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Cobenfy xanomeline and trospium chloride Kit — NDC 00003-5200-56 package photo

Cobenfy xanomeline and trospium chloride Kit

by E.R. Squibb & Sons, L.L.C. · 1 KIT in 1 CARTON (0003-5200-56) * 1 BLISTER PACK in 1 PACKAGE (0003-0050-04) / 4 CAPSULE, COATED PELLETS in 1 BLISTER PACK * 1 BLISTER PACK in 1 PACKAGE (0003-1100-01) / 52 CAPSULE, COATED PELLETS in 1 BLISTER PACK
NDC 00003-5200-56
🏷️ FDA NDC (as labeled) 0003-5200-56 billing pads the labeler segment with a zero
Rx only Brand On market Non-controlled
🗂️ Data synced Sep 10, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

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

🆔 Identity & classification

FDA NDC (as labeled) 0003-5200-56
Product NDC 0003-5200
11-digit billing NDC 00003520056
NCPDP billing unit EA — each (per item)
RxCUI 2694843, 2694850, 2694853, 2694855, 2694989, 2694991, 2694992, 2694993,
UNII 9ORI6L73CJ, 1E6682427E
UPC 0300030050601, 0300030125606
Application # NDA216158
SPL Set ID 8f0e73bf-6025-44f6-ab64-0983322de0df
Established class (EPC) Cholinergic Muscarinic Agonist
Mechanism of action Cholinergic Muscarinic Agonists; Cytochrome P450 3A4 Inhibitors; P-Glycoprotein Inhibitors
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2024-09-27
Dosage form KIT
GCN Seq No 086553
GCN 56277
HICL code 049888
Ingredient (HICL) Xanomeline Tart/Trospium Chlor
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H8
Therapeutic class — intermediate (HIC2) Psychoactive Drugs (Continued 2)
HIC3 code H82
Therapeutic class — specific (HIC3) Antipsychotics, Muscarinic Agonist/Antagonist Comb
AHFS code 28:16.08.92
AHFS class Antipsychotics, Miscellaneous
FDB label name COBENFY STARTER PACK
FDB brand name Cobenfy Starter Pack
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 0003-5200-56 — 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 → 00003-5200-56. 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 Cholinergic Muscarinic Antagonist class.

Pharmacologic class Cholinergic Muscarinic Antagonist
Drug family (ATC) Drugs for urinary frequency and incontinence, Other antipsychotics
How it works Cholinergic Muscarinic Antagonists
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerE.R. Squibb & Sons, L.L.C.
Application holderBRISTOL-MYERS SQUIBB CO
FDA applicationNDA216158 (NDA)
Labeler code00003
First marketedSep 2024
Product typeHuman Prescription Drug
Portfolio51 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name COBENFY STARTER PACK Ingredient Xanomeline Tart/Trospium Chlor
📖 What it is MedlinePlus · NLM

Xanomeline and trospium is used to treat schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions). Xanomeline and trospium is in a class of medications called muscarinic agonists. How it works to treat schizophrenia is not known.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Cobenfy is used to treat schizophrenia in adults. It combines two ingredients — xanomeline and trospium — and works differently from most other schizophrenia medications. Xanomelin...
  • Yes, it really does matter. You should take Cobenfy on an empty stomach — at least one hour before eating, or at least two hours after a meal. Food, especially fatty food, can dram...
  • How do I take Cobenfy, and does it matter if I eat first?
  • The most common side effects are stomach-related: nausea, indigestion, constipation, vomiting, abdominal pain, and diarrhea. Dizziness and a faster heart rate are also fairly commo...
📖 Read our full Trospium / Xanomeline 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.

💊 What it looks like

Color White / Brown / Orange
ShapeCapsule
ImprintKaruna;100;20
Size22 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

🧪 Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

The FDA label contains product information, but this exact NDC could not be matched safely to one product block. We intentionally withheld sibling strengths’ ingredients.
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.

💲 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 eaPer package
Retail pharmacies payNADAC · weekly $30.071 —
Medicaid paysCMS SDUD · 12 mo $30.07 —
Medicare drug plans payPart D · Q2 2026 $30.95 —
NADAC price history (per ea) — tap or hover for the price & month
Dec 2025 Jan 2026 Jul 2026 Aug 2026 $30.351 $29.756
▲ Up 1% over the last 4 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Cobenfythis 00003-5200-56 E.R. 4 capsules $30.071 — Availability likely —
Cobenfy 00003-5150-14 E.R. 4 capsules — — 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

🏛️
2024
First FDA approval
Sep 2024
📍
2026
Currently FDA-listed
2 years listed
🛡️
2039
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 2039. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Sep 26, 2024 RLD RS ⏳ ~13.1 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 11890378 — method of use (U-3513)
US 11890378 — method of use (U-3513)
US 11890378 — method of use (U-3513)
US 11471413 — method of use (U-3513)
US 11471413 — method of use (U-3513)
US 11471413 — method of use (U-3513)
US 11452692 — method of use (U-3513)
US 11452692 — method of use (U-3513)
US 11452692 — method of use (U-3513)
US 10933020 — method of use (U-3513)
US 10933020 — method of use (U-3513)
US 10933020 — method of use (U-3513)
US 10695339 — method of use (U-3513)
US 10695339 — method of use (U-3513)
US 10695339 — method of use (U-3513)
US 10369144 — method of use (U-3513)
US 10369144 — method of use (U-3513)
US 10369144 — method of use (U-3513)
US 10369143 — method of use (U-3513)
US 10369143 — method of use (U-3513)
US 10369143 — method of use (U-3513)
US 10265311 — method of use (U-3513)
US 10265311 — method of use (U-3513)
US 10265311 — method of use (U-3513)
US 10238643 — drug product
US 10238643 — drug product
US 12558317 — drug product
US 10925832 — drug product
US 10238643 — drug product
US 10925832 — drug product
US 12558317 — drug product
US 12558317 — drug product
US 10925832 — drug product
Exclusivity NCE
Exclusivity NCE
Exclusivity NCE
2024 2026 2028 2030 2032 2034 2036 2038
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

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

Listed patents (33)
PatentTypeUse codeExpires
US 11890378 ↗ Method of use U-3513 Sep 27, 2039
US 11890378 ↗ Method of use U-3513 Sep 27, 2039
US 11890378 ↗ Method of use U-3513 Sep 27, 2039
US 11471413 ↗ Method of use U-3513 Sep 27, 2039
US 11471413 ↗ Method of use U-3513 Sep 27, 2039
US 11471413 ↗ Method of use U-3513 Sep 27, 2039
US 11452692 ↗ Method of use U-3513 Sep 27, 2039
US 11452692 ↗ Method of use U-3513 Sep 27, 2039
US 11452692 ↗ Method of use U-3513 Sep 27, 2039
US 10933020 ↗ Method of use U-3513 Sep 27, 2039
US 10933020 ↗ Method of use U-3513 Sep 27, 2039
US 10933020 ↗ Method of use U-3513 Sep 27, 2039
US 10695339 ↗ Method of use U-3513 Jul 21, 2030
US 10695339 ↗ Method of use U-3513 Jul 21, 2030
US 10695339 ↗ Method of use U-3513 Jul 21, 2030
US 10369144 ↗ Method of use U-3513 Jul 21, 2030
US 10369144 ↗ Method of use U-3513 Jul 21, 2030
US 10369144 ↗ Method of use U-3513 Jul 21, 2030
US 10369143 ↗ Method of use U-3513 Jul 21, 2030
US 10369143 ↗ Method of use U-3513 Jul 21, 2030
US 10369143 ↗ Method of use U-3513 Jul 21, 2030
US 10265311 ↗ Method of use U-3513 Jul 21, 2030
US 10265311 ↗ Method of use U-3513 Jul 21, 2030
US 10265311 ↗ Method of use U-3513 Jul 21, 2030
US 10238643 ↗ Drug product — Jul 21, 2030
US 10238643 ↗ Drug product — Jul 21, 2030
US 12558317 ↗ Drug product — Oct 29, 2039
US 10925832 ↗ Drug product — Sep 27, 2039
US 10238643 ↗ Drug product — Jul 21, 2030
US 10925832 ↗ Drug product — Sep 27, 2039
US 12558317 ↗ Drug product — Oct 29, 2039
US 12558317 ↗ Drug product — Oct 29, 2039
US 10925832 ↗ Drug product — Sep 27, 2039
FDA exclusivity
CodeWhat it grantsExpires
NCENew Chemical Entity (5-year)Sep 26, 2029
NCENew Chemical Entity (5-year)Sep 26, 2029
NCENew Chemical Entity (5-year)Sep 26, 2029
Common questions
Is there a generic version of COBENFY STARTER PACK?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for COBENFY STARTER PACK. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Oct 2039 — an estimate, not a guaranteed launch date.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

🗺️ Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for 00003-5200-56, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
881
Units reimbursed last 4 qtrs
48.9K
Gross reimbursed last 4 qtrs
$1.47M
Avg / prescription
$1,669.84
Avg / unit
$30.0727
Latest quarter Q1 2026
248Rx
Medicaid pays / ea
$30.0727
gross reimbursed
vs
NADAC / ea
$30.0707
acquisition cost
=
Spread
+$0.0020
+0% vs cost
What Medicaid paid per ea (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care ⓘ
62% FFS 38% MCO
Fee-for-service · 547 Rx Managed care · 334 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: 4,424 units · 44.1 per 100k residents MI New York: 9,128 units · 46.6 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: 1,470 units · 21.4 per 100k residents IN Ohio: 3,738 units · 31.7 per 100k residents OH Pennsylvania: 2,102 units · 16.2 per 100k residents PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: 14,056 units · 36.1 per 100k residents CA Utah: no data reported UT Colorado: 2,800 units · 47.6 per 100k residents CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: 2,072 units · 27.9 per 100k residents AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: 3,416 units · 31.5 per 100k residents NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: 5,097 units · 16.7 per 100k residents TX Florida: 616 units · 2.7 per 100k residents FL
Units reimbursed · per 100k residents
2.747.6
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Colorado 47.6 /100k
2 New York 46.6 /100k
3 Michigan 44.1 /100k
4 California 36.1 /100k
5 Ohio 31.7 /100k
6 North Carolina 31.5 /100k
7 Arizona 27.9 /100k
8 Indiana 21.4 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

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

Medicare Part D (outpatient prescription) spending for Cobenfy — 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 Cobenfy. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$28.3M
Claims incl. refills
17.6K
Beneficiaries
6.7K
Spend / beneficiary
$4,199.55
Spend / claim
$1,608.51
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
00003-5200-56 You're viewing this 1 KIT in 1 CARTON (0003-5200-56) * 1 BLISTER PACK in 1 PACKAGE (0003-0050-04) / 4 CAPSULE, COATED PELLETS in 1 BLISTER PACK * 1 BLISTER PACK in 1 PACKAGE (0003-1100-01) / 52 CAPSULE, COATED PELLETS in 1 BLISTER PACK 2024-09-27 Active

🧭 About this NDC listing & data coverage

Finished prescription product Kit / multi-component package

Kit / multi-component package

This NDC identifies a kit — a package containing more than one component. Structured data (pricing, ingredients, equivalents) is often reported per component rather than for the kit NDC itself, which can make this page look thinner than the components' own pages.

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) ✓ Available
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) ✓ Available
“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

Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 0003-5200-56, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 00003-5200-56, written without dashes as 00003520056. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 00003-5200-56, the first segment (00003) is the labeler code FDA assigned to E.R. Squibb & Sons, L.L.C.; the middle segment (5200) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (56) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by E.R. Squibb & Sons, L.L.C.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
E.R. Squibb & Sons, L.L.C. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🎯 Indications and Usage 40 words ▾

1 INDICATIONS AND USAGE COBENFY is indicated for the treatment of schizophrenia in adults. COBENFY is a combination of xanomeline, a muscarinic agonist, and trospium chloride, a muscarinic antagonist, indicated for the treatment of schizophrenia in adults. ( 1 )

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND ADMINISTRATION • Assess liver enzymes and bilirubin prior to initiating treatment with COBENFY and as clinically indicated during treatment. ( 2.1 ) • Assess heart rate at baseline and as clinically indicated during treatment with COBENFY. ( 2.1 ) • Recommended starting dosage of COBENFY is 50 mg/20 mg orally twice daily for at least two days, then increase the dosage to 100 mg/20 mg twice daily for at least five days.

( 2.2 ) • Dosage may be increased to 125 mg/30 mg orally twice daily based on patient tolerability and response. ( 2.2 ) • See the full prescribing information for the recommended titration and maximum recommended dosage. ( 2.2 ) • Take at least 1 hour before a meal or at least 2 hours after a meal.

Do not open capsules. ( 2.2 ) • Geriatric patients: Recommended starting dosage of COBENFY is 50 mg/20 mg orally twice daily. Consider a slower titration.

The maximum recommended dosage is 100 mg/20 mg twice daily. ( 2.3 )

2.1Recommended Testing and Monitoring Prior to Initiation and During Treatment with COBENFY • Assess liver enzymes and bilirubin prior to initiating COBENFY and as clinically indicated during treatment [see Contraindications (4) and Warnings and Precautions (5.2 , 5.3) ] . • Assess heart rate at baseline and as clinically indicated during treatment [see Warnings and Precautions (5.7) ] .

2.2Recommended Dosage and Administration The recommended dosage of COBENFY is as follows: • The recommended starting dosage is one 50 mg/20 mg capsule (contains 50 mg of xanomeline and 20 mg of trospium chloride) orally twice daily for at least two days. • Increase the dosage to one 100 mg/20 mg capsule (contains 100 mg of xanomeline and 20 mg of trospium chloride) orally twice daily for at least five days. • The dosage may be increased to one 125 mg/30 mg capsule (contains 125 mg of xanomeline and 30 mg of trospium chloride) orally twice daily based on patient tolerability and response [see Clinical Studies (14) ] . • Maximum recommended dosage is 125 mg/30 mg orally twice daily.

Administer COBENFY orally at least one hour before a meal or at least two hours after a meal [see Clinical Pharmacology (12.3) ] . Do not open the capsules.

2.3Dosage Recommendations in Geriatric Patients The recommended starting dosage of COBENFY in geriatric patients is one 50 mg/20 mg capsule orally twice daily. Consider a slower titration for geriatric patients. The maximum recommended dosage in geriatric patients is one 100 mg/20 mg capsule twice daily [see Warnings and Precautions (5.1 , 5.8) and Use in Specific Populations (8.5) ] .

💊 Dosage Forms and Strengths 64 words ▾

3 DOSAGE FORMS AND STRENGTHS COBENFY is available as: • 50 mg/20 mg (xanomeline/trospium chloride): Buff capsules imprinted with Karuna 50/20 mg • 100 mg/20 mg (xanomeline/trospium chloride): Brown capsules imprinted with Karuna 100/20 mg • 125 mg/30 mg (xanomeline/trospium chloride): Swedish Orange capsules imprinted with Karuna 125/30 mg Capsules (xanomeline/trospium chloride): 50 mg/20 mg, 100 mg/20 mg, 125 mg/30 mg ( 3 )

⛔ Contraindications 127 words ▾

4 CONTRAINDICATIONS COBENFY is contraindicated in patients with: • urinary retention [see Warnings and Precautions (5.1) ] . • moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment [see Warnings and Precautions (5.2) ] . • gastric retention [see Warnings and Precautions (5.4) ] . • history of hypersensitivity to COBENFY or trospium chloride. Angioedema has been reported with COBENFY and trospium chloride [see Warnings and Precautions (5.5) ] . • untreated narrow-angle glaucoma [see Warnings and Precautions (5.6) ] .

COBENFY is contraindicated in: • urinary retention ( 4 ) • moderate or severe hepatic impairment ( 4 ) • gastric retention ( 4 ) • history of hypersensitivity to COBENFY or trospium chloride ( 4 ) • untreated narrow-angle glaucoma ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • Risk of Urinary Retention: COBENFY can cause urinary retention. Geriatric patients and patients with bladder outlet obstruction and incomplete bladder emptying are at increased risk. Monitor patients for symptoms of acute urinary retention.

( 5.1 ) • Risk of Use in Patients with Hepatic Impairment: COBENFY is contraindicated in patients with moderate to severe hepatic impairment and is not recommended in patients with mild hepatic impairment. ( 5.2 ) • Risk of Use in Patients with Biliary Disease: Assess liver enzymes and bilirubin prior to initiating COBENFY and as clinically indicated. Discontinue COBENFY in the presence of signs or symptoms of substantial liver injury.

( 5.3 ) • Decreased Gastrointestinal Motility: COBENFY may decrease gastrointestinal motility. Use with caution in patients with gastrointestinal obstructive disorders because of the risk of gastric retention. ( 5.4 ) • Risk of Angioedema: Angioedema of the face, lips, tongue and/or larynx has been reported with COBENFY.

( 5.5 ) • Risk of Use in Patients with Narrow-angle Glaucoma: Use COBENFY only if the potential benefits outweigh the risks and with careful monitoring. ( 5.6 ) • Increases in Heart Rate: COBENFY may increase heart rate. Assess heart rate at baseline and as clinically indicated during treatment with COBENFY.

( 5.7 ) • Anticholinergic Adverse Reactions in Patients with Renal Impairment: COBENFY is not recommended for use in patients with moderate and severe renal impairment. Anticholinergic adverse reactions are expected to be greater in these patients. ( 5.8 ) • Central Nervous System Effects: COBENFY may be associated with CNS effects.

Advise patients not drive or operate heavy machinery until they know how COBENFY affects them. ( 5.9 )

5.1Risk of Urinary Retention COBENFY can cause urinary retention [see Adverse Reactions (6.1 )] . Geriatric patients and patients with clinically significant bladder outlet obstruction and incomplete bladder emptying (e.g., patients with benign prostatic hyperplasia (BPH), diabetic cystopathy) may be at increased risk of urinary retention [see Use in Specific Populations (8.5) ] . COBENFY is contraindicated in patients with pre-existing urinary retention [see Contraindications (4) ] and is not recommended in patients with moderate or severe renal impairment [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] .

In patients taking COBENFY, monitor for symptoms of urinary retention, including urinary hesitancy, weak stream, incomplete bladder emptying, and dysuria. Instruct patients to be aware of the risk and promptly report symptoms of urinary retention to their healthcare provider. Urinary retention is a known risk factor for urinary tract infections.

In patients with symptoms of urinary retention, consider reducing the dose of COBENFY, discontinuing COBENFY, or referring patients for urologic evaluation as clinically indicated.

5.2Risk of Use in Patients with Hepatic Impairment Patients with hepatic impairment have higher systemic exposures of xanomeline, a component of COBENFY, compared to patients with normal hepatic function, which may result in increased incidence of COBENFY-related adverse reactions [see Clinical Pharmacology (12.3) ] . COBENFY is contraindicated in patients with moderate or severe hepatic impairment [see Contraindications (4) ] . COBENFY is not recommended in patients with mild hepatic impairment [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ] .

Assess liver enzymes prior to initiating COBENFY and as clinically indicated during treatment.

5.3Risk of Use in Patients with Biliary Disease In clinical studies with COBENFY, transient increases in liver enzymes with rapid decline occurred, consistent with transient biliary obstruction due to biliary contraction and possible gallstone passage [see Adverse Reactions (6.1) ] . COBENFY is not recommended for patients with active biliary disease such as symptomatic ga…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Risk of Urinary Retention [see Warnings and Precautions (5.1) ] • Risk of Use in Patients with Hepatic Impairment [see Warnings and Precautions (5.2) ] • Risk of Use in Patients with Biliary Disease [see Warnings and Precautions (5.3) ] • Decreased Gastrointestinal Motility [see Warnings and Precautions (5.4) ] • Risk of Angioedema [see Warnings and Precautions (5.5) ] • Risk of Use in Patients with Narrow-angle Glaucoma [see Warnings and Precautions (5.6) ] • Increases in Heart Rate [see Warnings and Precautions (5.7) ] • Anticholinergic Adverse Reactions in Patients with Renal Impairment [see Warnings and Precautions (5.8) ] • Central Nervous System Effects [see Warnings and Precautions (5.9) ] Most common adverse reactions (incidence ≥ 5% and at least twice placebo) were nausea, dyspepsia, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, dizziness, and gastrointestinal reflux disease.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. COBENFY was evaluated for safety in a total of 1,594 subjects exposed to one or more doses, including 1,135 adult patients with schizophrenia and 389 healthy subjects. A total of 347 COBENFY-treated patients had at least 6 months of exposure and 150 patients had at least 1 year of exposure (defined as ≥ 50 weeks) from open-label studies.

The adverse reaction findings are based on two pooled 5-week, placebo-controlled, flexible-dose studies in 504 adult patients with schizophrenia in which COBENFY or placebo was started at an initial dose of 50 mg/20 mg twice daily for the first 2 days followed by 100 mg/20 mg twice daily for the remainder of Week 1 (Days 3 to 7). On Day 8, dosing was titrated to 125 mg/30 mg twice daily unless the patient could not tolerate it. All patients had the option to return to 100 mg/20 mg twice daily for the remainder of the treatment period [see Clinical Studies (14) ] .

In the 5-week placebo-controlled studies, 6% of patients treated with COBENFY and 4% of placebo-treated patients discontinued participation due to adverse reactions. Adverse reactions that led to study discontinuation in ≥1% of patients treated with COBENFY include nausea (2%) and vomiting (1%). The most common adverse reactions (≥5% and at least twice placebo) were nausea, dyspepsia, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, dizziness, and gastroesophageal reflux disease.

Adverse reactions reported with COBENFY at an incidence of at least 2% in patients exposed to COBENFY and greater than the rate of placebo are shown in Table 1. Table 1: Adverse Reactions Reported in ≥2% of COBENFY-Treated Patients and Greater than Rate of Placebo in Two 5-week Schizophrenia Trials a Dyspepsia includes dyspepsia, esophageal discomfort b Hypertension includes hypertension, blood pressure increased, labile hypertension, orthostatic hypertension c Abdominal Pain includes abdominal discomfort, abdominal pain upper, abdominal pain, abdominal pain lower, abdominal tenderness d Tachycardia includes tachycardia, heart rate increased, sinus tachycardia e Cough: includes cough, productive cough f EPS (non-akathisia) includes dyskinesia, drooling, dystonia, extrapyramidal disorder, muscle contraction involuntary, muscle spasms COBENFY (N=251) Placebo (N=253) Nausea 19% 4% Dyspepsia a 18% 5% Constipation 17% 7% Vomiting 15% 1% Hypertension b 11% 2% Abdominal Pain c 8% 4% Diarrhea 6% 2% Tachycardia d 5% 2% Dizziness 5% 2% Gastroesophageal reflux disease 5% <1% Dry mouth…

🔄 Drug Interactions ~3 min read ▾

7 DRUG INTERACTIONS • Drugs Eliminated by Active Tubular Secretion: Monitor for increased frequency and/or severity of adverse reactions related to COBENFY and to drugs eliminated by active tubular secretion. ( 7.1 ) • Strong CYP2D6 Inhibitors: Monitor for increased frequency and/or severity of COBENFY-related adverse reactions. ( 7.1 ) • Sensitive Substrates of CYP3A4 or P-glycoprotein: Monitor for increased frequency and/or severity of adverse reactions from these substrates.

( 7.1 ) • Antimuscarinic Drugs: Monitor for increased frequency or severity of anticholinergic adverse reactions. ( 7.2 )

7.1Clinically Significant Drug Interactions with COBENFY Table 2 displays clinically significant drug interactions with COBENFY. Table 2: Clinically Significant Drug Interactions with COBENFY Strong Inhibitors of CYP2D6 Clinical Implication: CYP2D6 contributes significantly to the metabolism of xanomeline, a component of COBENFY. Concomitant use of COBENFY with strong CYP2D6 inhibitors may increase plasma concentrations of xanomeline, which may increase the frequency and/or severity of adverse reactions from COBENFY [see Clinical Pharmacology (12.3)] .

Prevention or Management: Monitor patients for increased frequency and/or severity of adverse reactions related to COBENFY in patients taking COBENFY with strong inhibitors of CYP2D6. Drugs Eliminated by Active Tubular Secretion Clinical Implication: Concomitant use of COBENFY with drugs that are eliminated by active tubular secretion may increase plasma concentrations of trospium a component of COBENFY, and/or the concomitantly used drug due to competition for this elimination pathway, which may increase the frequency and/or severity of adverse reactions from COBENFY or the drug eliminated by active tubular secretion [see Clinical Pharmacology (12.3)] .

Prevention or Management: Monitor patients for increased frequency and/or severity of adverse reactions related to COBENFY and adverse reactions related to drugs eliminated by active tubular secretion in patients concomitantly receiving such drugs. Oral Drugs That Are Sensitive Substrates of CYP3A4 Clinical Implication: Xanomeline, a component of COBENFY, transiently inhibits CYP3A4 locally in the gut but not systemically. Concomitant use of COBENFY with oral drugs that are sensitive substrates of CYP3A4 may result in increased plasma concentrations of the oral drugs that are sensitive substrates of CYP3A4.

This may increase the frequency and/or severity of adverse reactions from such substrates [see Clinical Pharmacology (12.3)] . Prevention or Management: Monitor patients for increased frequency and/or severity of adverse reactions related to oral drugs that are sensitive substrates of CYP3A4 in patients taking COBENFY with such substrates. Oral Drugs That Are Substrates of P-glycoprotein Clinical Implication: Xanomeline, a component of COBENFY, transiently inhibits P-glycoprotein locally in the gut but not systemically.

Concomitant use of COBENFY with oral drugs that are substrates of P-glycoprotein may result in increased plasma concentrations of the oral drugs that are substrates of P-glycoprotein, which may increase the frequency and/or severity of adverse reactions from such substrates [see Clinical Pharmacology (12.3)] . Prevention or Management: Monitor patients for increased frequency and/or severity of adverse reactions related to oral drugs that are narrow therapeutic index substrates of P-glycoprotein in patients taking COBENFY with such substrates.

7.2Other Antimuscarinic Drugs Concomitant use of COBENFY with other antimuscarinic drugs that produce anticholinergic adverse reactions (e.g., dry mouth, constipation) may increase the frequency and/or severity of such effects. Monitor patients for increased frequency and/or severity of anticholinergic adverse reactions when COBENFY is used concomitantly with other antimuscarinic drugs.

7.3Effects on Absorption of Drugs COBENFY may potentially alter the absorption of some co…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS • Moderate or Severe Renal Impairment: Not recommended. ( 8.6 ) • Mild Hepatic Impairment: Not recommended. ( 8.7 )

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors outcomes in women exposed to psychiatric medications, including COBENFY, during pregnancy. Healthcare providers are encouraged to advise patients to register by calling 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/atypicalantipsychotic/ . Risk Summary There are no available data on COBENFY use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.

There are risks to the mother associated with untreated schizophrenia ( see Clinical Considerations ). In animal reproduction studies, oral administration of xanomeline alone or in combination with trospium chloride during the period of organogenesis or during pregnancy and lactation caused maternal toxicities of adverse clinical signs, decreased body weight, weight gain and food consumption, and/or maternal death. At these maternally toxic doses, embryofetal and developmental toxicities included decreased fetal and neonatal weight, stillborn pups, and/or neonatal deaths.

The no observed adverse effect level (NOAEL) of xanomeline or xanomeline/trospium chloride combination for maternal, embryofetal, and/or developmental toxicity is equal to or higher than the xanomeline and trospium chloride dose at the maximum recommended human dose (MRHD) of 250/60 mg xanomeline/trospium chloride, based on mg/m 2 body surface area (BSA) (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background 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 There is a risk to the pregnant patient from untreated schizophrenia, including increased risk of relapse, hospitalization, and suicide. Schizophrenia is associated with adverse perinatal outcomes, including preterm birth.

It is not known if this is a direct result of the illness or other comorbid factors. Data Animal Data Pregnant rats were orally treated during the period of organogenesis with 150 mg/kg/day xanomeline alone, 100 mg/kg/day trospium chloride alone, or xanomeline/trospium chloride combination at 30/25, 75/50, and 150/100 mg/kg/day, respectively. Xanomeline alone and the high dose combination caused maternal toxicities of decreased body weight, weight gain, and food consumption.

At these maternally toxic doses, fetal weights were decreased. The NOAEL for maternal and embryofetal toxicity is 75/50 mg/kg/day for the combination, which is approximately 3 and 8 times the xanomeline and trospium chloride dose, respectively, at the MRHD of 250/60 mg xanomeline/trospium chloride, based on BSA. No fetal malformation was observed.

Trospium chloride alone did not cause maternal or embryofetal toxicity. Pregnant rabbits were orally treated during the period of organogenesis with120 mg/kg/day xanomeline alone, 80 mg/kg/day trospium chloride alone, or xanomeline/trospium chloride combination at 30/20, 60/40, and 120/80 mg/kg/day, respectively. Xanomeline alone and the high dose combination caused maternal toxicities of decreased body weight, weight gain, and food consumption, and/or early abortion.

At these maternally toxic doses, decreased fetal weight and decreased fetal viability (increased resorption and post-implantation loss) were observed. The NOAEL for maternal and embryofetal toxicity is 60/40 mg/kg/day for the xanomeline/trospium chloride combination, which is 5 and 13 times the xanomeline and trospium chloride dose, respectively at…

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors outcomes in women exposed to psychiatric medications, including COBENFY, during pregnancy. Healthcare providers are encouraged to advise patients to register by calling 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/atypicalantipsychotic/ . Risk Summary There are no available data on COBENFY use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.

There are risks to the mother associated with untreated schizophrenia ( see Clinical Considerations ). In animal reproduction studies, oral administration of xanomeline alone or in combination with trospium chloride during the period of organogenesis or during pregnancy and lactation caused maternal toxicities of adverse clinical signs, decreased body weight, weight gain and food consumption, and/or maternal death. At these maternally toxic doses, embryofetal and developmental toxicities included decreased fetal and neonatal weight, stillborn pups, and/or neonatal deaths.

The no observed adverse effect level (NOAEL) of xanomeline or xanomeline/trospium chloride combination for maternal, embryofetal, and/or developmental toxicity is equal to or higher than the xanomeline and trospium chloride dose at the maximum recommended human dose (MRHD) of 250/60 mg xanomeline/trospium chloride, based on mg/m 2 body surface area (BSA) (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background 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 There is a risk to the pregnant patient from untreated schizophrenia, including increased risk of relapse, hospitalization, and suicide. Schizophrenia is associated with adverse perinatal outcomes, including preterm birth.

It is not known if this is a direct result of the illness or other comorbid factors. Data Animal Data Pregnant rats were orally treated during the period of organogenesis with 150 mg/kg/day xanomeline alone, 100 mg/kg/day trospium chloride alone, or xanomeline/trospium chloride combination at 30/25, 75/50, and 150/100 mg/kg/day, respectively. Xanomeline alone and the high dose combination caused maternal toxicities of decreased body weight, weight gain, and food consumption.

At these maternally toxic doses, fetal weights were decreased. The NOAEL for maternal and embryofetal toxicity is 75/50 mg/kg/day for the combination, which is approximately 3 and 8 times the xanomeline and trospium chloride dose, respectively, at the MRHD of 250/60 mg xanomeline/trospium chloride, based on BSA. No fetal malformation was observed.

Trospium chloride alone did not cause maternal or embryofetal toxicity. Pregnant rabbits were orally treated during the period of organogenesis with120 mg/kg/day xanomeline alone, 80 mg/kg/day trospium chloride alone, or xanomeline/trospium chloride combination at 30/20, 60/40, and 120/80 mg/kg/day, respectively. Xanomeline alone and the high dose combination caused maternal toxicities of decreased body weight, weight gain, and food consumption, and/or early abortion.

At these maternally toxic doses, decreased fetal weight and decreased fetal viability (increased resorption and post-implantation loss) were observed. The NOAEL for maternal and embryofetal toxicity is 60/40 mg/kg/day for the xanomeline/trospium chloride combination, which is 5 and 13 times the xanomeline and trospium chloride dose, respectively at the MRHD, based on BSA. No fetal malformation was observed.

Trospium chloride alone did not cause maternal or embryofetal toxicity. Rats were oral…

🧒 Pediatric Use 16 words ▾

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

🧓 Geriatric Use 77 words ▾

8.5Geriatric Use Controlled clinical studies of COBENFY did not include patients older than 65 years of age to determine whether they respond differently from younger adult patients. Because COBENFY can increase the risk of urinary retention in geriatric patients, including older males with bladder outlet obstruction due to benign prostatic hyperplasia (BPH), a slower titration and lower maximum dosage is recommended in geriatric patients [see Dosage and Administration (2.3) and Warnings and Precautions (5.1) ] .

🆘 Overdosage 81 words ▾

10 OVERDOSAGE Overdose of COBENFY may produce cholinergic, anticholinergic or a combination of cholinergic and anticholinergic signs and symptoms: • Cholinergic Signs and Symptoms: seizures, vomiting, diarrhea, abdominal pain, hyperhidrosis, salivary hypersecretion, and hypotension possibly preceded by hypertension. • Anticholinergic Signs and Symptoms (geriatric patients may be more susceptible): delirium, agitation, garbled speech, dizziness, hypertension, tachycardia, dry mouth and eyes, ileus, blurred vision, and urinary retention.

Consider calling the Poison Help Line 1-800-222-1222 or a medical toxicologist for specific treatment recommendations.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The mechanism of action of xanomeline in the treatment of schizophrenia is unclear; however, its efficacy is thought to be due to its agonist activity at M1 and M4 muscarinic acetylcholine receptors in the central nervous system. Trospium chloride is a muscarinic antagonist. Trospium chloride antagonizes the muscarinic receptors primarily in the peripheral tissues.

12.2Pharmacodynamics Xanomeline binds to muscarinic receptors M1 to M5 with comparable affinity (Ki=10, 12, 17, 7, and 22 nM for the M1, M2, M3, M4, and M5 receptors, respectively) and exhibits higher agonist activity at the M1 and M4 receptors. Trospium chloride antagonizes the muscarinic receptors primarily in peripheral tissues. Cardiac Electrophysiology At the maximum recommended dosage of 125 mg/30 mg twice daily, COBENFY does not prolong the QT interval to any clinically relevant extent.

12.3Pharmacokinetics Following COBENFY administration, xanomeline area under the plasma concentration-time curve during a 12-hour dosing interval (AUC 0-12 ) at steady state and maximum concentration (C max ) increased 50% when the COBENFY dose increased from 100 mg/20 mg twice daily to 125 mg/30 mg twice daily. Trospium exposures increase dose-proportionally over the COBENFY dosage range of 100 mg/20 mg twice daily to 125 mg/30 mg twice daily. Pharmacokinetic properties of COBENFY are provided in Table 3.

Table 3: Pharmacokinetic Properties of COBENFY Parameter Xanomeline Trospium General Information Dose proportionality Greater than proportional Proportional Accumulation a 2 to 3-fold 2 to 3-fold Time to steady state 3 to 5 days 3 to 5 days Absorption T max 2 hours 1 hour Effect of food: PK in fed state (compared to fasted state) High fat meal b C max Unchanged Reduced 70% to 75% AUC Increased 30% Reduced 85% to 90% Low fat meal b C max Unchanged Reduced 70% to 75% AUC Unchanged Reduced 85% to 90% Distribution Central volume of distribution (oral) 10,800 Liters 531 Liters Plasma protein binding Approximately 95% Approximately 80% Elimination Half-life (t 1/2 ) 5 hours 6 hours Apparent clearance 1950 Liters/hour 796 Liters/hour Renal clearance 0.085 Liters/hour 21 Liters/hour Metabolism Primary metabolic pathways CYP450 2D6, 2B6, 1A2, 2C9, and 2C19 Unlikely Other Flavin monooxygenases (FMO1 and FMO3) Ester hydrolysis and glucuronic acid conjugation (not fully characterized) Excretion Urine Total 78% Unknown Unchanged Less than 0.01% 85-90% Tubular secretion Unknown Yes Feces Total 12% Unknown Unchanged Unknown Unknown Abbreviations: AUC = Area under the time-concentration curve; C max = Maximum concentration; T max =Time to C max a Dose-normalized accumulation at steady state b High-fat high-calorie meal is 800-1000 calories, 50% from fat; a low-fat meal is 400-500 calories, 25% from fat Specific Populations Geriatric Patients Population pharmacokinetic analysis suggests that AUC 0-12h and C max of trospium at steady state were 60% higher and 36% higher, respectively, in subjects 65 years and older compared to subjects younger than 65 years old.

The exposures (AUC 0-12h and C max ) of xanomeline at steady state were not different between subjects 65 years and older and subjects younger than 65 years old [see Dosage and Administration (2.3) and Use in Specific Populations (8.5) ] . Male and Female Patients Plasma concentrations of xanomeline and trospium are similar between females and males. Racial or Ethnic Groups Most subjects in clinical studies were Black.

Xanomeline and trospium exposure did not differ between Black and non-Black subjects. Studies have included too few subjects of Asian descent to evaluate comparisons. Patients with Renal Impairment The effect of renal impairment on xanomeline and trospium exposure was assessed in a dedicated study that enrolled healthy subjects and subjects with mild, moderate, or severe renal impairment.

Estimated glomerular filtration rate (eGFR) was determined by the MDRD equation.…

🧬 Mechanism of Action 58 words ▾

12.1Mechanism of Action The mechanism of action of xanomeline in the treatment of schizophrenia is unclear; however, its efficacy is thought to be due to its agonist activity at M1 and M4 muscarinic acetylcholine receptors in the central nervous system. Trospium chloride is a muscarinic antagonist. Trospium chloride antagonizes the muscarinic receptors primarily in the peripheral tissues.

📦 How Supplied / Storage and Handling 204 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied COBENFY is available as: • 50 mg/20 mg (xanomeline/trospium chloride): Buff capsules imprinted with Karuna 50/20 mg • 100 mg/20 mg (xanomeline/trospium chloride): Brown capsules imprinted with Karuna 100/20 mg • 125 mg/30 mg (xanomeline/trospium chloride): Swedish Orange capsules imprinted with Karuna 125/30 mg COBENFY capsules are packaged as described in Table 5. Table 5: COBENFY Packaging Configurations Capsule Strength Total Package Count Package Configuration Package Components NDC Code 50 mg/20 mg 60 Bottle N/A 0003-0050-60 100 Hospital Unit-Dose Blister 10 Blister Cards with 10 Capsules Each 0003-0050-98 100 mg/20 mg 60 Bottle N/A 0003-1100-60 100 Hospital Unit-Dose Blister 10 Blister Cards with 10 Capsules Each 0003-1100-98 125 mg/30 mg 60 Bottle N/A 0003-0125-60 100 Hospital Unit-Dose Blister 10 Blister Cards with 10 Capsules Each 0003-0125-98 50 mg/20 mg (4) 100 mg/20 mg (52) 56 Starter Pack for 100 mg/20 mg dose 1 Mixed Blister Wallet: four (4) 50 mg/20 mg capsules and ten (10) 100 mg/20 mg capsules and 3 Wallets: fourteen (14) 100 mg/20 mg capsules in each wallet 0003-5200-56 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

📋 Description ~1 min read ▾

11 DESCRIPTION COBENFY is a combination of xanomeline, a muscarinic agonist, and trospium chloride, a muscarinic antagonist. The chemical name of xanomeline tartrate is pyridine, 3-[4-(hexyloxy)-1,2,5-thiadiazol-3-yl]-1,2,5,6-tetrahydro-1-methyl-, (2R,3R)-2,3-dihydroxybutanedioate (1:1). Its molecular formula is C 14 H 23 N 3 OS.C 4 H 6 O 6 and its molecular weight is 431.51 g/mol.

Xanomeline tartrate is a white to slightly tan crystalline solid. Xanomeline tartrate is highly soluble in protic solvents, such as methanol and water, and in polar organic solvents such as DMF and dimethyl sulfoxide (DMSO). It is poorly soluble in lipophilic organic solvents, such as hexane or octanol.

The chemical structure of xanomeline tartrate is: Trospium chloride is a quaternary ammonium compound with the chemical name of spiro[8-azoniabicyclo[3.2.1]octane-8,1′-pyrrolidinium], 3-[(2-hydroxy-2,2-diphenylacetyl)oxy]-, chloride (1:1), (1α,3β,5α). The molecular formula of trospium chloride is C 25 H 30 NO 3 .Cl and its molecular weight is 427.96 g/mol. Trospium chloride is a fine, colorless to slightly yellow, crystalline solid.

Trospium chloride is highly soluble in water, freely soluble in methanol, and practically insoluble in methylene chloride. The chemical structure of trospium chloride is: COBENFY (xanomeline and trospium chloride) is for oral administration and is available in capsules in the following strengths: • 50 mg/20 mg (equivalent to 76.7 mg xanomeline tartrate and 18.3 mg trospium). • 100 mg/20 mg (equivalent to 153.3 mg xanomeline tartrate and 18.3 mg trospium). • 125 mg/30 mg (equivalent to 191.7 mg xanomeline tartrate and 27.5 mg trospium).

COBENFY capsules contain a combination of pellets of xanomeline and pellets of trospium chloride. Inactive ingredients: The xanomeline tartrate pellets contain ascorbic acid, microcrystalline cellulose, and talc. The trospium chloride pellets contain lactose monohydrate, microcrystalline cellulose, and talc.

The capsules, printed with black ink, contain black iron oxide (only 100 mg/20 mg), hypromellose, red iron oxide, titanium dioxide, and yellow iron oxide (only 50 mg/20 mg and 100 mg/20 mg). Chemical Structure Chemical Structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Risk of Urinary Retention Inform patients that COBENFY may cause urinary retention and that the risk of urinary retention is greater in some patients, including geriatric patients and those with bladder outlet obstruction (e.g., due to BPH) and patients with other causes of reduced bladder emptying (e.g., diabetic cystopathy). Urinary retention may occur at any time during treatment with COBENFY and is more likely when taking higher doses.

Advise patients to monitor for symptoms of urinary retention, such as urinary hesitancy, weak urinary stream, incomplete bladder emptying and pain with urination, and to promptly report these symptoms to their healthcare provider. Inform patients that urinary retention may increase the risk of urinary tract infection. Advise patients to seek immediate medical attention if they are unable to urinate [see Warnings and Precautions (5.1) ] .

Risk of Use in Patients with Hepatic Impairment Instruct patients to report signs of hepatic impairment (e.g., skin and eyes that appear yellowish, abdominal pain and swelling, itchy skin, dark urine color) and symptoms of hepatic injury (e.g., biliary spasm, pancreatitis, and cholangitis) to their healthcare provider [see Warnings and Precautions (5.2) ] . Risk of Use in Patients with Biliary Disease Inform patients that COBENFY can increase liver enzymes and about the need for specific monitoring, including liver enzymes and bilirubin levels.

Inform patients to report symptoms such as dyspepsia, nausea, vomiting, or upper abdominal pain to their healthcare provider [see Warnings and Precautions (5.3) ] . Decreased Gastrointestinal Motility Inform patients that COBENFY can delay or slow emptying of food in their stomach. Advise patients to inform their healthcare provider about the presence of or symptoms of gastrointestinal obstructive disorders and conditions such as ulcerative colitis, intestinal atony, and myasthenia gravis [see Warnings and Precautions (5.4) ] .

Risk of Angioedema Advise patients that hypersensitivity reactions to COBENFY could and occur and result in life-threatening airway obstruction. Instruct patients to seek medical attention if they experience edema of the tongue, edema of the laryngopharynx, or difficulty breathing occurs, discontinue COBENFY, and seek immediate medical attention [see Warnings and Precautions (5.5) ] . Risk of Use in Patients with Narrow-angle Glaucoma Inform patients pupillary dilation may occur with COBENFY use and in susceptible individuals, can lead to an episode of angle closure glaucoma [see Warnings and Precautions (5.6) ] .

Increases in Heart Rate Inform patients that COBENFY can increase heart rate [see Warnings and Precautions (5.7) ] . Anticholinergic Adverse Reactions in Patients with Renal Impairment Inform patients that COBENFY is associated with anticholinergic adverse reactions such as dry mouth, constipation, dyspepsia, urinary tract infection, and urinary retention and the effects are expected to be greater in patients with renal impairment [see Warnings and Precautions (5.8) ] . Central Nervous System Effects Advise patients that COBENFY is associated with central nervous system effects such as dizziness, confusion, hallucinations, and somnolence.

Caution patients about performing activities requiring mental alertness, such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that COBENFY therapy does not adversely affect their ability to engage in such activities [see Warnings and Precautions (5.9) ] . Administration Information Instruct patients to take COBENFY twice daily at least one hour before a meal or at least 2 hours after a meal and not to open the capsules [see Dosage and Administration (2.2) ] . Concomitant Medications Advise patients to inform their health care providers of any changes to their current prescription or ove…

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