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KISQALI FEMARA CO-PACK letrozole and ribociclib Kit

by Novartis Pharmaceuticals Corporation · 1 KIT in 1 KIT (0078-0909-61) * 28 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (0078-0881-50) * 21 TABLET in 1 BLISTER PACK (0078-0888-21)
NDC 00078-0909-61
🏷️ FDA NDC (as labeled) 0078-0909-61 billing pads the labeler segment with a zero
Rx only Brand Discontinued Non-controlled ⚠ Discontinued by firm
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

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

⚠️
Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. The listing was last certified through Aug 2026. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

🆔 Identity & classification

FDA NDC (as labeled) 0078-0909-61
Product NDC 0078-0909
11-digit billing NDC 00078090961
NCPDP billing unit EA — each (per item)
RxCUI 153124, 200064, 1873983, 1873989, 1923053, 1923054, 1923055, 1923056,
Application # NDA209935
SPL Set ID aa5e4446-19cd-4235-a382-5b48bf6c3b2f
DEA schedule Non-controlled
Marketing category NDA
Marketing status Discontinued
FDA listing status Discontinued by firm (certified through Aug 2026)
Marketing start 2017-05-04
Marketing end 2026-08-31
Dosage form KIT
GCN Seq No 077379
GCN 43366
HICL code 044246
Ingredient (HICL) Ribociclib Succinate/Letrozole
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V3
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs (Continued 1)
HIC3 code V31
Therapeutic class — specific (HIC3) Antineoplastic Comb - Kinase And Aromatase Inhibit
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name KISQALI FEMARA 200 MG CO-PACK
FDB brand name Kisqali Femara Co-Pack
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 0078-0909-61 — 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 → 00078-0909-61. 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 Aromatase Inhibitor class.

Pharmacologic class Aromatase Inhibitor
Drug family (ATC) Aromatase inhibitors
How it works Aromatase Inhibitors
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

LabelerNovartis Pharmaceuticals Corporation
Application holderNOVARTIS PHARMACEUTICALS CORP
FDA applicationNDA209935 (NDA)
Labeler code00078
First marketedMay 2017
Product typeHuman Prescription Drug
Portfolio209 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 KISQALI FEMARA 200 MG CO-PACK Ingredient Ribociclib Succinate/Letrozole
📖 What it is MedlinePlus · NLM

Letrozole is used treat early breast cancer in women who have experienced menopause (change of life; end of monthly menstrual periods) and who have had other treatments, such as radiation or surgery to remove the tumor. It is also used to treat early breast cancer in women who have experienced menopause and who have already been treated with a medication called tamoxifen (Nolvadex) for 5 years. Letrozole is also used in women who have experienced menopause as a first treatment of breast cancer that has spread within the breast or to other areas of the body or in women whose breast cancer has w...

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It's a co-packaged product that contains two different cancer medicines — ribociclib (KISQALI) and letrozole (FEMARA) — that work in different ways to fight the same type of breast...
  • What exactly is KISQALI FEMARA CO-PACK and why did my doctor prescribe both medicines together?
  • The two medicines follow slightly different schedules within the same 28-day cycle. Letrozole is taken every single day throughout the cycle. Ribociclib is taken once a day for 21...
  • How do I take these medicines — do I take both pills every day?
📖 Read our full Letrozole / Ribociclib 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 Yellow / Purple
ShapeRound
ImprintRIC;NVR
Size11 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.

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

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Kisqali Femara Co-Packthis 00078-0909-61 Novartis 21 tablets — — Discontinued —
Kisqali Femara Co-Pack 00078-0916-61 Novartis 14 tablets — — Discontinued —
Kisqali Femara Co-Pack 00078-0923-61 Novartis 21 tablets — — Discontinued —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

⏳ Availability & generic status

🏛️
2017
First FDA approval
May 2017
📍
2026
Currently FDA-listed
9 years listed
🛡️
2036
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 2036. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved May 4, 2017 RLD RS ⏳ ~10.1 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 8962630 — method of use (U-2505)
US 9416136 — method of use (U-2505)
US 9868739 — method of use (U-3998)
US 9416136 — method of use (U-3998)
US 8962630 — method of use (U-3998)
US 12544380 — method of use (U-3264)
US 12544380 — method of use (U-3998)
US 9868739 — method of use (U-2505)
US 8962630 — method of use (U-3264)
US 9416136 — method of use (U-3264)
US 9868739 — method of use (U-3264)
US 8415355 — drug substance
US 12419894 — drug product
US 10799506 — drug product
US 8324225 — drug substance
US 12064434 — drug product
US 8685980 — drug substance
US 9193732 — drug substance
US 8415355*PED — drug product
US 8324225*PED — drug product
US 9416136*PED — drug product
US 8962630*PED — drug product
US 8685980*PED — drug product
US 9193732*PED — drug product
US 9868739*PED — drug product
US 10799506*PED — drug product
US 12064434*PED — drug product
US 12419894*PED — drug product
US 12544380*PED — drug product
Exclusivity I-951
Exclusivity PED
2017 2019 2021 2023 2025 2027 2029 2031 2033 2035
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

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

Listed patents (29)
PatentTypeUse codeExpires
US 8962630 ↗ Method of use U-2505 Dec 9, 2029
US 9416136 ↗ Method of use U-2505 Aug 20, 2029
US 9868739 ↗ Method of use U-3998 Nov 9, 2031
US 9416136 ↗ Method of use U-3998 Aug 20, 2029
US 8962630 ↗ Method of use U-3998 Dec 9, 2029
US 12544380 ↗ Method of use U-3264 Aug 7, 2034
US 12544380 ↗ Method of use U-3998 Aug 7, 2034
US 9868739 ↗ Method of use U-2505 Nov 9, 2031
US 8962630 ↗ Method of use U-3264 Dec 9, 2029
US 9416136 ↗ Method of use U-3264 Aug 20, 2029
US 9868739 ↗ Method of use U-3264 Nov 9, 2031
US 8415355 ↗ Drug substance — Mar 13, 2031
US 12419894 ↗ Drug product — Apr 14, 2036
US 10799506 ↗ Drug product — Apr 14, 2036
US 8324225 ↗ Drug substance — Jun 17, 2028
US 12064434 ↗ Drug product — Apr 14, 2036
US 8685980 ↗ Drug substance — May 25, 2030
US 9193732 ↗ Drug substance — Nov 9, 2031
US 8415355*PED ↗ Drug product — Sep 13, 2031
US 8324225*PED ↗ Drug product — Dec 17, 2028
US 9416136*PED ↗ Drug product — Feb 20, 2030
US 8962630*PED ↗ Drug product — Jun 9, 2030
US 8685980*PED ↗ Drug product — Nov 25, 2030
US 9193732*PED ↗ Drug product — May 9, 2032
US 9868739*PED ↗ Drug product — May 9, 2032
US 10799506*PED ↗ Drug product — Oct 14, 2036
US 12064434*PED ↗ Drug product — Oct 14, 2036
US 12419894*PED ↗ Drug product — Oct 14, 2036
US 12544380*PED ↗ Drug product — Feb 7, 2035
FDA exclusivity
CodeWhat it grantsExpires
I-951New indication (3-year)Sep 17, 2027
PEDPediatric Exclusivity (+6 months)Mar 17, 2028
Common questions
Is there a generic version of KISQALI FEMARA 200 MG CO-PACK?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for KISQALI FEMARA 200 MG CO-PACK. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Oct 2036 — 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.

🔬 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 KISQALI FEMARA CO-PACK (this brand).

Top reported reactions

Fatigue63
Nausea49
Death43
White Blood Cell Count Decreased37
Diarrhoea34
Rash25
Malaise24

Age at onset

Adult5
Elderly2

Reporter sex

540 reports
Male · 2%
Female · 98%

Serious outcomes

Hospitalization72
Death53
Life-threatening7
Disabling3
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 90 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
00078-0909-61 You're viewing this 1 KIT in 1 KIT (0078-0909-61) * 28 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (0078-0881-50) * 21 TABLET in 1 BLISTER PACK (0078-0888-21) 2017-05-04 Discontinued by firm

🧭 About this NDC listing & data coverage

Finished prescription product Kit / multi-component package No longer marketed (per FDA listing data)

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 — Not published for this NDC No photo available yet for this listing.
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available.
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
What does the discontinued status mean for this NDC?
The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 0078-0909-61, 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: 00078-0909-61, written without dashes as 00078090961. 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 00078-0909-61, the first segment (00078) is the labeler code FDA assigned to Novartis Pharmaceuticals Corporation; the middle segment (0909) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (61) identifies this exact package size and type. Together they name one specific package of one specific product.
Who lists this product with the FDA?
Novartis Pharmaceuticals Corporation 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 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🎯 Indications and Usage 152 words ▾

1 INDICATIONS AND USAGE KISQALI FEMARA CO-PACK, a co-packaged product containing ribociclib, a kinase inhibitor, and letrozole, an aromatase inhibitor, is indicated: for the adjuvant treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer at high risk of recurrence. ( 1 ) as initial endocrine-based therapy for the treatment of adults with HR-positive, HER2-negative advanced or metastatic breast cancer therapy. ( 1 )

1.1Early Breast Cancer KISQALI ® FEMARA ® CO-PACK is indicated for the adjuvant treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer at high risk of recurrence.

1.2Advanced or Metastatic Breast Cancer KISQALI ® FEMARA ® CO-PACK indicated as initial endocrine-based therapy for the treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION KISQALI FEMARA CO-PACK tablets are taken in combination orally with or without food. ( 2 ) Early Breast Cancer KISQALI recommended starting dose: 400 mg orally (two 200 mg tablets) taken once daily for 21 consecutive days followed by 7 days off KISQALI treatment. ( 2.1 ) Advanced or Metastatic Breast Cancer KISQALI recommended starting dose: 600 mg orally (three 200 mg tablets) taken once daily for 21 consecutive days followed by 7 days off KISQALI treatment.

( 2.1 ) KISQALI dose interruption, reduction, and/or discontinuation may be required based on individual safety and tolerability. ( 2.2 ) FEMARA: 2.5 mg (one tablet) continuously for a 28-day cycle. ( 2.1 )

2.1Recommended Dosage Important Administration Instructions The KISQALI FEMARA CO-PACK is comprised of ribociclib tablets co-packaged with letrozole tablets, to provide a 28-day treatment regimen. KISQALI FEMARA CO-PACK can be taken with or without food [ see Clinical Pharmacology (12.3) ]. Pre/perimenopausal women, or men, treated with KISQALI FEMARA CO-PACK should be treated with a luteinizing hormone-releasing hormone (LHRH) agonist according to current clinical practice standards.

Patients should take their doses of KISQALI FEMARA CO-PACK at approximately the same time each day, preferably in the morning. If the patient vomits after taking the dose or misses a dose, no additional dose should be taken that day. The next prescribed dose should be taken at the usual time.

Tablets should be swallowed whole (tablets should not be chewed, crushed or split prior to swallowing). No tablet should be ingested if it is broken, cracked, or otherwise not intact. Early Breast Cancer KISQALI: The recommended dosage of KISQALI is 400 mg (two 200 mg film-coated tablets) taken orally, once daily for 21 consecutive days followed by 7 days off in 28-day treatment cycles.

FEMARA: 2.5 mg (one tablet) taken once daily throughout the 28-day cycle. In patients with early breast cancer, treatment with KISQALI should continue for 3 years or until disease recurrence or unacceptable toxicity occurs. Advanced or Metastatic Breast Cancer KISQALI: The recommended dosage for KISQALI is 600 mg (three 200 mg film-coated tablets) taken orally, once daily for 21 consecutive days followed by 7 days off in 28-day treatment cycles.

FEMARA: 2.5 mg (one tablet) taken once daily throughout the 28-day cycle. Refer to the Full Prescribing Information for the recommended dosage for each product.

2.2Dose Modifications Dose Modifications for Adverse Reactions The recommended dose modifications of KISQALI for adverse reactions are listed in Table 1. Dose modifications are not recommended for FEMARA when administered with KISQALI for the adverse reactions of KISQALI, including neutropenia, hepatobiliary toxicity, or QT prolongation [see Dosage and Administration (2)] . Table 1: Recommended Dose Modification of KISQALI FEMARA CO-PACK for Adverse Reactions Level KISQALI FEMARA Dose Number of tablets Dose Number of tablets Early breast cancer Starting dose 400 mg/day two 200 mg tablets 2.5 mg/day one 2.5 mg tablet Dose reduction 200 mg/day * one 200 mg tablet 2.5 mg/day one 2.5 mg tablet Advanced or metastatic breast cancer Starting dose 600 mg/day three 200 mg tablets 2.5 mg/day one 2.5 mg tablet First dose reduction 400 mg/day two 200 mg tablets 2.5 mg/day one 2.5 mg tablet Second dose reduction 200 mg/day* one 200 mg tablet 2.5 mg/day one 2.5 mg tablet *If dose reduction below 200 mg/day is required, discontinue KISQALI.

Tables 2, 3, 4, 5, 6, and 7 summarize recommendations for dose interruption, reduction, or discontinuation of KISQALI in the management of specific adverse reactions. Dose modification of KISQALI FEMARA CO-PACK is recommended based on individual patient safety and tolerability. Table 2: Dose Modification and Management for Interstitial Lung Disease/Pneumonitis Grade 1 (asymptomatic) Grade 2 (symptomatic) Grade 3 (severe symptomatic) or 4 (life-threatening) ILD/Pneumon…

💊 Dosage Forms and Strengths 88 words ▾

3 DOSAGE FORMS AND STRENGTHS KISQALI FEMARA CO-PACK is KISQALI (ribociclib) tablets co-packaged with FEMARA (letrozole) tablets. Tablet: 200 mg ribociclib (equivalent to 254.40 mg ribociclib succinate). Film-coated, light greyish violet, round, curved with beveled edges, debossed with “RIC” on one side and “NVR” on the other side.

Tablet: 2.5 mg letrozole. Dark yellow, film-coated, round, slightly biconvex, with beveled edges (imprinted with the letters “FV” on one side and “CG” on the other side). Tablets: KISQALI: 200 mg ( 3 ) FEMARA: 2.5 mg ( 3 )

⛔ Contraindications 35 words ▾

4 CONTRAINDICATIONS Known hypersensitivity to the active substance (letrozole), or to any of the excipients of FEMARA. Refer to FEMARA Prescribing Information. Known hypersensitivity to letrozole, or to any excipients of FEMARA. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life threatening, or fatal ILD/pneumonitis can occur with KISQALI treatment. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Interrupt and evaluate patients with new or worsening respiratory symptoms suspected to be due to ILD/pneumonitis.

Permanently discontinue KISQALI in patients with recurrent symptomatic or severe ILD/pneumonitis. ( 2.2 , 5.1 ) Severe Cutaneous Adverse Reactions (SCARs): SCARS including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) can occur with KISQALI treatment. Permanently discontinue KISQALI in patients with SCARs or other life-threatening cutaneous reactions.

( 2.2 , 5.2 ) QT Interval Prolongation: KISQALI has been shown to prolong the QT interval in a concentration-dependent manner. Monitor electrocardiograms (ECGs) and electrolytes prior to initiation of treatment with KISQALI. Repeat ECGs at approximately Day 14 of the first cycle, and as clinically indicated.

Monitor electrolytes at the beginning of each cycle for 6 cycles, and as clinically indicated. Avoid using KISQALI with drugs known to prolong QT interval and/or strong CYP3A inhibitors. ( 2.2 , 5.3 , 7.1 , 7.4 ) Hepatobiliary Toxicity: Increases in serum transaminase and bilirubin levels have been observed.

Perform liver function tests (LFTs) before initiating treatment with KISQALI FEMARA CO-PACK. Monitor LFTs every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated. ( 2.2, 5.4 ) Neutropenia: Perform complete blood count (CBC) before initiating therapy with KISQALI FEMARA CO-PACK.

Monitor CBC every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated. ( 2.2, 5.5 ) Embryo-Fetal Toxicity: Can cause fetal harm when administered to pregnant women. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during therapy.

( 5.6 , 8.1 , 8.3 )

5.1Interstitial Lung Disease/Pneumonitis Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with KISQALI and other CDK4/6 inhibitors. In patients with early breast cancer (NATALEE) who received 400 mg KISQALI plus a non-steroidal aromatase inhibitor (NSAI), 1.5% of patients had ILD/pneumonitis (Grade 1-2). In patients with advanced or metastatic breast cancer (MONALEESA-2, MONALEESA-7), 1.2% of KISQALI-treated patients had ILD/pneumonitis (any grade, 0.3% had Grade 3-4).

Additional cases of ILD/pneumonitis have occurred in the postmarketing setting, some resulting in death [see Adverse Reactions (6.2)] . Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis which may include hypoxia, cough, and dyspnea. In patients who have new or worsening respiratory symptoms suspected to be due to ILD or pneumonitis, interrupt KISQALI immediately and evaluate the patient.

Permanently discontinue KISQALI in patients with severe ILD/pneumonitis or any recurrent symptomatic ILD/pneumonitis [see Dosage and Administration (2.2)] . Refer to the Full Prescribing Information for KISQALI ® .

5.2Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS), can occur in patients treated with KISQALI [see Adverse Reactions (6.2)] . If signs or symptoms of SCARs occur, interrupt KISQALI until the etiology of the reaction has been determined [see Dosage and Administration (2.2)] . Early consultation with a dermatologist is recommended to ensure greater diagnostic accuracy and appropriate management.

If SJS, TEN, or DiHS/DRESS is confirmed, permanently discontinue KISQALI. Do not reintroduce KISQALI in patients who have…

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.1)] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.2)] QT Interval Prolongation [see Warnings and Precautions (5.3)] Hepatobiliary Toxicity [see Warnings and Precautions (5.4)] Neutropenia [see Warnings and Precautions (5.5)] In patients with early breast cancer, the most common (incidence ≥ 20%) adverse reactions, including laboratory abnormalities, are lymphocytes decreased, leukocytes decreased, neutrophils decreased, hemoglobin decreased, alanine aminotransferase increased, aspartate aminotransferase increased, infections, creatinine increased, platelets decreased, headache, nausea, and fatigue.

( 6 ) In patients with advanced or metastatic breast cancer, the most common (incidence ≥ 20%) adverse reactions, including laboratory abnormalities, are leukocytes decreased, neutrophils decreased, hemoglobin decreased, lymphocytes decreased, alanine aminotransferase increased, aspartate aminotransferase increased, infections, nausea, fatigue, platelets decreased, diarrhea, headache, alopecia, vomiting, back pain, constipation, cough, rash, creatinine increased, and abdominal pain. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described in WARNINGS AND PRECAUTIONS reflect exposure to KISQALI plus non-steroidal aromatase inhibitor (NSAI) in 2526 patients with early breast cancer (NATALEE), of whom 51% completed 36 months of KISQALI treatment.

The most common (≥ 20%) adverse reactions, including laboratory abnormalities, were lymphocytes decreased (97%), leukocytes decreased (95%), neutrophils decreased (94%), hemoglobin decreased (47%), alanine aminotransferase increased (45%), aspartate aminotransferase increased (44%), infections (37%), creatinine increased (33%), platelets decreased (28%), headache (23%), nausea (23%), and fatigue (22%). In additions, the pooled safety population described in the WARNINGS AND PRECAUTIONS reflects exposure to KISQALI in 582 patients with advanced or metastatic breast cancer (MONALEESA-2 and MONALEESA-7), of whom 80% were exposed for 6 months or longer and 65% were exposed for greater than one year.

The most common (≥ 20%) adverse reactions, including laboratory abnormalities, were leukocytes decreased (94%), neutrophils decreased (94%), hemoglobin decreased (72%), lymphocytes decreased (59%), alanine aminotransferase increased (53%), aspartate aminotransferase increased (53%), infections (46%), nausea (46%), fatigue (36%), platelets decreased (34%), diarrhea (33%), headache (29%), alopecia (29%), vomiting (29%), back pain (25%), constipation (25%), cough (24%), rash (22%), creatinine increased (20%), and abdominal pain (20%).

NATALEE: KISQALI in Combination with a Non-steroidal Aromatase Inhibitor as Adjuvant Treatment Adults with HR-positive, HER2-negative Stage II and III Early Breast Cancer at High Risk of Recurrence The safety of KISQALI was evaluated in NATALEE, a clinical trial of 5101 patients who received KISQALI plus NSAI or NSAI alone, with or without goserelin [see Clinical Studies (14)] . The median duration of exposure to KISQALI was 33 months. Serious adverse reactions occurred in 14% of patients who received KISQALI.

Serious adverse reactions in > 0.5% of patients who received KISQALI included COVID-19 (1.1%), pneumonia (0.8%), and pulmonary embolism (0.6%). Fatal adverse reactions occurred in 0.6% of patients who received KISQALI. Fatal adverse reactions in ≥ 0.1%…

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Ribociclib CYP3A4 Inhibitors: Avoid concomitant use of KISQALI FEMARA CO-PACK with strong CYP3A inhibitors. If strong inhibitors cannot be avoided, reduce KISQALI dose. ( 2.2, 7.1 ) CYP3A4 Inducers: Avoid concomitant use of KISQALI FEMARA CO-PACK with strong CYP3A inducers.

( 7.2 ) CYP3A Substrates: The dose of CYP3A substrates with narrow therapeutic indices may need to be reduced when given concurrently with KISQALI FEMARA CO-PACK. ( 7.3 ) Drugs Known to Prolong QT Interval: Avoid concomitant use of drugs known to prolong QT interval, such as anti-arrhythmic medicines. ( 7.4 )

7.1Drugs That May Increase Ribociclib Plasma Concentrations CYP3A4 Inhibitors Coadministration of a strong CYP3A4 inhibitors increases ribociclib exposure [see Clinical Pharmacology (12.3)] . Increased ribociclib concentrations may increase the incidence and severity of adverse reactions, including QTcF prolongation [see Warnings and Precautions (5.3)] . Avoid concomitant use of strong CYP3A inhibitors with KISQALI and consider alternative concomitant medications with less potential for CYP3A inhibition.

In patients with early breast cancer, if coadministration of KISQALI with a strong CYP3A inhibitor cannot be avoided, reduce the dose of KISQALI to 200 mg once daily. In patients with advanced or metastatic breast cancer, if coadministration of KISQALI with a strong CYP3A inhibitor cannot be avoided, reduce the dose of KISQALI to 400 mg once daily [see Dosage and Administration (2.2)] .

7.2Drugs That May Decrease Ribociclib Plasma Concentrations CYP3A4 Inducers Coadministration of a strong CYP3A4 inducers decreases the plasma exposure of ribociclib [see Clinical Pharmacology (12.3)] . Avoid concomitant use of strong CYP3A inducers and consider an alternate concomitant medication with no or minimal potential to induce CYP3A.

7.3Effect of KISQALI on Other Drugs CYP3A Substrates Coadministration of sensitive CYP3A4 substrates with multiple doses of KISQALI increases the substrate exposure [see Clinical Pharmacology (12.3)] . For CYP3A substrates where minimal increases in the concentration may increase CYP3A substrate adverse reactions, monitor for increased adverse reactions of the CYP3A substrate during treatment with KISQALI. The dose of a sensitive CYP3A substrate may need to be reduced as KISQALI can increase its exposure.

7.4Drugs That Prolong the QT Interval Avoid coadministration of KISQALI with products with a known potential to prolong QT interval, such as antiarrhythmic drugs that are known to prolong the QT interval. If concomitant use cannot be avoided, monitor ECG when initiating, during concomitant use, and as clinically indicated [see Warnings and Precautions (5.3), Clinical Pharmacology (12.2)] .

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 )

8.1Pregnancy Risk Summary Based on findings from animal studies and the mechanisms of action, KISQALI FEMARA CO-PACK can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)] . There are no available human data informing the drug-associated risk. In animal reproduction studies, administration of ribociclib to pregnant animals during organogenesis resulted in increased incidences of post implantation loss and reduced fetal weights in rats and increased incidences of fetal abnormalities in rabbits at exposures 0.6 or 1.5 times the exposure in humans, respectively, at the highest recommended dose of 600 mg/day based on AUC (see Data) .

Advise pregnant women of the potential risk to a fetus. In animal reproduction studies, administration of letrozole to pregnant animals during organogenesis resulted in increased post-implantation pregnancy loss and resorptions, fewer live fetuses, and fetal malformations affecting the renal and skeletal systems in rats and rabbits at doses approximately 0.1 times the daily MRHD on a mg/m 2 basis (see Data) . The background risk of major birth defects and miscarriage for the indicated population is unknown.

However, the background risk of major birth defects is 2% - 4% and of miscarriage is 15% - 20% of clinically recognized pregnancies in the U.S. general population. Data Animal Data - Ribociclib In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of ribociclib up to 1000 mg/kg/day and 60 mg/kg/day, respectively, during the period of organogenesis. In rats, 300 mg/kg/day resulted in reduced maternal body weight gain and reduced fetal weights accompanied by skeletal changes related to the lower fetal weights.

There were no significant effects on embryo-fetal viability or fetal morphology at 50 or 300 mg/kg/day. In rabbits at doses ≥ 30 mg/kg/day, there were adverse effects on embryo-fetal development, including increased incidences of fetal abnormalities (malformations and external, visceral, and skeletal variants) and fetal growth (lower fetal weights). These findings included reduced/small lung lobes, additional vessel on the descending aorta, additional vessel on the aortic arch, small eyes, diaphragmatic hernia, absent accessory lobe or (partly) fused lung lobes, reduced/small accessory lung lobe, extra/rudimentary 13 th ribs, misshapen hyoid bone, bent hyoid bone alae and reduced number of phalanges in the pollex.

There was no evidence of increased incidence of embryo-fetal mortality. There was no maternal toxicity observed at 30 mg/kg/day. At 300 mg/kg/day in rats and 30 mg/kg/day in rabbits, the maternal systemic exposures (AUC) were approximately 0.6 and 1.5 times, respectively, the exposure in patients at the highest recommended dose of 600 mg/day.

Animal Data - Letrozole In a fertility and early embryonic developmental toxicity study in female rats, oral administration of letrozole starting 2 weeks before mating until pregnancy day 6 resulted in an increase in pre-implantation loss at doses ≥ 0.003 mg/kg/day (approximately 0.01 times the MRHD on a mg/m 2 basis). In an embryo-fetal developmental toxicity study in rats, daily administration of oral letrozole during the period of organogenesis at doses ≥ 0.003 mg/kg (approximately 0.01 times the MRHD on a mg/m 2 basis) resulted in embryo-fetal toxicity, including intrauterine mortality, increased resorptions and postimplantation loss, decreased numbers of live fetuses and fetal anomalies, including absence and shortening of renal papilla, dilation of ureter, edema and incomplete ossification of frontal skull and metatarsals.

Letrozole was teratogenic to rats at a dose of 0.03 mg/kg (approximately 0.1 times the MRHD on a mg/m 2 basis) and caused fetal domed head and cervical/centrum vertebral fusion. In an embryo-fetal developmental toxicity study in rabbits, daily administration of oral let…

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary Based on findings from animal studies and the mechanisms of action, KISQALI FEMARA CO-PACK can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)] . There are no available human data informing the drug-associated risk. In animal reproduction studies, administration of ribociclib to pregnant animals during organogenesis resulted in increased incidences of post implantation loss and reduced fetal weights in rats and increased incidences of fetal abnormalities in rabbits at exposures 0.6 or 1.5 times the exposure in humans, respectively, at the highest recommended dose of 600 mg/day based on AUC (see Data) .

Advise pregnant women of the potential risk to a fetus. In animal reproduction studies, administration of letrozole to pregnant animals during organogenesis resulted in increased post-implantation pregnancy loss and resorptions, fewer live fetuses, and fetal malformations affecting the renal and skeletal systems in rats and rabbits at doses approximately 0.1 times the daily MRHD on a mg/m 2 basis (see Data) . The background risk of major birth defects and miscarriage for the indicated population is unknown.

However, the background risk of major birth defects is 2% - 4% and of miscarriage is 15% - 20% of clinically recognized pregnancies in the U.S. general population. Data Animal Data - Ribociclib In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of ribociclib up to 1000 mg/kg/day and 60 mg/kg/day, respectively, during the period of organogenesis. In rats, 300 mg/kg/day resulted in reduced maternal body weight gain and reduced fetal weights accompanied by skeletal changes related to the lower fetal weights.

There were no significant effects on embryo-fetal viability or fetal morphology at 50 or 300 mg/kg/day. In rabbits at doses ≥ 30 mg/kg/day, there were adverse effects on embryo-fetal development, including increased incidences of fetal abnormalities (malformations and external, visceral, and skeletal variants) and fetal growth (lower fetal weights). These findings included reduced/small lung lobes, additional vessel on the descending aorta, additional vessel on the aortic arch, small eyes, diaphragmatic hernia, absent accessory lobe or (partly) fused lung lobes, reduced/small accessory lung lobe, extra/rudimentary 13 th ribs, misshapen hyoid bone, bent hyoid bone alae and reduced number of phalanges in the pollex.

There was no evidence of increased incidence of embryo-fetal mortality. There was no maternal toxicity observed at 30 mg/kg/day. At 300 mg/kg/day in rats and 30 mg/kg/day in rabbits, the maternal systemic exposures (AUC) were approximately 0.6 and 1.5 times, respectively, the exposure in patients at the highest recommended dose of 600 mg/day.

Animal Data - Letrozole In a fertility and early embryonic developmental toxicity study in female rats, oral administration of letrozole starting 2 weeks before mating until pregnancy day 6 resulted in an increase in pre-implantation loss at doses ≥ 0.003 mg/kg/day (approximately 0.01 times the MRHD on a mg/m 2 basis). In an embryo-fetal developmental toxicity study in rats, daily administration of oral letrozole during the period of organogenesis at doses ≥ 0.003 mg/kg (approximately 0.01 times the MRHD on a mg/m 2 basis) resulted in embryo-fetal toxicity, including intrauterine mortality, increased resorptions and postimplantation loss, decreased numbers of live fetuses and fetal anomalies, including absence and shortening of renal papilla, dilation of ureter, edema and incomplete ossification of frontal skull and metatarsals.

Letrozole was teratogenic to rats at a dose of 0.03 mg/kg (approximately 0.1 times the MRHD on a mg/m 2 basis) and caused fetal domed head and cervical/centrum vertebral fusion. In an embryo-fetal developmental toxicity study in rabbits, daily administration of oral letrozole during the period of organogenesis at doses ≥ 0.002 mg/kg (approxima…

🧒 Pediatric Use ~1 min read ▾

8.4Pediatric Use The safety and effectiveness of KISQALI FEMARA CO-PACK in pediatric patients have not been established. The safety and efficacy of KISQALI in combination with chemotherapy was assessed but not established in an open-label, dose-finding multicenter study (Study CLEE011Q12101; NCT05429502) in 12 patients, including 9 pediatric patients aged 4 to <17 years with relapsed or refractory neuroblastoma and other solid tumors. The study was terminated early due to dose-limiting toxicities (DLTs) preventing the identification of a safe dosing regimen for the investigational combination.

DLTs included neutropenia, anemia, thrombocytopenia, ventricular tachycardia, respiratory failure, and infection. Ribociclib exposures in pediatric patients aged 1 to < 17 years were within the range of values previously observed in adults based on body surface area. Letrozole administration to young (postnatal Day 7) rats for 12 weeks duration at 0.003, 0.03, 0.3 mg/kg/day by oral gavage resulted in adverse skeletal/growth effects (bone maturation, bone mineral density) and neuroendocrine and reproductive developmental perturbations of the hypothalamic-pituitary axis.

Administration of 0.3 mg/kg/day resulted in AUC values that were similar to the AUC in adult patients receiving the recommended dose of 2.5 mg/day. Decreased fertility was accompanied by hypertrophy of the hypophysis and testicular changes that included degeneration of the seminiferous tubular epithelium and atrophy of the female reproductive tract. Young rats in this study were allowed to recover following discontinuation of letrozole treatment for 42 days.

Histopathological changes were not reversible at clinically relevant exposures.

🧓 Geriatric Use 136 words ▾

8.5Geriatric Use Of the 2549 adults with early breast cancer who received KISQALI in NATALEE, 407 patients (16%) were ≥ 65 years of age and 123 patients (2.4%) were ≥ 75 years of age. No overall differences in safety or effectiveness of KISQALI were observed between older and younger adults with early breast cancer. Of 334 patients with advanced or metastatic breast cancer who received KISQALI plus letrozole in MONALEESA-2, 150 patients (45%) were ≥ 65 years of age and 35 patients (11%) were ≥ 75 years of age.

No overall differences in safety or effectiveness of KISQALI plus letrozole were observed between older and younger adults with advanced or metastatic breast cancer. Of 248 patients with advanced or metastatic breast cancer who received KISQALI in MONALEESA-7, no patients were ≥ 65 years of age.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Ribociclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. These kinases are activated upon binding to D-cyclins and are downstream of signaling pathways, which lead to cell cycle progression and cellular proliferation. The cyclin D-CDK4/6 complex regulates cell cycle progression through phosphorylation of the retinoblastoma protein (pRb).

In vitro , ribociclib decreased pRb phosphorylation, resulting in arrest in the G1 phase of the cell cycle and reduced cell proliferation in breast cancer-derived lines. In vivo , treatment with single agent ribociclib in a rat xenograft model with human tumor cells led to decreased tumor volumes, which correlated with inhibition of pRb phosphorylation. Letrozole is a nonsteroidal competitive inhibitor of the aromatase enzyme system by competitively binding to the heme of the cytochrome P450 subunit of the enzyme, resulting in a reduction of estrogen biosynthesis in all tissues.

In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol. The suppression of estrogen biosynthesis in peripheral tissues and in the cancer tissue itself can therefore be achieved by specifically inhibiting the aromatase enzyme. In studies, using patient-derived estrogen receptor positive breast cancer xenograft models, combination of ribociclib and antiestrogen (e.g., letrozole) therapies resulted in increased tumor growth inhibition compared to each drug alone.

12.2Pharmacodynamics The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of KISQALI have not been fully characterized in patients. Ribociclib Cardiac Electrophysiology A concentration-QT analysis of the data in patients with breast cancer treated with KISQALI at doses ranging from 50 to 1200 mg (0.083 to 2 times of the approved recommended high dose) suggested that ribociclib causes concentration-dependent increases in the QTcF interval. In patients with early breast cancer, the estimated mean QTcF interval change from baseline for the KISQALI 400 mg in combination with non-steroidal aromatase inhibitor (NSAI) was 10.0 ms (90% CI: 8.0, 11.9) at the mean steady-state C max [see Warnings and Precautions (5.3, 5.4)] .

In patients with advanced or metastatic breast cancer the estimated mean QTcF interval change from baseline for KISQALI 600 mg in combination with aromatase inhibitors was 22.0 ms (90% CI: 22.0, 23.4), and was 34.7 ms (90% CI: 31.6, 37.8) in combination with tamoxifen at the mean C max at steady-state [see Warnings and Precautions (5.3)] . Letrozole In postmenopausal patients with advanced breast cancer, daily doses of 0.1 mg to 5 mg FEMARA (letrozole) suppress plasma concentrations of estradiol, estrone, and estrone sulfate by 75% to 95% from baseline with maximal suppression achieved within two-three days.

Suppression is dose-related, with doses of 0.5 mg and higher giving many values of estrone and estrone sulfate that were below the limit of detection in the assays. Estrogen suppression was maintained throughout treatment in all patients treated at 0.5 mg or higher. Letrozole is highly specific in inhibiting aromatase activity.

There is no impairment of adrenal steroidogenesis. No clinically relevant changes were found in the plasma concentrations of cortisol, aldosterone, 11-deoxycortisol, 17-hydroxy-progesterone, adrenocorticotropic hormone (ACTH) or in plasma renin activity among postmenopausal patients treated with a daily dose of FEMARA 0.1 mg to 5 mg. The ACTH stimulation test performed after 6 and 12 weeks of treatment with daily doses of 0.1, 0.25, 0.5, 1, 2.5, and 5 mg did not indicate any attenuation of aldosterone or cortisol production.

Glucocorticoid or mineralocorticoid supplementation is, therefore, not necessary. No changes were noted in plasma concentrations of androgens…

🧬 Mechanism of Action ~1 min read ▾

12.1Mechanism of Action Ribociclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. These kinases are activated upon binding to D-cyclins and are downstream of signaling pathways, which lead to cell cycle progression and cellular proliferation. The cyclin D-CDK4/6 complex regulates cell cycle progression through phosphorylation of the retinoblastoma protein (pRb).

In vitro , ribociclib decreased pRb phosphorylation, resulting in arrest in the G1 phase of the cell cycle and reduced cell proliferation in breast cancer-derived lines. In vivo , treatment with single agent ribociclib in a rat xenograft model with human tumor cells led to decreased tumor volumes, which correlated with inhibition of pRb phosphorylation. Letrozole is a nonsteroidal competitive inhibitor of the aromatase enzyme system by competitively binding to the heme of the cytochrome P450 subunit of the enzyme, resulting in a reduction of estrogen biosynthesis in all tissues.

In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol. The suppression of estrogen biosynthesis in peripheral tissues and in the cancer tissue itself can therefore be achieved by specifically inhibiting the aromatase enzyme. In studies, using patient-derived estrogen receptor positive breast cancer xenograft models, combination of ribociclib and antiestrogen (e.g., letrozole) therapies resulted in increased tumor growth inhibition compared to each drug alone.

📦 How Supplied / Storage and Handling ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING KISQALI FEMARA CO-PACK is dispensed in a carton for a total of 28 days of therapy. Each carton contains individual ribociclib and letrozole drug products as follows: KISQALI (ribociclib) Tablets: 200 mg tablets. Light greyish violet, round, curved with beveled edge, debossed with “RIC” on one side and “NVR” on the other side.

FEMARA (letrozole) Tablets: 2.5 mg tablets. Dark yellow, round, slightly biconvex, with beveled edges, imprinted with the letters “FV” on one side and “CG” on the other side. KISQALI FEMARA CO-PACK Cartons: NDC 0078-0923-61 – Carton of 3 blister packs (63 tablets total) – each blister pack contains a 7-day supply of 21 tablets (200 mg per tablet) (600 mg daily dose) of KISQALI plus one 28-tablet count bottle of FEMARA NDC 0078-0916-61 – Carton of 3 blister packs (42 tablets total) – each blister pack contains a 7-day supply of 14 tablets (200 mg per tablet) (400 mg daily dose) of KISQALI plus one 28-tablet count bottle of FEMARA NDC 0078-0909-61 – Carton of 1 blister pack (21 tablets total) – each blister pack contains a 21-day supply of 21 tablets (200 mg per tablet) (200 mg daily dose) of KISQALI plus one 28-tablet count bottle of FEMARA Store at room temperature at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F).

Store in the original blister package in order to protect from moisture.

📋 Description ~1 min read ▾

11 DESCRIPTION KISQALI FEMARA CO-PACK consists of ribociclib 200 mg film-coated tablets co-packaged with letrozole 2.5 mg tablets. Ribociclib KISQALI (ribociclib) is a kinase inhibitor. Ribociclib succinate is a light yellow to yellowish brown crystalline powder.

The chemical name of ribociclib succinate is: Butanedioic acid—7-cyclopentyl- N , N -dimethyl-2-{[5-(piperazin-1-yl) pyridin-2-yl]amino}-7 H -pyrrolo[2,3- d ]pyrimidine-6-carboxamide (1/1). The molecular formula for ribociclib succinate is C 23 H 30 N 8 O.C 4 H 6 O 4 and the molecular weight is 552.64 g/mol [Free base: 434.55 g/mol] . The chemical structure of ribociclib is shown below: KISQALI film-coated tablets are supplied for oral use and contain 200 mg of ribociclib free base (equivalent to 254.40 mg ribociclib succinate).

The tablets also contain colloidal silicon dioxide, crospovidone, hydroxypropylcellulose, magnesium stearate, and microcrystalline cellulose. The film-coating contains iron oxide black, iron oxide red, lecithin (soya), polyvinyl alcohol (partially hydrolyzed), talc, titanium dioxide, and xanthan gum as inactive ingredients. Letrozole FEMARA (letrozole) is a nonsteroidal aromatase inhibitor (inhibitor of estrogen synthesis).

Letrozole is a white to yellowish crystalline powder, practically odorless, freely soluble in dichloromethane, slightly soluble in ethanol, and practically insoluble in water. It has a molecular weight of 285.31 g/mol, empirical formula C 17 H 11 N 5 , and a melting range of 184°C to 185°C. The chemical name of letrozole is 4,4'-(1H-1,2,4-Triazol-1ylmethylene) dibenzonitrile, and its structural formula is FEMARA is available as 2.5 mg tablets for oral administration.

Inactive Ingredients: colloidal silicon dioxide, ferric oxide, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, maize starch, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, talc, and titanium dioxide. ribociclib structure letrozole structure

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). For additional information on KISQALI and FEMARA, refer to the full prescribing information for each product. Interstitial Lung Disease/Pneumonitis Advise patients to immediately report new or worsening respiratory symptoms [see Warnings and Precautions (5.1)] .

Severe Cutaneous Adverse Reactions Inform patients of the signs and symptoms of severe cutaneous adverse reactions (e.g., skin pain/burning, rapidly-spreading skin rash, and/or mucosal lesions accompanied by fever or flu-like symptoms). Advise patients to contact their healthcare provider immediately if they develop signs and symptoms of severe cutaneous adverse reactions [see Warnings and Precautions (5.2)] . QT Prolongation Inform patients of the signs and symptoms of QT prolongation.

Advise patients to contact their healthcare provider immediately for signs or symptoms of QT prolongation [see Warnings and Precautions (5.3)] . Hepatobiliary Toxicity Inform patients of the signs and symptoms of hepatobiliary toxicity. Advise patients to contact their healthcare provider immediately for signs or symptoms of hepatobiliary toxicity [see Warnings and Precautions (5.4)] .

Neutropenia Advise patients of the possibility of developing neutropenia and to immediately contact their healthcare provider should they develop a fever, particularly in association with any suggestion of infection [see Warnings and Precautions (5.5)] . Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.6), Use in Specific Populations (8.1)] .

Advise females of reproductive potential to use effective contraception during KISQALI FEMARA CO-PACK therapy and for at least 3 weeks after the last dose. [see Use in Specific Populations (8.3)] . Lactation Advise lactating women not to breastfeed during treatment with KISQALI FEMARA CO-PACK and for at least 3 weeks after the last dose [see Use in Specific Populations (8.2)]. Drug Interactions Inform patients to avoid strong CYP3A inhibitors, strong CYP3A inducers, and drugs known to prolong the QT interval [see Drug Interactions (7.1, 7.2, 7.4)] .

Infertility Inform males of reproductive potential that KISQALI may impair fertility [see Use in Specific Populations (8.3)] . Dosing Instruct patients to take the doses of KISQALI FEMARA CO-PACK at approximately the same time every day and to swallow tablets whole (do not chew, crush, or split them prior to swallowing) [see Dosage and Administration (2.1)] . If patient vomits or misses a dose, advise the patient to take the next prescribed dose at the usual time [see Dosage and Administration (2.1)] .

Advise the patient that KISQALI FEMARA CO-PACK may be taken with or without food [see Dosage and Administration (2.1)] . Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936 © Novartis T2026-22

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.