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SIMBRINZA brinzolamide/brimonidine tartrate 10 mg/mL; 2 mg/mL Suspension/ Drops, 1 bottle — NDC 00065-4147-25 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

SIMBRINZA brinzolamide/brimonidine tartrate 10 mg/mL; 2 mg/mL Suspension/ Drops, 1 bottle — NDC 0065-4147-25 (Billing 00065-4147-25)

by Alcon Laboratories, Inc. · 1 BOTTLE, DROPPER in 1 CARTON / 2.5 mL in 1 BOTTLE, DROPPER

This is a package of 1 bottle of SIMBRINZA brinzolamide/brimonidine tartrate 10 mg/mL; 2 mg/mL Suspension/ Drops from Alcon Laboratories, Inc., marketed since May 2013 and currently FDA-listed.

NDC 00065-4147-25
🏷️ FDA NDC (as labeled) 0065-4147-25 billing pads the labeler segment with a zero
This package
Contains1 bottle Pack sizes2 compare ↓
Also priced by: Part D plans $26.22/unit — full pricing hub ↓
Product page 00065-4147-27 Also comes in: 8 mL 0065-4147-27
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Aug 27, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 0065-4147-25
Product NDC 0065-4147
11-digit billing NDC 00065414725
RxCUI 1421451, 1421456
UNII 9451Z89515, 4S9CL2DY2H
Application # NDA204251
SPL Set ID a49c157e-6310-0011-7b7f-e26fc1820d59
Established class (EPC) Carbonic Anhydrase Inhibitor
Mechanism of action Carbonic Anhydrase Inhibitors
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2013-05-06
Route OPHTHALMIC
Dosage form SUSPENSION/ DROPS
Substance BRINZOLAMIDE; BRIMONIDINE TARTRATE

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 86609902201820
GPI class Simbrinza
GCN Seq No 070913
GCN 34579
HICL code 040260
Ingredient (HICL) Brinzolamide/Brimonidine Tart
HIC1 code Q
Therapeutic class — broad (HIC1) Ear/Eye/Nose/Rectum/Topical/Vagina/Other
HIC2 code Q6
Therapeutic class — intermediate (HIC2) Ophthalmic Preparations
HIC3 code Q6G
Therapeutic class — specific (HIC3) Miotics And Other Intraocular Pressure Reducers
AHFS code 52:40.04.00
AHFS class Alpha-Adrenergic Agonists (52:40)
FDB label name SIMBRINZA 1%-0.2% EYE DROP
FDB brand name Simbrinza
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 070913
  • GCN: 34579
  • GPI-14 (Medi-Span): 86609902201820
  • HICL (First Databank): 040260
  • AHFS class code: 52:40.04.00
  • RxCUI (RxNorm): 1421451
Why two NDCs? The FDA registers this code as 0065-4147-25 — a 4-4-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the labeler segment → 00065-4147-25. 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 alpha-Adrenergic Agonist class.

Pharmacologic class alpha-Adrenergic Agonist
Drug family (ATC) Other dermatologicals, Sympathomimetics in glaucoma therapy, Sympathomimetics used as decongestants
How it works Adrenergic alpha-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

Label name SIMBRINZA 1%-0.2% EYE DROP Ingredient Brinzolamide/Brimonidine Tart
📖 What it is MedlinePlus · NLM

Ophthalmic brimonidine is used to lower pressure in the eyes in patients who have glaucoma (a condition in which increased pressure in the eye can lead to gradual loss of vision) or ocular hypertension (increased pressure in the eyes). Brimonidine is in a class of drugs called alpha adrenergic agonists. Brimonidine works by decreasing the amount of fluid in the eyes.

Read the full MedlinePlus article ↗

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 mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $26.22 $65.56 / 2.5 ml
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 Per unit Per pack Marketing startMarketing endStatus
00065-4147-25 You're viewing this 1 BOTTLE, DROPPER in 1 CARTON / 2.5 mL in 1 BOTTLE, DROPPER Sample — — 2013-05-06 — Active
00065-4147-27 0065-4147-27 Main listing 1 BOTTLE, DROPPER in 1 CARTON / 8 mL in 1 BOTTLE, DROPPER $26.04 / mL $208.31 2013-05-06 — Active

This pack shows little to no recent Medicaid volume — a different pack size carries most fills. See all packs ↓

Pack size FAQ

What quantity is in this package?
This package contains 1 bottle — 1 bottle, dropper in 1 carton / 2.5 ml in 1 bottle, dropper.
What NDC number is used to bill for this package of SIMBRINZA brinzolamide/brimonidine tartrate 10 mg/mL; 2 mg/mL Suspension/ Drops?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

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

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Simbrinza 10 mg/mL; 2 mg/mLthis 00065-4147-25 Alcon 1 bottle — — FDA listed —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2013
First FDA approval
Apr 2013
📍
2026
Currently FDA-listed
13 years listed
🛡️
2030
Latest patent/protection listed
not a guaranteed launch date
🔒No FDA-approved generic found

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

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Oct 2030. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Apr 19, 2013 RLD RS ⏳ ~4.1 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 9044484 — drug product
US 9421265 — drug product
2013 2015 2017 2019 2021 2023 2025 2027 2029
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 (2)
PatentTypeUse codeExpires
US 9044484 ↗ Drug product — Oct 30, 2030
US 9421265 ↗ Drug product — Jun 17, 2030
Common questions
Is there a generic version of SIMBRINZA 1%-0.2% EYE DROP?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for SIMBRINZA 1%-0.2% EYE DROP. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Oct 2030 — 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.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII F5UM2KM3W7
    Benzalkonium chloride is a chemical compound that works as a preservative and antimicrobial agent in medications. It prevents bacterial and fungal growth in liquid formulations to keep the product safe during storage and use.
  • UNII R57ZHV85D4
    Boric acid is a weak acid derived from boron. In medicines, it typically serves as a buffer to help maintain the product's pH level and may act as a preservative in certain formulations.
  • UNII HHT01ZNK31
    Carbomer Homopolymer Type B is a synthetic polymer made from acrylic acid. It absorbs water and forms a gel, so it's used in medicines as a thickener, suspending agent, and to help create a smooth texture in creams, gels, and lotions.
  • UNII QTT17582CB
    A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
  • UNII 3OWL53L36A
    A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
  • UNII 6DC9Q167V3
    Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
  • UNII 451W47IQ8X
    Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
  • UNII 55X04QC32I
    A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
  • UNII Y27PUL9H56
    Tyloxapol is a synthetic detergent and surfactant used in medications as a solubilizer and emulsifier. It helps dissolve or blend ingredients that don't naturally mix well, improving how the medicine disperses in liquid formulations.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

10 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

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

Manufacturer & labeler

LabelerAlcon Laboratories, Inc.
Application holderALCON LABORATORIES INC
FDA applicationNDA204251 (NDA)
Labeler code00065
First marketedMay 2013
Product typeHuman Prescription Drug
Portfolio55 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

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 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 78 words ▾

1 INDICATIONS AND USAGE SIMBRINZA (brinzolamide/brimonidine tartrate ophthalmic suspension) 1%/0.2% is a fixed combination of a carbonic anhydrase inhibitor and an alpha 2 adrenergic receptor agonist indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. SIMBRINZA is a combination of brinzolamide, a carbonic anhydrase inhibitor, and brimonidine tartrate, an alpha adrenergic agonist, indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

(1)

⏱️ Dosage and Administration 95 words ▾

2 DOSAGE AND ADMINISTRATION The recommended dose is one drop of SIMBRINZA in the affected eye(s) three times daily. Shake well before use. SIMBRINZA ophthalmic suspension may be used concomitantly with other topical ophthalmic drug products to lower IOP.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart. Shake well before use. Instill one drop in the affected eye(s) three times daily.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart. (2)

💊 Dosage Forms and Strengths 32 words ▾

3 DOSAGE FORMS & STRENGTHS Ophthalmic suspension containing 1% (10 mg/mL) brinzolamide and 0.2% (2 mg/mL) brimonidine tartrate. Ophthalmic suspension containing 1% (10 mg/mL) brinzolamide and 0.2% (2 mg/mL) brimonidine tartrate. (3)

⛔ Contraindications 67 words ▾

4 CONTRAINDICATIONS Hypersensitivity to any component of this product. (4.1) Neonates and infants (under the age of two years). (4.2)

4.1Hypersensitivity SIMBRINZA is contraindicated in patients who are hypersensitive to any component of this product.

4.2Neonates and Infants (under the age of two years) SIMBRINZA is contraindicated in neonates and infants (under the age of two years ) [see Use in Specific Populations (8.4) ].

⚠️ Warnings and Cautions ~2 min read ▾

5 WARNINGS AND PRECAUTIONS Potential for sulfonamide hypersensitivity reactions because of the brinzolamide component (5.1) Potential for corneal endothelium cell loss (5.2) Severe renal impairment may limit the metabolism of the brinzolamide component (5.3)

5.1Sulfonamide Hypersensitivity Reactions SIMBRINZA contains brinzolamide, a sulfonamide, and although administered topically is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration of SIMBRINZA. Fatalities have occurred due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias.

Sensitization may recur when a sulfonamide is re-administered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation immediately. [see Adverse Reactions (6.2) and Patient Counseling Information (17) ].

5.2Corneal Endothelium Carbonic anhydrase activity has been observed in both the cytoplasm and around the plasma membranes of the corneal endothelium. There is an increased potential for developing corneal edema in patients with low endothelial cell counts. Caution should be used when prescribing SIMBRINZA to this group of patients.

5.3Severe Renal Impairment SIMBRINZA has not been specifically studied in patients with severe renal impairment (CrCl less than 30 mL/min). Since brinzolamide and its metabolite are excreted predominantly by the kidney, SIMBRINZA is not recommended in such patients.

5.4Acute Angle-Closure Glaucoma The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents. SIMBRINZA has not been studied in patients with acute angle-closure glaucoma.

5.5Contact Lens Wear The preservative in SIMBRINZA, benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed during instillation of SIMBRINZA but may be reinserted 15 minutes after instillation [see Patient Counseling Information (17) ] .

5.6Severe Cardiovascular Disease Brimonidine tartrate, a component of SIMBRINZA, has a less than 5% mean decrease in blood pressure two hours after dosing in clinical studies; caution should be exercised in treating patients with severe cardiovascular disease.

5.7Severe Hepatic Impairment Because brimonidine tartrate, a component of SIMBRINZA, has not been studied in patients with hepatic impairment, caution should be exercised in such patients.

5.8Potentiation of Vascular Insufficiency Brimonidine tartrate, a component of SIMBRINZA, may potentiate syndromes associated with vascular insufficiency. SIMBRINZA should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic hypotension, or thromboangiitis obliterans.

5.9Contamination of Topical Ophthalmic Products After Use There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers have been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface [see Patient Counseling Information (17) ] .

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS Most common adverse reactions occurring in approximately 3% to 5% of patients included blurred vision, eye irritation, dysgeusia (bad taste), dry mouth, eye allergy. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Alcon Laboratories, Inc. at 1-800-757-9195 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice. SIMBRINZA In two clinical trials of three months duration 435 patients were treated with SIMBRINZA, and 915 were treated with the two individual components. The most frequently reported adverse reactions in patients treated with SIMBRINZA occurring in approximately 3% to 5% of patients in descending order of incidence were blurred vision, eye irritation, dysgeusia (bad taste), dry mouth, and eye allergy.

Rates of adverse reactions reported with the individual components were comparable. Treatment discontinuation, mainly due to adverse reactions, was reported in 11% of SIMBRINZA patients. Other adverse reactions that have been reported with the individual components during clinical trials are listed below.

Brinzolamide 1% In clinical studies of brinzolamide ophthalmic suspension 1%, the most frequently reported adverse reactions reported in 5% to 10% of patients were blurred vision and bitter, sour or unusual taste. Adverse reactions occurring in 1% to 5% of patients were blepharitis, dermatitis, dry eye, foreign body sensation, headache, hyperemia, ocular discharge, ocular discomfort, ocular keratitis, ocular pain, ocular pruritus and rhinitis. The following adverse reactions were reported at an incidence below 1%: allergic reactions, alopecia, chest pain, conjunctivitis, diarrhea, diplopia, dizziness, dry mouth, dyspnea, dyspepsia, eye fatigue, hypertonia, keratoconjunctivitis, keratopathy, kidney pain, lid margin crusting or sticky sensation, nausea, pharyngitis, tearing and urticaria.

Brimonidine Tartrate 0.2% In clinical studies of brimonidine tartrate 0.2%, adverse reactions occurring in approximately 10% to 30% of the subjects, in descending order of incidence, included oral dryness, ocular hyperemia, burning and stinging, headache, blurring, foreign body sensation, fatigue/drowsiness, conjunctival follicles, ocular allergic reactions, and ocular pruritus. Reactions occurring in approximately 3% to 9% of the subjects, in descending order included corneal staining/erosion, photophobia, eyelid erythema, ocular ache/pain, ocular dryness, tearing, upper respiratory symptoms, eyelid edema, conjunctival edema, dizziness, blepharitis, ocular irritation, gastrointestinal symptoms, asthenia, conjunctival blanching, abnormal vision and muscular pain.

The following adverse reactions were reported in less than 3% of the patients: lid crusting, conjunctival hemorrhage, abnormal taste, insomnia, conjunctival discharge, depression, hypertension, anxiety, palpitations/arrhythmias, nasal dryness and syncope.

6.2Postmarketing Experience Brinzolamide The following adverse reactions have been identified during postapproval use of brinzolamide containing products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Serious skin and subcutaneous tissue reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) may occur with the use of brinzolamide due to the sulfonamide component [see Warnings and Precautions (5.1) and Patient Counseling Information Sulfonamide Reactions (17) ].

Brimonidine Tartrate The following reactions have been identified during postmarketing use of brimonidine tartrate ophthalmic solutions in clinical practice. Because they a… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS Oral Carbonic Anhydrase Inhibitors (7.1) High-dose Salicylate Therapy (7.2) Central Nervous System Depressants (7.3) Antihypertensives/Cardiac Glycosides (7.4) Tricyclic Antidepressants (7.5) Monoamine Oxidase (MAO) Inhibitors (7.6)

7.1Oral Carbonic Anhydrase Inhibitors There is a potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition in patients receiving an oral carbonic anhydrase inhibitor and brinzolamide ophthalmic suspension 1%, a component of SIMBRINZA ophthalmic suspension. The concomitant administration of SIMBRINZA and oral carbonic anhydrase inhibitors is not recommended.

7.2High-Dose Salicylate Therapy Carbonic anhydrase inhibitors may produce acid-base and electrolyte alterations. These alterations were not reported in the clinical trials with brinzolamide ophthalmic suspension 1%. However, in patients treated with oral carbonic anhydrase inhibitors, rare instances of acid-base alterations have occurred with high-dose salicylate therapy.

Therefore, the potential for such drug interactions should be considered in patients receiving SIMBRINZA.

7.3Central Nervous System Depressants Although specific drug interaction studies have not been conducted with SIMBRINZA, the possibility of an additive or potentiating effect with Central Nervous System (CNS) depressants (alcohol, opiates, barbiturates, sedatives, or anesthetics) should be considered.

7.4Antihypertensives/Cardiac Glycosides Because brimonidine tartrate, a component of SIMBRINZA, may reduce blood pressure, caution in using drugs such as antihypertensives and/or cardiac glycosides with SIMBRINZA is advised.

7.5Tricyclic Antidepressants Tricyclic antidepressants have been reported to blunt the hypotensive effect of systemic clonidine. It is not known whether the concurrent use of these agents with SIMBRINZA in humans can lead to resulting interference with the IOP lowering effect. Caution is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines.

7.6Monoamine Oxidase Inhibitors Monoamine oxidase (MAO) inhibitors may theoretically interfere with the metabolism of brimonidine tartrate and potentially result in an increased systemic side-effect such as hypotension. Caution is advised in patients taking MAO inhibitors which can affect the metabolism and uptake of circulating amines.

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Developmental toxicity studies with brinzolamide in rabbits at oral doses of 1, 3, and 6 mg/kg/day (20, 60, and 120 times the recommended human ophthalmic dose) produced maternal toxicity at 6 mg/kg/day and a significant increase in the number of fetal variations, such as accessory skull bones, which was only slightly higher than the historic value at 1 and 6 mg/kg. In rats, statistically decreased body weights of fetuses from dams receiving oral doses of 18 mg/kg/day (180 times the recommended human ophthalmic dose) during gestation were proportional to the reduced maternal weight gain, with no statistically significant effects on organ or tissue development.

Increases in unossified sternebrae, reduced ossification of the skull, and unossified hyoid that occurred at 6 and 18 mg/kg were not statistically significant. No treatment-related malformations were seen. Following oral administration of 14 C-brinzolamide to pregnant rats, radioactivity was found to cross the placenta and was present in the fetal tissues and blood.

Developmental toxicity studies performed in rats with oral doses of 0.66 mg brimonidine base/kg revealed no evidence of harm to the fetus. Dosing at this level resulted in a plasma drug concentration approximately 100 times higher than that seen in humans at the recommended human ophthalmic dose. In animal studies, brimonidine crossed the placenta and entered into the fetal circulation to a limited extent.

There are no adequate and well-controlled studies in pregnant women. SIMBRINZA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

8.2Lactation In a study of brinzolamide in lactating rats, decreases in body weight gain in offspring at an oral dose of 15 mg/kg/day (150 times the recommended human ophthalmic dose) were observed during lactation. No other effects were observed. However, following oral administration of 14 C-brinzolamide to lactating rats, radioactivity was found in milk at concentrations below those in the blood and plasma.

In animal studies, brimonidine was excreted in breast milk. It is not known whether brinzolamide and brimonidine tartrate are excreted in human milk following topical ocular administration. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from SIMBRINZA (brinzolamide/brimonidine tartrate ophthalmic suspension) 1%/0.2%, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

8.4Pediatric Use The individual component, brinzolamide, has been studied in pediatric glaucoma patients 4 weeks to 5 years of age. The individual component, brimonidine tartrate, has been studied in pediatric patients 2 to 7 years old. Somnolence (50-83%) and decreased alertness was seen in patients 2 to 6 years old. SIMBRINZA ophthalmic suspension is contraindicated in children under the age of 2 years [see Contraindications (4.2) ].

8.5Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and adult patients.

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Developmental toxicity studies with brinzolamide in rabbits at oral doses of 1, 3, and 6 mg/kg/day (20, 60, and 120 times the recommended human ophthalmic dose) produced maternal toxicity at 6 mg/kg/day and a significant increase in the number of fetal variations, such as accessory skull bones, which was only slightly higher than the historic value at 1 and 6 mg/kg. In rats, statistically decreased body weights of fetuses from dams receiving oral doses of 18 mg/kg/day (180 times the recommended human ophthalmic dose) during gestation were proportional to the reduced maternal weight gain, with no statistically significant effects on organ or tissue development.

Increases in unossified sternebrae, reduced ossification of the skull, and unossified hyoid that occurred at 6 and 18 mg/kg were not statistically significant. No treatment-related malformations were seen. Following oral administration of 14 C-brinzolamide to pregnant rats, radioactivity was found to cross the placenta and was present in the fetal tissues and blood.

Developmental toxicity studies performed in rats with oral doses of 0.66 mg brimonidine base/kg revealed no evidence of harm to the fetus. Dosing at this level resulted in a plasma drug concentration approximately 100 times higher than that seen in humans at the recommended human ophthalmic dose. In animal studies, brimonidine crossed the placenta and entered into the fetal circulation to a limited extent.

There are no adequate and well-controlled studies in pregnant women. SIMBRINZA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

🧒 Pediatric Use 68 words ▾

8.4Pediatric Use The individual component, brinzolamide, has been studied in pediatric glaucoma patients 4 weeks to 5 years of age. The individual component, brimonidine tartrate, has been studied in pediatric patients 2 to 7 years old. Somnolence (50-83%) and decreased alertness was seen in patients 2 to 6 years old. SIMBRINZA ophthalmic suspension is contraindicated in children under the age of 2 years [see Contraindications (4.2) ].

🧓 Geriatric Use 18 words ▾

8.5Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and adult patients.

🆘 Overdosage 104 words ▾

10 OVERDOSAGE Although no human data are available, electrolyte imbalance, development of an acidotic state, and possible nervous system effects may occur following an oral overdose of brinzolamide. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored. Very limited information exists on accidental ingestion of brimonidine in adults; the only adverse event reported to date has been hypotension.

Symptoms of brimonidine overdose have been reported in neonates, infants, and children receiving brimonidine as part of medical treatment of congenital glaucoma or by accidental oral ingestion. Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should be maintained.

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action SIMBRINZA is comprised of two components: brinzolamide (carbonic anhydrase inhibitor) and brimonidine tartrate (alpha 2 adrenergic receptor agonist). Each of these two components decreases elevated IOP. Elevated IOP is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss.

The higher the level of IOP, the greater the likelihood of glaucomatous field loss and optic nerve damage. Brinzolamide inhibits carbonic anhydrase in the ciliary processes of the eye to decrease aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. Brinzolamide has a peak ocular hypotensive effect occurring at 2 to 3 hours post-dosing.

Fluorophotometric studies in animals and humans suggest that brimonidine tartrate has a dual mechanism of action by reducing aqueous humor production and increasing uveoscleral outflow. Brimonidine tartrate has a peak ocular hypotensive effect occurring at two hours post-dosing. The result is a reduction in intraocular pressure (IOP).

12.3Pharmacokinetics Following topical ocular administration, brinzolamide is absorbed into the systemic circulation. Due to its affinity for CA-II, brinzolamide distributes extensively into the Red Blood Cells (RBC) and exhibits a long half-life in whole blood (approximately 111 days). In humans, the metabolite N-desethyl brinzolamide is formed, which also binds to CA and accumulates in RBCs.

This metabolite binds mainly to CA-I in the presence of brinzolamide. In plasma, both parent brinzolamide and N-desethyl brinzolamide concentrations are <10 ng/mL. Binding to plasma proteins is approximately 60%.

Brinzolamide is eliminated predominantly in the urine as unchanged drug. N-Desethyl brinzolamide is also found in the urine along with lower concentrations of the N-desmethoxypropyl and O-desmethyl metabolites. After ocular administration of a 0.2% solution of brimonidine tartrate, plasma concentrations peaked within 1 to 4 hours and declined with a systemic half-life of approximately 3 hours.

In humans, systemic metabolism of brimonidine is extensive. It is metabolized primarily by the liver. Urinary excretion is the major route of elimination of the drug and its metabolites.

Approximately 87% of an orally-administered radioactive dose was eliminated within 120 hours, with 74% found in the urine. In humans, a study was conducted to evaluate the pharmacokinetics of the fixed combination of brinzolamide/brimonidine tartrate 1%/0.2% ophthalmic suspension. Healthy volunteers were randomly assigned to receive twice or three times a day either the fixed combination, or either of its individual components, brinzolamide or brimonidine.

Subjects who were assigned to the brinzolamide alone or combination arms were administered oral brinzolamide capsules for two weeks prior to beginning dosing with the topical ocular suspension. The results demonstrate that the systemic plasma exposure (AUC and Cmax) to brinzolamide and brimonidine in humans is similar after dosing with the fixed combination to that observed following dosing with the individual components.

🧬 Mechanism of Action 160 words ▾

12.1Mechanism of Action SIMBRINZA is comprised of two components: brinzolamide (carbonic anhydrase inhibitor) and brimonidine tartrate (alpha 2 adrenergic receptor agonist). Each of these two components decreases elevated IOP. Elevated IOP is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss.

The higher the level of IOP, the greater the likelihood of glaucomatous field loss and optic nerve damage. Brinzolamide inhibits carbonic anhydrase in the ciliary processes of the eye to decrease aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. Brinzolamide has a peak ocular hypotensive effect occurring at 2 to 3 hours post-dosing.

Fluorophotometric studies in animals and humans suggest that brimonidine tartrate has a dual mechanism of action by reducing aqueous humor production and increasing uveoscleral outflow. Brimonidine tartrate has a peak ocular hypotensive effect occurring at two hours post-dosing. The result is a reduction in intraocular pressure (IOP).

📦 How Supplied / Storage and Handling 68 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING SIMBRINZA (brinzolamide/brimonidine tartrate ophthalmic suspension) 1%/0.2% is supplied in white low density polyethylene (LDPE) DROP-TAINER ® bottles with a natural LDPE dispensing-tip and light green polypropylene cap as follows: 8 mL in a 10 mL bottle NDC 0065-4147-27 Storage and Handling Store SIMBRINZA at 2°C to 25°C (36°F to 77°F). After opening, SIMBRINZA can be used until the expiration date on the bottle.

📋 Description ~1 min read ▾

11 DESCRIPTION SIMBRINZA (brinzolamide/brimonidine tartrate ophthalmic suspension) 1%/0.2% is a fixed combination of a carbonic anhydrase inhibitor and an alpha 2 adrenergic receptor agonist for topical ophthalmic use. Brinzolamide is described chemically as: (R)-(+)-4-Ethylamino-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno [3,2-e]-1,2-thiazine-6-sulfonamide-1,1- dioxide. Its empirical formula is C 12 H 21 N 3 O 5 S 3 , and its structural formula is: Brinzolamide has a molecular weight of 383.5 g/mol.

It is a white powder, which is insoluble in water, very soluble in methanol and soluble in ethanol. Brimonidine tartrate is described chemically as: 5-bromo-6-(2-imidazolidinylideneamino) quinoxaline L-tartrate. Its empirical formula of C 11 H 10 BrN 5 – C 4 H 6 O 6 and its structural formula is: Brimonidine tartrate has a molecular weight of 442.2 g/mol.

It is a white to yellow powder that is soluble in water (34 mg/mL) at pH 6.5. SIMBRINZA (brinzolamide/brimonidine tartrate ophthalmic suspension) 1%/0.2% is supplied as a sterile, aqueous suspension which has been formulated to be readily suspended following shaking. It has a pH of approximately 6.5 and an osmolality of approximately 270 mOsm/kg.

Each mL of SIMBRINZA (brinzolamide/brimonidine tartrate ophthalmic suspension) 1%/0.2% contains: Active ingredients: brinzolamide 10 mg, brimonidine tartrate 2 mg (equivalent to 1.32 mg as brimonidine free base); Preservative: benzalkonium chloride 0.03 mg; Inactive ingredients: boric acid, carbomer 974P, mannitol , propylene glycol, purified water, sodium chloride and tyloxapol. Hydrochloric acid and/or sodium hydroxide may be added to adjust pH.

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Sulfonamide Hypersensitivity Reactions Advise patients that if serious or unusual ocular or systemic reactions or signs of hypersensitivity occur, they should discontinue the use of the product and consult their physician immediately [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.2 )] . Temporary Blurred Vision Vision may be temporarily blurred following dosing with SIMBRINZA. Care should be exercised in operating machinery or driving a motor vehicle [ see Adverse Reactions ( 6.1 ) ]. .

Effect on Ability to Drive and Use Machinery As with other drugs in this class, SIMBRINZA may cause fatigue and/or drowsiness in some patients. Caution patients who engage in hazardous activities of the potential for a decrease in mental alertness. Avoiding Contamination of the Product Instruct patients that ocular solutions, if handled improperly or if the tip of the dispensing container contacts the eye or surrounding structures, can become contaminated by common bacteria known to cause ocular infections.

Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions [see Warnings and Precautions (5.9) ] . Always replace the cap after using. If solution changes color or becomes cloudy, do not use.

Do not use the product after the expiration date marked on the bottle. Intercurrent Ocular Conditions Advise patients that if they have ocular surgery or develop an intercurrent ocular condition (e.g., trauma or infection) they should immediately seek their physician's advice concerning the continued use of the present multi-dose container. Concomitant Topical Ocular Therapy If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart [see Dosage and Administration ] .

Contact Lens Wear The preservative in SIMBRINZA, benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed during instillation of SIMBRINZA, but may be reinserted 15 minutes after instillation [see Warnings and Precautions ( 5.5 )]. ©2023 Alcon Inc. U.S.

Pat.: www.alconpatents.com Alcon Distributed by: ALCON LABORATORIES, INC. Fort Worth, Texas 76134 USA

🧬 Pharmacokinetics ~1 min read ▾

12.3Pharmacokinetics Following topical ocular administration, brinzolamide is absorbed into the systemic circulation. Due to its affinity for CA-II, brinzolamide distributes extensively into the Red Blood Cells (RBC) and exhibits a long half-life in whole blood (approximately 111 days). In humans, the metabolite N-desethyl brinzolamide is formed, which also binds to CA and accumulates in RBCs.

This metabolite binds mainly to CA-I in the presence of brinzolamide. In plasma, both parent brinzolamide and N-desethyl brinzolamide concentrations are <10 ng/mL. Binding to plasma proteins is approximately 60%.

Brinzolamide is eliminated predominantly in the urine as unchanged drug. N-Desethyl brinzolamide is also found in the urine along with lower concentrations of the N-desmethoxypropyl and O-desmethyl metabolites. After ocular administration of a 0.2% solution of brimonidine tartrate, plasma concentrations peaked within 1 to 4 hours and declined with a systemic half-life of approximately 3 hours.

In humans, systemic metabolism of brimonidine is extensive. It is metabolized primarily by the liver. Urinary excretion is the major route of elimination of the drug and its metabolites.

Approximately 87% of an orally-administered radioactive dose was eliminated within 120 hours, with 74% found in the urine. In humans, a study was conducted to evaluate the pharmacokinetics of the fixed combination of brinzolamide/brimonidine tartrate 1%/0.2% ophthalmic suspension. Healthy volunteers were randomly assigned to receive twice or three times a day either the fixed combination, or either of its individual components, brinzolamide or brimonidine.

Subjects who were assigned to the brinzolamide alone or combination arms were administered oral brinzolamide capsules for two weeks prior to beginning dosing with the topical ocular suspension. The results demonstrate that the systemic plasma exposure (AUC and Cmax) to brinzolamide and brimonidine in humans is similar after dosing with the fixed combination to that observed following dosing with the individual components.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES Two clinical trials of 3 months duration were conducted in patients with open-angle glaucoma or ocular hypertension to compare the IOP-lowering effect of SIMBRINZA (brinzolamide/brimonidine tartrate ophthalmic suspension) 1%/0.2% dosed three times daily to individually administered 1% brinzolamide three times daily and 0.2% brimonidine tartrate three times daily. Mean IOP values at baseline are presented in Table 1. Table 1.

Mean (SD) IOP values at baseline SIMBRINZA Brinzolamide Brimonidine Study 1 (n=209) (n=224) (n=216) 8 AM 26.9 (2.63) 27.1 (2.64) 27.0 (2.56) 10 AM 25.3 (2.76) 25.4 (2.74) 25.4 (2.78) 3 PM 23.7 (2.98) 23.8 (3.24) 24.0 (3.27) 5 PM 23.2 (3.08) 23.6 (3.39) 23.7 (3.30) Study 2 (n=218) (n=229) (n=232) 8 AM 27.2 (2.75) 27.2 (2.72) 27.3 (2.73) 10 AM 25.8 (3.09) 26.0 (3.20) 25.8 (3.02) 3 PM 24.4 (3.67) 24.4 (3.58) 24.0 (3.39) 5 PM 24.1 (3.71) 24.2 (3.86) 23.7 (3.58) The IOP-lowering effect of SIMBRINZA ophthalmic suspension was 1 to 3 mmHg greater than monotherapy with either 1% brinzolamide or 0.2% brimonidine tartrate throughout the duration of the trials.

Least Square Mean IOP (mmHg) and the results at Week 2, Week 6 and Month 3 for each study are provided in Table 2. Table 2 Mean IOP (mmHg) by Treatment Group and Treatment Difference in Mean IOP** SIMBRINZA Brinzolamide Brimonidine Study 1 (N=209) (N=224) (N=216) Mean Mean Difference (95%CI)† Mean Difference (95%CI)† Week 2 8 AM 20.4 22.0 -1.6 (-2.3, -0.9) 22.4 -2.0 (-2.7, -1.3) 10 AM 17.1 20.5 -3.4 (-4.1, -2.7) 19.4 -2.3 (-3.0, -1.6) 3 PM 18.4 20.4 -1.9 (-2.6, -1.3) 20.6 -2.2 (-2.9, -1.5) 5 PM 16.6 19.7 -3.2 (-3.9, -2.5) 18.4 -1.9 (-2.6, -1.2) Week 6 8 AM 20.4 21.9 -1.5 (-2.2, -0.8) 22.6 -2.3 (-3.0, -1.6) 10 AM 17.5 20.2 -2.7 (-3.4, -2.0) 19.5 -2.0 (-2.7, -1.3) 3 PM 18.9 20.2 -1.2 (-1.9, -0.5) 21.1 -2.1 (-2.8, -1.4) 5 PM 17.0 19.7 -2.6 (-3.3, -1.9) 18.6 -1.5 (-2.2, -0.8) Month 3 8 AM 20.5 21.6 -1.1 (-1.8, -0.4) 23.3 -2.8 (-3.5, -2.1) 10 AM 17.2 20.4 -3.2 (-3.9, -2.5) 19.7 -2.5 (-3.2, -1.8) 3 PM 18.7 20.4 -1.8 (-2.5, -1.1) 21.3 -2.6 (-3.3, -1.9) 5 PM 17.0 20.0 -3.0 (-3.7, -2.3) 18.8 -1.8 (-2.5, -1.1) Study 2 (N=218) (N=229) (N=232) Week 2 8 AM 20.5 22.2 -1.7 (-2.4, -1.0) 22.8 -2.4 (-3.1, -1.7) 10 AM 17.4 20.7 -3.3 (-4.0, -2.6) 19.2 -1.8 (-2.5, -1.2) 3 PM 18.7 20.5 -1.7 (-2.4, -1.1) 21.1 -2.3 (-3.0, -1.6) 5 PM 16.5 20.1 -3.6 (-4.3, -2.9) 18.3 -1.8 (-2.4, -1.1) Week 6 8 AM 20.7 21.9 -1.2 (-1.9, -0.5) 23.2 -2.5 (-3.2, -1.8) 10 AM 17.4 20.5 -3.1 (-3.8, -2.4) 19.7 -2.3 (-3.0, -1.6) 3 PM 19.3 20.2 -0.8 (-1.5, -0.2) 21.2 -1.9 (-2.6, -1.2) 5 PM 16.9 19.9 -3.0 (-3.7, -2.3) 18.5 -1.7 (-2.4, -1.0) Month 3 8 AM 21.1 22.0 -1.0 (-1.7, -0.3) 23.2 -2.2 (-2.9, -1.5) 10 AM 18.0 20.8 -2.8 (-3.5, -2.1) 19.9 -1.9 (-2.6, -1.2) 3 PM 19.5 20.7 -1.2 (-1.9, -0.5) 21.5 -2.0 (-2.7, -1.3) 5 PM 17.2 20.4 -3.2 (-3.9, -2.5) 18.9 -1.7 (-2.4, -1.0) Abbreviations: CI, 95% Confidence Interval; IOP, intraocular pressure. **Based on the Intent-to-Treat Population defined as all patients who received study drug and completed at least 1 on-therapy study visit. †The estimates are based on least square means derived from a linear mixed model that accounts for correlated IOP measurements within patient; Treatment difference is SIMBRINZA minus individual component.

CI=95% Confidence Interval Figures 1 and 2 present the mean of individual subject IOP changes from baseline at Week 2, Week 6, and at Month 3 based on the observed data for the intent-to-treat population. Figure 1. Mean IOP Change from Baseline (Study 1) Figure 2.

Mean IOP Change from Baseline (Study 2)

🧪 Nonclinical Toxicology ~2 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Brinzolamide caused urinary bladder tumors in female mice at oral doses of 10 mg/kg/day and in male rats at oral doses of 8 mg/kg/day in 2 year studies. Brinzolamide was not carcinogenic in male mice or female rats dosed orally for up to 2 years. The carcinogenicity appears secondary to kidney and urinary bladder toxicity.

These levels of exposure cannot be achieved with topical ophthalmic dosing in humans. The following tests for mutagenic potential of brinzolamide were negative: (1) in vivo mouse micronucleus assay; (2) in vivo sister chromatid exchange assay; and (3) Ames E. coli test. The in vitro mouse lymphoma forward mutation assay was negative in the absence of activation, but positive in the presence of microsomal activation.

In this assay, there was no consistent dose-response relationship to the increased mutation frequency and cytotoxicity likely contributed to the high mutation frequency. Carbonic anhydrase inhibitors, as a class, are not mutagenic and the weight of evidence supports that brinzolamide is consistent with the class. In reproduction studies of brinzolamide in rats, there were no adverse effects on the fertility or reproductive capacity of males or females at doses up to 18 mg/kg/day (180 times the recommended human ophthalmic dose).

Brimonidine tartrate was not carcinogenic in either a 21-month mouse or 24-month rat study. In these studies, dietary administration of brimonidine tartrate at doses up to 2.5 mg/kg/day in mice and 1 mg/kg/day in rats resulted in plasma drug concentrations 80 and 120 times higher than the human plasma drug level at the recommended clinical dose, respectively. Brimonidine tartrate was not mutagenic or cytogenic in a series of in vitro and in vivo studies including the Ames test, chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells, a host-mediated assay and cytogenic studies in mice, and a dominant lethal assay.

In reproductive studies performed in rats with oral doses of 0.66 mg brimonidine base/kg (approximately 100 times the plasma drug concentration level seen in humans following multiple ophthalmic doses), fertility was not impaired.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~2 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Brinzolamide caused urinary bladder tumors in female mice at oral doses of 10 mg/kg/day and in male rats at oral doses of 8 mg/kg/day in 2 year studies. Brinzolamide was not carcinogenic in male mice or female rats dosed orally for up to 2 years. The carcinogenicity appears secondary to kidney and urinary bladder toxicity.

These levels of exposure cannot be achieved with topical ophthalmic dosing in humans. The following tests for mutagenic potential of brinzolamide were negative: (1) in vivo mouse micronucleus assay; (2) in vivo sister chromatid exchange assay; and (3) Ames E. coli test. The in vitro mouse lymphoma forward mutation assay was negative in the absence of activation, but positive in the presence of microsomal activation.

In this assay, there was no consistent dose-response relationship to the increased mutation frequency and cytotoxicity likely contributed to the high mutation frequency. Carbonic anhydrase inhibitors, as a class, are not mutagenic and the weight of evidence supports that brinzolamide is consistent with the class. In reproduction studies of brinzolamide in rats, there were no adverse effects on the fertility or reproductive capacity of males or females at doses up to 18 mg/kg/day (180 times the recommended human ophthalmic dose).

Brimonidine tartrate was not carcinogenic in either a 21-month mouse or 24-month rat study. In these studies, dietary administration of brimonidine tartrate at doses up to 2.5 mg/kg/day in mice and 1 mg/kg/day in rats resulted in plasma drug concentrations 80 and 120 times higher than the human plasma drug level at the recommended clinical dose, respectively. Brimonidine tartrate was not mutagenic or cytogenic in a series of in vitro and in vivo studies including the Ames test, chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells, a host-mediated assay and cytogenic studies in mice, and a dominant lethal assay.

In reproductive studies performed in rats with oral doses of 0.66 mg brimonidine base/kg (approximately 100 times the plasma drug concentration level seen in humans following multiple ophthalmic doses), fertility was not impaired.

📄 Recent Major Changes 10 words ▾

Warnings and Precautions, Sulfonamide Hypersensitivity Reactions ( 5.1 ) 5/2023

📄 Package Label / Principal Display Panel 181 words ▾

PRINCIPAL DISPLAY PANEL NDC 0065-4147-27 SIMBRINZA ® (brinzolamide/brimonidine tartrate ophthalmic suspension) 1% / 0.2% Sterile 8 mL Alcon Rx Only FOR TOPICAL OPHTHALMIC USE ONLY USUAL DOSAGE: Instill one drop in the affected eye three times daily. SHAKE WELL BEFORE USE STORAGE: Store at 2 - 25 °C (36 - 77°F) U.S. Pat.: www.alconpatents.com Each mL contains: Active ingredients: brinzolamide 10 mg, brimonidine tartrate 2 mg (equivalent to 1.32 mg as brimonidine free base); Preservative: benzalkonium chloride 0.03 mg; Inactive ingredients: boric acid, carbomer 974P, mannitol, propylene glycol, purified water, sodium chloride, and tyloxapol.

Hydrochloric acid, and/or sodium hydroxide may be added to adjust pH. ALCON ALCON LABORATORIES, INC. 6201 South Freeway Fort Worth, Texas 76134 USA 1-800-757-9195 [email protected] Printed in USA 300049177-0521 SN: LOT: EXP: GTIN: 00300654147275 PRINCIPAL DISPLAY PANEL NDC 0065-4147-27 SIMBRINZA ® (brinzolamide/brimonidine tartrate ophthalmic suspension) 1% / 0.2% Sterile 8 mL Alcon Alcon Laboratories, Inc Fort Worth, TX 76134 USA Each mL contains: Active: brinzolamide 1%/brimonidine tartrate 0.2% Storage: Store at 2 - 25 °C (36 - 77°F) Usual Dosage: Read insert Rx Only LOT: EXP: 300049176-0521

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

Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
1 bottle00065-4147-27 20,269 Rx · $4,610,377
1 bottle this page00065-4147-25 No Medicaid data
Drug total (last 4 qtrs): 20,269 Rx · 174,674 units · $4,610,377 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

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

Medicare Part D (outpatient prescription) spending for Simbrinza — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Simbrinza. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$17.69M
Claims incl. refills
63.9K
Beneficiaries
40.4K
Spend / beneficiary
$437.39
Spend / claim
$276.97
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for SIMBRINZA (this brand).

Top reported reactions

Treatment Failure381
Ocular Hyperaemia363
Eye Irritation350
Vision Blurred258
Eye Pain231
Hypersensitivity198
Dizziness197

Age at onset

Adolescent1
Adult85
Elderly268

Reporter sex

4,140 reports
Male · 40%
Female · 60%
Unknown · 0%

Serious outcomes

Hospitalization433
Death149
Disabling72
Life-threatening60
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 753 109
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
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The 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.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Alcon Laboratories, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 1 bottle (00065-4147-27). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Alcon Laboratories, 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.
← 00065-4011-05 · Alcon 00065-4274-01 · Alcon →
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.