Home › NDC Lookup › Ingredients › Beclomethasone Dipropionate/Formoterol F... › 10122-0590-02
Trimbow beclomethasone dipropionate/formoterol fumarate/glycopyrrolate 172 ug; 4.9 ug; 10.6 ug Aerosol, Metered — NDC 10122-0590-02 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Trimbow beclomethasone dipropionate/formoterol fumarate/glycopyrrolate 172 ug; 4.9 ug; 10.6 ug Aerosol, Metered — NDC 10122-590-02 (Billing 10122-0590-02)

by Chiesi USA, Inc. · 1 CANISTER in 1 CARTON / 120 AEROSOL, METERED in 1 CANISTER

This is a package of Trimbow beclomethasone dipropionate/formoterol fumarate/glycopyrrolate 172 ug; 4.9 ug; 10.6 ug Aerosol, Metered from Chiesi USA, Inc., no longer marketed (first marketed May 2026), no longer in the FDA NDC Directory. It is this product's only package size.

NDC 10122-0590-02
🏷️ FDA NDC (as labeled) 10122-590-02 billing pads the product segment with a zero
Rx only Brand Discontinued Non-controlled ⚠ Discontinued by firm ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 8, 2026 · this listing last changed Sep 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

NDC database record

One package, one record: these facts belong to NDC 10122-590-02 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
10122 labeler · 590 product · 02 package
Package marketed since
May 14, 2026
Sample package
Yes — professional sample, not for sale
Listing certified through
Dec 31, 2027
Barcode (UPC-A, from the NDC)
3 1012259002 1
FDA record last changed
Sep 24, 2026
⚠️
Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. The listing was last certified through Sep 2026. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 10122-590-02
Product NDC 10122-590
11-digit billing NDC 10122059002
RxCUI 2747295, 2747302, 2747312, 2747315
UNII 5B307S63B2, W34SHF8J2K, V92SO9WP2I
Application # NDA219622
SPL Set ID 4e13e70f-f550-4603-bbfb-346f80df3c4f
Established class (EPC) Anticholinergic; Cholinergic Muscarinic Antagonist; Corticosteroid; beta2-Adrenergi
Mechanism of action Adrenergic beta2-Agonists; Cholinergic Antagonists; Cholinergic Muscarinic Antagonists; Corticosteroid Hormone Receptor Agonists
DEA schedule Non-controlled
Marketing category NDA
Marketing status Discontinued
FDA listing status Discontinued by firm (certified through Sep 2026)
Marketing start 2026-05-14
Route RESPIRATORY (INHALATION)
Dosage form AEROSOL, METERED
Substance BECLOMETHASONE DIPROPIONATE; FORMOTEROL FUMARATE; GLYCOPYRROLATE
Quick answers
  • RxCUI (RxNorm): 2747295
Why two NDCs? The FDA registers this code as 10122-590-02 — 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 → 10122-0590-02. 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 Corticosteroid class.

Pharmacologic class Corticosteroid
Drug family (ATC) Corticosteroids acting locally, Corticosteroids, potent (group III), Corticosteroids
How it works Corticosteroid Hormone Receptor Agonists
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

📗 Our plain-language guide HelloPharmacist
  • It is a daily maintenance inhaler for asthma in adults 18 and older. It helps keep your airways calm and open over time. It is not meant to stop a sudden asthma attack.
  • No. Use a fast-acting rescue inhaler for sudden symptoms. If you are needing it more often, call your doctor, because your asthma may be getting worse.
  • You take 2 puffs twice a day, morning and evening. Prime a new inhaler first and again if you have not used it in 30 days. Rinse your mouth with water and spit it out afterward to...
  • Common ones include bronchitis, a hoarse voice, higher blood pressure, colds or flu, back pain and muscle spasms. Call your doctor if you get white patches in your mouth, eye pain...
📖 Read our full Beclomethasone / Formoterol / Glycopyrrolate guide →

Supplement & herbal interactions

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

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
10122-0590-02 You're viewing this Main listing 1 CANISTER in 1 CARTON / 120 AEROSOL, METERED in 1 CANISTER Sample 2026-05-14 — Discontinued by firm

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Trimbow 172 ug/1; 4.9 ug/1; 10.6 ug 10122-0121-02 Chiesi 1 canister — — Discontinued —
Trimbow 172 ug/1; 4.9 ug/1; 10.6 ugthis 10122-0590-02 Chiesi 1 canister — — Discontinued —
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

🏛️
2026
First FDA approval
May 2026
📍
2026
Currently FDA-listed
listed with the FDA
🛡️
2034
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 Dec 2034. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved May 14, 2026 RLD RS ⏳ ~8.2 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 12357568 — method of use (U-4538)
US 12357568 — method of use (U-4538)
US 11590074 — method of use (U-4538)
US 11590074 — method of use (U-4538)
US 10617638 — method of use (U-4538)
US 10617638 — method of use (U-4538)
US 10159645 — method of use (U-4538)
US 10159645 — method of use (U-4538)
US 10806701 — drug product
US 11389401 — drug product
US 11389401 — drug product
US 10806701 — drug product
Exclusivity NP
Exclusivity NP
2026 2028 2030 2032 2034
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 (12)
PatentTypeUse codeExpires
US 12357568 ↗ Method of use U-4538 Dec 23, 2030
US 12357568 ↗ Method of use U-4538 Dec 23, 2030
US 11590074 ↗ Method of use U-4538 Dec 23, 2030
US 11590074 ↗ Method of use U-4538 Dec 23, 2030
US 10617638 ↗ Method of use U-4538 Dec 23, 2034
US 10617638 ↗ Method of use U-4538 Dec 23, 2034
US 10159645 ↗ Method of use U-4538 Dec 23, 2030
US 10159645 ↗ Method of use U-4538 Dec 23, 2030
US 10806701 ↗ Drug product — Dec 23, 2030
US 11389401 ↗ Drug product — Dec 23, 2030
US 11389401 ↗ Drug product — Dec 23, 2030
US 10806701 ↗ Drug product — Dec 23, 2030
FDA exclusivity
CodeWhat it grantsExpires
NPNew ProductMay 14, 2029
NPNew ProductMay 14, 2029
Common questions
Is there a generic version of this drug?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for this drug. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Dec 2034 — 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.

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.

🧪 Avoiding an ingredient? See Beclomethasone / Formoterol / Glycopyrrolate inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerChiesi USA, Inc.
Application holderCHIESI FARMACEUTICI SPA
FDA applicationNDA219622 (NDA)
Labeler code10122
First marketedMay 2026
Product typeHuman Prescription Drug
Portfolio25 products on file

More NDCs from Chiesi USA, Inc. labeler code 10122

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📖 Instructions for Use 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 102 words ▾

1 INDICATIONS AND USAGE TRIMBOW is indicated for the maintenance treatment of asthma in adult patients aged 18 years and older. Limitati ons of Use TRIMBOW is NOT indicated for relief of acute bronchospasm [see Warnings and Precautions ( 5.2 ) ] . TRIMBOW is a combination of beclomethasone dipropionate (BDP) (an inhaled corticosteroid [ICS]), formoterol fumarate (FF) (a long-acting beta 2 -adrenergic agonist [LABA]), and glycopyrrolate (G) (an anticholinergic) indicated for the maintenance treatment of asthma in adult patients aged 18 years and older.

( 1 ) Limitation s of Use Not indicated for relief of acute bronchospasm. ( 1 )

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND ADMINISTRATION For oral inhalation only. ( 2.1 ) Prime TRIMBOW before first time use and re-prime if not used for 30 days or longer. ( 2.1 ) Recommended Dosage : TRIMBOW 172 mcg/9.8 mcg/21.2 mcg (administered as 2 actuations of beclomethasone dipropionate 86 mcg, formoterol fumarate 4.9 mcg, and glycopyrrolate 10.6 mcg) twice daily by oral inhalation or TRIMBOW 344 mcg/9.8 mcg/21.2 mcg (administered as 2 actuations of beclomethasone dipropionate 172 mcg, formoterol fumarate 4.9 mcg, and glycopyrrolate 10.6 mcg) twice daily by oral inhalation.

( 2.2 )

2.1Preparation and Admini stration Information Administer TRIMBOW by oral inhalation. After inhalation, rinse the mouth with water without swallowing it to help reduce the risk of oropharyngeal candidiasis [see Warnings and Precautions ( 5.4 )] . Priming Before Use Prime TRIMBOW by actuating 2 times prior to using the first dose from a new canister.

Re-prime if the inhaler has not been used for 30 days or longer . Dose Counter TRIMBOW has a dose counter attached to the canister. The counter starts at 122 and counts down each time a spray is released.

The correct amount of medication in each actuation cannot be assured after the counter reads 000, even though the canister is not completely empty and will continue to operate. The inhaler should be discarded when the counter reads 000 or if 2 months have passed since first use date, whichever comes first.

2.2Recommen d ed Dosage The recommended dosage of: TRIMBOW is beclomethasone dipropionate 172 mcg, formoterol fumarate 9.8 mcg, and glycopyrrolate 21.2 mcg (administered as 2 actuations of TRIMBOW 86 mcg/4.9 mcg/10.6 mcg [beclomethasone dipropionate 86 mcg, formoterol fumarate 4.9 mcg, and glycopyrrolate 10.6 mcg]) twice daily (in the morning and evening) by oral inhalation. or TRIMBOW is beclomethasone dipropionate 344 mcg, formoterol fumarate 9.8 mcg, and glycopyrrolate 21.2 mcg (administered as 2 actuations of TRIMBOW 172 mcg/4.9 mcg/10.6 mcg [beclomethasone dipropionate 172 mcg, formoterol fumarate 4.9 mcg, glycopyrrolate 10.6 mcg]) twice daily (in the morning and evening) by oral inhalation The recommended starting dosage for TRIMBOW is based upon patients' asthma severity or level of control of asthma symptoms on current inhaled corticosteroids.

For patients who do not respond adequately to a starting dose of TRIMBOW 172 mcg/9.8 mcg/21.2 mcg (2 actuations of TRIMBOW 86 mcg/4.9 mcg/10.6 mcg [beclomethasone dipropionate 86 mcg, formoterol fumarate 4.9 mcg, and glycopyrrolate 10.6 mcg]) twice daily, additional asthma control may be provided by replacement with a dose of TRIMBOW 344 mcg/9.8 mcg/21.2 mcg (2 actuations of TRIMBOW 172 mcg/4.9 mcg/10.6 mcg [beclomethasone dipropionate 344 mcg, formoterol fumarate 9.8 mcg, and glycopyrrolate 21.2 mcg]) twice daily. For patients who do not respond adequately to a dose of TRIMBOW 344 mcg/9.8 mcg/21.2 mcg twice daily, the therapeutic regimen should be re-evaluated and additional therapeutic options should be considered.

The maximum recommended dosage is TRIMBOW 344 mcg/9.8 mcg/21.2 mcg (2 actuations of TRIMBOW 172 mcg/4.9 mcg/10.6 mcg [beclomethasone dipropionate 344 mcg, formoterol fumarate 9.8 mcg, and glycopyrrolate 21.2 mcg]) twice daily by oral inhalation. Do not take more than two oral inhalations twice daily.

💊 Dosage Forms and Strengths 124 words ▾

3 DOSAGE FORMS AND STRENGTHS Inhalation aerosol: a pressurized metered dose inhaler that delivers a combination of 86 mcg/4.9 mcg/10.6 mcg (beclomethasone dipropionate 86 mcg, formoterol fumarate 4.9 mcg, and glycopyrrolate 10.6 mcg) per actuation. Inhaler supplied with a grey plastic actuator, dose counter, grey mouthpiece and red cap. 172 mcg/4.9 mcg/10.6 mcg (beclomethasone dipropionate 172 mcg, formoterol fumarate 4.9 mcg, and glycopyrrolate 10.6 mcg) per actuation.

Inhaler supplied with grey plastic actuator, dose counter, grey mouthpiece and green cap. Inhalation aerosol: 86 mcg/4.9 mcg/10.6 mcg (beclomethasone dipropionate 86 mcg, formoterol fumarate 4.9 mcg, and glycopyrrolate 10.6 mcg) per actuation. ( 3 ) 172 mcg/4.9 mcg/10.6 mcg (beclomethasone dipropionate 172 mcg, formoterol fumarate 4.9 mcg, and glycopyrrolate 10.6 mcg) per actuation.

( 3 )

⛔ Contraindications 85 words ▾

4 CONTRAINDICATIONS TRIMBOW is contraindicated in the following conditions: Primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required [ see Wa rnings and Precautions ( 5.2 ) ] . Hypersensitivity to beclomethasone dipropionate, formoterol fumarate, glycopyrrolate or to any of the excipients [see Warnings and Precautions ( 5.9 ) and Description ( 11 )] . Primary treatment of status asthmaticus or asthma requiring intensive measures.

( 4 ) Severe hypersensitivity to any of the ingredients. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS LABA monotherapy increases the risk of serious asthma-related events. ( 5.1 ) Do not initiate in acutely deteriorating asthma. Do not use to treat acute symptoms.

( 5.2 ) Avoid use in combination with additional therapy containing a LABA because of 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 ) 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. ( 5.5 ) Risk of impaired adrenal function when transferring from systemic corticosteroids. Wean patients slowly from systemic corticosteroids if transferring to TRIMBOW.

( 5.6 ) Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue TRIMBOW slowly. ( 5.7 ) If paradoxical bronchospasm occurs, discontinue TRIMBOW and institute alternative therapy.

( 5.8 ) Use with caution in patients with cardiovascular disorders because of beta-adrenergic stimulation. ( 5.10 ) Assess for decrease in bone mineral density initially and periodically thereafter. ( 5.11 ) 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 TRIMBOW long term.

( 5.12 ) 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. ( 5.13 ) Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis.

( 5.14 ) Be alert to hypokalemia and hyperglycemia. ( 5.15 )

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 (TRIMBOW is not indicated for pediatric patients). These findings are considered a class effect of LABA monotherapy.

When LABA are 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 Inhaled Corticosteroid/Long-acting Beta2-adrenergic Agonists ) . Serious Asthma-Related Events with Inhaled Corticosteroid/Long-acting Beta 2 -adrenergic Agonists Four large, 26-week, randomized, double-blind, 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 with ICS alone in patients with asthma.

Three trials included adult and adolescent patients aged 12 years and older: 1 trial compared budesonide/formoterol fumarate with budesonide, 1 trial compared fluticasone propionate/salmeterol inhalation powder with fluticasone propionate inhalation powder, and 1 trial compared mometasone furoate/formoterol fumarate with mometasone furoate. The fourth trial included pediatric subjects aged 4 to 11 years and compared fluticasone propionate/salmeterol inhalation powder with fluticasone propionate inhalation powder. The primary saf… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in labeling: Serious Asthma-Related Events – Hospitalizations, Intubations, Death [ see Warnings and Precautions ( 5.1 ) ] Oropharyngeal Candidiasis [ see Warnings and Precautions ( 5.4 ) ] Immunosuppression and Risk of Infections [ see Warnings and Precautions ( 5.5 )] Hypercorticism and Adrenal Suppression [ see Warnings and Precautions ( 5.7 ) ] Paradoxical Bronchospasm [ see Warnings and Precautions ( 5.8 )] Cardiovascular Effects [ see Warnings and Precautions ( 5.10 )] Reduction in Bone Mineral Density [ see Warnings and Precautions ( 5.11 )] Worsening of Narrow-Angle Glaucoma [ see Warnings and Precautions ( 5.12 )] Worsening of Urinary Retention [ see Warnings and Precautions ( 5.13 ) ] 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.

Most common adverse reactions (incidence ≥ 1%) are bronchitis, hypertension, back pain, blood pressure increased, dysphonia, upper respiratory tract infection, influenza, anemia, muscle spasms, laryngitis, oropharyngeal pain, and sinusitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Chiesi USA, Inc. at 1-888-661-9260 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience The safety of TRIMBOW in asthma is based on the safety data from two randomized, double-blind, parallel-group, active-controlled trials of 52 weeks’ duration (TRIMARAN and TRIGGER) that included 2,294 adult patients with asthma who received TRIMBOW or BDP/FF comparator [ see Clinical Studies ( 14 ) ] . The incidence of adverse reactions occurring in ≥1% of the patients treated with a dose of TRIMBOW 172 mcg/9.8 mcg/21.2 mcg or a dose of TRIMBOW 344 mcg/9.8 mcg/21.2 mcg, both doses at twice daily by oral inhalation, is shown in Table 2.

Table 2. Adverse Reactions with TRIMBOW with ≥1% Incidence and Greater than Active Control in Adult Patients with Asthma in the TRIMARAN and TRIGGER 52-week Trials Adverse Reactions in TRIMARAN ( n , %) TRIMBOW 172 mcg / 9.8 mcg /2 1. 2 mcg twice daily (N = 576) BDP/FF 172 mcg / 9.8 mcg twice daily (N = 574) Hypertension 16 (3) 9 (2) Blood pressure increased 12 (2) 7 (1) Dysphonia 11 (2) 3 (<1) Upper respiratory tract infection 11 (2) 10 (2) Influenza 9 (2) 7 (1) Anemia 8 (1) 5 (1) Adverse Reactions in TRIGGER ( n , %) TRIMBOW 344 mcg / 9.8 mcg /2 1.

2 mcg twice daily (N = 571) BDP/FF 344 mcg / 9.8 mcg twice daily (N = 57 3 ) Bronchitis 18 (3) 18 (3) Back pain 12 (2) 5 (1) Dysphonia 11 (2) 9 (2) Hypertension 10 (2) 7 (1) Influenza 7 (1) 6 (1) Muscle spasms 6 (1) 6 (1) Laryngitis 6 (1) 3 (<1) Oropharyngeal pain 6 (1) 3 (<1) Sinusitis 6 (1) 3 (<1) Abbreviations: BDP, beclomethasone dipropionate; FF, formoterol fumarate; N, number of patients

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Other adrenergic drugs may potentiate effect: Use with caution. ( 7.1 ) Diuretics, xanthine derivatives or steroids may potentiate hypokalemia or ECG changes. Use with caution.

( 7.2 ) Monoamine oxidase inhibitors and tricyclic antidepressants: Use with extreme caution. May potentiate effect of formoterol fumarate on cardiovascular system. ( 7.3 ) Beta-blockers: Use with caution.

May block bronchodilatory effects of beta-agonists and produce severe bronchospasm. ( 7.4 ) Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administration of TRIMBOW with other anticholinergic-containing drugs.

( 7.6 ) 7. 1 Adrenergic Drugs If additional adrenergic drugs are to be administered by any route, they should be used with caution because the sympathetic effects of formoterol fumarate, a component of TRIMBOW, may be potentiated [see Warnings and Precautions ( 5.3 )] . 7.

2 Xanthine 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 fumarate, a component of TRIMBOW. 7. 3 Monoamine Oxidase Inhibitors, Tricyclic Antidepressants, and QTc Prolonging Drugs Formoterol, as with other beta 2 -agonists, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, macrolides or 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 have an increased risk of ventricular arrhythmias. 7. 4 Beta-adre ner gic Receptor Blocking Agents Beta-adrenergic receptor antagonists (beta-blockers) and formoterol may inhibit the effect of each other when administered concurrently.

Beta-blockers not only block the therapeutic effects of beta2-agonists, such as formoterol, but may produce severe bronchospasm in asthmatic patients. Therefore, patients with 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 asthma.

In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution. 7. 5 Non-Potassium-Sparing Diuretics The electrocardiographic changes and/or hypokalemia that may result from the administration of non–potassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.

7. 6 Anticholinergics There is potential for an additive interaction with concomitantly used anticholinergic medicines. Therefore, avoid coadministration of TRIMBOW with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects [see Warnings and Precautions ( 5.12 , 5.13 )] .

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Hepatic impairment: formoterol fumarate systemic exposure may increase in patients with severe hepatic impairment. Monitor for systemic beta-agonists effects. ( 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 TRIMBOW or its individual components, beclomethasone dipropionate, formoterol fumarate, and glycopyrrolate in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes (See Clinical Considerations ) . In animal reproduction studies, beclomethasone dipropionate (BDP) resulted in adverse developmental effects in mice and rabbits at subcutaneous doses equal to or greater than approximately 0.6 times the maximum recommended human daily inhalation dose (MRHDID) in adults (800 mcg/day) [see Data ] .

In rats exposed to beclomethasone dipropionate by inhalation, dose-related gross injury to the fetal adrenal glands was observed at doses greater than 140 times the MRHDID, but there was no evidence of external or skeletal malformations or embryolethality at inhalation doses of up to 350 times the MRHDID. In animal reproduction studies, formoterol fumarate (FF) produced malformations that included umbilical hernia and brachygnathia (a skeletal malformation) in rats at oral doses 1,200 and 6,100 times the MRHDID in adults, respectively.

In rabbits, formoterol fumarate produced subcapsular cysts on the liver at oral doses 49,000 times the MRHDID in adults. In rats exposed to formoterol fumarate by inhalation, no teratogenic effects were observed at 500 times the MRHDID in adults. Glycopyrrolate (G) administered by the oral route in rats and rabbits did not cause structural abnormalities or affect fetal survival at exposures approximately 179 and 50 times MRHDID, respectively.

TRIMBOW administered by the oral route in rats caused reduction in fetal weights and increased incidence of visceral variations at doses 83 and 0.8 times the MRHDID and higher for BDP (metabolite- B17MP) and FF, respectively. TRIMBOW also caused decreased pup survival, increase in post-implantation loss and reduced mean litter size in rats at 1.9, 3.7, and 7.7 times the MRHDID (based on a mg/m 2 ) for BDP, FF, and G, respectively. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown.

All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryofetal Risk: In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal outcomes such as pre-eclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate.

Pregnant women should be closely monitored, and medication adjusted as necessary to maintain optimal control of asthma. Labor or Delivery : There are no well-controlled human trials that have investigated the effects of TRIMBOW on preterm labor or labor at term. TRIMBOW should be used during late gestation and labor only if the potential benefit justifies the potential for risks related to beta-agonists interfering with uterine contractility.

Infants and neonates born to mothers receiving substantial doses should be observed for adrenal suppression. If treatment during pregnancy is necessary, the lowest effective dose should be used. Data Animal Data Beclomethasone dipropionate (BDP) In an embryofetal development study in pregnant rats, beclomethasone dipropionate administration during organogenesis from gestation days 6 to 15 at inhaled doses 140 times the MRHDID in a… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary There are no adequate and well-controlled studies with TRIMBOW or its individual components, beclomethasone dipropionate, formoterol fumarate, and glycopyrrolate in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes (See Clinical Considerations ) . In animal reproduction studies, beclomethasone dipropionate (BDP) resulted in adverse developmental effects in mice and rabbits at subcutaneous doses equal to or greater than approximately 0.6 times the maximum recommended human daily inhalation dose (MRHDID) in adults (800 mcg/day) [see Data ] .

In rats exposed to beclomethasone dipropionate by inhalation, dose-related gross injury to the fetal adrenal glands was observed at doses greater than 140 times the MRHDID, but there was no evidence of external or skeletal malformations or embryolethality at inhalation doses of up to 350 times the MRHDID. In animal reproduction studies, formoterol fumarate (FF) produced malformations that included umbilical hernia and brachygnathia (a skeletal malformation) in rats at oral doses 1,200 and 6,100 times the MRHDID in adults, respectively.

In rabbits, formoterol fumarate produced subcapsular cysts on the liver at oral doses 49,000 times the MRHDID in adults. In rats exposed to formoterol fumarate by inhalation, no teratogenic effects were observed at 500 times the MRHDID in adults. Glycopyrrolate (G) administered by the oral route in rats and rabbits did not cause structural abnormalities or affect fetal survival at exposures approximately 179 and 50 times MRHDID, respectively.

TRIMBOW administered by the oral route in rats caused reduction in fetal weights and increased incidence of visceral variations at doses 83 and 0.8 times the MRHDID and higher for BDP (metabolite- B17MP) and FF, respectively. TRIMBOW also caused decreased pup survival, increase in post-implantation loss and reduced mean litter size in rats at 1.9, 3.7, and 7.7 times the MRHDID (based on a mg/m 2 ) for BDP, FF, and G, respectively. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown.

All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryofetal Risk: In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal outcomes such as pre-eclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate.

Pregnant women should be closely monitored, and medication adjusted as necessary to maintain optimal control of asthma. Labor or Delivery : There are no well-controlled human trials that have investigated the effects of TRIMBOW on preterm labor or labor at term. TRIMBOW should be used during late gestation and labor only if the potential benefit justifies the potential for risks related to beta-agonists interfering with uterine contractility.

Infants and neonates born to mothers receiving substantial doses should be observed for adrenal suppression. If treatment during pregnancy is necessary, the lowest effective dose should be used. Data Animal Data Beclomethasone dipropionate (BDP) In an embryofetal development study in pregnant rats, beclomethasone dipropionate administration during organogenesis from gestation days 6 to 15 at inhaled doses 140 times the MRHDID in adults and higher (on a mg/m 2 basis at maternal doses of 11,500 and 28,300 mcg/kg/day) produced dose-dependent gross injury (characterized by red foci) of the adrenal glands in fetuses.

There were no findings in the adrenal glands of rat fetuses at an inhaled dose that was 30 times the MRHDID in adults (on a mg/m 2 basis at a maternal dose of 2,400 mcg/kg/day).… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use 16 words ▾

8.4Pediatric Use The safety and effectiveness of TRIMBOW have not been established in pediatric patients.

🧓 Geriatric Use 62 words ▾

8.5Geriatric Use Of the total number of TRIMBOW-treated patients in clinical studies for asthma, 204 (18%) were 65 years of age and older [see Clinical Studies ( 14 )] . No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between elderly and younger patients.

🆘 Overdosage 215 words ▾

10 OVERDOSAGE TRIMBOW contains beclomethasone dipropionate, formoterol fumarate, and glycopyrrolate; therefore, the risks associated with overdosage for the individual components described below apply to TRIMBOW. Treatment of overdosage consists of discontinuation of TRIMBOW 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 medicine can produce bronchospasm.

Cardiac monitoring is recommended in cases of overdosage. Beclomethasone Dipropionate If used at excessive doses for prolonged periods, systemic corticosteroid effects, such as hypercorticism may occur [ see Warnings and Precautions ( 5.7 ) ] . Formoterol Fumarate The signs and symptoms with overdosage of formoterol fumarate are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the signs and symptoms: angina, hypertension or hypotension, tachycardia, with rates up to 200 beats/min., arrhythmias, nervousness, headache, tremor, seizures, muscle cramps, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, hypokalemia, hyperglycemia, and insomnia.

Metabolic acidosis may also occur. Cardiac arrest and even death may be associated with an overdose of formoterol fumarate. Glycopyrrolate High doses of glycopyrrolate, a component of TRIMBOW, 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.

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action TRIMBOW contains beclomethasone dipropionate, formoterol fumarate and glycopyrrolate. The mechanism of action described below for the individual components applies to TRIMBOW. These drugs represent three different classes of medications (an inhaled corticosteroid, a long-acting beta 2 -adrenergic agonist and an anticholinergic) that have different effects on clinical physiology.

Beclomethasone Dipropionate Beclomethasone dipropionate is a corticosteroid demonstrating potent anti-inflammatory activity. The precise mechanism through which beclomethasone dipropionate effects asthma symptoms is not known. Corticosteroids have been shown to have multiple anti-inflammatory effects, inhibiting both inflammatory cells (e.g., mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils) and release of inflammatory mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines).

These anti-inflammatory actions of corticosteroids contribute to their efficacy in asthma. Beclomethasone dipropionate is a prodrug that is rapidly activated by hydrolysis to the active monoester, 17-monopropionate (17-BMP). Beclomethasone 17-monopropionate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor, which is approximately 13 times that of dexamethasone, 6 times that of triamcinolone acetonide, 1.5 times that of budesonide and 25 times that of beclomethasone dipropionate.

The clinical relevance of these findings is unknown. 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 fumarate has more than 200-fold greater agonist activity at beta 2 -receptors than at beta 1 -receptors. 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, especially from mast cells. 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. In preclinical in vitro as well as in vivo studies, prevention of acetylcholine, ovalbumin, acetaldehyde and histamine-induced bronchoconstrictive effects was dose-dependent.

The clinical relevance of these findings is unknown. The bronchodilation following inhalation of glycopyrrolate is predominantly a site-specific effect.

12.2Pharmacodynamics Cardiac Electrophysiology A randomized, double-blind, placebo controlled, single dose study in 95 healthy volunteers assessed the effect of beclomethasone dipropionate, formoterol fumarate, and glycopyrrolate (BDP/FF/G) on the heart rate corrected QT interval based on the Fridericia's correction (QTcF) using electrocardiographic monitoring. The maximum mean (90% two-sided upper confidence bound) difference in QTcF from placebo after baseline correction was 4.4 (5.9) milliseconds and 11.8… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action ~2 min read ▾

12.1Mechanism of Action TRIMBOW contains beclomethasone dipropionate, formoterol fumarate and glycopyrrolate. The mechanism of action described below for the individual components applies to TRIMBOW. These drugs represent three different classes of medications (an inhaled corticosteroid, a long-acting beta 2 -adrenergic agonist and an anticholinergic) that have different effects on clinical physiology.

Beclomethasone Dipropionate Beclomethasone dipropionate is a corticosteroid demonstrating potent anti-inflammatory activity. The precise mechanism through which beclomethasone dipropionate effects asthma symptoms is not known. Corticosteroids have been shown to have multiple anti-inflammatory effects, inhibiting both inflammatory cells (e.g., mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils) and release of inflammatory mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines).

These anti-inflammatory actions of corticosteroids contribute to their efficacy in asthma. Beclomethasone dipropionate is a prodrug that is rapidly activated by hydrolysis to the active monoester, 17-monopropionate (17-BMP). Beclomethasone 17-monopropionate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor, which is approximately 13 times that of dexamethasone, 6 times that of triamcinolone acetonide, 1.5 times that of budesonide and 25 times that of beclomethasone dipropionate.

The clinical relevance of these findings is unknown. 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 fumarate has more than 200-fold greater agonist activity at beta 2 -receptors than at beta 1 -receptors. 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, especially from mast cells. 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. In preclinical in vitro as well as in vivo studies, prevention of acetylcholine, ovalbumin, acetaldehyde and histamine-induced bronchoconstrictive effects was dose-dependent.

The clinical relevance of these findings is unknown. The bronchodilation following inhalation of glycopyrrolate is predominantly a site-specific effect.

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

16 HOW SUPPLIED/STORAGE AND HANDLING TRIMBOW (beclomethasone dipropionate/formoterol fumarate/glycopyrrolate) Inhalation Aerosol: TRIMBOW 86 mcg/4.9 mcg/10.6 mcg: is supplied as a pressurized aluminum container, a grey plastic actuator with the dose counter on the back, a grey mouthpiece and a red cap. TRIMBOW 172 mcg/4.9 mcg/10.6 mcg: is supplied as a pressurized aluminum container, a grey plastic actuator with the dose counter on the back, a grey mouthpiece and a green cap. Each pressurized container of TRIMBOW is packaged in a carton containing one canister, one actuator, a Patient Information leaflet, and the Instructions for Use.

TRIMBOW is available as presented in Table 4. Table 4 Package Information for TRIMBOW Strength ( beclomethasone dipropionate/formoterol fumarate/glycopyrrolate) Number of Actuations per Canister Net Fill Weight NDC 86 mcg/4.9 mcg/10.6 mcg 120 11.8 grams NDC 10122-120-02 172 mcg/4.9 mcg/10.6 mcg 120 11.8 grams NDC 10122-121-02 The TRIMBOW container should only be used with the TRIMBOW actuator, and the TRIMBOW actuator should not be used with any other inhalation drug product. Prime the inhaler according to Instructions for Use .

If the inhaler has not been used for 30 days or longer, re-prime the inhaler by releasing 2 actuations (puffs) into the air, away from the face and eyes, before use. Dose Counter TRIMBOW has a dose counter attached to the canister. The counter starts at 122 and counts down each time a spray is released.

The correct amount of medication in each actuation cannot be assured after the counter reads 000, even though the canister is not completely empty and will continue to operate. The inhaler should be discarded when the counter reads 000 or if 2 months have passed since first use date, whichever comes first. Contents under Pressure Do not puncture.

Do not use or store near heat or open flame. Exposure to temperatures above 122°F may cause bursting. Never throw container into fire or incinerator.

Keep out of reach of children. Do not spray into eyes. Storage: Prior to first use: Store refrigerated at 36°F to 46°F (2°C to 8°C).

After first use: Store the inhaler below 77°F (25°C) for a maximum of two months. Do not freeze. Do not expose to temperatures higher than 122°F (50°C) as this may cause bursting.

📋 Description ~3 min read ▾

11 DESCRIPTION TRIMBOW (beclomethasone dipropionate, formoterol fumarate and glycopyrrolate) Inhalation Aerosol is a pressurized metered-dose inhaler that delivers a combination of beclomethasone dipropionate [an inhaled corticosteroid (ICS)], formoterol fumarate [an inhaled long-acting beta 2 -adrenergic agonist (a LABA)] and glycopyrrolate (an anticholinergic) for oral inhalation. Beclomethasone dipropionate, an inhaled corticosteroid [ICS], has the chemical name [2-[(8S,9R,10S,11S,13S,14S,16S,17R)-9-chloro-11-hydroxy-10,13,16-trimethyl-3-oxo-17-propanoyloxy-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl] propanoate.

Beclomethasone dipropionate is a white to creamy white, odorless powder, insoluble in water, freely soluble in acetone, and sparingly soluble in alcohol, with a molecular weight of 521.04218 g/mol, and the molecular formula is C 28 H 37 ClO 7 . The structural formula is as follows: Formoterol fumarate, a long-acting β2 agonist has the chemical name (E)-but-2-enedioic acid; N -[2-hydroxy-5-[(1 R )-1-hydroxy-2-[[(1 R )-2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]phenyl]-formamide dihydrate. Formoterol fumarate is a powder that is slightly soluble in water.

Formoterol fumarate has a molecular weight of 840.91 g/mol, and the molecular formula is C 42 H 52 N 4 O 12 . 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) . Glycopyrrolate is a quarternary ammonium bromide salt with the following chemical name: [ RS- ]-3-[( SR )-(cyclopentylhydroxyphenylacetyl)oxy]-1,1-dimethyl-Pyrrolidinium bromide.

Two asymmetric atoms of carbon are present in the molecule: Glycopyrronium bromide is represented by the (R,S)-(S,R) racemic pair of enantiomers, corresponding to the threo diastereoisomeric structure. Glycopyrrolate is a powder that is freely soluble in water. Glycopyrrolate has a molecular weight of 398.33 g/mol, and the molecular formula is C 19 H 28 BrNO 3 .

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. TRIMBOW 86 mcg/4.9 mcg/10.6 mcg and TRIMBOW 172 mcg/4.9 mcg/10.6 mcg are formulated as a hydrofluoroalkane (HFA 134a) propelled pressurized, metered-dose inhalers, each containing 120 actuations.

The canister is supplied with a grey plastic actuator with an integrated dose counter mechanism and mouthpiece, and a red cap (TRIMBOW 86 mcg/4.9 mcg/10.6 mcg) or a green cap (TRIMBOW 172 mcg/4.9 mcg/10.6 mcg). As a solution, TRIMBOW does not need to be shaken before use. TRIMBOW should be “primed” by actuating 2 times prior to using the first dose from a new canister.

If the inhaler has not been used for 30 days or longer, re-prime the inhaler [ see How Supplied/Storage and Handling ( 16 ) ] . After priming, each actuation meters 100 or 200 mcg of beclomethasone dipropionate, 6.0 mcg of formoterol fumarate (equivalent to 5.7 mcg of formoterol fumarate anhydrous), and 12.5 mcg of glycopyrrolate (equivalent to 10 mcg of glycopyrronium) in 73.8 mg of solution from the valve and delivers 86 or 172 mcg of beclomethasone dipropionate, 4.9 mcg of formoterol fumarate (equivalent to 4.2 mcg of formoterol fumarate anhydrous), and 10.6 mcg of glycopyrrolate (equivalent to 8.5 mcg of glycopyrronium) from the actuator.

The actual amount of drug delivered to the lung may depend on patient factors, such as coordination of the device (metered dose inhaler [MDI]) actuation with the inhalation maneuver, inspiratory flow and peak inspiratory flow through the delivery system, which may vary in patients with asthma and other pulmonary diseases and conditions. Avoid spraying in the eyes or face while using TRIMBOW. TRIMBOW contains dehydrated alcohol (18% v/v), HFA 134a, and hydrochloric acid as excipients in the formulation.

The struct… [Excerpted — this section continues on DailyMed.]

💬 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 TRIMBOW, there is not a significant increase in the risk of these events [See Warnings and Precautions ( 5.1 )] .

Not for Acute Symptoms Inform patients that TRIMBOW is not meant to relieve acute symptoms of asthma and extra doses should not be used for that purpose [see Warnings and Precautions ( 5.2 )] . Advise patients to treat acute symptoms with an inhaled, short-acting beta 2 -agonist/corticosteroid or short-acting beta 2 -agonist. Provide patients with such medication and instruct them 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 beta2-agonist/corticosteroid combination, or inhaled, short-acting beta 2 -agonists Need for more inhalations than usual of inhaled, short acting beta 2 -agonists/corticosteroid combination, or inhaled short acting beta 2 -agonists Significant decrease in lung function as outlined by the healthcare provider Tell the patient they should not stop therapy with TRIMBOW without physician/provider guidance since symptoms may recur after discontinuation [See Warnings and Precautions ( 5.2 )] .

Avoid Use of Additional Long-acting Beta 2 -agonists Instruct patients not to use other LABA drugs for asthma [See Warnings and Precautions ( 5.3 )] . Oropharyngeal Candidiasis Inform patients that localized infections with Candida albicans occurred in the mouth and pharynx (i.e., thrush) in some patients. If oropharyngeal candidiasis develops, treat it with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing therapy with TRIMBOW, but at times therapy with TRIMBOW 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 )] . 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 ( 5.5 ) ] .

Hypercorticism and Adrenal Suppression Advise patients that TRIMBOW 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 TRIMBOW [See Warnings and Precautions ( 5.7 )] .

Paradoxical Bronchospasm As with other inhaled medicines, TRIMBOW can cause paradoxical bronchospasm. If paradoxical bronchospasm occurs, instruct patients to discontinue TRIMBOW and contact their healthcare provider right away [See Warnings and Precautions ( 5.8 )] . Hypersensitivity Reactions, including Anaphylaxis Advise patients that hypersensitivity reactions have been reported after administration.

If signs suggesting allergic reactions occur, in particular, angioedema (including difficulties in breathing or swallowing, swelling of the tongue, lips and face), urticaria or skin rash, instruct patients to discontinue TRIMBOW immediately [See Warnings and Precautions ( 5.9 )] . Reduction in Bone Mineral Density Advise patients who are at an increased risk for decreased BMD that the use of corticosteroids may pose an additional risk [ See Warnings and Precautions ( 5.11 ) ] . Ocular Effects suc… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics The systemic exposure of beclomethasone dipropionate and 17-BMP approximately doubles following a single dose (4 inhalations) of TRIMBOW 172 mcg/4.9 mcg/10.6 mcg compared to a single dose (4 inhalations) of TRIMBOW 86 mcg/4.9 mcg/10.6 mcg in healthy subjects. Meanwhile, the systemic exposure of formoterol and glycopyrrolate was generally similar between TRIMBOW 172 mcg/4.9 mcg/10.6 mcg and TRIMBOW 86 mcg/4.9 mcg/10.6 mcg after inhalation. Absorption Beclomet h asone dipropionate Following inhaled administration of TRIMBOW 86 mcg/4.9 mcg/10.6 mcg in healthy subjects the median time to reach C max was 5 minutes for beclomethasone dipropionate and 30 minutes for 17-BMP.

Formoterol fumarate Following inhaled administration of TRIMBOW 86 mcg/4.9 mcg/10.6 mcg in healthy subjects the median time to reach C max was 5 minutes. As with drug products for oral inhalation, it is likely that the majority of the inhaled formoterol fumarate is swallowed and then absorbed from the gastrointestinal tract. Glycopyrrolate Following inhaled administration of TRIMBOW 86/4.9 mcg/10.6 mcg in healthy subjects the median time to reach C max was 5 minutes.

Following glycopyrrolate inhalation, the absolute bioavailability was 9.6% and 11.9% with or without oral ingestion of charcoal block, respectively, when compared to intravenous infusion. Distribution Beclomet h asone dipropionate Apparent volume of distribution at steady state for 17-BMP in subjects with asthma following inhaled administration of TRIMBOW 86 mcg/4.9 mcg/10.6 mcg was estimated to be approximately 135 L, via population PK analysis. The in vitro protein binding for 17-BMP was reported to be 94% to 96% over the concentration range of 1000 to 5000 pg/mL.

Protein binding was constant over the concentration range evaluated. There is no evidence of tissue storage of beclomethasone dipropionate or its metabolites. Formoterol fumarate Apparent volume of distribution at steady state in subjects with asthma following inhaled administration of TRIMBOW 86 mcg/4.9 mcg/10.6 mcg was estimated to be approximately 1560 L, via population PK analysis.

Plasma protein binding of formoterol fumarate is 61-64% at concentrations from 0.1 to 100 ng/mL. Binding to human serum albumin in vitro was 31% to 38% over a range of 5 to 500 ng/mL. Glycopyrrolate Apparent volume of distribution at steady state in subjects with asthma following inhaled administration of TRIMBOW 86 mcg/4.9 mcg/10.6 mcg was estimated to be approximately 3895 L, via population PK analysis.

Glycopyrronium binding to plasma proteins was 71 ± 4% over the range of 50-250 pg/mL. Elimination Beclomet h asone dipropionate Beclomethasone dipropionate is excreted in feces in the form of metabolites. Only negligible amounts of unchanged beclomethasone dipropionate and its metabolites have been detected in urine.

The mean elimination half-life of beclomethasone dipropionate and 17-BMP in subjects with asthma following inhaled administration of TRIMBOW 172 mcg/4.9 mcg/10.6 mcg was 0.3 hours and 5 hours, respectively . Formoterol fumarate The excretion of formoterol in urine was studied in seventeen healthy subjects, as part of the investigation of the effect of renal impairment on the pharmacokinetics of inhaled TRIMBOW. In that study, 4.7% of the administered formoterol dose was excreted in urine as unchanged formoterol.

The mean elimination half-life of formoterol in subjects with asthma following inhaled administration of TRIMBOW 172 mcg/4.9 mcg/10.6 mcg was 6.7 hours. Glycopyrrolate The excretion of glycopyrrolate in urine was studied in seventeen healthy subjects, as part of the investigation of the effect of renal impairment on the pharmacokinetics of inhaled TRIMBOW. In that study, 7% of the inhaled dose was excreted in urine as unchanged glycopyrronium.

Metabolism Beclomethasone dipropionate Beclomethasone dipropionate is cleared very rapidly from the systemic circulation by metabolism mediated via esterases found in most ti… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics ~1 min read ▾

12.2Pharmacodynamics Cardiac Electrophysiology A randomized, double-blind, placebo controlled, single dose study in 95 healthy volunteers assessed the effect of beclomethasone dipropionate, formoterol fumarate, and glycopyrrolate (BDP/FF/G) on the heart rate corrected QT interval based on the Fridericia's correction (QTcF) using electrocardiographic monitoring. The maximum mean (90% two-sided upper confidence bound) difference in QTcF from placebo after baseline correction was 4.4 (5.9) milliseconds and 11.8 (13.4) milliseconds for BDP/FF/G with 172 mcg/9.8 mcg/21.2 mcg of BDP/FF/G and 4 times the dose of 172 mcg/9.8 mcg/ 21.2 mcg of BDP/FF/G, respectively.

A dose-dependent increase in heart rate was also observed. The maximum mean (90% two-sided CI) difference in heart rate between BDP/FF/G and placebo after baseline-correction was 3.8 (2.3; 5.4) beats/min observed 10 min post-dose at 172 mcg/9.8 mcg/21.2 mcg of BDP/FF/G and 10.3 (9.3; 11.3) beats/min observed 2 h post-dose at 4 times the dose of 172 mcg/9.8 mcg/ 21.2 mcg of BDP/FF/G. HPA Axis Effects The potential systemic effects of TRIMBOW on the HPA axis have not been evaluated.

The systemic effects of inhaled corticosteroids are related to the systemic exposure to such drugs. Pharmacokinetic studies have demonstrated that the systemic exposure to BDP/17-BMP at a single BDP/FF/G dose of 344 mcg/9.8 mcg/21.2 mcg was lower compared with the highest dose of a BDP MDI product (640 mcg administered as a single dose). Therefore, the systemic effects on HPA-axis of BDP/17-BMP delivered from TRIMBOW would be expected to be no greater than that of a BDP MDI product.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES The efficacy of TRIMBOW was evaluated in two randomized, double-blind, parallel-group, active-controlled trials (TRIMARAN [NCT02676076] and TRIGGER [NCT02676089]) of 52 weeks duration in adult patients with asthma. In TRIMARAN and TRIGGER, patients with an Asthma Control Questionnaire (ACQ-7) score ≥1.5 on their current asthma combination therapy of medium- or high-dose ICS plus a LABA entered a 2-week run-in period of treatment with a dose of beclomethasone dipropionate/formoterol fumarate (BDP/FF) 172 mcg/9.8 mcg (TRIMARAN) or 344 mcg/9.8 mcg (TRIGGER) administered by oral inhalation twice daily.

Only patients who remained inadequately controlled with an ACQ-7 score ≥1.5 after the run-in period were randomized. In TRIMARAN, patients were randomized 1:1 to a dose of TRIMBOW 172 mcg/9.8 mcg/21.2 mcg or BDP/FF 172 mcg/9.8 mcg, both administered by oral inhalation twice daily. In TRIGGER, patients were randomized 1:1 to a dose of TRIMBOW 344 mcg/9.8 mcg/21.2 mcg or BDP/FF 344 mcg/9.8 mcg, both administered by oral inhalation twice daily.

The efficacy population consisted of 2291 patients who received at least 1 dose of TRIMBOW or BDP/FF and had at least 1 post-baseline evaluation of efficacy in TRIMARAN (N = 1149) and TRIGGER (N = 1142). Across the treatment groups in TRIMARAN and TRIGGER, most patients were female (61%), White (99.9%), and had never smoked (86%), with a mean age of 53 years (range: 18 to 75 years), a mean asthma duration of 25 years (range: 1 to 67 years), and past smokers (14%) having an average smoking history of 4.6 pack-years. The trials excluded patients who were current smokers.

All patients had at least one documented asthma exacerbation (requiring treatment with systemic corticosteroids or an emergency department visit or in-patient hospitalization) in the 12 months prior to screening. Across the treatment groups in TRIMARAN and TRIGGER, the mean pre-bronchodilator percent predicted FEV 1 was 53.6% (SD: 12.9%), the mean percent reversibility was 32.6% (SD: 21.9%), the mean absolute reversibility was 496 mL (SD: 283 mL), and the mean ACQ-7 score was 2.69 (SD: 0.61) at screening; at randomization, the mean ACQ-7 score was 2.36 (SD: 0.54) and the mean trough percent predicted FEV 1 was 58.5% (SD: 12.5%).

Lung Function In TRIMARAN and TRIGGER , the efficacy of TRIMBOW was measured by the mean change from baseline in trough FEV 1 at Week 26. Patients treated with TRIMBOW at doses of 172 mcg/9.8 mcg/21.2 mcg and 344 mcg/9.8 mcg/21.2 mcg by oral inhalation twice daily showed improvements in the mean change from baseline in trough FEV 1 at Week 26 compared with BDP/FF at doses of 172 mcg/9.8 mcg and 344 mcg/9.8 mcg by oral inhalation twice daily, respectively ( Table 3 , Figures 1 and 2 ). Table 3.

Least Squares Mean Change from Baseline in Trough FEV 1 (mL) at Week 26 TRIMARAN TRIGGER TRIMBOW 172/9.8 /2 1. 2 mcg twice daily (N=575) BDP/FF 172/9.8 mcg twice daily (N=574) TRIMBOW 344/9.8/2 1. 2 mcg twice daily (N=571) BDP/FF 344/9.8 mcg twice daily (N=571) n (%) 571 (99) 567 (99) 568 (99) 562 (98) LS mean change (95% CI) 185 (155, 214) 127 (98, 157) 229 (196, 263) 157 (123, 190) TRIMBOW vs.

BDP/FF Difference in LS means (95% CI) 57 (15, 99) 73 (26, 120) BDP/FF = beclomethasone dipropionate/formoterol fumarate, CI = confidence interval, FEV 1 = forced expiratory volume in 1 second, LS = least squares, mcg = micrograms, N = number of patients in the intent-to-treat population; n = number of patients included in the analysis Figure 1. Least Squares Mean Change from Baseline in Trough FEV 1 (mL) with TRIMBOW 172 mcg / 9.8 mcg /2 1. 2 mcg Twice Daily over 26 Weeks ( TRIMARAN ) Figure 2.

Least Squares Mean Change from Baseline in Trough FEV 1 (mL) with TRIMBOW 344 mcg / 9.8 mcg /2 1. 2 mcg Twice Daily over 26 Weeks ( TRIGGER ) The difference in the mean change from baseline in trough FEV 1 at Week 26 for TRIMBOW at doses of 172 mcg/9.8 mcg/21.2 mcg and 344 mcg/9.8 mcg/21.2 mcg by oral inhalation tw… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~3 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility No studies of carcinogenicity or mutagenicity were conducted with TRIMBOW; however, separate studies of beclomethasone dipropionate, formoterol fumarate and glycopyrrolate are described below. Beclomethasone dipropionate The carcinogenicity of beclomethasone dipropionate was evaluated in rats which were exposed for a total of 95 weeks, 13 weeks at inhalation doses up to 0.4 mg/kg/day and the remaining 82 weeks at combined oral and inhalation doses up to 2.4 mg/kg/day.

There was no evidence of treatment-related increases in the incidence of tumors in this study at the highest dose, which is approximately 30 times the MRHDID in adults on a mg/m 2 basis. Beclomethasone dipropionate did not induce gene mutation in bacterial cells or mammalian Chinese hamster ovary (CHO) cells in vitro . No significant clastogenic effect was seen in cultured CHO cells in vitro or in the mouse micronucleus test in vivo .

Formoterol fumarate The carcinogenic potential of formoterol fumarate has been evaluated in 2-year drinking water and dietary studies in both rats and mice. In rats, the incidence of ovarian leiomyomas was increased at doses of 15 mg/kg and above in the drinking water study and at 20 mg/kg in the dietary study, but not at dietary doses up to 5 mg/kg (AUC exposure approximately 450 times human exposure at the maximum recommended daily inhalation dose). In the dietary study, the incidence of benign ovarian theca-cell tumors was increased at doses of 0.5 mg/kg and above (AUC exposure at the low dose of 0.5 mg/kg was approximately 45 times human exposure at the maximum recommended daily inhalation dose).

This finding was not observed in the drinking water study, nor was it seen in mice (see below). In mice, the incidence of adrenal subcapsular adenomas and carcinomas was increased in males at doses of 69 mg/kg and above in the drinking water study, but not at doses up to 50 mg/kg (AUC exposure approximately 590 times human exposure at the maximum recommended daily inhalation dose) in the dietary study. The incidence of hepatocarcinomas was increased in the dietary study at doses of 20 and 50 mg/kg in females and 50 mg/kg in males, but not at doses up to 5 mg/kg in either males or females (AUC exposure approximately 60 times human exposure at the maximum recommended daily inhalation dose).

Also in the dietary study, the incidence of uterine leiomyomas and leiomyosarcomas was increased at doses of 2 mg/kg and above (AUC exposure at the low dose of 2 mg/kg was approximately 25 times human exposure at the maximum recommended daily inhalation dose). Increases in leiomyomas of the rodent female genital tract have been similarly demonstrated with other beta-agonist drugs. Formoterol fumarate was not mutagenic or clastogenic in the following tests: mutagenicity tests in bacterial and mammalian cells, chromosomal analyses in mammalian cells, unscheduled DNA synthesis repair tests in rat hepatocytes and human fibroblasts, transformation assay in mammalian fibroblasts and micronucleus tests in mice and rats.

Glycopyrrolate There was no evidence of treatment-related increases in the incidence of tumors in an oral 26-week carcinogenicity study in transgenic Tg-rasH2 mice and in a 2-year inhalation study in rats at up to 81 times the MRHDID in adults on a mg/m 2 basis. Glycopyrrolate was not mutagenic or clastogenic in the following tests: Ames assay in bacterial and mammalian cells, chromosomal aberrations in mammalian cells, and micronucleus tests in mice and rats. Impairment of Fertility Beclomethasone Dipropionate In rats, beclomethasone dipropionate caused decreased conception rates at an oral dose of 16 mg/kg/day (approximately 250 times the MRHDID in adults on a mg/m 2 basis).

Impairment of fertility, as evidenced by inhibition of the estrous cycle in dogs, was observed following treatment by the oral route at a dose of 0.5 mg/kg/day (approximately 25 times the… [Excerpted — this section continues on DailyMed.]

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

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility No studies of carcinogenicity or mutagenicity were conducted with TRIMBOW; however, separate studies of beclomethasone dipropionate, formoterol fumarate and glycopyrrolate are described below. Beclomethasone dipropionate The carcinogenicity of beclomethasone dipropionate was evaluated in rats which were exposed for a total of 95 weeks, 13 weeks at inhalation doses up to 0.4 mg/kg/day and the remaining 82 weeks at combined oral and inhalation doses up to 2.4 mg/kg/day.

There was no evidence of treatment-related increases in the incidence of tumors in this study at the highest dose, which is approximately 30 times the MRHDID in adults on a mg/m 2 basis. Beclomethasone dipropionate did not induce gene mutation in bacterial cells or mammalian Chinese hamster ovary (CHO) cells in vitro . No significant clastogenic effect was seen in cultured CHO cells in vitro or in the mouse micronucleus test in vivo .

Formoterol fumarate The carcinogenic potential of formoterol fumarate has been evaluated in 2-year drinking water and dietary studies in both rats and mice. In rats, the incidence of ovarian leiomyomas was increased at doses of 15 mg/kg and above in the drinking water study and at 20 mg/kg in the dietary study, but not at dietary doses up to 5 mg/kg (AUC exposure approximately 450 times human exposure at the maximum recommended daily inhalation dose). In the dietary study, the incidence of benign ovarian theca-cell tumors was increased at doses of 0.5 mg/kg and above (AUC exposure at the low dose of 0.5 mg/kg was approximately 45 times human exposure at the maximum recommended daily inhalation dose).

This finding was not observed in the drinking water study, nor was it seen in mice (see below). In mice, the incidence of adrenal subcapsular adenomas and carcinomas was increased in males at doses of 69 mg/kg and above in the drinking water study, but not at doses up to 50 mg/kg (AUC exposure approximately 590 times human exposure at the maximum recommended daily inhalation dose) in the dietary study. The incidence of hepatocarcinomas was increased in the dietary study at doses of 20 and 50 mg/kg in females and 50 mg/kg in males, but not at doses up to 5 mg/kg in either males or females (AUC exposure approximately 60 times human exposure at the maximum recommended daily inhalation dose).

Also in the dietary study, the incidence of uterine leiomyomas and leiomyosarcomas was increased at doses of 2 mg/kg and above (AUC exposure at the low dose of 2 mg/kg was approximately 25 times human exposure at the maximum recommended daily inhalation dose). Increases in leiomyomas of the rodent female genital tract have been similarly demonstrated with other beta-agonist drugs. Formoterol fumarate was not mutagenic or clastogenic in the following tests: mutagenicity tests in bacterial and mammalian cells, chromosomal analyses in mammalian cells, unscheduled DNA synthesis repair tests in rat hepatocytes and human fibroblasts, transformation assay in mammalian fibroblasts and micronucleus tests in mice and rats.

Glycopyrrolate There was no evidence of treatment-related increases in the incidence of tumors in an oral 26-week carcinogenicity study in transgenic Tg-rasH2 mice and in a 2-year inhalation study in rats at up to 81 times the MRHDID in adults on a mg/m 2 basis. Glycopyrrolate was not mutagenic or clastogenic in the following tests: Ames assay in bacterial and mammalian cells, chromosomal aberrations in mammalian cells, and micronucleus tests in mice and rats. Impairment of Fertility Beclomethasone Dipropionate In rats, beclomethasone dipropionate caused decreased conception rates at an oral dose of 16 mg/kg/day (approximately 250 times the MRHDID in adults on a mg/m 2 basis).

Impairment of fertility, as evidenced by inhibition of the estrous cycle in dogs, was observed following treatment by the oral route at a dose of 0.5 mg/kg/day (approximately 25 times the MRHDID in adults on a mg/… [Excerpted — this section continues on DailyMed.]

📄 Patient Package Insert ~3 min read ▾

PATIENT INFORMATION TRIMBOW ® (trim-bow) (beclomethasone dipropionate, formoterol fumarate and glycopyrrolate) inhalation aerosol, for oral inhalation use What is TRIMBOW? TRIMBOW combines 3 medicines in 1 inhaler, an inhaled corticosteroid (ICS) medicine (beclomethasone dipropionate), a long-acting beta 2 -adrenergic agonist (LABA) medicine (formoterol fumarate) and an anticholinergic medicine (glycopyrrolate). ICS medicines like beclomethasone dipropionate help to decrease inflammation in the lungs.

Inflammation in the lungs can lead to breathing problems. LABA medicines such as formoterol fumarate and anticholinergic medicines such as glycopyrrolate help the muscles around the airways in your lungs stay relaxed to prevent symptoms, such as wheezing, cough, chest tightness, and shortness of breath. These symptoms can happen when the muscles around the airways tighten.

This makes it hard to breathe. TRIMBOW is a prescription medicine used long term (chronic) to prevent and control symptoms of asthma for better breathing and prevent symptoms such as wheezing. TRIMBOW is not used to relieve sudden breathing problems and will not replace a rescue inhaler.

TRIMBOW contains formoterol fumarate. LABA medicines such as formoterol fumarate when used alone increase the risk of hospitalizations and death from asthma problems. TRIMBOW contains an ICS, a LABA and an anticholinergic.

When an ICS and LABA are used together, there is not a significant increased risk in hospitalizations and death from asthma problems. TRIMBOW should not be used in children. It is not known if TRIMBOW is safe and effective in children.

Do not use TRIMBOW: to treat sudden, severe symptoms of asthma. if you are allergic to beclomethasone dipropionate, formoterol fumarate, glycopyrrolate or any of the ingredients in TRIMBOW. See the end of this Patient Information for a complete list of ingredients in TRIMBOW. Before using TRIMBOW, tell your healthcare provider about all of your medical conditions, including if you: have heart problems. have high blood pressure. have seizures. have thyroid problems. have diabetes. have liver problems. have kidney problems. have weak bones (osteoporosis). have an immune system problem. have eye problems such as glaucoma, increased pressure in your eye, cataracts, blurred vision, or other changes in vision.

TRIMBOW may make your glaucoma worse. have prostate or bladder problems, or problems passing urine. TRIMBOW may make these problems worse. have any type of viral, bacterial, parasitic, or fungal infection. are exposed to chickenpox or measles. are pregnant or plan to become pregnant. It is not known if TRIMBOW may harm your unborn baby. are breastfeeding or plan to breastfeed.

It is not known if the medicines in TRIMBOW pass into your breast milk and if they can harm your baby. Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. TRIMBOW and certain other medicines may affect each other.

This may cause serious side effects. Especially tell your healthcare provider if you take: anticholinergics (including tiotropium, ipratropium, aclidinium) atropine other LABA (including salmeterol, formoterol fumarate, arformoterol, vilanterol, olodaterol, and indacaterol) antifungal or anti-HIV medicines. Know the medicines you take.

Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I use TRIMBOW? Read the step-by-step instructions for using TRIMBOW at the end of this Patient Information.

Do not use TRIMBOW unless your healthcare provider has taught you how to use the inhaler and you understand how to use it correctly. TRIMBOW comes in 2 different strengths. Your healthcare provider prescribed the strength that is best for you.

If you have been using a different inhaler containing beclomethasone dipropionate previously, ask your healthcare provider for advice, as the effective dose of b… [Excerpted — this section continues on DailyMed.]

📖 Instructions for Use ~3 min read ▾

INSTRUCTIONS FOR USE TRIMBOW ® (trim-bow) (beclomethasone dipropionate, formoterol fumarate and glycopyrrolate) inhalation aerosol, for oral inhalation use Read this Instructions for Use before you start using TRIMBOW and each time you get a new refill. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. TRIMBOW is available in one size providing 120 puffs.

Parts of your inhaler ( See Figure A ) - The pressurized container (1) fits into an actuator (5) and holds the medicine. - The mouthpiece (2) delivers the medicine from the pressurized container (1). - The dose counter (3) shows how many doses are left. Each time you press the pressurized container (1), a puff of medicine is released, and the dose counter will count down by 1. - The protective cap (4) covers the mouthpiece when the inhaler is not in use. Preparing to use TRIMBOW Write the date you first use TRIMBOW on the carton box.

Check 2 months have not passed since the first use date. If more than 2 months have passed, throw away your inhaler. Before using the inhaler for the first time, you must prime it 2 times to make sure that it is working properly.

Check that the dose counter displays 122 doses ( See Figure B ). Remove the protective cap from the mouthpiece. Hold your inhaler in the upright position with the mouthpiece at the bottom.

Point the mouthpiece away from your face and firmly press the pressurized container 2 times to release 2 puffs. Check the dose counter. After priming, the dose counter should display 120 remaining doses ( See Figure B).

How to use your inhaler Important information you need to know before using TRIMBOW For oral inhalation use only - Take 2 inhalations of medicine in the morning and 2 inhalations of medicine in the evening. - Use the pressurized container only with the actuator supplied with TRIMBOW. - Do not use parts of the TRIMBOW inhaler with parts from any other inhalation medicine. Do not remove the pressurized container from the actuator because: - You may not receive the correct amount of medicine. - The dose counter may not function . - Reinsertion may cause the dose counter to count down by 1 and may discharge a puff.

Never try to change the numbers on the dose counter or remove the dose counter from the actuator. Step 1. Remove the protective cap from the mouthpiece and check that the mouthpiece is clean and does not have any foreign objects ( See Figure C ).

Step 2. Breathe out as slowly and fully as you comfortably can through your mouth to empty your lungs ( See Figure D ). Do not breathe into the inhaler.

Step 3. Hold the inhaler upright with the mouthpiece at the bottom and place the mouthpiece into mouth and close lips around the mouthpiece (See Figure E) . Avoid spraying the inhaler towards the eyes.

If spray enters eyes, rinse with water and get medical advice if irritation continues. Step 4. Breathe in slowly and deeply through your mouth to fill your lungs with air and at the same time, press down firmly and fully on the top of the pressurized container until it stops moving in the actuator ( See Figure F ).

Take your finger off the pressurized container. Cleaning your TRIMBOW inhaler The mouthpiece should be cleaned after every 7 days of use. It is very important to keep your inhaler clean so that medicine will not build up.

Routine cleaning instructions - Do not remove the pressurized container from the actuator. - Remove the protective cap from the mouthpiece. - Wipe the inside and outside surfaces of the mouthpiece with a clean, dry, lint-free cloth or tissue. - Do not use water or other liquids to clean your inhaler. - Replace the protective cap on the mouthpiece after cleaning. Storing TRIMBOW Before first use: Store TRIMBOW in a refrigerator between 36°F to 46°F (2°C to 8°C). After first use: Store TRIMBOW below 77°F (25°C) for a maximum of 2 months. - Keep TRIMBOW and all medicines out of the reach of children. - The inhaler can be stor… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel 196 words ▾

PRINC I PAL DISPLAY PANEL TRIMBOW ® (beclomethasone dipropionate/formoterol fumarate/glycopyrrolate) 172 mcg/4.9 mcg/10.6 mcg per actuation 1 pressurized container of 120 actuations NDC 10122-121-02 Rx Only TRIMBOW® (beclomethasone dipropionate/formoterol fumarate/glycopyrrolate) 172 mcg/4.9 mcg/10.6 mcg per actuation 1 pressurized container of 120 actuations NDC 10122-121-02 Rx Only

PRINCIPAL DISPLAY PANEL TRIMBOW ® (beclomethasone dipropionate/formoterol fumarate/glycopyrrolate) 86 mcg/4.9 mcg/10.6 mcg per actuation 1 pressurized container of 120 actuations NDC 10122-120-02 Rx Only TRIMBOW® (beclomethasone dipropionate/formoterol fumarate/glycopyrrolate) 86 mcg/4.9 mcg/10.6 mcg per actuation 1 pressurized container of 120 actuations NDC 10122-120-02 Rx Only

PRINC I PAL DISPLAY PANEL SAMPLE Not for Sale TRIMBOW ® (beclomethasone dipropionate/formoterol fumarate/glycopyrrolate) 172 mcg/4.9 mcg/10.6 mcg per actuation 1 pressurized container of 120 actuations NDC 10122-590-02 Rx Only SAMPLE Not for Sale TRIMBOW® (beclomethasone dipropionate/formoterol fumarate/glycopyrrolate) 172 mcg/4.9 mcg/10.6 mcg per actuation 1 pressurized container of 120 actuations NDC 10122-590-02 Rx Only

PRINCIPAL DISPLAY PANEL SAMPLE Not for Sale TRIMBOW ® (beclomethasone dipropionate/formoterol fumarate/glycopyrrolate) 86 mcg/4.9 mcg/10.6 mcg per actuation 1 pressurized container of 120 actuations NDC 10122-460-02 Rx Only SAMPLE Not for Sale TRIMBOW® (beclomethasone dipropionate/formoterol fumarate/glycopyrrolate) 86 mcg/4.9 mcg/10.6 mcg per actuation 1 pressurized container of 120 actuations NDC 10122-460-02 Rx Only

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

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 Beclomethasone dipropionate/formoterol fumarate/glycopyrrolate — the ingredient across all brands.

Top reported reactions

Dyspnoea162
Diarrhoea87
Pneumonia83
Acute Kidney Injury72
Chronic Obstructive Pulmonary Disease72
Vomiting70
Headache66

Reporter sex

1,660 reports

Serious outcomes

Hospitalization767
Life-threatening140
Disabling132
Death118
Reports over time (by year) — tap or hover for the count & year
2025 2026 388 203
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.

About this NDC listing & data coverage

Finished prescription product No longer marketed (per FDA listing data)
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) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is 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.
What does the discontinued status mean for this NDC?
The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Who lists this product with the FDA?
Chiesi USA, Inc. 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.
← 10122-0550-28 · Chiesi 10122-0610-10 · Chiesi →
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.