Capecitabine 500mg 500 mg Tablet, Film Coated, 120-count
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Nucleoside Metabolic Inhibitor class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Capecitabine is used to treat certain types of breast cancer, colon or rectal cancer (cancer that begins in the large intestine), pancreatic cancer, and stomach or esophageal (tube that connects the throat with the stomach) cancers. Capecitabine is in a class of medications called antimetabolites. It works by stopping or slowing the growth of cancer cells.
Read the full MedlinePlus article ↗- 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...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Capecitabine — tap one for details:
Capecitabine may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
Where does this data come from?
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII 3SY5LH9PMK
Anhydrous lactose is a milk sugar with no water content. It acts as a filler and binder in tablets and capsules, adding bulk and helping ingredients stick together.
-
UNII M28OL1HH48
Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
-
UNII 1K09F3G675
Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
-
UNII EX438O2MRT
Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
-
UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
-
UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
-
UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
-
UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
-
UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
9 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 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 system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.481 | $57.71 / 120 tablets |
| 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. | |
| Medicare Part B allowsASP · NONE | No ASP payment limit on file for NONE this quarter. | |
Where does this data come from?
🧾 Billing & reimbursement
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Capecitabine 500 mg 00093-7474-89 | Teva | 120 tablets | $0.468 | AB | Availability likely | save 3% |
| Capecitabine 500 mg 16729-0073-29 | Accord | 120 tablets | $0.468 | AB | Availability likely | save 3% |
| capecitabine 500 mg 31722-0775-12 | Camber | 120 tablets | $0.468 | AB | Availability likely | save 3% |
| capecitabine 500 mg 55111-0497-04 | Dr. | 120 tablets | $0.468 | AB | Availability likely | save 3% |
| Capecitabine 500 mg 59651-0205-08 | Aurobindo | 120 tablets | $0.468 | AB | Availability likely | save 3% |
| Capecitabine 500 mg 60687-0149-94 | American | 1 tablet | $0.468 | AB | Availability likely | save 3% |
| Capecitabine 500 mg 67877-0459-12 | Ascend | 120 tablets | $0.468 | AB | Availability likely | save 3% |
| Capecitabine 500 mg 68001-0644-07 | BluePoint | 120 tablets | $0.468 | AB | Availability likely | save 3% |
| Capecitabine 500 mg 69097-0948-08 | Cipla | 120 tablets | $0.468 | AB | Availability likely | save 3% |
| Capecitabine 500 mg 70756-0816-22 | Lifestar | 120 tablets | $0.468 | AB | Availability likely | save 3% |
| Capecitabine 500 mg 72205-0007-92 | Novadoz | 120 tablets | $0.468 | AB | Availability likely | save 3% |
| capecitabine 500 mg 72603-0303-01 | NorthStar | 120 tablets | $0.468 | AB | Availability likely | save 3% |
| Capecitabine 500 mg 82009-0112-12 | Quallent | 120 tablets | $0.468 | AB | Availability likely | save 3% |
| Capecitabine 500 mg 82249-0210-12 | CivicaScript | 120 tablets | $0.468 | AB | Availability likely | save 3% |
| Capecitabine 500 mg 68001-0488-07 | BluePoint | 120 tablets | $0.481 | AB | FDA listed | — |
| Capecitabine 500mg 500 mgthis 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 mg 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 | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 72485-0205-12 You're viewing this | 1 BOTTLE in 1 CARTON (72485-205-12) / 120 TABLET, FILM COATED in 1 BOTTLE | 2019-03-01 | Active |
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: CAPECITABINE-WARFARIN INTERACTION Capecitabine Warfarin Interaction: Patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored frequently in order to adjust the anticoagulant dose accordingly. A clinically important capecitabine-Warfarin drug interaction was demonstrated in a clinical pharmacology trial [see Warnings and Precautions (5.2) and Drug Interactions (7.1) ] . Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking capecitabine concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon.
Post marketing reports have shown clinically significant increases in prothrombin time (PT) and INR in patients who were stabilized on anticoagulants at the time capecitabine was introduced. These events occurred within several days and up to several months after initiating capecitabine therapy and, in a few cases, within 1 month after stopping capecitabine. These events occurred in patients with and without liver metastases.
Age greater than 60 and a diagnosis of cancer independently predispose patients to an increased risk of coagulopathy. WARNING: CAPECITABINE -WARFARIN INTERACTION See full prescribing information for complete boxed warning. Patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulants such as warfarin and phenprocoumon should have their anticoagulant response (INR or prothrombin time) monitored frequently in order to adjust the anticoagulant dose accordingly.
Altered coagulation parameters and/or bleeding, including death, have been reported during concomitant use. Occurrence: Within several days and up to several months after initiating capecitabine therapy; may also be seen within 1 month after stopping capecitabine Predisposing factors: age>60 and diagnosis of cancer
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Capecitabine tablets are a nucleoside metabolic inhibitor with antineoplastic activity indicated for: • Adjuvant Colon Cancer (1.1) – Patients with Dukes' C colon cancer • Metastatic Colorectal Cancer (1.1) – First-line as monotherapy when treatment with fluoropyrimidine therapy alone is preferred • Metastatic Breast Cancer (1.2) – In combination with docetaxel after failure of prior anthracycline containing therapy – As monotherapy in patients resistant to both paclitaxel and an anthracycline-containing regimen
1.1Colorectal Cancer Capecitabine tablets are indicated as a single agent for adjuvant treatment in patients with Dukes' C colon cancer who have undergone complete resection of the primary tumor when treatment with fluoropyrimidine therapy alone is preferred. Capecitabine tablets are non-inferior to 5-fluorouracil and leucovorin (5-FU/LV) for disease-free survival (DFS). Physicians should consider results of combination chemotherapy trials, which have shown improvement in DFS and OS, when prescribing single-agent capecitabine tablets in the adjuvant treatment of Dukes' C colon cancer.
Capecitabine tablets are indicated as first-line treatment of patients with metastatic colorectal carcinoma when treatment with fluoropyrimidine therapy alone is preferred. Combination chemotherapy has shown a survival benefit compared to 5-FU/LV alone. A survival benefit over 5-FU/LV has not been demonstrated with capecitabine tablets monotherapy.
Use of capecitabine tablets instead of 5-FU/LV in combinations has not been adequately studied to assure safety or preservation of the survival advantage.
1.2Breast Cancer Capecitabine tablets in combination with docetaxel is indicated for the treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing chemotherapy. Capecitabine tablets monotherapy is also indicated for the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen or resistant to paclitaxel and for whom further anthracycline therapy is not indicated (e.g., patients who have received cumulative doses of 400 mg/m 2 of doxorubicin or doxorubicin equivalents).
Resistance is defined as progressive disease while on treatment, with or without an initial response, or relapse within 6 months of completing treatment with an anthracycline-containing adjuvant regimen.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Take capecitabine tablets with water within 30 min after a meal (2.1) Monotherapy: 1250 mg/m 2 twice daily orally for 2 weeks followed by a one week rest period in 3-week cycles (2.2) Adjuvant treatment is recommended for a total of 6 months (8 cycles) (2.2) In combination with docetaxel, the recommended dose of capecitabine tablets is 1250 mg/m 2 twice daily for 2 weeks followed by a 7-day rest period, combined with docetaxel at 75 mg/m 2 as a 1-hour IV infusion every 3 weeks (2.2) Capecitabine tablets dosage may need to be individualized to optimize patient management (2.3) Reduce the dose of capecitabine tablets by 25% in patients with moderate renal impairment (2.4)
2.1Important Administration Instructions Capecitabine tablets should be swallowed whole with water within 30 minutes after a meal. Capecitabine is a cytotoxic drug. Follow applicable special handling and disposal procedures.
1 If Capecitabine tablets must be cut or crushed, this should be done by a professional trained in safe handling of cytotoxic drugs using appropriate equipment and safety procedures. Capecitabine Tablets dose is calculated according to body surface area.
2.2Standard Starting Dose Monotherapy (Metastatic Colorectal Cancer, Adjuvant Colorectal Cancer, Metastatic Breast Cancer) The recommended dose of capecitabine tablets are 1250 mg/m 2 administered orally twice daily (morning and evening; equivalent to 2500 mg/m 2 total daily dose) for 2 weeks followed by a 1-week rest period given as 3-week cycles (see Table 1 ). Adjuvant treatment in patients with Dukes' C colon cancer is recommended for a total of 6 months [ie, capecitabine tablets 1250 mg/m 2 orally twice daily for 2 weeks followed by a 1-week rest period, given as 3-week cycles for a total of 8 cycles (24 weeks)].
Table 1 Capecitabine Tablets Dose Calculation According to Body Surface Area Dose Level 1250 mg/m 2 Twice a Day Number of Tablets to be Taken at Each Dose (Morning and Evening) Surface Area (m 2 ) Total Daily Dose Total Daily Dose divided by 2 to allow equal morning and evening doses (mg) 150mg 500mg ≤ 1.25 3000 0 3 1.26-1.37 3300 1 3 1.38-1.51 3600 2 3 1.52-1.65 4000 0 4 1.66-1.77 4300 1 4 1.78-1.91 4600 2 4 1.92-2.05 5000 0 5 2.06-2.17 5300 1 5 ≥ 2.18 5600 2 5 In Combination With Docetaxel (Metastatic Breast Cancer) In combination with docetaxel, the recommended dose of capecitabine tablets are 1250 mg/m 2 twice daily for 2 weeks followed by a 1-week rest period, combined with docetaxel at 75 mg/m 2 as a 1-hour intravenous infusion every 3 weeks.
Pre-medication, according to the docetaxel labeling, should be started prior to docetaxel administration for patients receiving the capecitabine tablets plus docetaxel combination. Table 1 displays the total daily dose of capecitabine tablets by body surface area and the number of tablets to be taken at each dose.
2.3Dose Management Guidelines General Capecitabine tablets dosage may need to be individualized to optimize patient management. Patients should be carefully monitored for toxicity and doses of capecitabine tablets should be modified as necessary to accommodate individual patient tolerance to treatment [see Clinical Studies (14) ] . Toxicity due to capecitabine tablets administration may be managed by symptomatic treatment, dose interruptions and adjustment of capecitabine tablets dose.
Once the dose has been reduced, it should not be increased at a later time. Doses of capecitabine tablets omitted for toxicity are not replaced or restored; instead the patient should resume the planned treatment cycles. The dose of phenytoin and the dose of coumarin-derivative anticoagulants may need to be reduced when either drug is administered concomitantly with capecitabine tablets [see Drug Interactions (7.1) ] .
Monotherapy (Metastatic Colorectal Cancer, Adjuvant Colorectal Cancer, Metastatic Breast Cancer) Capecitabine tablets dose modification scheme as described below (see Table 2 ) is recommended for…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Capecitabine tablets USP are supplied in strengths of 150 mg and 500 mg for oral administration. 150 mg : Light pink coloured, capsule shaped, biconvex film coated tablet debossed with one side CAP and other side 150. 500 mg : Dark pink coloured, capsule shaped, biconvex film coated tablet debossed with one side CAP and other side 500. Tablets: 150 mg and 500 mg (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS Severe Renal Impairment (4.1) Hypersensitivity (4.2)
4.1Severe Renal Impairment Capecitabine tablets are contraindicated in patients with severe renal impairment (creatinine clearance below 30 mL/min [Cockroft and Gault]) [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ] .
4.2Hypersensitivity Capecitabine tablets are contraindicated in patients with known hypersensitivity to capecitabine or to any of its components. Capecitabine tablets are contraindicated in patients who have a known hypersensitivity to 5-fluorouracil.
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Coagulopathy: May result in bleeding, death. Monitor anticoagulant response (e.g., INR) and adjust anticoagulant dose accordingly. (5.1) Diarrhea: May be severe.
Interrupt Capecitabine tablets treatment immediately until diarrhea resolves or decreases to grade 1. Recommend standard antidiarrheal treatments. (5.2) Cardiotoxicity: Common in patients with a prior history of coronary artery disease.
(5.3) Increased Risk of Severe or Fatal Adverse Reactions in Patients with Lo w or Absent Dihydropyrimidine Dehydrogenase (DPD) Activity: Withhold or permanently discontinue Capecitabine tablets in patients with evidence of acute early-onset or unusually severe toxicity, which may indicate near complete or total absence of DPD activity. No Capecitabine tablets dose has been proven safe in patients with absent DPD activity. ( 5.4 ) Dehydration and Renal Failure: Interrupt Capecitabine tablets treatment until dehydration is corrected.
Potential risk of acute renal failure secondary to dehydration. Monitor and correct dehydration. (5.5) .
Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. (5.6 , 8.1, 8.3) Mucocutaneous and Dermatologic Toxicity: Severe mucocutaneous reactions, Steven-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), have been reported.
Capecitabine tablets should be permanently discontinued in patients who experience a severe mucocutaneous reaction during treatment. Capecitabine tablets may induce hand-and-foot syndrome. Persistent or severe hand-and-foot syndrome can lead to loss of fingerprints which could impact patient identification.
In Interrupt Capecitabine tablets treatment until the hand-and-foot syndrome event resolves or decreases in intensity. (5.7) Hyperbilirubinemia: Interrupt capecitabine tablet treatment immediately until the hyperbilirubinemia resolves or decreases in intensity. (5.8) Hematologic: Do not treat patients with neutrophil counts <1.5 x 10 9 /L or thrombocyte counts <100 x 10 9 /L.
If grade 3-4 neutropenia or thrombocytopenia occurs, stop therapy until condition resolves. (5.9)
5.1Coagulopathy Patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored closely with great frequency and the anticoagulant dose should be adjusted accordingly [see Boxed Warning and Drug Interactions (7.1) ]
5.2Diarrhea Capecitabine can induce diarrhea, sometimes severe. Patients with severe diarrhea should be carefully monitored and given fluid and electrolyte replacement if they become dehydrated. In 875 patients with either metastatic breast or colorectal cancer who received capecitabine monotherapy, the median time to first occurrence of grade 2 to 4 diarrhea was 34 days (range from 1 to 369 days).
The median duration of grade 3 to 4 diarrhea was 5 days. National Cancer Institute of Canada (NCIC) grade 2 diarrhea is defined as an increase of 4 to 6 stools/day or nocturnal stools, grade 3 diarrhea as an increase of 7 to 9 stools/day or incontinence and malabsorption, and grade 4 diarrhea as an increase of ≥10 stools/day or grossly bloody diarrhea or the need for parenteral support. If grade 2, 3 or 4 diarrhea occurs, administration of capecitabine should be immediately interrupted until the diarrhea resolves or decreases in intensity to grade 1. [see Dosage and Administration (2.3) ] .
Standard antidiarrheal treatments (eg, loperamide) are recommended. Necrotizing enterocolitis (typhlitis) has been reported.
5.3Cardiotoxicity The cardiotoxicity observed with capecitabine tablets includes myocardial infarction/ischemia, angina, dysrhythmias, cardiac arrest, cardiac failure, sudden death, electrocardiographic changes, and cardiomyopathy. These adverse reactions may be more common in patients with a prior history of coronary artery disease.
5.4 Dihydropyrimidine D…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS 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. Most common adverse reactions (≥30%) were diarrhea, hand-and-foot syndrome, nausea, vomiting, abdominal pain, fatigue/weakness, and hyperbilirubinemia. Other adverse reactions, including serious adverse reactions, have been reported.
(6) To report SUSPECTED ADVERSE REACTIONS, contact 1-888-557-1212 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Adjuvant Colon Cancer Table 4 shows the adverse reactions occurring in ≥5% of patients from one phase 3 trial in patients with Dukes' C colon cancer who received at least one dose of study medication and had at least one safety assessment. A total of 995 patients were treated with 1250 mg/m 2 twice a day of capecitabine administered for 2 weeks followed by a 1-week rest period, and 974 patients were administered 5- FU and leucovorin (20 mg/m 2 leucovorin IV followed by 425 mg/m 2 IV bolus 5-FU on days 1-5 every 28 days).
The median duration of treatment was 164 days for capecitabine-treated patients and 145 days for 5-FU/LV-treated patients. A total of 112 (11%) and 73 (7%) capecitabine and 5-FU/LV-treated patients, respectively, discontinued treatment because of adverse reactions. A total of 18 deaths due to all causes occurred either on study or within 28 days of receiving study drug: 8 (0.8%) patients randomized to capecitabine and 10 (1.0%) randomized to 5-FU/LV.
Table 5 shows grade 3/4 laboratory abnormalities occurring in ≥1% of patients from one phase 3 trial in patients with Dukes' C colon cancer who received at least one dose of study medication and had at least one safety assessment. Table 4 Percent Incidence of Adverse Reactions Reported in ≥5% of Patients Treated With Capecitabine or 5-FU/LV for Colon Cancer in the Adjuvant Setting (Safety Population) Adjuvant Treatment for Colon Cancer (N=1969) Capecitabine (N=995) 5-FU/LV (N=974) Body System/ Adverse Event All Grades Grade 3/4 All Grades Grade 3/4 Gastrointestinal Disorders 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 Constipation 9 - 11 <1 Upper Abdominal Pain 7 <1 7 <1 Dyspepsia 6 <1 5 - Skin and Subcutaneous Tissue Disorders Hand-and-Foot Syndrome 60 17 9 <1 Alopecia 6 - 22 <1 Rash 7 - 8 - Erythema 6 1 5 <1 General Disorders and Administration Site Conditions Fatigue 16 <1 16 1 Pyrexia 7 <1 9 <1 Asthenia 10 <1 10 1 Lethargy 10 <1 9 <1 Nervous System Disorders Dizziness 6 <1 6 - Headache 5 <1 6 <1 Dysgeusia 6 - 9 - Metabolism and Nutrition Disorders Anorexia 9 <1 11 <1 Eye Disorders Conjunctivitis 5 <1 6 <1 Blood and Lymphatic System Disorders Neutropenia 2 <1 8 5 Respiratory Thoracic and Mediastinal Disorders Epistaxis 2 - 5 - Table 5 Percent Incidence of Grade 3/4 Laboratory Abnormalities Reported in ≥1% of Patients Receiving Capecitabine Monotherapy for Adjuvant Treatment of Colon Cancer (Safety Population) Adverse Event Capecitabine (n=995) Grade 3/4 % IV 5-FU/LV (n=974) Grade 3/4 % Increased ALAT (SGPT) Increased calcium Decreased calcium Decreased hemoglobin Decreased lymphocytes Decreased neutrophils The incidence of grade 3/4 white blood cell abnormalities was 1.3% in the capecitabine arm and 4.9% in the IV 5-FU/LV arm. ** It should be noted that grading was according to NCIC CTC Version 1 (May, 1994).
In the NCIC-CTC Version 1, hyperbilirubinemia grade 3 indicates a bilirubin value of 1.5 to 3.0 x upper limit of normal (ULN) range, and grade 4 a value of > 3.0 x ULN. The NCI CTC Version2 and above define a grade 3 bilirubin value of >3.0 to 10.0 x ULN, and grade 4 values >10.0 x ULN. Decreased neutrophils/granulocytes Decreased platelets Increased bilirubin ** 1.6 1.1 2.3 1.0 13.0 2.2 2.4 1.0 20 0.6 0.7 2.2 1.2 13.0 26.2 26.4 0.7 6.3
6.2 Metastatic Colorectal Cancer Mo…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Anticoagulants: Monitor anticoagulant response (INR or prothrombin time) frequently in order to adjust the anticoagulant dose as needed. (5.2 , 7.1) Phenytoin: Monitor phenytoin levels in patients taking capecitabine concomitantly with phenytoin. The phenytoin dose may need to be reduced.
(7.1) Leucovorin: The concentration of 5-fluorouracil is increased and its toxicity may be enhanced by leucovorin. (7.1) CYP2C9 substrates: Care should be exercised when capecitabine is coadministered with CYP2C9 substrates. (7.1) Allopurinol: Avoid the use of allopurinol during treatment with Capecitabine tablets.
Food reduced both the rate and extent of absorption of capecitabine. (2 , 7.2 , 12.3)
7.1Drug-Drug Interactions Anticoagulants Altered coagulation parameters and/or bleeding have been reported in patients taking capecitabine concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon [ see Boxed Warning ]. These events occurred within several days and up to several months after initiating capecitabine therapy and, in a few cases, within 1 month after stopping capecitabine. These events occurred in patients with and without liver metastases.
In a drug interaction study with single dose warfarin administration, there was a significant increase in the mean AUC of S-warfarin [ see Clinical Pharmacology ( 12.3 ) ]. The maximum observed INR value increased by 91%. This interaction is probably due to an inhibition of cytochrome P450 2C9 by capecitabine and/or its metabolites.
Phenytoin The level of phenytoin should be carefully monitored in patients taking capecitabine and phenytoin dose may need to be reduced [ see Dosage and Administration ( 2.3 ) ]. Postmarketing reports indicate that some patients receiving capecitabine and phenytoin had toxicity associated with elevated phenytoin levels. Formal drug-drug interaction studies with phenytoin have not been conducted, but the mechanism of interaction is presumed to be inhibition of the CYP2C9 isoenzyme by capecitabine and/or its metabolites.
Leucovorin The concentration of 5-fluorouracil is increased and its toxicity may be enhanced by leucovorin. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin and fluorouracil. CYP2C9 substrates Other than warfarin, no formal drug-drug interaction studies between capecitabine and other CYP2C9 substrates have been conducted.
Care should be exercised when capecitabine is coadministered with CYP2C9 substrates. Allopurinol Concomitant use with allopurinol may decrease concentration of capecitabine’s active metabolites [ see Clinical Pharmacology ( 12.3 ) ], which may decrease capecitabine tablets efficacy. Avoid the use of allopurinol during treatment with capecitabine tablets.
7.2Drug-Food Interaction Food was shown to reduce both the rate and extent of absorption of capecitabine [see Clinical Pharmacology (12.3) ] . In all clinical trials, patients were instructed to administer capecitabine within 30 minutes after a meal. It is recommended that capecitabine be administered with food [see Dosage and Administration (2) ].
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise women not to breast feeding. (8.2) Females and males of reproductive potential: Verify pregnancy status of females prior to initiation of Capecitabine tablets. Advise males with female partners of reproductive potential to use effective contraception.
(8.3) Geriatric: Greater incidence of adverse reactions. Monitoring required. (8.5) Hepatic Impairment: Monitoring is recommended in patients with mild to moderate hepatic impairment.
(8.6) Renal Impairment: Reduce capecitabine starting dose in patients with moderate renal impairment ( 2.4 , 8.7 , 12.3)
8.1Pregnancy: Risk Summary Based on findings in animal reproduction studies and its mechanism of action, Capecitabine can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . Limited available human data are not sufficient to inform the drug-associated risk during pregnancy. In animal reproduction studies, administration of capecitabine to pregnant animals during the period of organogenesis caused embryo lethality in monkeys at 0.2 and 0.6 times the exposure (AUC) in patients receiving the recommended dose respectively[see Data].
Apprise 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. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognised pregnancies is 2-4% and 15-20% respectively.
Data Animal Data Oral administration of capecitabine to pregnant mice during the period of organogenesis at a dose of 198mg/kg/day caused malformations and embryo lethality. In separate pharmacokinetic studies, this dose in mice produced 5'-DFURAUC values that were approximately 0.2 times the AUC values in patients administered the recommended daily dose. Malformations in mice included cleft palate, anopthalmia, micropthalmia, 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 90mg/kg/day, caused fetal lethality. This dose produced 5'-DFURAUC 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 in human milk, or on its effect on milk production or the breast-fed infant. Capecitabine metabolites were present in the milk of lactating mice [see Data]. Because of the potential for serious adverse reactions from capecitabine exposure in breast-fed infants, advise women not to breastfeed during treatment with capecitabine and for 2 weeks after the final dose.
Data Lactating mice given a single oral dose of capecitabine excreted significant amounts of capecitabine metabolise into the milk
8.3Females and Males of Reproductive Potential Pregnancy Testing Pregnancy testing is recommended for females of reproductive potential prior to initiating capecitabine. Contraception Females Capecitabine can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the final dose of capecitabine.
Males Based on genetic toxicity findings, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months following the last dose of capecitabine [see Nonclinical Toxicology (13.1) ] Infertility Based on animal studies, capecitabine may impair fertility in females and males of reproductive potential [see Nonclinical Toxicology (13.1) ]
8.4Pediatric Use The safety and effectiveness of capecitabine tablets in pediatric patients have not been established. No clinical benefit was demonstrated in two single arm trials in pediatric patients with newly diagnosed brainst…
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of capecitabine tablets in pediatric patients have not been established. No clinical benefit was demonstrated in two single arm trials in pediatric patients with newly diagnosed brainstem gliomas and high grade 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 capecitabine was similar. The first trial was conducted in 22 pediatric patients (median age 8 years, range 5-17 years) with newly diagnosed non-disseminated intrinsic diffuse brainstem gliomas and high grade gliomas. In the dose-finding portion of the trial, patients received capecitabine with concomitant radiation therapy at doses ranging from 500 mg/m 2 to 850 mg/m 2 every 12 hours for upto 9 weeks.
After a 2 week break, patients received 1250 mg/m 2 capecitabine every 12 hours on Days 1-14 of a 21day cycle for upto 3 cycles. The maximum tolerated dose (MTD) of capecitabine administered concomitantly with radiation therapy was 650 mg/m 2 every 12 hours. The major dose limiting toxicities were palmar-plantar erythrodysesthesia and alanine aminotransferase(ALT) elevation.
The second trial was conducted in 34 additional pediatric patients with newly diagnosed non-disseminated intrinsic diffuse brainstem gliomas (median age 7 years, range 3-16 years) and 10 pediatric patients who received the MTD of capecitabine in the dose-finding trial and met the eligibility criteria for this trial. All patients received 650 mg/m 2 capecitabine every 12 hours with concomitant radiation therapy for upto 9 weeks. After a 2 week break, patients received 1250 mg/m 2 capecitabine every 12 hours on Days 1-14 of a 21-day cycle for upto 3 cycles.
There was no improvement in one-year progression-fee survival rate and one-year overall survival rate in pediatric patients with newly diagnosed intrinsic brainstem gliomas who received capecitabine relative to a similar population of pediatric patients who participated in other clinical trials. The adverse reaction profile of capecitabine was consistent with the known adverse reaction profile in 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%), leukopenia (73%), hypokalemia (68%), thrombocytopenia (57%), hypoalbuminemia (55%), neutropenia (50%), low hematocrit (50%), hypoclacemia (48%),hypophosphatemia (45%) and hyponatremia (45%).
🧓 Geriatric Use ▾
8.5Geriatric Use Physicians should pay particular attention to monitoring the adverse effects of capecitabine in the elderly [ see Warnings and Precautions ( 5.10 ) ].
🆘 Overdosage ▾
10 OVERDOSAGE The manifestations of acute overdose would include nausea, vomiting, diarrhea, gastrointestinal irritation and bleeding, and bone marrow depression. Medical management of overdose should include customary supportive medical interventions aimed at correcting the presenting clinical manifestations. Although no clinical experience using dialysis as a treatment for capecitabine 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.
Single doses of capecitabine were not lethal to mice, rats, and monkeys at doses up to 2000 mg/kg (2.4, 4.8, and 9.6 times the recommended human daily dose on a mg/m 2 basis).
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Enzymes convert capecitabine to 5-fluorouracil (5-FU) in vivo . Both normal and tumor cells metabolize 5-FU 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.
12.3Pharmacokinetics Absorption Following oral administration of 1255 mg/m 2 BID to cancer patients, capecitabine reached peak blood levels in about 1.5 hours (T max ) with peak 5-FU levels occurring slightly later, at 2 hours. Food reduced both the rate and extent of absorption of capecitabine with mean C max and AUC 0-∞ decreased by 60% and 35%, respectively. The C max and AUC 0-∞ of 5-FU were also reduced by food by 43% and 21%, respectively.
Food delayed T max of both parent and 5-FU by 1.5 hours [see Warnings and Precautions (5) , Dosage and Administration (2) , and Drug-Food Interaction (7.2) ] . The pharmacokinetics of capecitabine and its metabolites have been evaluated in about 200 cancer patients over a dosage range of 500 to 3500 mg/m 2 /day. Over this range, the pharmacokinetics of capecitabine and its metabolite, 5'-DFCR were dose proportional and did not change over time.
The increases in the AUCs of 5'-DFUR and 5-FU, however, were greater than proportional to the increase in dose and the AUC of 5-FU was 34% higher on day 14 than on day 1. The interpatient variability in the C max and AUC of 5-FU was greater than 85%. 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%). Capecitabine tablet has a low potential for pharmacokinetic interactions related to plasma protein binding. Bioactivation and Metabolism Capecitabine is extensively metabolized enzymatically to 5-FU.
In the liver, a 60 kDa carboxylesterase hydrolyzes much of the compound to 5'-deoxy-5-fluorocytidine (5'-DFCR). Cytidine deaminase, an enzyme found in most tissues, including tumors, subsequently converts 5'DFCR to 5'-DFUR. The enzyme, thymidine phosphorylase (dThdPase), then hydrolyzes 5'-DFUR to the active drug 5-FU.
Many tissues throughout the body express thymidine phosphorylase. Some human carcinomas express this enzyme in higher concentrations than surrounding normal tissues. Following oral administration of capecitabine 7 days before surgery in patients with colorectal cancer, the median ratio of 5-FU concentration in colorectal tumors to adjacent tissues was 2.9 (range from 0.9 to 8.0).
These ratios have not been evaluated in breast cancer patients or compared to 5-FU infusion. Metabolic Pathway of capecitabine to 5-FU3 The enzyme dihydropyrimidine dehydrogenase hydrogenates 5-FU, the product of capecitabine metabolism, to the much less toxic 5-fluoro-5, 6-dihydro-fluorouracil (FUH 2 ). Dihydropyrimidinase cleaves the pyrimidine ring to yield 5-fluoro-ureido-propionic acid (FUPA).
Finally, β-ureido- propionase cleaves FUPA to α-fluoro-β-alanine (FBAL) which is cleared in the urine. In vitro enzymatic studies with human liver microsomes indicated that capecitabine and its metabolites (5'-DFUR, 5'-DFCR, 5-FU, and FBAL) did not inhibit the metabolism of test substrates by cytochrome P450 isoenzymes 1A2, 2A6, 3A4, 2C19, 2D6, and 2E1. Excretion Capecitabine and its metabolites are predominan…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Enzymes convert capecitabine to 5-fluorouracil (5-FU) in vivo . Both normal and tumor cells metabolize 5-FU 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 ▾
16 HOW SUPPLIED/STORAGE AND HANDLING 150 mg: Light pink coloured, capsule shaped, biconvex film coated tablet debossed with one side CAP and other side 150. 150 mg tablets are packaged in bottles of 60 (NDC 72485-204-60). 500 mg: Dark pink coloured, capsule shaped, biconvex film coated tablet debossed with one side CAP and other side 500.
500 mg tablets are packaged in bottles of 120 (NDC 72485-205-12). Storage and Handling Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature]. KEEP TIGHTLY CLOSED.
Capecitabine is a cytotoxic drug. Follow applicable special handling and disposal procedures. 1 Any unused product should be disposed of in accordance with local requirements, or drug take back program.
📋 Description ▾
11 DESCRIPTION Capecitabine tablets USP are fluoropyrimidine carbamate with antineoplastic activity. It is an orally administered systemic prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR) which is converted to 5- fluorouracil. The chemical name for Capecitabine, USP is 5'-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine and has a molecular weight of 359.35.
Capecitabine has the following structural formula: Capecitabine, USP is a white to off-white crystalline powder with an aqueous solubility of 26 mg/mL at 20ºC. Capecitabine tablets USP are supplied as capsule shaped, biconvex film coated tablets for oral administration. Each light pink-colored tablet contains 150 mg capecitabine and each dark pink-colored tablet contains 500 mg capecitabine.
The inactive ingredients in Capecitabine tablets USP include: anhydrous lactose, croscarmellose sodium, hydroxypropyl methylcellulose, microcrystalline cellulose, magnesium stearate and purified water. The light or dark pink film coating contains hydroxypropyl methylcellulose, talc, titanium dioxide, yellow iron oxide, and red iron oxide. Structural Formula
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). 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 capecitabine tablets. Advise patients on the use of antidiarrheal treatments (e.g., loperamide) to manage diarrhea. [ see Warnings and Precautions ( 5.2 ) ] Cardiotoxicity Advise patients of the risk of cardiotoxicity and to immediately contact their healthcare provider or to go to an emergency room for new onset of chest pain, shortness of breath, dizziness, or lightheadedness [ see Warnings and Precautions ( 5.3 ) ].
Dihydropyrimidine Dehydrogenase Deficiency Advise patients to notify their healthcare provider if they have a known DPD deficiency. Advise patients if they have complete or near complete absence of DPD activity they are at an increased risk of acute early-onset of toxicity and severe, life-threatening, or fatal adverse reactions caused by capecitabine tablets (e.g., mucositis, diarrhea, neutropenia, and neurotoxicity) [ see Warnings and Precautions ( 5.4) ]. Dehydration and Renal Failure Instruct patients experiencing grade 2 or higher dehydration (IV fluids indicated < 24 hours) to stop taking capecitabine tablets immediately and to call their healthcare provider to correct the dehydration.
Advise patients to not restart capecitabine tablets until rehydrated and any precipitating causes have been corrected or controlled [ see Warnings and Precautions ( 5.5 ) ]. Important Administration Instructions Advise patients to swallow capecitabine tablets whole with water within 30 minutes of a meal. Advise patients and caregivers not to crush or cut capecitabine tablets.
Advise patients if they cannot swallow capecitabine tablets whole, to inform their healthcare provider [ see Dosage and Administration ( 2.1 )] . Nausea Instruct patients experiencing grade 2 nausea (food intake significantly decreased but able to eat intermittently) or greater to stop taking capecitabine tablets immediately and to contact their healthcare provider for management of nausea [ see Adverse Reactions ( 6.1 ) ]. Vomiting Instruct patients experiencing grade 2 vomiting (2 to 5 episodes in a 24-hour period) or greater to stop taking capecitabine tablets immediately and to contact their healthcare provider for management of vomiting [ see Adverse Reactions ( 6.1 ) ].
Hand-and-Foot Syndrome Instruct patients experiencing grade 2 hand-and-foot syndrome (painful erythema and swelling of the hands and/or feet and/or discomfort affecting the patients’ activities of daily living) or greater to stop taking capecitabine tablets 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 Adverse Reactions ( 6.1 ) ].
Stomatitis Inform patients experiencing grade 2 stomatitis (painful erythema, edema or ulcers of the mouth or tongue, but able to eat) or greater to stop taking capecitabine tablets immediately and to contact their healthcare provider [ see Adverse Reactions ( 6.1 ) ]. Fever and Neutropenia Inform patients who develop a fever of 100.5°F or greater or other evidence of potential infection to contact their healthcare provider [ see Adverse Reactions ( 6.1 )]. Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment with capecitabine and for 6 months after the last dose.
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 and 8.3 ) . Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ca…
💬 Patient Medication Information ▾
Patient Information Capecitabine Tablets USP, Film Coated (KAP-e-SYE-ta-been) What is the most important information I should know about Capecitabine tablets? Capecitabine tablets can cause serious side effects, including: Capecitabine tablets can interact with blood thinner medicines, such as warfarin (COUMADIN). Taking Capecitabine tablets with these medicines can cause changes in how fast your blood clots, and can cause bleeding that can lead to death.
This can happen as soon as a few days after you start taking Capecitabine tablets, or later during treatment, and possibly even within 1 month after you stop taking Capecitabine tablets. Your risk may be higher because you have cancer, and if you are over 60 years of age. Before taking Capecitabine tablets, tell your healthcare provider if you are taking warfarin (COUMADIN) or another blood thinner medicine.
If you take warfarin (COUMADIN) or another blood thinner that is like warfarin (COUMADIN) during treatment with Capecitabine tablets, your healthcare provider should do blood tests often, to check how fast your blood clots during and after you stop treatment with Capecitabine tablets. Your healthcare provider may change your dose of the blood thinner medicine if needed. See "What are the possible side effects of Capecitabine tablets?" for more information about side effects.
What is Capecitabine tablets? Capecitabine tablets is a prescription medicine used to treat people with: cancer of the colon that has spread to lymph nodes in the area close to the colon (Dukes' C stage), after they have surgery. cancer of the colon or rectum (colorectal) that has spread to other parts of the body (metastatic). breast cancer that has spread to other parts of the body (metastatic) together with another medicine called docetaxel after treatment with certain other anticancer medicines have not worked. breast cancer that has spread to other parts of the body and has not improved after treatment with paclitaxel and certain other anti-cancer medicines, or who cannot receive any more treatment with certain anti-cancer medicines.
It is not known if Capecitabine tablets are safe and effective in children. Who should not take Capecitabine tablets? Do not take Capecitabine tablets if you: have severe kidney problems. are allergic to capecitabine, 5-fluorouracil, or any of the ingredients in Capecitabine tablets.
See the end of this leaflet for a complete list of ingredients in Capecitabine tablets. Talk to your healthcare provider before taking Capecitabine tablets if you are not sure if you have any of the conditions listed above. Before taking Capecitabine tablets, tell your healthcare provider about all your medical conditions, including if you: See "What is the most important information I should know about Capecitabine tablets?" .
Before you take Capecitabine tablets, tell your doctor if you: have had heart problems. have kidney or liver problems. have been told that you lack the enzyme DPD (dihydropyrimidine dehydrogenase) have any other medical conditions. are pregnant or plan to become pregnant. Capecitabine tablets can harm your unborn baby. Your healthcare provider should do a pregnancy test before you start treatment with capecitabine tablets.
Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with capecitabine tablets. Ø Females who are able to become pregnant should use effective birth control during treatment and for 6 months after the final dose. Talk to your healthcare provider about birth control choices that may be right for you during treatment with capecitabine tablets Ø Males who have female partners who are able to become pregnant should use effective birth control during treatment and for 3 months after the final dose. are breastfeeding or plan to breastfeed.
It is not known if Capecitabine tablets passes into your breast milk. You and your doctor should decide if you will take Capecitabine tablets or breastfeed.…