 28 aerosol, metered in 1 inhaler.
What is the difference between NDC 00310-4616-28 and NDC 00310-4616-39?
Both are BREZTRI budesonide, glycopyrrolate, and formoterol fumarate 160 ug; 9 ug; 4.8 ug Aerosol, Metered — the drug itself is identical. NDC 00310-4616-28 is the 28-count package, while NDC 00310-4616-39 is the 28 aerosols package.
What NDC number is used to bill for this package of BREZTRI budesonide, glycopyrrolate, and formoterol fumarate 160 ug; 9 ug; 4.8 ug Aerosol, Metered?
Bill NDC 00310-4616-28 — the 11-digit billing format is 00310461628. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

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

🧭 About this NDC listing & data coverage

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

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 0310-4616-28, 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: 00310-4616-28, written without dashes as 00310461628. 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 00310-4616-28, the first segment (00310) is the labeler code FDA assigned to AstraZeneca Pharmaceuticals LP; the middle segment (4616) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (28) 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 AstraZeneca Pharmaceuticals LP. 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 2 other package presentations of this same product, including 28 aerosols (00310-4616-39), 120 aerosols (00310-4616-12). 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?
AstraZeneca Pharmaceuticals LP is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🎯 Indications and Usage 159 words ▾

1 INDICATIONS AND USAGE BREZTRI AEROSPHERE is a combination of budesonide, an inhaled corticosteroid (ICS); glycopyrrolate, an anticholinergic; and formoterol fumarate, a long-acting beta 2 -adrenergic agonist (LABA), indicated for: • the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients. ( 1.1 ) • the maintenance treatment of asthma in adult and pediatric patients 12 years of age and older. ( 1.2 ) Limitations of Use: Not indicated for the relief of acute bronchospasm.

( 1.3 , 5.1 , 5.2 )

1.1Maintenance Treatment of Chronic Obstructive Pulmonary Disease BREZTRI AEROSPHERE is indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients.

1.2Maintenance Treatment of Asthma BREZTRI AEROSPHERE is indicated for the maintenance treatment of asthma in adult and pediatric patients 12 years of age and older.

1.3Limitations of Use BREZTRI AEROSPHERE is not indicated for the relief of acute bronchospasm [see Warnings and Precautions (5.1 , 5.2) ] .

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION • For oral inhalation only. ( 2 ) • Prime BREZTRI AEROSPHERE before first time use and re-prime if not used for more than 7 days. ( 2.1 ) • Maintenance treatment of COPD: 2 inhalations of BREZTRI AEROSPHERE 160 mcg/9 mcg/4.8 mcg twice daily administered by oral inhalation. ( 2.2 ) • Maintenance treatment of asthma: 2 inhalations of BREZTRI AEROSPHERE 160 mcg/18 mcg/4.8 mcg twice daily administered by oral inhalation. ( 2.3 )

2.1Preparation and Administration Information BREZTRI AEROSPHERE should be administered as 2 inhalations twice daily, in the morning and in the evening, by oral inhalation. Do not take more than two inhalations twice daily. After inhalation, rinse mouth with water without swallowing [see Warnings and Precautions (5.4) ] .

Priming Before Use Priming BREZTRI AEROSPHERE is essential to ensure appropriate drug content in each actuation. Prime BREZTRI AEROSPHERE before using for the first time. Prime BREZTRI AEROSPHERE by releasing 4 sprays into the air away from the face, shaking well before each spray.

Re-prime BREZTRI AEROSPHERE if the inhaler has not been used for more than 7 days, is dropped, or after weekly rinsing. Prime BREZTRI AEROSPHERE by releasing 2 sprays into the air away from the face, shaking well before each spray. Dose counter BREZTRI AEROSPHERE canister has an attached dose indicator (also known as puff indicator), which indicates how many inhalations (puffs) remain.

The dose indicator display has a pointer which will move after every actuation. When nearing the end of the usable inhalations, the pointer is in the yellow zone. BREZTRI AEROSPHERE should be discarded when the pointer is at zero in the red zone of the dose indicator.

2.2Recommended Dosage for Maintenance Treatment of Chronic Obstructive Pulmonary Disease The recommended dosage of BREZTRI AEROSPHERE for treatment of COPD is budesonide 320 mcg, glycopyrrolate 18 mcg, and formoterol fumarate 9.6 mcg (administered as 2 inhalations of BREZTRI AEROSPHERE 160 mcg/9 mcg/4.8 mcg [budesonide 160 mcg, glycopyrrolate 9 mcg, and formoterol fumarate 4.8 mcg]) twice daily, in the morning and in the evening, by oral inhalation.

2.3Recommended Dosage for Maintenance Treatment of Asthma The recommended dosage of BREZTRI AEROSPHERE for maintenance treatment of asthma is budesonide 320 mcg, glycopyrrolate 36 mcg, and formoterol fumarate 9.6 mcg (administered as 2 inhalations of BREZTRI AEROSPHERE 160 mcg/18 mcg/4.8 mcg [budesonide 160 mcg, glycopyrrolate 18 mcg, and formoterol fumarate 4.8 mcg]) twice daily, in the morning and in the evening, by oral inhalation.

2.1Preparation and Administration Information BREZTRI AEROSPHERE should be administered as 2 inhalations twice daily, in the morning and in the evening, by oral inhalation. Do not take more than two inhalations twice daily. After inhalation, rinse mouth with water without swallowing [see Warnings and Precautions (5.4) ] .

Priming Before Use Priming BREZTRI AEROSPHERE is essential to ensure appropriate drug content in each actuation. Prime BREZTRI AEROSPHERE before using for the first time. Prime BREZTRI AEROSPHERE by releasing 4 sprays into the air away from the face, shaking well before each spray.

Re-prime BREZTRI AEROSPHERE if the inhaler has not been used for more than 7 days, is dropped, or after weekly rinsing. Prime BREZTRI AEROSPHERE by releasing 2 sprays into the air away from the face, shaking well before each spray. Dose counter BREZTRI AEROSPHERE canister has an attached dose indicator (also known as puff indicator), which indicates how many inhalations (puffs) remain.

The dose indicator display has a pointer which will move after every actuation. When nearing the end of the usable inhalations, the pointer is in the yellow zone. BREZTRI AEROSPHERE should be discarded when the pointer is at zero in the red zone of the dose indicator.

2.2Recommended Dosage for Maintenance Treatment of Chronic Obstructive Pulmonary Disease The recommended dosage o…

💊 Dosage Forms and Strengths 123 words ▾

3 DOSAGE FORMS AND STRENGTHS Inhalation aerosol: a pressurized metered dose inhaler with an attached dose indicator, a yellow plastic actuator, a white mouthpiece, and a grey plastic dust cap that delivers a combination of: • 160 mcg/9 mcg/4.8 mcg (budesonide 160 mcg, glycopyrrolate 9 mcg, and formoterol fumarate 4.8 mcg) per inhalation. • 160 mcg/18 mcg/4.8 mcg (budesonide 160 mcg, glycopyrrolate 18 mcg, and formoterol fumarate 4.8 mcg) per inhalation. Inhalation aerosol: Pressurized metered dose inhaler with a combination of: • 160 mcg/9 mcg/4.8 mcg (budesonide 160 mcg, glycopyrrolate 9 mcg, and formoterol fumarate 4.8 mcg) per inhalation.

( 3 ) • 160 mcg/18 mcg/4.8 mcg (budesonide 160 mcg, glycopyrrolate 18 mcg, and formoterol fumarate 4.8 mcg) per inhalation. ( 3 )

⛔ Contraindications 93 words ▾

4 CONTRAINDICATIONS BREZTRI AEROSPHERE is contraindicated in the following conditions: • Primary treatment of status asthmaticus or other acute episodes of COPD or asthma where intensive measures are required [see Warnings and Precautions (5.2) ] . • Hypersensitivity to budesonide, glycopyrrolate, formoterol, or any of the excipients [see Warnings and Precautions (5.11) and Description (11) ] . • Primary treatment of status asthmaticus or other acute episodes of asthma or COPD requiring intensive measures. ( 4 ) • Hypersensitivity to budesonide, glycopyrrolate, formoterol fumarate, or to any of the excipients.

( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • LABA as monotherapy (without an inhaled-corticosteroid) is associated with an increased risk of serious asthma-related events. ( 5.1 ) • Do not initiate in acutely deteriorating COPD or asthma. Do not use to relieve acute symptoms.

( 5.2 ) • Do not use in combination with an additional therapy containing a LABA because of the risk of overdose. ( 5.3 ) • Candida albicans infection of the mouth and pharynx may occur. Monitor patients periodically.

Advise the patient to rinse his/her mouth with water without swallowing after inhalation to help reduce the risk. ( 5.4 ) • Increased risk of pneumonia in patients with COPD. Monitor patients for signs and symptoms of pneumonia.

( 5.5 ) • Potential worsening of infections (e.g., existing tuberculosis; fungal, bacterial, viral, or parasitic infections; ocular herpes simplex). Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients.

( 5.6 ) • Risk of impaired adrenal function when transferring from systemic corticosteroids. Taper patients slowly from systemic corticosteroids if transferring to BREZTRI AEROSPHERE. ( 5.7 ) • Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage in susceptible individuals.

If such changes occur, consider appropriate therapy. ( 5.8 ) • If paradoxical bronchospasm occurs, discontinue BREZTRI AEROSPHERE and institute alternative therapy. ( 5.10 ) • Use with caution in patients with cardiovascular disorders because of beta-adrenergic stimulation.

( 5.12 ) • Assess for decrease in bone mineral density initially and periodically thereafter. ( 5.13 ) • Monitor growth in pediatric patients. ( 5.14 ) • Glaucoma and cataracts may occur with long-term use of ICS.

Worsening of narrow-angle glaucoma may occur. Use with caution in patients with narrow-angle glaucoma and instruct patients to contact a healthcare provider immediately if symptoms occur. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use BREZTRI AEROSPHERE long term.

( 5.15 ) • Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction and instruct patients to contact a healthcare provider immediately if symptoms occur. ( 5.16 ) • Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis.

( 5.17 ) • Be alert to hypokalemia and hyperglycemia. ( 5.18 )

5.1Serious Asthma-Related Events – Hospitalizations, Intubations, Death Use of long-acting beta 2 -adrenergic agonists (LABA) as monotherapy [without inhaled corticosteroid (ICS)] for asthma is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA monotherapy.

When a LABA is used in fixed‑dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone (see Serious Asthma-Related Events with ICS/LABA) . Available data do not suggest an increased risk of death with use of LABA in patients with COPD. Serious Asthma-Related Events with ICS/LABA Four large, 26-week, randomized, blinded, active-controlled clinical safety trials were conducted to evaluate the risk of serious asthma-related events when LABA were used in fixed-dose combination with ICS compared to ICS alone in patients with asthma.

Three trials included adult and adolescent patients aged ≥12 years: one trial compared budesonide/formoterol to budesonide; one trial compared fluticasone propionate/salmeterol inhalation powder to fluticasone propionate inhalation powder; and one trial compared mometasone furoate/formoterol to m…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling. • Serious asthma-related events – hospitalizations, intubations, death [see Warnings and Precautions (5.1) ] • Oropharyngeal candidiasis infection [see Warnings and Precautions (5.4) ] • Increased risk of pneumonia in COPD [see Warnings and Precautions (5.5) ] • Immunosuppression and risk of infections [see Warnings and Precautions (5.6) ] • Hypercorticism and adrenal suppression [see Warnings and Precautions (5.8) ] • Paradoxical bronchospasm [see Warnings and Precautions (5.10) ] • Hypersensitivity reactions including anaphylaxis [see Contraindications (4) and Warnings and Precautions (5.11) ] • Cardiovascular effects [see Warnings and Precautions (5.12) ] • Reduction in bone mineral density [see Warnings and Precautions (5.13) ] • Growth effects in pediatric patients [see Warnings and Precautions (5.14) ] • Worsening of narrow-angle glaucoma and cataracts [see Warnings and Precautions (5.15) ] • Worsening of urinary retention [see Warnings and Precautions (5.16) ] Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. • COPD: Most common adverse reactions (incidence ≥ 2%) are upper respiratory tract infection, pneumonia, back pain, oral candidiasis, influenza, muscle spasm, urinary tract infection, cough, sinusitis and diarrhea.

( 6.1 ) • Asthma: Most common adverse reactions (incidence ≥ 2%) are nasopharyngitis, pneumonia, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Chronic Obstructive Pulmonary Disease The safety of BREZTRI AEROSPHERE in COPD is based on the safety data from one 52-week exacerbation trial (ETHOS) and one 24-week lung function trial with a 28-week safety extension study, resulting in up to 52 weeks of treatment (KRONOS). In ETHOS and KRONOS, a total of 2783 subjects have received at least 1 dose of BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg [see Clinical Studies (14.1) ]. In ETHOS and KRONOS, subjects received one of the following treatments: BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg, glycopyrrolate and formoterol fumarate (GFF MDI 18 mcg/9.6 mcg), or budesonide and formoterol fumarate (BFF MDI 320 mcg/9.6 mcg).

Each treatment was administered twice daily. In ETHOS, a 52-week, randomized, double-blind clinical trial, a total of 2144 subjects with COPD received at least 1 dose of BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg (mean age: 64.7 years, 84.9% Caucasian, 59.7% male across all treatments) [see Clinical Studies (14.1) ] . In KRONOS, a 24-week, randomized, double-blind clinical trial, with a 28-week long-term safety extension resulting in up to 52 weeks of treatment, a total of 639 subjects received at least 1 dose of BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg (mean age: 65.2 years, 50.1% Caucasian, 71.2% male across all treatments) [see Clinical Studies (14.1) ] .

The incidence of adverse reactions from the 52-week trial (ETHOS) is presented in Table 2 for subjects treated with BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg, GFF MDI 18 mcg/9.6 mcg, or BFF MDI 320 mcg/9.6 mcg. Table 2: Adverse Reactions Occurring at an Incidence of ≥ 2% of Subjects with COPD and More Common in BREZTRI AEROSPHERE Compared to GFF MDI and/or BFF MDI (ETHOS) Adverse Reaction BREZTRI AEROSPHERE BREZTRI AEROSPHERE = budesonide/glycopyrrolate/formoterol fumarate 320 mcg/18 mcg/9.6 mcg; GFF MDI = glycopyrrolate/formoterol fumarate 18 mcg/9.6 mcg; BFF MDI = budesonide/formoterol fumarate 320 mcg/9.6 mcg; all treatments were administered twice daily.

320 mcg/18 mcg/9.6 mcg N=2144 (%) GFF MDI 18 mcg/9.6 mcg N=2125 (%) BFF MDI 320 mcg/9.6 mcg N=2136 (%) Upper Respiratory Tract Infec…

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS No formal drug interaction studies have been performed with BREZTRI AEROSPHERE. • Strong cytochrome P450 3A4 inhibitors (e.g. ritonavir): Use with caution. May cause systemic corticosteroid effects. ( 7.1 ) • Other adrenergic drugs may potentiate effect: Use with caution.

( 7.2 ) • Diuretics, xanthine derivatives or steroids may potentiate hypokalemia or ECG changes. Use with caution. ( 7.3 , 7.4 ) • Monoamine oxidase inhibitors and tricyclic antidepressants: Use with extreme caution.

May potentiate effect of formoterol fumarate on cardiovascular system. ( 7.5 ) • Beta-blockers: Use with caution. May block bronchodilatory effects of beta-agonists and produce severe bronchospasm.

( 7.6 ) • Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administration of BREZTRI AEROSPHERE with other anticholinergic-containing drugs. ( 7.7 )

7.1Inhibitors of Cytochrome P450 3A4 The main route of metabolism of corticosteroids, including budesonide, a component of BREZTRI AEROSPHERE, is via cytochrome P450 isoenzyme 3A4 (CYP3A4). After oral administration of ketoconazole, a strong inhibitor of CYP3A4, the mean plasma concentration of orally administered budesonide increased. Concomitant administration of a CYP3A4 inhibitor may inhibit the metabolism of, and increase the systemic exposure to, budesonide.

Caution should be exercised when considering the coadministration of BREZTRI AEROSPHERE with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Warnings and Precautions (5.9) ] .

7.2Adrenergic Drugs If additional adrenergic drugs are to be administered by any route, they should be used with caution because the sympathetic effects of formoterol, a component of BREZTRI AEROSPHERE, may be potentiated [see Warnings and Precautions (5.3) ] .

7.3Xanthine Derivatives, Steroids, or Diuretics Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate the hypokalemic effect of beta 2 -adrenergic agonists such as formoterol, a component of BREZTRI AEROSPHERE.

7.4Non-Potassium Sparing Diuretics The hypokalemia and/or ECG changes that may result from the administration of non-potassium sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta 2 -agonists, especially when the recommended dose of the beta 2 -agonist is exceeded.

7.5Monoamine Oxidase Inhibitors, Tricyclic Antidepressants, QTc Prolonging Drugs BREZTRI AEROSPHERE, as with other beta 2 -agonists, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants or other drugs known to prolong the QTc interval because the action of adrenergic agonists on the cardiovascular system may be potentiated by these agents. Drugs that are known to prolong the QTc interval may be associated with an increased risk of ventricular arrhythmias.

7.6Beta-adrenergic Receptor Blocking Agents Beta-adrenergic receptor antagonists (beta-blockers) and BREZTRI AEROSPHERE may interfere with the effect of each other when administered concurrently. Beta-blockers not only block the therapeutic effects of beta 2 -agonists, but may produce severe bronchospasm in COPD and asthma patients. Therefore, patients with COPD or asthma should not normally be treated with beta-blockers.

However, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-blockers in patients with COPD or asthma. In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.

7.7Anticholinergics There is a potential for an additive interaction with concomitantly used anticholinergic medications. Therefore, avoid coadministration of BREZTRI AEROSPHERE with other anticholinergic-containing…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Hepatic impairment: Budesonide and formoterol fumarate systemic exposure may increase in patients with severe hepatic impairment. Monitor patients for signs of increased drug exposure. ( 8.6 , 12.3 ) Renal impairment: In patients with severe renal impairment, use should be considered only if the potential benefit of the treatment outweighs the risk ( 8.7 ).

8.1Pregnancy Risk Summary There are no adequate and well-controlled studies with BREZTRI AEROSPHERE or with two of its individual components, glycopyrrolate or formoterol fumarate, in pregnant women to inform a drug-associated risk; however, studies are available for the other component, budesonide. In animal reproduction studies, budesonide alone, administered by the subcutaneous route, caused structural abnormalities, was embryocidal, and reduced fetal weights in rats and rabbits at 0.3 and 0.75 times maximum recommended human daily inhaled dose (MRHDID), respectively, but these effects were not seen in rats that received inhaled doses up to 4 times the MRHDID.

Studies of pregnant women who received inhaled budesonide alone during pregnancy have not shown increased risk of abnormalities. Experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans. Formoterol fumarate alone, administered by the oral route in rats and rabbits, caused structural abnormalities at 1500 and 61,000 times the MRHDID, respectively.

Formoterol fumarate was also embryocidal, increased pup loss at birth and during lactation, and decreased pup weight in rats at 110 times the MRHDID. These adverse effects generally occurred at large multiples of the MRHDID when formoterol fumarate was administered by the oral route to achieve high systemic exposures. No structural abnormalities, embryocidal, or developmental effects were seen in rats that received inhalation doses up to 350 times the MRHDID.

Glycopyrrolate alone, administered by the subcutaneous route in rats and rabbits, did not cause structural abnormalities or affect fetal survival at exposures approximately 1350 and 2700 times from MRHDID, respectively. Glycopyrrolate had no effects on the physical, functional, and behavioral development of rat pups with exposures up to 1350 times the MRHDID. 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 Disease-Associated Maternal and/or Embryo/Fetal risk: In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control.

Labor or Delivery: There are no well-controlled human trials that have investigated the effects of BREZTRI AEROSPHERE on preterm labor or labor at term. Because of the potential for beta-agonist interference with uterine contractility, use of BREZTRI AEROSPHERE during labor should be restricted to those patients in whom the benefits clearly outweigh the risks. Data Human Data Studies of pregnant women have not shown that inhaled budesonide increases the risk of abnormalities when administered during pregnancy.

The results from a large population-based prospective cohort epidemiological study reviewing data from three Swedish registries covering approximately 99% of the pregnancies from 1995-1997 (i.e., Swedish Medical Birth Registry; Registry of Congenital Malformations; Child Cardiology Registry) indicate no increased risk for congenital malformations from the use of inhaled budesonide during early pregnancy. Congenital malformations were stud…

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary There are no adequate and well-controlled studies with BREZTRI AEROSPHERE or with two of its individual components, glycopyrrolate or formoterol fumarate, in pregnant women to inform a drug-associated risk; however, studies are available for the other component, budesonide. In animal reproduction studies, budesonide alone, administered by the subcutaneous route, caused structural abnormalities, was embryocidal, and reduced fetal weights in rats and rabbits at 0.3 and 0.75 times maximum recommended human daily inhaled dose (MRHDID), respectively, but these effects were not seen in rats that received inhaled doses up to 4 times the MRHDID.

Studies of pregnant women who received inhaled budesonide alone during pregnancy have not shown increased risk of abnormalities. Experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans. Formoterol fumarate alone, administered by the oral route in rats and rabbits, caused structural abnormalities at 1500 and 61,000 times the MRHDID, respectively.

Formoterol fumarate was also embryocidal, increased pup loss at birth and during lactation, and decreased pup weight in rats at 110 times the MRHDID. These adverse effects generally occurred at large multiples of the MRHDID when formoterol fumarate was administered by the oral route to achieve high systemic exposures. No structural abnormalities, embryocidal, or developmental effects were seen in rats that received inhalation doses up to 350 times the MRHDID.

Glycopyrrolate alone, administered by the subcutaneous route in rats and rabbits, did not cause structural abnormalities or affect fetal survival at exposures approximately 1350 and 2700 times from MRHDID, respectively. Glycopyrrolate had no effects on the physical, functional, and behavioral development of rat pups with exposures up to 1350 times the MRHDID. 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 Disease-Associated Maternal and/or Embryo/Fetal risk: In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control.

Labor or Delivery: There are no well-controlled human trials that have investigated the effects of BREZTRI AEROSPHERE on preterm labor or labor at term. Because of the potential for beta-agonist interference with uterine contractility, use of BREZTRI AEROSPHERE during labor should be restricted to those patients in whom the benefits clearly outweigh the risks. Data Human Data Studies of pregnant women have not shown that inhaled budesonide increases the risk of abnormalities when administered during pregnancy.

The results from a large population-based prospective cohort epidemiological study reviewing data from three Swedish registries covering approximately 99% of the pregnancies from 1995-1997 (i.e., Swedish Medical Birth Registry; Registry of Congenital Malformations; Child Cardiology Registry) indicate no increased risk for congenital malformations from the use of inhaled budesonide during early pregnancy. Congenital malformations were studied in 2014 infants born to mothers reporting the use of inhaled budesonide for asthma in early pregnancy (usually 10-12 weeks after the last menstrual period), the period when most major organ malformations occur.

The rate of recorded congenital malformations was similar compared to the general population rate (3.8% vs. 3.5%, respectively). In addition, after exposure to inhaled budeson…

🧒 Pediatric Use 183 words ▾

8.4Pediatric Use The safety and effectiveness of BREZTRI AEROSPHERE have been established for the maintenance treatment of asthma in pediatric patients 12 years of age and older. Use of BREZTRI AEROSPHERE for this indication is supported by evidence from two adequate and well-controlled studies (KALOS and LOGOS) in adults and pediatric patients 12 years of age and older, in which 30 pediatric patients 12 years to less than 18 years of age were treated with BREZTRI AEROSPHERE 320 mcg/36 mcg/9.6 mcg twice daily by oral inhalation [see Adverse Reactions (6.1) and Clinical Studies (14.2) ] .

The safety and effectiveness of BREZTRI AEROSPHERE in pediatric patients less than 12 years of age have not been established. Controlled clinical studies have shown that ICS agents, including budesonide, one of the components of BREZTRI AEROSPHERE, may cause a reduction in growth velocity in pediatric patients. The effects of long-term treatment of pediatric patients with ICS on final adult height are not known.

The potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained [see Warnings and Precautions (5.14) ] .

🧓 Geriatric Use 135 words ▾

8.5Geriatric Use Based on available data, no adjustment of the dosage of BREZTRI AEROSPHERE in geriatric patients is necessary, but greater sensitivity in some older individuals cannot be ruled out. In the COPD trials, ETHOS and KRONOS, 1100 subjects and 343 subjects, respectively, aged 65 years and older were administered BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg twice daily [see Clinical Studies (14.1) ] . In both trials, no overall differences in safety or effectiveness were observed between these subjects and younger subjects.

In the asthma trials, KALOS and LOGOS, 141 subjects and 124 subjects, respectively, aged 65 years and older were administered BREZTRI AEROSPHERE 320 mcg/36 mcg/9.6 mcg twice daily [see Clinical Studies (14.2) ] . In both trials, no overall differences in safety or effectiveness were observed between these subjects and younger subjects.

🆘 Overdosage 201 words ▾

10 OVERDOSAGE BREZTRI AEROSPHERE contains budesonide, glycopyrrolate, and formoterol fumarate; therefore, the risks associated with overdosage for the individual components described below apply to BREZTRI AEROSPHERE. Treatment of overdosage consists of discontinuation of BREZTRI AEROSPHERE together with institution of appropriate symptomatic and/or supportive therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm.

Cardiac monitoring is recommended in case of overdosage. Budesonide If used at excessive doses for prolonged periods, systemic corticosteroid effects, such as hypercorticism may occur [see Warnings and Precautions (5.8) ] . Glycopyrrolate High doses of glycopyrrolate, a component of BREZTRI AEROSPHERE, may lead to anticholinergic signs and symptoms such as nausea, vomiting, dizziness, lightheadedness, blurred vision, increased intraocular pressure (causing pain, vision disturbances or reddening of the eye), obstipation, or difficulties in voiding.

Formoterol Fumarate An overdose of formoterol fumarate would likely lead to an exaggeration of effects that are typical for beta 2 -agonists: seizures, angina, hypertension, hypotension, tachycardia, atrial and ventricular tachyarrhythmias, nervousness, headache, tremor, palpitations, muscle cramps, nausea, dizziness, sleep disturbances, metabolic acidosis, hyperglycemia, hypokalemia. As with all sympathomimetic medications, cardiac arrest, and even death may be associated with overdosage of formoterol fumarate.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action BREZTRI AEROSPHERE BREZTRI AEROSPHERE contains budesonide, glycopyrrolate, and formoterol fumarate. The mechanism of action described below for the individual components applies to BREZTRI AEROSPHERE. These drugs represent three different classes of medications (a synthetic corticosteroid, an anticholinergic, and a long-acting selective beta 2 -adrenoceptor agonist) that have different effects on clinical physiology and inflammatory indices of COPD and asthma.

Budesonide Budesonide is an anti-inflammatory corticosteroid that exhibits potent glucocorticoid activity and weak mineralocorticoid activity. In standard in vitro and animal models, budesonide has approximately a 200-fold higher affinity for the glucocorticoid receptor and a 1000-fold higher topical anti-inflammatory potency than cortisol (rat croton oil ear edema assay). As a measure of systemic activity, budesonide is 40 times more potent than cortisol when administered subcutaneously and 25 times more potent when administered orally in the rat thymus involution assay.

In glucocorticoid receptor affinity studies, the 22R epimer of budesonide was two times as active as the 22S epimer. In vitro studies indicated that the two forms of budesonide do not interconvert. Inflammation is an important component in the pathogenesis of COPD and asthma.

Corticosteroids have a wide range of inhibitory activities against multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic and non-allergic-mediated inflammation. These anti-inflammatory actions of corticosteroids may contribute to their efficacy. Glycopyrrolate Glycopyrrolate is a long-acting antimuscarinic agent which is often referred to as an anticholinergic.

It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of the M3 receptor at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations.

In preclinical in vitro as well as in vivo studies, prevention of methylcholine and acetylcholine-induced bronchoconstrictive effects was dose-dependent and lasted more than 12 hours. The clinical relevance of these findings is unknown. The bronchodilation following inhalation of glycopyrrolate is predominantly a site-specific effect.

Formoterol Fumarate Formoterol fumarate is a long-acting selective beta 2 -adrenergic agonist (beta 2 -agonist) with a rapid onset of action. Inhaled formoterol fumarate acts locally in the lung as a bronchodilator. In vitro studies have shown that formoterol has more than 200-fold greater agonist activity at beta 2 -receptors than at beta 1 -receptors.

The in vitro binding selectivity to beta 2 - over beta 1 -adrenoceptors is higher for formoterol than for albuterol (5 times), whereas salmeterol has a higher (3 times) beta 2 -selectivity ratio than formoterol. Although beta 2 -receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta 1 -receptors are the predominant receptors in the heart, there are also beta 2 -receptors in the human heart comprising 10% to 50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta 2 -agonists may have cardiac effects.

The pharmacologic effects of beta 2 -adrenoceptor agonist drugs, including formoterol fumarate, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypers…

🧬 Mechanism of Action ~3 min read ▾

12.1Mechanism of Action BREZTRI AEROSPHERE BREZTRI AEROSPHERE contains budesonide, glycopyrrolate, and formoterol fumarate. The mechanism of action described below for the individual components applies to BREZTRI AEROSPHERE. These drugs represent three different classes of medications (a synthetic corticosteroid, an anticholinergic, and a long-acting selective beta 2 -adrenoceptor agonist) that have different effects on clinical physiology and inflammatory indices of COPD and asthma.

Budesonide Budesonide is an anti-inflammatory corticosteroid that exhibits potent glucocorticoid activity and weak mineralocorticoid activity. In standard in vitro and animal models, budesonide has approximately a 200-fold higher affinity for the glucocorticoid receptor and a 1000-fold higher topical anti-inflammatory potency than cortisol (rat croton oil ear edema assay). As a measure of systemic activity, budesonide is 40 times more potent than cortisol when administered subcutaneously and 25 times more potent when administered orally in the rat thymus involution assay.

In glucocorticoid receptor affinity studies, the 22R epimer of budesonide was two times as active as the 22S epimer. In vitro studies indicated that the two forms of budesonide do not interconvert. Inflammation is an important component in the pathogenesis of COPD and asthma.

Corticosteroids have a wide range of inhibitory activities against multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic and non-allergic-mediated inflammation. These anti-inflammatory actions of corticosteroids may contribute to their efficacy. Glycopyrrolate Glycopyrrolate is a long-acting antimuscarinic agent which is often referred to as an anticholinergic.

It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of the M3 receptor at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations.

In preclinical in vitro as well as in vivo studies, prevention of methylcholine and acetylcholine-induced bronchoconstrictive effects was dose-dependent and lasted more than 12 hours. The clinical relevance of these findings is unknown. The bronchodilation following inhalation of glycopyrrolate is predominantly a site-specific effect.

Formoterol Fumarate Formoterol fumarate is a long-acting selective beta 2 -adrenergic agonist (beta 2 -agonist) with a rapid onset of action. Inhaled formoterol fumarate acts locally in the lung as a bronchodilator. In vitro studies have shown that formoterol has more than 200-fold greater agonist activity at beta 2 -receptors than at beta 1 -receptors.

The in vitro binding selectivity to beta 2 - over beta 1 -adrenoceptors is higher for formoterol than for albuterol (5 times), whereas salmeterol has a higher (3 times) beta 2 -selectivity ratio than formoterol. Although beta 2 -receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta 1 -receptors are the predominant receptors in the heart, there are also beta 2 -receptors in the human heart comprising 10% to 50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta 2 -agonists may have cardiac effects.

The pharmacologic effects of beta 2 -adrenoceptor agonist drugs, including formoterol fumarate, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, es…

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

16 HOW SUPPLIED/STORAGE AND HANDLING BREZTRI AEROSPHERE Inhalation Aerosol: • is supplied as a pressurized aluminum canister with an attached dose indicator, a yellow plastic actuator, a white mouthpiece, and a grey plastic dust cap. • each canister of BREZTRI AEROSPHERE is packaged in a foil laminate pouch with a desiccant sachet and is placed into a carton. • each carton contains one canister and Patient Information. BREZTRI AEROSPHERE is available as presented in Table 7. Table 7: Package Information for BREZTRI AEROSPHERE Strength (budesonide/glycopyrrolate/formoterol fumarate) Number of Inhalations per Canister Net Fill Weight (g) NDC 160 mcg/9 mcg/4.8 mcg 120 10.7 0310-4616-12 160 mcg/9 mcg/4.8 mcg (institutional pack) 28 5.9 0310-4616-39 160 mcg/18 mcg/4.8 mcg 120 10.7 0310-6616-01 160 mcg/18 mcg/4.8 mcg (institutional pack) 28 5.9 0310-6616-39 The BREZTRI AEROSPHERE canister should only be used with the BREZTRI AEROSPHERE actuator, and the BREZTRI AEROSPHERE actuator should not be used with any other inhalation drug product.

Dose Counter The correct amount of medication in each inhalation cannot be assured after the label number of inhalations from the canister have been used, when the dose indicator pointer is at zero in the red zone, even though the canister may not feel completely empty. BREZTRI AEROSPHERE should be discarded when the dose indicator pointer is at zero in the red zone or 3 months (for the 120-inhalation canister) or 3 weeks (for the 28-inhalation canister) after removal from the foil pouch, whichever comes first. Never immerse the canister into water to determine the amount remaining in the canister (“float test”).

Storage Store at controlled room temperature 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP]. Keep in a dry place away from heat and sunlight. For best results, the canister should be at room temperature before use.

Shake well before using. Keep out of reach of children. Contents under pressure.

Do not puncture. Do not use or store near heat or open flames. Exposure to temperatures above 120°F (49°C) may cause bursting.

Never throw canister into fire or incinerator. Avoid spraying in eyes.

📋 Description ~2 min read ▾

11 DESCRIPTION BREZTRI AEROSPHERE (budesonide, glycopyrrolate and formoterol fumarate) Inhalation Aerosol is a pressurized metered-dose inhaler that delivers a combination of micronized budesonide [an inhaled corticosteroid (ICS)], micronized glycopyrrolate (an anticholinergic), and micronized formoterol fumarate [an inhaled long-acting beta 2 -adrenergic agonist (a LABA)] for oral inhalation. Budesonide is a corticosteroid with the following chemical name: (RS)-11β, 16α, 17,21-Tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with butyraldehyde.

Budesonide is a white to off-white, powder which is practically insoluble in water. The molecular formula is C 25 H 34 O 6 and the molecular weight is 430.54. The structural formula is as follows: Budesonide contains nine chiral centers and is a mixture of the two epimers (22R and 22S).

Glycopyrrolate is a quaternary ammonium salt with the following chemical name: (RS)-[3-(SR)-Hydroxy-1,1-dimethylpyrrolidinium bromide] α-cyclopentylmandelate. Glycopyrrolate is a powder that is freely soluble in water. The molecular formula is C 19 H 28 BrNO 3 , and the molecular weight is 398.33 g/mol.

The structural formula is as follows: Glycopyrrolate contains two chiral centers and is a racemate of a 1:1 mixture of the R,S and S,R diastereomers. The active moiety, glycopyrronium, is the positively charged ion of glycopyrrolate. Formoterol fumarate has the chemical name N-[2-Hydroxy-5-[(1RS)-1-hydroxy-2-[[(1RS)-2-(4-methoxyphenyl)-1-methylethyl]-amino] ethyl]phenyl] formamide, (E)-2-butenedioate dihydrate.

Formoterol fumarate is a powder that is slightly soluble in water. The molecular formula is (C 19 H 24 N 2 O 4 ) 2 ·C 4 H 4 O 4 ·2H 2 O and the molecular weight is 840.91 g/mol. The structural formula is as follows: Formoterol fumarate contains two chiral centers and consists of a single enantiomeric pair (a racemate of R,R and S,S).

BREZTRI AEROSPHERE is formulated as a hydrofluoroalkane (HFA 134a) propelled pressurized metered dose inhaler containing 28 or 120 inhalations. The canister has an attached dose indicator and is supplied with a yellow plastic actuator and white mouthpiece with a grey dust cap. After priming, each actuation of the inhaler meters 170 mcg of budesonide, 9.6 or 19.1 mcg of glycopyrrolate (equivalent to 7.7 or 15.3 mcg of glycopyrronium), and 5.1 mcg of formoterol fumarate (equivalent to 4.4 mcg of formoterol) from the valve which delivers 160 mcg of budesonide, 9.0 or 18 mcg of glycopyrrolate (equivalent to 7.2 or 14.4 mcg of glycopyrronium), and 4.8 mcg of formoterol fumarate (equivalent to 4.1 mcg of formoterol) from the actuator.

The actual amount of drug delivered to the lung may depend on patient factors, such as the coordination between actuation of the device and inspiration through the delivery system. BREZTRI AEROSPHERE also contains porous particles that form a co-suspension with the drug crystals. The porous particles are comprised of the phospholipid, 1,2-distearoyl- sn -glycero-3-phosphocholine (DSPC), and calcium chloride.

Porous particles and HFA 134a are excipients in the formulation. Budesonide Chemical Structure Glycopyrrolate Chemical Structure Formoterol Fumarate Chemical Structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Serious Asthma-Related Events Inform patients with asthma that LABA when used alone increases the risk of asthma-related hospitalization or asthma‑related death. Available data show that when ICS and LABA are used together, such as with BREZTRI AEROSPHERE, there is not a significant increase in the risk of these events [see Warnings and Precautions (5.1) ] .

Not for Treatment of Acute Symptoms Inform patients that BREZTRI AEROSPHERE is not meant to relieve acute symptoms of COPD or asthma and extra doses should not be used for that purpose. Advise patients to treat acute symptoms with an inhaled, short-acting beta 2 -agonist/corticosteroid for asthma or, an inhaled, short-acting beta 2 -agonist for asthma or COPD [see Warnings and Precautions (5.2) ] . Provide patients with such medication and instruct them on how it should be used.

Instruct patients to seek medical attention immediately if they experience any of the following: • Decreasing effectiveness of inhaled, short-acting beta 2 -agonist/corticosteroid combination, or inhaled, short-acting beta 2 -agonists. • Need for more inhalations than usual of inhaled, short-acting beta 2 -agonist/corticosteroid combination, or inhaled, short-acting beta 2 -agonists. • Significant decrease in lung function as outlined by the health care practitioner. Tell patients they should not stop therapy with BREZTRI AEROSPHERE without physician guidance since symptoms may recur after discontinuation [see Warnings and Precautions (5.2) ].

Do Not Use Additional Long-acting Beta 2 -agonists or Anticholinergics Instruct patients not to use other LABA or anticholinergic medicines [see Warnings and Precautions (5.3) ]. Oropharyngeal Candidiasis Inform patients that localized infections with Candida albicans occurred in the mouth and pharynx in some patients. If oropharyngeal candidiasis develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing therapy with BREZTRI AEROSPHERE, but at times therapy with BREZTRI AEROSPHERE may need to be temporarily interrupted under close medical supervision.

Advise patients to rinse the mouth with water without swallowing after inhalation to help reduce the risk of thrush [see Warnings and Precautions (5.4) ]. Pneumonia Patients with COPD have a higher risk of pneumonia; instruct them to contact their healthcare providers if they develop symptoms of pneumonia [see Warnings and Precautions (5.5) ]. Immunosuppression and Risk of Infections Warn patients who are on immunosuppressant doses of corticosteroids to avoid exposure to chickenpox or measles and, if exposed, to consult their physicians without delay.

Inform patients of potential worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infections, or ocular herpes simplex [see Warnings and Precautions (5.6) ] . Hypercorticism and Adrenal Suppression Advise patients that BREZTRI AEROSPHERE may cause systemic corticosteroid effects of hypercorticism and adrenal suppression. Additionally, inform patients that deaths due to adrenal insufficiency have occurred during and after transfer from systemic corticosteroids.

Patients should taper slowly from systemic corticosteroids if transferring to BREZTRI AEROSPHERE [see Warnings and Precautions (5.8) ]. Paradoxical Bronchospasm As with other inhaled medicines, BREZTRI AEROSPHERE can cause paradoxical bronchospasm. If paradoxical bronchospasm occurs, instruct patients to discontinue BREZTRI AEROSPHERE and contact their healthcare provider right away [see Warnings and Precautions (5.10) ].

Hypersensitivity Reactions, including Anaphylaxis Advise patients that hypersensitivity reactions (e.g., anaphylaxis, angioedema, rash, urticaria) may occur after administration of BREZTRI AEROSPHERE. Instruct patients to discontinue BREZTRI AEROSPHERE if such reactio…

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