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XELODA capecitabine 500 mg Tablet, Film Coated, 120-count

by H2-Pharma, LLC · 120 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (61269-475-12)
NDC 61269-0475-12
🏷️ FDA NDC (as labeled) 61269-475-12 billing pads the product segment with a zero
Rx only Brand On market Non-controlled
🗂️ 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

🆔 Identity & classification

FDA NDC (as labeled) 61269-475-12
Product NDC 61269-475
11-digit billing NDC 61269047512
NCPDP billing unit EA — each (per item)
RxCUI 200327, 200328, 213292, 213293
UNII 6804DJ8Z9U
Application # NDA020896
SPL Set ID e702d84d-7162-4751-bf37-d724cc7e45a5
Established class (EPC) Nucleoside Metabolic Inhibitor
Mechanism of action Nucleic Acid Synthesis Inhibitors
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 1998-04-30
Route ORAL
Dosage form TABLET, FILM COATED
Substance CAPECITABINE
GCN Seq No 039781
GCN 31612
HICL code 018385
Ingredient (HICL) Capecitabine
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V1B
Therapeutic class — specific (HIC3) Antineoplastic - Antimetabolites
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name XELODA 500 MG TABLET
FDB brand name Xeloda
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 61269-475-12 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 61269-0475-12. 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 Nucleoside Metabolic Inhibitor class.

Pharmacologic class Nucleoside Metabolic Inhibitor
Drug family (ATC) Pyrimidine analogues
How it works Nucleic Acid Synthesis 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

LabelerH2-Pharma, LLC
Application holderCHEPLAPHARM ARZNEIMITTEL GMBH
FDA applicationNDA020896 (NDA)
Labeler code61269
First marketedApr 1998
Product typeHuman Prescription Drug
Portfolio27 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 XELODA 500 MG TABLET Ingredient Capecitabine
📗 Our plain-language guide HelloPharmacist
  • Capecitabine is used for several types of cancer — most commonly colorectal (colon and rectal) cancer, advanced or metastatic breast cancer, and, depending on the product, cancers...
  • What kinds of cancer does capecitabine treat?
  • Yes — this one really matters. You should take capecitabine within 30 minutes after eating a meal, and swallow the tablets whole with water. Taking it on an empty stomach significa...
  • The most common side effects are hand-and-foot syndrome (redness, soreness, or peeling on your palms and soles), diarrhea, nausea, fatigue, and mouth sores. Many of these can be ma...
📖 Read our full Capecitabine guide →
1
Nutrient depletion considerations

Capecitabine may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Capecitabine nutrient depletion report →
An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

🧪 Inactive Ingredients / Excipients

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

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

Inactive ingredient FAQ

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

💲 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 $44.12 $5,294.69 / 120 tablets
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · NONE No ASP payment limit on file for NONE this quarter.
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.

🧾 Billing & reimbursement

FDA NDC (as labeled)61269-475-12
11-digit billing NDC61269-0475-12
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeNONE
DescriptorCAPECITABINE, ORAL, 50 MG
Billing units / pkg10 units
Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Capecitabine 500 mg 00093-7474-89 Teva 120 tablets $0.468 AB Availability likely —
Capecitabine 500 mg 16729-0073-29 Accord 120 tablets $0.468 AB Availability likely —
capecitabine 500 mg 31722-0775-12 Camber 120 tablets $0.468 AB Availability likely —
capecitabine 500 mg 55111-0497-04 Dr. 120 tablets $0.468 AB Availability likely —
Capecitabine 500 mg 59651-0205-08 Aurobindo 120 tablets $0.468 AB Availability likely —
Capecitabine 500 mg 60687-0149-94 American 1 tablet $0.468 AB Availability likely —
Capecitabine 500 mg 67877-0459-12 Ascend 120 tablets $0.468 AB Availability likely —
Capecitabine 500 mg 68001-0644-07 BluePoint 120 tablets $0.468 AB Availability likely —
Capecitabine 500 mg 69097-0948-08 Cipla 120 tablets $0.468 AB Availability likely —
Capecitabine 500 mg 70756-0816-22 Lifestar 120 tablets $0.468 AB Availability likely —
Capecitabine 500 mg 72205-0007-92 Novadoz 120 tablets $0.468 AB Availability likely —
capecitabine 500 mg 72603-0303-01 NorthStar 120 tablets $0.468 AB Availability likely —
Capecitabine 500 mg 82009-0112-12 Quallent 120 tablets $0.468 AB Availability likely —
Capecitabine 500 mg 82249-0210-12 CivicaScript 120 tablets $0.468 AB Availability likely —
Capecitabine 500 mg 68001-0488-07 BluePoint 120 tablets $0.481 AB FDA listed —
Capecitabine 500mg 500 mg 72485-0205-12 Armas 120 tablets $0.481 AB FDA listed —
Capecitabine 500 mg 51407-0640-12 Golden 120 tablets — AB FDA listed —
Xeloda 500 mgthis 61269-0475-12 H2-Pharma, 120 tablets — — FDA listed —
Capecitabine 500 mg 62756-0239-18 Sun 1000 tablets — — FDA listed —
Capecitabine 500 mg 82511-0002-50 Teyro 120 tablets — BX FDA listed —
About this product: this is the brand-name version. FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available.
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

🏛️
1998
On the market since
Apr 1998
📍
2026
Currently FDA-listed
28 years listed
🔓
·
Generic versions listed
see equivalents
✅Generic appears available

FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.

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 61269-0475-12, 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 – Q4 2025 · 4 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
395
Units reimbursed last 4 qtrs
30.9K
Gross reimbursed last 4 qtrs
$1.36M
Avg / prescription
$3,449.15
Avg / unit
$44.1224
Latest quarter Q4 2025
0Rx
Fee-for-service vs managed care ⓘ
91% MCO
Fee-for-service · 37 Rx Managed care · 358 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: no data reported MI New York: no data reported 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: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: no data reported CA Utah: no data reported UT Colorado: no data reported 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: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: no data reported 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: no data reported TX Florida: 30,878 units · 137 per 100k residents FL
Units reimbursed · per 100k residents
137137
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 Florida 137 /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 Capecitabine (matched by generic name) — 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 Capecitabine. 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
$750.66
Claims incl. refills
13
Beneficiaries
—
Spend / beneficiary
—
Spend / claim
$57.74
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
61269-0475-12 You're viewing this 120 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (61269-475-12) 1998-04-30 Active

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos — 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 — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
HCPCS J-code billing crosswalk ✓ Available
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

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 61269-475-12, 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: 61269-0475-12, written without dashes as 61269047512. 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 61269-0475-12, the first segment (61269) is the labeler code FDA assigned to H2-Pharma, LLC; the middle segment (0475) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (12) 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 H2-Pharma, LLC. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
H2-Pharma, LLC 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.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code NONE for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.
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.
🚨 Boxed Warning 🎯 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 📦 Storage and Handling 📋 Description 💬 Information for Patients
🚨 Boxed Warning ~1 min read ▾

WARNING: SERIOUS ADVERSE REACTIONS OR DEATH IN PATIENTS WITH COMPLETE DPD DEFICIENCY and INCREASED RISK OF BLEEDING WITH CONCOMITANT USE OF VITAMIN K ANTAGONISTS Increased risk of serious adverse reactions or death in patients with complete DPD deficiency • Test patients for genetic variants of DPYD prior to initiating XELODA unless immediate treatment is necessary. Avoid use of XELODA in patients with certain homozygous or compound heterozygous DPYD variants that result in complete DPD deficiency [see Warnings and Precautions (5.1) ].

Increased risk of bleeding with concomitant use of Vitamin K antagonists • Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking XELODA concomitantly with oral vitamin K antagonists, such as warfarin [see Warnings and Precautions (5.2) , Drug Interactions (7.2) ] . • Clinically significant increases in prothrombin time (PT) and international normalized ratio (INR) have been reported in patients who were on stable doses of a vitamin K antagonist at the time XELODA was introduced.

These events occurred in patients with and without liver metastases. • Monitor INR more frequently and adjust the dose of the vitamin K antagonist as appropriate [see Drug Interactions (7.2) ]. WARNING: SERIOUS ADVERSE REACTIONS OR DEATH IN PATIENTS WITH COMPLETE DPD DEFICIENCY and BLEEDING WITH CONCOMITANT USE OF VITAMIN K ANTAGONISTS See full prescribing information for complete boxed warning . Serious adverse reactions or death may occur in patients with complete DPD deficiency.

Test patients for genetic variants of DPYD prior to initiating XELODA unless immediate treatment is necessary. Avoid use of Xeloda in patients with certain homozygous or compound heterozygous DPYD variants that result in complete DPD deficiency. ( 5.1 ) Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking XELODA concomitantly with oral vitamin K antagonists.

( 5.2 , 7.2 ) Monitor international normalized ratio (INR) more frequently and adjust the dose of the vitamin K antagonist as appropriate. ( 7.2 )

🎯 Indications and Usage ~2 min read ▾

1 INDICATIONS AND USAGE XELODA (capecitabine) is a nucleoside metabolic inhibitor indicated for: Colorectal Cancer adjuvant treatment of patients with Stage III colon cancer as a single agent or as a component of a combination chemotherapy regimen. ( 1.1 ) perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy. ( 1.1 ) treatment of patients with unresectable or metastatic colorectal cancer as a single agent or as a component of a combination chemotherapy regimen.

( 1.1 ) Breast Cancer treatment of patients with advanced or metastatic breast cancer as a single agent if an anthracycline- or taxane-containing chemotherapy is not indicated. ( 1.2 ) treatment of patients with advanced or metastatic breast cancer in combination with docetaxel after disease progression on prior anthracycline-containing chemotherapy. ( 1.2 ) Gastric, Esophageal, or Gastroesophageal Junction Cancer treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component of a combination chemotherapy regimen.

( 1.3 ) treatment of adults with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease as a component of a combination regimen. ( 1.3 ) Pancreatic Cancer adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen. ( 1.4 )

1.1Colorectal Cancer XELODA is indicated for the: adjuvant treatment of patients with Stage III colon cancer as a single agent or as a component of a combination chemotherapy regimen. perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy. treatment of patients with unresectable or metastatic colorectal cancer as a single agent or as a component of a combination chemotherapy regimen.

1.2Breast Cancer XELODA is indicated for the: treatment of patients with advanced or metastatic breast cancer as a single agent if an anthracycline- or taxane-containing chemotherapy is not indicated. treatment of patients with advanced or metastatic breast cancer in combination with docetaxel after disease progression on prior anthracycline-containing chemotherapy.

1.3Gastric, Esophageal, or Gastroesophageal Junction Cancer XELODA is indicated for the: treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component of a combination chemotherapy regimen. treatment of adults with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease as a component of a combination regimen.

1.4Pancreatic Cancer XELODA is indicated for the adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Adjuvant Treatment of Colon Cancer Single agent: 1,250 mg/m 2 twice daily orally for the first 14 days of each 21-day cycle for a maximum of 8 cycles. ( 2.1 ) In combination with Oxaliplatin-Containing Regimens: 1,000 mg/m 2 orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles in combination with oxaliplatin 130 mg/m 2 administered intravenously on day 1 of each cycle. ( 2.1 ) Perioperative Treatment of Rectal Cancer With Concomitant Radiation Therapy: 825 mg/m 2 orally twice daily ( 2.2 ) Without Radiation Therapy: 1,250 mg/m 2 orally twice daily ( 2.2 ) Unresectable or Metastatic Colorectal Cancer: Single agent: 1,250 mg/m 2 twice daily orally for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity.

( 2.2 ) In Combination with Oxaliplatin: 1,000 mg/m 2 orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with oxaliplatin 130 mg/m 2 administered intravenously on day 1 of each cycle. ( 2.2 ) Advanced or Metastatic Breast Cancer: Single agent: 1,000 mg/m 2 or 1,250 mg/m 2 twice daily orally for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity. ( 2.3 ) In combination with docetaxel: 1,000 mg/m 2 or 1,250 mg/m 2 orally twice daily for the first 14 days of a 21-day cycle, until disease progression or unacceptable toxicity in combination with docetaxel at 75 mg/m 2 administered intravenously on day 1 of each cycle ( 2.3 ) Unresectable or Metastatic Gastric, Esophageal, or Gastroesophageal Junction Cancer 625 mg/m 2 orally twice daily on days 1 to 21 of each 21-day cycle for a maximum of 8 cycles in combination with platinum-containing chemotherapy.

( 2.4 ) OR 850 mg/m 2 or 1,000 mg/m 2 orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with oxaliplatin 130 mg/m 2 administered intravenously on day 1 of each cycle. ( 2.4 ) HER2-overexpressing metastatic adenocarcinoma of the gastroesophageal junction or stomach 1,000 mg/m 2 orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with cisplatin and trastuzumab. ( 2.4 ) Pancreatic cancer 830 mg/m 2 orally twice daily for the first 21 days of each 28-day cycle for maximum of 6 cycles in combination with gemcitabine 1,000 mg/m 2 administered intravenously on days 1, 8, and 15 of each cycle.

( 2.5 ) Refer to Sections 2.5 and 2.6 for information related to dosage modifications for adverse reactions and renal impairment ( 2.5 and 2.6 ).

2.1Evaluation and Testing for DPD Deficiency Before Initiating XELODA Prior to initiating XELODA, test patients for genetic variants of the DPYD gene unless immediate treatment is necessary. An FDA-authorized test for the detection of the DPYD gene to identify patients at risk of serious adverse reactions with XELODA is not currently available. Currently available tests used to identify DPYD variants may vary in accuracy and design (e.g., which DPYD variant(s) they identify).

Avoid use of XELODA in patients known to have certain homozygous or compound heterozygous DPYD variants that result in complete DPD deficiency. No XELODA dose has been proven safe for patients with complete DPD deficiency. For patients with partial DPD deficiency, individualize the dosage and modify based on tolerability and intent of treatment [see Warnings and Precautions (5.1) ].

2.2Recommended Dosage for Colorectal Cancer Adjuvant Treatment of Colon Cancer Single Agent The recommended dosage of XELODA is 1,250 mg/m 2 orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles. In Combination with Oxaliplatin-Containing Regimens The recommended dosage of XELODA is 1,000 mg/m 2 orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles in combination with oxaliplatin…

💊 Dosage Forms and Strengths 48 words ▾

3 DOSAGE FORMS AND STRENGTHS Tablets, film-coated: 150 mg: biconvex, oblong, light-peach colored, with "XELODA" on one side and "150" on the other 500 mg: biconvex, oblong, peach colored, with "XELODA on one side and "500" on the other Tablets: 150 mg and 500 mg ( 3 )

⛔ Contraindications 35 words ▾

4 CONTRAINDICATIONS XELODA is contraindicated in patients with history of severe hypersensitivity reaction to fluorouracil or capecitabine [see Adverse Reactions (6.1) ] . History of severe hypersensitivity reactions to fluorouracil or capecitabine ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Cardiotoxicity : May be more common in patients with a prior history of coronary artery disease. Withhold XELODA for cardiotoxicity as appropriate. The safety of resumption of XELODA in patients with cardiotoxicity that has resolved has not been established.

( 2.5 , 5.3 ) Diarrhea : Withhold XELODA and then resume at same or reduced dose, or permanently discontinue, based on severity and occurrence. (2.5, 5.4) Dehydration : Optimize hydration before starting XELODA. Monitor hydration status and kidney function at baseline and as clinically indicated.

Withhold XELODA and then resume at same or reduced dose, or permanently discontinue, based on severity and occurrence. ( 2.5 , 5.5 ) Renal Toxicity : Monitor renal function at baseline and as clinically indicated. Optimize hydration before starting XELODA.

Withhold XELODA and then resume at same or reduced dose, or permanently discontinue, based on severity and occurrence. ( 2.5 , 5.6 ) Serious Skin Toxicities : Monitor for new or worsening serious skin reactions. Permanently discontinue XELODA in patients who experience a severe cutaneous adverse reaction.

( 5.7 ) Palmar-Plantar Erythrodysesthesia Syndrome : Withhold XELODA then resume at same or reduced dose, or permanently discontinue, based on severity and occurrence. ( 2.5 , 5.8 ) Myelosuppression : Monitor complete blood count at baseline and before each cycle. XELODA is not recommended in patients with baseline neutrophil counts <1.5 × 10 9 /L or platelet counts <100 × 10 9 /L.

For grade 3 or 4 myelosuppression, withhold XELODA and then resume at same or reduced dose, or permanently discontinue, based on occurrence. ( 2.5 , 5.9 ) Hyperbilirubinemia : Patients with Grade 3-4 hyperbilirubinemia may resume treatment once the event is Grade 2 or less (≤3 × ULN), using the percent of current dose as shown in column 3 of Table 1 ( 2.5 , 5.10 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

( 5.11 , 8.1 , 8.3 )

5.1Serious Adverse Reactions or Death from Dihydropyrimidine Dehydrogenase (DPD) Deficiency Patients with certain homozygous or compound heterozygous variants in the DPYD gene known to result in complete or near complete absence of DPD activity (complete DPD deficiency) are at increased risk for acute early-onset toxicity and serious, including fatal, adverse reactions due to XELODA (e.g., mucositis, diarrhea, neutropenia, and neurotoxicity). Patients with partial DPD activity (partial DPD deficiency) may also have increased risk of serious or fatal, adverse reactions.

Prior to initiating XELODA, test patients for genetic variants of the DPYD gene unless immediate treatment is necessary [see Clinical Pharmacology (12.5) ]. Serious adverse reactions may still occur even if no DPYD variants are identified. Avoid use of XELODA in patients with certain homozygous or compound heterozygous DPYD variants that result in complete DPD deficiency.

Withhold or permanently discontinue XELODA based on clinical assessment of the onset, duration, and severity of adverse reactions in patients with evidence of acute early-onset or unusually severe reactions. No XELODA dose has been proven safe for patients with complete DPD deficiency. There are insufficient data to recommend a specific dose in patients with partial DPD deficiency.

For patients with partial DPD deficiency, individualize the dosage and modify based on tolerability and intent of treatment. An FDA-authorized test for the detection of genetic variants of the DPYD gene to identify patients at risk of serious adverse reactions with XELODA treatment is not currently available. Currently available tests used to identify DPYD variants may vary in accuracy and design (e.g., which DPYD variant(s) they identify).

5.2Increased Risk of Bleeding With Concomitant Use of Vitamin K Antagonists Altered coagulation parameters and/or bleeding, including death, have been reported in pa…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Cardiotoxicity [see Warnings and Precautions (5.3) ] Diarrhea [see Warnings and Precautions (5.4) ] Dehydration [see Warnings and Precautions (5.5) ] Renal Toxicity [see Warnings and Precautions (5.6) ] Serious Skin Toxicities [see Warnings and Precautions (5.7) ] Palmar-Plantar Erythrodysesthesia Syndrome [see Warnings and Precautions (5.8) ] Myelosuppression [see Warnings and Precautions (5.9) ] Hyperbilirubinemia [see Warnings and Precautions (5.10) ] Most common adverse reactions in patients who received XELODA as a single agent for the adjuvant treatment for colon cancer (≥30%) were palmar-plantar erythrodysesthesia syndrome, diarrhea, and nausea.

( 6.1 ) Most common adverse reactions (≥30%) in patients with metastatic colorectal cancer who received XELODA as a single agent were anemia, diarrhea, palmar-plantar erythrodysesthesia syndrome, hyperbilirubinemia, nausea, fatigue, and abdominal pain. ( 6.1 ) Most common adverse reactions (≥30%) in patients with metastatic breast cancer who received XELODA with docetaxel were diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome, nausea, alopecia, vomiting, edema, and abdominal pain. ( 6.1 ) Most common adverse reactions (≥30%) in patients with metastatic breast cancer who received XELODA as a single agent were lymphopenia, anemia, diarrhea, hand-and-foot syndrome, nausea, fatigue, vomiting, and dermatitis.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact 1-866-995-4272 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. Adjuvant Treatment of Colon Cancer Single Agent The safety of XELODA as a single agent was evaluated in patients with Stage III colon cancer in X-ACT [see Clinical Studies (14.1) ] . Patients received XELODA 1,250 mg/m 2 orally twice daily for the first 14 days of a 21-day cycle (N=995) or leucovorin 20 mg/m 2 intravenously followed by fluorouracil 425 mg/m 2 as an intravenous bolus on days 1 to 5 of each 28-day cycle (N=974).

Among patients who received XELODA, the median duration of treatment was 5.4 months. Deaths due to all causes occurred in 0.8% of patients who received XELODA on study or within 28 days of receiving study drug. Permanent discontinuation due to an adverse reaction occurred in 11% of patients who received XELODA.

Most common adverse reactions (>30%) were palmar-plantar erythrodysesthesia syndrome, diarrhea, and nausea. Tables 2 and 3 summarize the adverse reactions and laboratory abnormalities in X-ACT. Table 2 Adverse Reactions (≥10%) in Patients Who Received XELODA for Adjuvant Treatment of Colon Cancer in X-ACT Adverse Reaction XELODA (N=995) Fluorouracil + Leucovorin (N=974) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Skin and Subcutaneous Tissue Palmar-plantar erythrodysesthesia syndrome 60 17 9 <1 Gastrointestinal Diarrhea 47 12 65 14 Nausea 34 2 47 2 Stomatitis 22 2 60 14 Vomiting 15 2 21 2 Abdominal pain 14 3 16 2 General Fatigue 16 <1 16 1 Asthenia 10 <1 10 1 Lethargy 10 <1 9 <1 Clinically relevant adverse reactions in <10% of patients are presented below: Eye: conjunctivitis Gastrointestinal: constipation, upper abdominal pain, dyspepsia General: pyrexia Metabolism and Nutrition: anorexia Nervous System: dizziness, dysgeusia, headache Skin & Subcutaneous Tissue: rash, alopecia, erythema Table 3 Grade 3 or 4 Laboratory Abnormalities (>1%) in Patients Who Received XELODA as a Single Agent for Adjuvant Treatment of Colon Cancer in X-ACT Laboratory Abnormality XELODA (N=995) Fluorouracil + Leucovorin (N=974) Grade 3 or 4 Grade 3 or 4 (%) (%) Bilirubin increased 20 6 Lymphocytes decreased 13 13 Ne…

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Allopurinol: Avoid concomitant use of allopurinol with XELODA. ( 7.1 ) Leucovorin: Closely monitor for toxicities when XELODA is coadministered with leucovorin. ( 7.1 ) CYP2C9 substrates: Closely monitor for adverse reactions when CYP2C9 substrates are coadministered with XELODA.

( 7.2 ) Vitamin K antagonists: Monitor INR more frequently and dose adjust oral vitamin K antagonist as appropriate Phenytoin : Closely monitor phenytoin levels in patients taking XELODA concomitantly with phenytoin and adjust the phenytoin dose as appropriate. ( 7.2 ) Nephrotoxic drugs: Closely monitor for signs of renal toxicity when XELODA is used concomitantly with nephrotoxic drugs. ( 7.3 )

7.1Effect of Other Drugs on XELODA Allopurinol Concomitant use with allopurinol may decrease concentration of capecitabine's active metabolites [see Clinical Pharmacology (12.3) ] , which may decrease efficacy. Avoid concomitant use of allopurinol with XELODA. Leucovorin The concentration of fluorouracil is increased and its toxicity may be enhanced by leucovorin, folic acid, or folate analog products.

Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin and fluorouracil. Instruct patients not to take products containing folic acid or folate analog products unless directed to do so by their healthcare provider.

7.2Effect of Xeloda on Other Drugs CYP2C9 Substrates XELODA increased exposure of CYP2C9 substrates [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions related to these substrates. Closely monitor for adverse reactions of CYP2C9 substrates where minimal concentration changes may lead to serious adverse reactions when used concomitantly with XELODA (e.g., anticoagulants, antidiabetic drugs). Vitamin K Antagonists XELODA increases exposure of vitamin K antagonist [see Clinical Pharmacology (12.3) ], which m ay alter coagulation parameters and/or bleeding and could result in death [see Warning and Precautions (5.1) ] .

These events may occur within days of treatment initiation and up to 1 month after discontinuation of XELODA. Monitor INR more frequently and refer to the prescribing information of oral vitamin K antagonist for dosage adjustment, as appropriate, when XELODA is used concomitantly with vitamin K antagonist. Phenytoin XELODA may increases exposure of phenytoin, which may increase the risk of adverse reactions related to phenytoin.

Closely monitor phenytoin levels and refer to the prescribing information of phenytoin for dosage adjustment, as appropriate, when XELODA is used concomitantly with phenytoin.

7.3Nephrotoxic Drugs Due of the additive pharmacologic effect, concomitant use of XELODA with other drugs known to cause renal toxicity may increase the risk of renal toxicity [see Warnings and Precautions (5.6) ]. Closely monitor for signs of renal toxicity when XELODA is used concomitantly with nephrotoxic drugs (e.g. platinum salts, irinotecan, methotrexate, intravenous bisphosphonates).

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) Hepatic Impairment: Monitor patients with hepatic impairment more frequently for adverse reactions. ( 8.7 )

8.1Pregnancy Risk Summary Based on findings in animal reproduction studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , XELODA can cause fetal harm when administered to a pregnant woman. Available human data with XELODA use in pregnant women is not sufficient to inform the drug-associated risk. In animal reproduction studies, administration of capecitabine to pregnant animals during the period of organogenesis caused embryolethality and teratogenicity in mice and embryolethality in monkeys at 0.2 and 0.6 times the exposure (AUC) in patients receiving the recommended dose of 1,250 mg/m 2 twice daily, respectively (see Data ) .

Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of 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. Data Animal Data Oral administration of capecitabine to pregnant mice during the period of organogenesis at a dose of 198 mg/kg/day caused malformations and embryo lethality. In separate pharmacokinetic studies, this dose in mice produced 5'-DFUR AUC values that were approximately 0.2 times the AUC values in patients administered the recommended daily dose.

Malformations in mice included cleft palate, anophthalmia, microphthalmia, oligodactyly, polydactyly, syndactyly, kinky tail and dilation of cerebral ventricles. Oral administration of capecitabine to pregnant monkeys during the period of organogenesis at a dose of 90 mg/kg/day, caused fetal lethality. This dose produced 5'-DFUR AUC values that were approximately 0.6 times the AUC values in patients administered the recommended daily dose.

8.2Lactation Risk Summary There is no information regarding the presence of capecitabine or its metabolites in human milk, or on its effects on milk production or the breastfed child. Capecitabine metabolites were present in the milk of lactating mice (see Data ) . Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with XELODA and for 1 week after the last dose.

Data Lactating mice given a single oral dose of capecitabine excreted significant amounts of capecitabine metabolites into the milk.

8.3Females and Males of Reproductive Potential XELODA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating XELODA. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with XELODA and for 6 months after the last dose.

Males Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with XELODA and for 3 months after the last dose [see Nonclinical Toxicology (13.1) ]. Infertility Based on animal studies, XELODA may impair fertility in females and males of reproductive potential [see Nonclinical Toxicology (13.1) ] .

8.4Pediatric Use The safety and effectiveness of XELODA in pediatric patients have not been established. Safety and effectiveness were assessed, but not established in two single arm studies in 56 pediatric patients aged 3 months to <17 years with newly diagnosed gliomas. In both trials, pediatric patients received an investigational pediatric formulation of capecitabine concomitantly with and following completion of radiation therapy (total dose of 5580 cGy in 180 cGy fractions).

The relative bioavailability of the investigational f…

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary Based on findings in animal reproduction studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , XELODA can cause fetal harm when administered to a pregnant woman. Available human data with XELODA use in pregnant women is not sufficient to inform the drug-associated risk. In animal reproduction studies, administration of capecitabine to pregnant animals during the period of organogenesis caused embryolethality and teratogenicity in mice and embryolethality in monkeys at 0.2 and 0.6 times the exposure (AUC) in patients receiving the recommended dose of 1,250 mg/m 2 twice daily, respectively (see Data ) .

Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of 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. Data Animal Data Oral administration of capecitabine to pregnant mice during the period of organogenesis at a dose of 198 mg/kg/day caused malformations and embryo lethality. In separate pharmacokinetic studies, this dose in mice produced 5'-DFUR AUC values that were approximately 0.2 times the AUC values in patients administered the recommended daily dose.

Malformations in mice included cleft palate, anophthalmia, microphthalmia, oligodactyly, polydactyly, syndactyly, kinky tail and dilation of cerebral ventricles. Oral administration of capecitabine to pregnant monkeys during the period of organogenesis at a dose of 90 mg/kg/day, caused fetal lethality. This dose produced 5'-DFUR AUC values that were approximately 0.6 times the AUC values in patients administered the recommended daily dose.

🧒 Pediatric Use 140 words ▾

8.4Pediatric Use The safety and effectiveness of XELODA in pediatric patients have not been established. Safety and effectiveness were assessed, but not established in two single arm studies in 56 pediatric patients aged 3 months to <17 years with newly diagnosed gliomas. In both trials, pediatric patients received an investigational pediatric formulation of capecitabine concomitantly with and following completion of radiation therapy (total dose of 5580 cGy in 180 cGy fractions).

The relative bioavailability of the investigational formulation to XELODA was similar. The adverse reaction profile was consistent with that of adults, with the exception of laboratory abnormalities which occurred more commonly in pediatric patients. The most frequently reported laboratory abnormalities (per-patient incidence ≥ 40%) were increased ALT (75%), lymphocytopenia (73%), hypokalemia (68%), thrombocytopenia (57%), hypoalbuminemia (55%), neutropenia (50%), low hematocrit (50%), hypocalcemia (48%), hypophosphatemia (45%) and hyponatremia (45%).

🧓 Geriatric Use 146 words ▾

8.5Geriatric Use Of 7938 patients with colorectal cancer who were treated with XELODA, 33% were older than 65 years. Of the 4536 patients with metastatic breast cancer who were treated with XELODA, 18% were older than 65 years. Of 1951 patients with gastric, esophageal, or gastrointestinal junction cancer who were treated with XELODA, 26% were older than 65 years.

Of 364 patients with pancreatic cancer who received adjuvant treatment with XELODA, 47% were 65 years or older. No overall differences in efficacy were observed comparing older versus younger patients with colorectal cancer, gastric, esophageal or gastrointestinal junction cancer, or pancreatic cancer using the approved recommended dosages and treatment regimens. Older patients experience increased gastrointestinal toxicity due to XELODA compared to younger patients.

Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin and fluorouracil [see Drug Interactions (7.1) ].

🆘 Overdosage 46 words ▾

10 OVERDOSAGE Administer uridine triacetate within 96 hours for management of XELODA overdose. Although no clinical experience using dialysis as a treatment for XELODA overdose has been reported, dialysis may be of benefit in reducing circulating concentrations of 5'-DFUR, a low–molecular-weight metabolite of the parent compound.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Capecitabine is metabolized to fluorouracil in vivo. Both normal and tumor cells metabolize fluorouracil to 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). These metabolites cause cell injury by two different mechanisms.

First, FdUMP and the folate cofactor, N 5-10 -methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex. This binding inhibits the formation of thymidylate from 2'-deoxyuridylate. Thymidylate is the necessary precursor of thymidine triphosphate, which is essential for the synthesis of DNA, so that a deficiency of this compound can inhibit cell division.

Second, nuclear transcriptional enzymes can mistakenly incorporate FUTP in place of uridine triphosphate (UTP) during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis.

12.2Pharmacodynamics Population-based exposure-effect analyses demonstrated a positive association between AUC of fluorouracil and grade 3-4 hyperbilirubinemia.

12.3Pharmacokinetics The AUC of capecitabine and its metabolite 5'-DFCR increases proportionally over a dosage range of 500 mg/m 2 /day to 3,500 mg/m 2 /day (0.2 to 1.4 times the approved recommended dosage). The AUC of capecitabine's metabolites 5'-DFUR and fluorouracil increased greater than proportional to the dose. The interpatient variability in the C max and AUC of fluorouracil was greater than 85%.

Absorption Following oral administration of XELODA 1,255 mg/m 2 orally twice daily (the recommended dosage when used as single agent), the median T max of capecitabine and its metabolite fluorouracil was approximately 1.5 hours and 2 hours, respectively. Effect of Food Following administration of a meal (breakfast medium-rich in fat and carbohydrates), the mean C max and AUC 0-INF of capecitabine was decreased by 60% and 34%, respectively. The mean C max and AUC 0-INF of fluorouracil were also decreased by 37 % and 12%, respectively.

The T max of both capecitabine and fluorouracil was delayed by 1.5 hours. Distribution Plasma protein binding of capecitabine and its metabolites is less than 60% and is not concentration-dependent. Capecitabine was primarily bound to human albumin (approximately 35%).

Following oral administration of XELODA 7 days before surgery in patients with colorectal cancer, the median ratio of concentration for the active metabolite fluorouracil in colorectal tumors to adjacent tissues was 2.9 (range: 0.9 to 8.0). Elimination The elimination half-lives of capecitabine and fluorouracil were approximately 0.75 hour. Metabolism Capecitabine undergoes metabolism by carboxylesterase and is hydrolyzed to 5'-DFCR.

5'-DFCR is subsequently converted to 5'-DFUR by cytidine deaminase. 5'-DFUR is then hydrolized by thymidine phosphorylase (dThdPase) enzymes to the active metabolite fluorouracil. Fluorouracil is subsequently metabolized by dihydropyrimidine dehydrogenase to 5-fluoro-5, 6-dihydro-fluorouracil (FUH 2 ).

The pyrimidine ring of FUH 2 is cleaved by dihydropyrimidinase to yield 5-fluoro-ureido-propionic acid (FUPA). Finally, FUPA is cleaved by β-ureido-propionase to α-fluoro-β-alanine (FBAL). Excretion Following administration of radiolabeled capecitabine, 96% of the administered capecitabine dose was recovered in urine (3% unchanged and 57% as metabolite FBAL) and 2.6% in feces.

Specific Populations Following therapeutic doses of XELODA, no clinically meaningful difference in the pharmacokinetics of 5'-DFUR, fluorouracil or FBAL were observed based on sex (202 females and 303 males) and race (455 White, 22 Black, and 28 Other). No clinically meaningful difference on the pharmacokinetics of 5'-DFUR and fluorouracil were observed based on age (range: 27 to 86 years); however, the AUC of FBAL increased by 15% following a 20% increase in age. Racial or Ethnic Groups Following administration of XELODA 825 mg/m 2 orally twice daily for 14…

🧬 Mechanism of Action 122 words ▾

12.1Mechanism of Action Capecitabine is metabolized to fluorouracil in vivo. Both normal and tumor cells metabolize fluorouracil to 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). These metabolites cause cell injury by two different mechanisms.

First, FdUMP and the folate cofactor, N 5-10 -methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex. This binding inhibits the formation of thymidylate from 2'-deoxyuridylate. Thymidylate is the necessary precursor of thymidine triphosphate, which is essential for the synthesis of DNA, so that a deficiency of this compound can inhibit cell division.

Second, nuclear transcriptional enzymes can mistakenly incorporate FUTP in place of uridine triphosphate (UTP) during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis.

📦 How Supplied / Storage and Handling 115 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING XELODA (capecitabine) tablets are supplied as follows: 150 mg, biconvex, oblong, film-coated, light peach tablets with "XELODA" on one side and "150" on the other; available in bottles of 60 tablets (NDC 61269-470-60), individually packaged in a carton. 500 mg, biconvex, oblong, film-coated, peach tablets with "XELODA" on one side and "500" on the other; available in bottles of 120 tablets (NDC 61269-475-12), individually packaged in a carton. Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature] .

KEEP TIGHTLY CLOSED. XELODA is a hazardous drug. Follow applicable special handling and disposal procedures.

1

📦 Storage and Handling 42 words ▾

Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature] . KEEP TIGHTLY CLOSED. XELODA is a hazardous drug. Follow applicable special handling and disposal procedures. 1

📋 Description 126 words ▾

11 DESCRIPTION Capecitabine is a nucleoside metabolic inhibitor. The chemical name is 5'-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine and has a molecular formula of C 15 H 22 FN 3 O 6 and a molecular weight of 359.35. Capecitabine has the following structural formula: Capecitabine is a white to off-white crystalline powder with an aqueous solubility of 26 mg/mL at 20°C.

XELODA (capecitabine) is supplied as biconvex, oblong film-coated tablets for oral use. Each light peach-colored tablet contains 150 mg capecitabine and each peach-colored tablet contains 500 mg capecitabine. The inactive ingredients in XELODA include: anhydrous lactose, croscarmellose sodium, hydroxypropyl methylcellulose, microcrystalline cellulose, magnesium stearate and purified water.

The peach or light peach film coating contains hydroxypropyl methylcellulose, talc, titanium dioxide, and synthetic yellow and red iron oxides. Chemical Structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Serious Adverse Reactions or Death from Dihydropyrimidine Dehydrogenase (DPD) Deficiency Prior to initiating XELODA treatment, inform patients of the potential for serious or fatal adverse reactions due to DPD deficiency and testing for genetic variants of DPYD . Advise patients to immediately contact their healthcare provider if symptoms of severe mucositis, diarrhea, neutropenia, and neurotoxicity occur [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.5) ].

Increased Risk of Bleeding with Concomitant Use of Vitamin K Antagonists Advise patients on vitamin K antagonists, such as warfarin, that they are at an increased risk of severe bleeding while taking XELODA. Advise these patients that INR should be monitored more frequently, and dosage modifications of the vitamin K antagonist may be required, while taking and after discontinuation of XELODA. Advise these patients to immediately contact their healthcare provider if signs or symptoms of bleeding occur [see Warnings and Precautions (5.2) ].

Cardiotoxicity Advise patients of the risk of cardiotoxicity and to immediately contact their healthcare provider for new onset of chest pain, shortness of breath, dizziness, or lightheadedness [see Warnings and Precautions (5.3) ] . Diarrhea Inform patients experiencing grade 2 diarrhea (an increase of 4 to 6 stools/day or nocturnal stools) or greater or experiencing severe bloody diarrhea with severe abdominal pain and fever to stop taking XELODA. Advise patients on the use of antidiarrheal treatments (e.g., loperamide) to manage diarrhea [see Warnings and Precautions (5.4) ] .

Dehydration Instruct patients experiencing grade 2 or higher dehydration to stop taking XELODA immediately and to contact their healthcare provider. Advise patients to not restart XELODA until rehydrated and any precipitating causes have been corrected or controlled [see Warnings and Precautions (5.5) ] . Renal Toxicity Instruct patients experiencing decreased urinary output or other signs and symptoms of renal toxicity to immediately contact their healthcare provider [see Warnings and Precautions (5.6) ] .

Serious Skin Toxicities Instruct patients skin rash, blistering, or peeling to immediately contact their healthcare provider [see Warnings and Precautions (5.7) ] . Palmar-Plantar Erythrodysesthesia Syndrome Instruct patients experiencing grade 2 palmar-plantar erythrodysesthesia syndrome or greater to stop taking XELODA immediately and to contact their healthcare provider. Inform patients that initiation of symptomatic treatment is recommended and hand-and-foot syndrome can lead to loss of fingerprints which could impact personal identification [see Warnings and Precautions (5.8) ] .

Myelosuppression Inform patients who develop a fever of 100.5°F or greater or other evidence of potential infection to immediately contact their healthcare provider [see Warnings and Precautions (5.9) ] . Hyperbilirubinemia Inform patients who develop jaundice or icterus to immediately contact their healthcare provider [see Warnings and Precautions (5.10) ] . Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus.

Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.11) , Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment with XELODA and for 6 months after the last dose [see Use in Specific Populations (8.3) ] . Advise males with female partners of reproductive potential to use effective contraception during treatment with XELODA and for 3 months after the last dose [see Use in Specific Populations (8.3) ] .

Lactation Advise females not to breastfeed during treatment with XELODA and for 1 week after the last dose [see Use i…

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