Capecitabine

359.35000

359.35

6804DJ8Z9U

DTXSID3046451

C1794

White to off-white crystalline powder|Crystals from ethyl acetate

L01BC06|L - Antineoplastic and immunomodulating agents

2934999090

122.91000

0.6

white to beige

1.49 g/cm3

88-89 °C

437.874ºC at 760 mmHg

218.619ºC

1.7

2.48e-01 g/L

Store in original container in a cool dark place.

0mmHg at 25°C

Henry's Law constant = 2.9X10-19 atm-cu m/mol at 25 °C (est)

pKa1 = 1.9 (amide)

Hydroxyl radical reaction rate constant = 8.27X10-11 cu cm/molec-sec at 25 °C (est)|Ozone reaction rate constant = 7.0X10-15 cu cm/molec-sec at 25 °C (est)

NONH for all modes of transport

3

45-60-61-68

53-22-36/37-45

T

Capecitabine tablets reportedly are stable for at least 9 months when stored in tightly closed containers at room temperature.

P201-P308 + P313

H341-H350-H360FD

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All contaminated disposables should be contained in sealable bags for transfer to larger waste containers. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All bottles must be discarded as contaminated waste after decontamination of the biohazard cabinet. All protective apparel (gown, gloves, goggles, and respirator) should be discarded as contaminated waste. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The contaminated filters must be removed, bagged in thick plastic and prepared for disposal in a hazardous waste dump site or incinerator licensed by the Environmental Protection Agency (EPA). /Antineoplastic agents/|For more Disposal Methods (Complete) data for CAPECITABINE (8 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl capecitabine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Danger|H315 (14.29%): Causes skin irritation [Warning Skin corrosion/irritation]|P201, P202, P264, P280, P281, P302+P352, P305+P351+P338, P308+P313, P321, P332+P313, P337+P313, P362, P405, and P501|Aggregated GHS information provided by 49 companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Protective apparel: Disposable closed-front gown or coveralls, disposable utility gloves over disposable latex gloves, NIOSH-approved air-purifying half-mask respirator equipped with a high efficiency filter, and eye protection should be worn. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Class 100 clean-air work stations, both horizontal and vertical airflow (with no containment characteristics), are inappropriate engineering controls for handling hazardous drugs because they provide no personnel protection and permit environmental contamination. Although there are no engineering controls designed specifically for the safe handling of hazardous chemicals as sterile products, Class II contained vertical-flow biological safety cabinets (biohazard cabinets) have been adopted for this use. Biohazard cabinetry is, however, designed for the handling of infectious agents, not hazardous chemicals. ... Based on design, ease of use, and cost considerations, Class II contained-vertical-flow biohazard cabinetry is currently recommended for use in preparing sterile doses of hazardous drugs. Class II cabinetry design and performance specifications are defined in NSF Standard 49. Biological safety cabinets selected for use with hazardous drugs should meet NSF Standard 49 specifications to ensure the maximum protection from these engineering controls. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers should wear powder free, disposable surgical latex gloves of good quality when preparing hazardous drugs. Selection criteria for gloves should include thickness (especially at the fingertips where stress is the greatest), fit, length, and tactile sensation. ... The practice of double gloving is supported by research that indicates that many glove materials vary in drug permeability even within lots; therefore, double gloving is recommended. ... In general, surgical latex gloves fit better, have appropriate elasticity for double gloving and maintaining the integrity of the glove-gown interface, and have sufficient tactile sensation (even during double gloving) for stringent aseptic procedures. ... Powdered gloves should be avoided. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers who are not protected by the containment environment of a biohazard cabinet should use respiratory protection when handling hazardous drugs. Respiratory protection should be an adjunct to and not a substitute for engineering controls. Surgical masks of all types provide no respiratory protection against powdered or liquid aerosols of hazardous drugs. In situations where workers may be exposed to potential eye contact with hazardous drugs, an appropriate plastic face shield or splash goggles should be worn. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ During compounding of hazardous drugs (eg, crushing, dissolving, and preparing an ointment), workers should wear low permeability gowns and double gloves. Compounding should take place in a protective area such as a disposable glove box. If compounding must be done in the open, an area away from drafts and traffic must be selected, and the worker should use appropriate respiratory protection. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Spill kits containing all materials needed to clean up spills of hazardous drugs should be assembled or purchased. These kits should be readily available in all areas where hazardous drugs are routinely handled. If hazardous drugs are being prepared or administered in a nonroutine area (home setting or unusual patient-care area), a spill kit should be obtained by the drug handler. The kit should include two pairs of disposable gloves (one outer pair of utility gloves and one inner latex pair); low-permeability, disposable protective garments (coveralls or gown and shoe covers); safety glasses or splash goggles; respirator; absorbent, plastic-backed sheets or spill pads; disposable toweling; at least 2 sealable thick plastic hazardous waste disposal bags (prelabeled with an appropriate warning label); a disposable scoop for collecting glass fragments; and a puncture-resistant container for glass fragments. All individuals who routinely handle hazardous drugs must be trained in proper spill management and cleanup procedures. Spills and breakages must be cleaned up immediately according to the following procedures. If the spill is not located in a confined space, the spill area should be identified and other people should be prevented from approaching and spreading the contamination. Wearing protective apparel from the spill kit, workers should remove any broken glass fragments and place them in the puncture-resistant container. Liquids should be absorbed with a spill pad; powder should be removed with damp disposable gauze pads or soft toweling. The hazardous material should be completely removed and the area rinsed with water and then cleaned with detergent. The spill cleanup should proceed progressively from areas of lesser to greater contamination. The detergent should be thoroughly rinsed and removed. All contaminated materials should be placed in the disposal bags provided and sealed and transported to a designated containment receptacle. Spills occurring in the biohazard cabinet should be cleaned up immediately; a spill kit should be used if the volume exceeds 150 ml or the contents of one drug vial or ampule. If there is broken glass, utility gloves should be worn to remove it and place it in the puncture-resistant container located in the biohazard cabinet. The biological safety cabinet, including the drain spillage trough, should be thoroughly cleaned. If the spill is not easily and thoroughly contained, the biological safety cabinet should be decontaminated after cleanup. If the spill contaminates the high efficiency particulate air filter, use of the biological safety cabinet should be suspended until the cabinet has been decontaminated and the high efficiency particulate air filter replaced. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ If hazardous drugs are routinely prepared or administered in carpeted areas, special equipment is necessary to remove the spill. Absorbent powder should be substituted for pads or sheets and left in place on the spill for the time recommended by the manufacturer. The powder should then be picked up with a small vacuum unit reserved for hazardous drug cleanup. The carpet should then be cleaned according to usual procedures. The vacuum bag should be removed and discarded or cleaned, and the exterior of the vacuum cleaner should be washed with detergent and rinsed before being covered and stored. The contaminated powder should be discarded into a sealable plastic bag and segregated with other contaminated waste materials. Alternatively, inexpensive wet or dry vacuum units may be purchased for this express use and used with appropriate cleaners. All such units are contaminated, once used, and must be cleaned, stored, and ultimately discarded /properly/ ... The circumstances and handling of spills should be documented. Health-care personnel exposed during spill management should also complete an incident report or exposure form. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Accidental contamination of the health-care environment, resulting in exposure of personnel, patients, visitors, and family members to hazardous substances, is prevented by maintaining the physical integrity and security of packages of hazardous drugs. 1. Access to all areas where hazardous drugs are stored is limited to specified authorized staff. 2. A method should be present for identifying to personnel those drugs that require special precautions (eg, cytotoxics). One way to accomplish this is to apply appropriate warning labels to all hazardous drug containers, shelves, and bins where the drug products are stored. ... 3. A method of identifying, for patients and family members, those drugs that require special precautions in the home should be in place. This may be accomplished in the health-care setting, by providing specific labeling for discharge medications, along with written instructions. 4. Methods for identifying shipping cartons of hazardous drugs should be required from manufacturers and distributors of these drugs. 5. Written procedures for handling damaged packages of hazardous drugs should be maintained. Personnel involved in shipping and receiving hazardous drugs should be trained in these procedures, including the proper use of protective garments and equipment. Damaged shipping cartons of hazardous drugs should be received and opened in an isolated area (eg, in a laboratory fume hood, if available, not in a vertical laminar airflow biological safety cabinet used for preparing sterile products). /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Facilities (eg, shelves, carts, counters, and trays) for storing hazardous drugs are designed to prevent breakage and to limit contamination in the event of leakage. Bins, shelves with barriers at the front, or other design features that reduce the chance of drug containers falling to the floor should be used. Hazardous drugs requiring refrigeration should be stored separately from nonhazardous drugs in individual bins designed to prevent breakage and to contain leakage. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Until the reproductive risks (or lack thereof) associated with handling hazardous drugs within a safety program have been substantiated, staff who are pregnant or breast-feeding should be allowed to avoid contact with these drugs. Policies should be in effect that provide these individuals with alternative tasks or responsibilities if they so desire. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The pharmacy should provide access to information on toxicity, treatment of acute exposure (if available), chemical inactivators, solubility and stability of hazardous drugs (including investigational agents) used in the workplace. /Antineoplastic agents/|For more Preventive Measures (Complete) data for CAPECITABINE (19 total), please visit the HSDB record page.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Methods for transporting hazardous drugs to the health-care setting should be consistent with environmental protection and national or local regulations for transporting hazardous substances. When hazardous drugs are being transported to the home-care setting, appropriate containers (eg, lined cardboard boxes) and procedures should be used to prevent breakage and contain leakage. ... The drugs must be securely capped or sealed and properly packaged and protected during transport to reduce further the chance of breakage and spillage in a public area such as a corridor or elevator. /Antineoplastic agents/

Ocular irritation occurred in 5-15% of patients receiving capecitabine for metastatic breast cancer or metastatic colorectal cancer. Abnormal vision occurred in 5% of patients receiving capecitabine monotherapy for metastatic colorectal cancer. Severe ocular irritation and corneal deposits were reported in 2 patients with a history of keratoconjunctivitis sicca who received higher doses of capecitabine for metastatic breast cancer or metastatic colon cancer. Ophthalmic examination is recommended for patients receiving capecitabine who experience severe ocular symptoms or decreased visual acuity. Increased lacrimation was reported in 12% of patients receiving capecitabine and docetaxel and in 7% of those receiving docetaxel alone for metastatic breast cancer. Among patients receiving capecitabine alone as adjuvant therapy for stage III colon cancer, conjunctivitis occurred in 5% of patients. Conjunctivitis and lacrimal duct stenosis each occurred in less than 5% of patients receiving capecitabine monotherapy for metastatic breast cancer or metastatic colorectal cancer in clinical trials.

Serum aminotransferase elevations occur in a proportion of patients on conventional doses of capecitabine therapy, but elevations above 5 times the upper limit of normal are uncommon, occurring in

Concomitant use of folic acid may affect the metabolism of capecitabine.|In 4 patients receiving chronic administration of capecitabine 1250 mg/sq m twice daily with a single dose of warfarin 20 mg, the mean area under the concentration-time curve (AUC) of S-warfarin was increased by 57% and clearance was decreased by 37%. The baseline corrected AUC of INR in these patients increased by 2.8-fold, and the maximum observed mean INR increased by 91%. The mechanism for this interaction probably involves inhibition of cytochrome P-450 (CYP) 2C9 isoenzyme by capecitabine and/or its metabolites. Because the decreased rate of anticoagulant metabolism may increase patient response to coumarin and indandione derivatives, capecitabine and these agents should be used concomitantly with great caution.|Leucovorin potentiates the antineoplastic activity of fluorouracil (the active drug of capecitabine) and also may increase its toxicity. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in geriatric patients receiving a weekly regimen of combination therapy with leucovorin and fluorouracil.|Concomitant use of phenytoin and capecitabine may result in toxicity from increased serum phenytoin concentrations. The mechanism of interaction is presumed to be inhibition of the metabolism of phenytoin by capecitabine and/or its metabolites through inhibition of the cytochrome P-450 (CYP) 2C9 isoenzyme. In patients receiving capecitabine, serum concentrations of phenytoin must be monitored carefully, and reduction in the phenytoin dosage may be necessary.|For more Interactions (Complete) data for CAPECITABINE (6 total), please visit the HSDB record page.

Capecitabine is contraindicated in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency. In rare instances, unexpected, severe toxicity (eg, stomatitis, diarrhea, neutropenia, neurotoxicity) associated with fluorouracil has been attributed to a deficiency of DPD activity. A causal relationship between decreased DPD activity and increased, potentially fatal, fluorouracil toxicity (and thus capecitabine toxicity) cannot be ruled out.|.../Investigators/ performed a retrospective evaluation of hypokalemia in 77 patients, who received capecitabine for gastrointestinal malignancies between April 2002 and November 2004. Hypokalemia was defined as K(+) level <3.2 mEq/L. Patients with documented >/=grade 2 vomiting or diarrhea, diuretics, hypomagnesemia, hypokalemia, renal insufficiency, endocrine dysfunction (thyroid, adrenal, diabetic) were excluded. Hypokalemic patients were graded as: mild (grade 1: 3.0-3.2 mEq/L), moderate (grade 3: 2.5-2.9 mEq/L) and severe (grade 4: <2.5 mEq/L). /Investigators/ also reviewed the literature. Fifty-four patients met the above criteria. The most common cause of exclusion was >/= grade 2 diarrhea (23 patients; 30%). Overall, hypokalemia was encountered in 11 patients (20.4%). Among hypokalemic patients, 8 patients (73%) presented with mild/grade 1 hypokalemia (3.0-3.2 mEq/L), 2 patients (18.18%) with moderate/grade 3 hypokalemia (2.5-2.9 mEq/L) and 1 patient (9.09%) with severe/grade 4 hypokalemia (<2.5 mEq/L) 8 (73%). Dose of capecitabine ranged between 1000-2000 mg/sq m. Hypokalemia occurred after an average of 83.7 days of capecitabine administration. No cardiac or neuromuscular complications were noticed. Replacement of K(+) was required in 6 patients (2 intravenous and 4 oral), while 2 patients (3.7%) required oral supplements >4 weeks. No patient had to stop capecitabine due to hypokalemia. One patient had persistent hypokalemia even after stopping capecitabine. Normalization of K(+) levels was achieved in 91% of patients. Four patients were on K(+) sparing diuretics for ascites and never presented with hypokalemia. Mean urine K(+) was 28 mEq/L. Only 5.5% patients had >/=grade 3 hypokalemia in our study compared with 2% and 14% in two other studies. ...|Leucovorin potentiates the antineoplastic activity of fluorouracil (the active drug of capecitabine) and also may increase its toxicity. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in geriatric patients receiving a weekly regimen of combination therapy with leucovorin and fluorouracil.|Although the safety and efficacy of capecitabine in geriatric patients have not been specifically studied to date, the manufacturer reports that elderly individuals may experience increased frequency and severity of the toxic effects of capecitabine and its metabolites. Among 21 patients aged 80 years or older receiving capecitabine for metastatic breast cancer or metastatic colorectal cancer in clinical trials, 62% experienced a grade 3 or 4 adverse effect. In particular, severe adverse GI effects (grade 3 or 4 diarrhea, nausea, or vomiting) or severe hand-foot syndrome associated with capecitabine may occur more frequently in such patients. ... Geriatric patients should be monitored closely for the occurrence of capecitabine-induced adverse effects.

< 60% (mainly albumin)

For the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen. May also be used in combination with docetaxel for the treatment of metastatic breast cancer in patients who have failed to respond to, or recurred or relasped during or following anthracycline-containing chemotherapy. Capecitabine is used alone as an adjuvant therapy following the complete resection of primary tumor in patients with stage III colon cancer when monotherapy with fluroprymidine is preferred. The use or capecitabine in combination regimens for advanced gastric cancer is currently being investigated.|FDA Label|Capecitabine Medac is indicated for the adjuvant treatment of patients following surgery of stage-III (Dukes' stage-C) colon cancer.Capecitabine Medac is indicated for the treatment of metastatic colorectal cancer.Capecitabine Medac is indicated for first-line treatment of advanced gastric cancer in combination with a platinum-based regimen.Capecitabine Medac in combination with docetaxel is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline.Capecitabine Medac is also indicated as monotherapy for the treatment of patients with locally advanced or metastatic breast cancer after failure of taxanes and an anthracycline-containing chemotherapy regimen or for whom further anthracycline therapy is not indicated.|Capecitabine Accord is indicated for the adjuvant treatment of patients following surgery of stage-III (Dukes' stage-C) colon cancer.Capecitabine Accord is indicated for the treatment of metastatic colorectal cancer.Capecitabine Accord is indicated for first-line treatment of advanced gastric cancer in combination with a platinum-based regimen.Capecitabine Accord in combination with docetaxel is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline.Capecitabine Accord is also indicated as monotherapy for the treatment of patients with locally advanced or metastatic breast cancer after failure of taxanes and an anthracycline containing chemotherapy regimen or for whom further anthracycline therapy is not indicated.|Ecansya is indicated for the adjuvant treatment of patients following surgery of stage-III (Dukes' stage-C) colon cancer.Ecansya is indicated for the treatment of metastatic colorectal cancer.Ecansya is indicated for first-line treatment of advanced gastric cancer in combination with a platinum-based regimen.Ecansya in combination with docetaxel is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline. Ecansya is also indicated as monotherapy for the treatment of patients with locally advanced or metastatic breast cancer after failure of taxanes and an anthracycline containing chemotherapy regimen or for whom further anthracycline therapy is not indicated.|Capecitabine Teva is indicated for the adjuvant treatment of patients following surgery of stage III (Dukes' stage C) colon cancer.Capecitabine Teva is indicated for the treatment of metastatic colorectal cancer.Capecitabine Teva is indicated for first‑line treatment of advanced gastric cancer in combination with a platinum‑based regimen.Capecitabine Teva in combination with docetaxel is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline. Capecitabine Teva is also indicated as monotherapy for the treatment of patients with locally advanced or metastatic breast cancer after failure of taxanes and an anthracycline containing chemotherapy regimen or for whom further anthracycline therapy is not indicated.|Xeloda is indicated for the adjuvant treatment of patients following surgery of stage III (Dukes' stage C) colon cancer.Xeloda is indicated for the treatment of metastatic colorectal cancer.Xeloda is indicated for first-line treatment of advanced gastric cancer in combination with a platinum-based regimen.Xeloda in combination with docetaxel is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline. Xeloda is also indicated as monotherapy for the treatment of patients with locally advanced or metastatic breast cancer after failure of taxanes and an anthracycline-containing chemotherapy regimen or for whom further anthracycline therapy is not indicated.|Capecitabine is indicated for the adjuvant treatment of patients following surgery of stage-III (Dukes' stage-C) colon cancer.Capecitabine is indicated for the treatment of metastatic colorectal cancer.Capecitabine is indicated for first-line treatment of advanced gastric cancer in combination with a platinum-based regimen.Capecitabine in combination with docetaxel is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy. Previous therapy should have included an anthracycline. Capecitabine is also indicated as monotherapy for the treatment of patients with locally advanced or metastatic breast cancer after failure of taxanes and an anthracycline-containing chemotherapy regimen or for whom further anthracycline therapy is not indicated.|Drug: Capecitabine|Drug: Capox|Drug: Xeliri|Drug: Xelox

Capecitabine is a pyrimidine analogue used as an antineoplastic agent to treat metastatic and advanced forms of breast and colon cancer, often in combination with other agents. Capecitabine is associated with a low rate of transient serum aminotransferase elevations during therapy but has been only rarely implicated in cases of clinically apparent acute liver injury.

Antineoplastic Agents

Capecitabine has known transformation products that include 2',3'-di-O-acetyl-5'-deoxy-5-fluorocytidine.

Antimetabolites, Antineoplastic Agent|Capecitabine is 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 was non-inferior to 5-fluorouracil and leucovorin (5-FU/LV) for disease-free survival (DFS). Although neither Capecitabine nor combination chemotherapy prolongs overall survival (OS), combination chemotherapy has been demonstrated to improve disease-free survival compared to 5-FU/LV. Physicians should consider these results when prescribing single-agent capecitabine in the adjuvant treatment of Dukes' C colon cancer. /Included in US product label/|Capecitabine is 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 monotherapy. Use of capecitabine instead of 5-FU/LV in combinations has not been adequately studied to assure safety or preservation of the survival advantage. /Included in US product label/.|Capecitabine in combination with docetaxel is indicated for the treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing chemotherapy. /Included in US product label/|Capecitabine 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, eg, patients who have received cumulative doses of 400 mg/sq m 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. /Included in US product label/

Diarrhea, a dose-limiting and common adverse effect of capecitabine, occurs in 55-67% of patients receiving the drug for metastatic breast cancer or metastatic colorectal cancer, and is severe or life-threatening in 15% of patients. Nausea and vomiting occur in 43-53% and 27-37%, respectively, of patients receiving capecitabine for metastatic breast cancer or metastatic colorectal cancer. Among patients with metastatic breast cancer who developed severe nausea and/or vomiting associated with capecitabine monotherapy, onset of these adverse GI effects was early, usually occurring during the first month of treatment.|Among patients receiving capecitabine alone as adjuvant therapy for stage III colon cancer, diarrhea occurred in 47% of patients and was severe or life-threatening (grade 3 or 4) in 12%; nausea occurred in 34%, and vomiting in 15%, of patients.|Severe adverse GI effects associated with capecitabine may occur more frequently in geriatric patients. Among 21 patients aged 80 years or older receiving capecitabine monotherapy for metastatic breast cancer or metastatic colorectal cancer in clinical trials, severe or life-threatening (grade 3 or 4) diarrhea, nausea, or vomiting occurred in 29, 14, or 10%, respectively. Among 10 patients aged 70-80 years receiving capecitabine in combination with docetaxel for metastatic breast cancer, grade 3 or 4 diarrhea and stomatitis each occurred in 30%.|Capecitabine-induced diarrhea may respond to standard antidiarrheal therapy (eg, loperamide). Patients with severe diarrhea should be closely monitored and given fluid and electrolyte replacement for dehydration as indicated.|For more Drug Warnings (Complete) data for CAPECITABINE (38 total), please visit the HSDB record page.

Capecitabine is a fluoropyrimidine carbamate with antineoplastic activity indicated for the treatment of metastatic breast cancer and colon cancer. It is an orally administered systemic prodrug that has little pharmacologic activity until it is converted to fluorouracil by enzymes that are expressed in higher concentrations in many tumors. Fluorouracil it then metabolized both normal and tumor cells to 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP).

Antimetabolites that are useful in cancer chemotherapy. (See all compounds classified as Antimetabolites, Antineoplastic.)

Readily absorbed through the GI tract (~70%)|Capecitabine and its metabolites are predominantly excreted in urine; 95.5% of administered capecitabine dose is recovered in urine. Fecal excretion is minimal (2.6%). The major metabolite excreted in urine is FBAL which represents 57% of the administered dose.About 3% of the administered dose is excreted in urine as unchanged drug.|Capecitabine is readily absorbed from the GI tract; on average, at least 70% of an oral dose of the drug is absorbed. Although in vitro studies have shown that capecitabine is unstable under highly acidic conditions, the drug appears to be absorbed intact immediately upon dissolution without degradation secondary to the acidic pH of the stomach.|According to the manufacturer, peak plasma concentrations of capecitabine occur in about 1.5 hours, and peak plasma concentrations of fluorouracil, its active drug, occur slightly later at 2 hours.|In adults with cancer who received a capecitabine dosage of 2510 mg/sq m daily in 2 divided doses, administered approximately 12 hours apart within 30 minutes following the end of a meal, blood samples drawn on day 1 of the treatment cycle showed that peak plasma concentrations of 3.93 and 0.66 ug/mL for capecitabine and fluorouracil, respectively, were achieved in about 2 hours.|Considerable interindividual variations (ie, exceeding 85%) in peak plasma concentrations and areas under the concentration-time curves (AUCs) have been reported following oral administration of capecitabine.|For more Absorption, Distribution and Excretion (Complete) data for CAPECITABINE (12 total), please visit the HSDB record page.

Metabolized by thymidine phosphorylase to fluoruracil.|Capecitabine, an anticancer prodrug, is thought to be biotransformed into active 5-fluorouracil (5-FU) by three enzymes. After oral administration, capecitabine is first metabolized to 5'-deoxy-5-fluorocytidine (5'-DFCR) by carboxylesterase (CES), then 5'-DFCR is converted to 5'-deoxy-5-fluorouridine (5'-DFUR) by cytidine deaminase. 5'-DFUR is activated to 5-FU by thymidine phosphorylase. Although high activities of drug metabolizing enzymes are expressed in human liver, the involvement of the liver in capecitabine metabolism is not fully understood. In this study, the metabolism of capecitabine in human liver was investigated in vitro. 5'-DFCR, 5'-DFUR, and 5-FU formation from capecitabine were investigated in human liver S9, microsomes, and cytosol in the presence of the inhibitor of dihydropyrimidine dehydrogenase, 5-chloro-2,4-dihydroxypyridine. 5'-DFCR, 5'-DFUR, and 5-FU were formed from capecitabine in cytosol and in the combination of microsomes and cytosol. Only 5'-DFCR formation was detected in microsomes. The apparent K(m) and V(max) values of 5-FU formation catalyzed by cytosol alone and in combination with microsomes were 8.1 mM and 106.5 pmol/min/mg protein, and 4.0 mM and 64.0 pmol/min/mg protein, respectively. The interindividual variability in 5'-DFCR formation in microsomes and cytosol among 14 human liver samples was 8.3- and 12.3-fold, respectively. Capecitabine seems to be metabolized to 5-FU in human liver. 5'-DFCR formation was exhibited in cytosol with large interindividual variability, although CES is located in microsomes in human liver. In the present study, it has been clarified that the cytosolic enzyme would be important in 5'-DFCR formation, as is CES.|Capecitabine (Xeloda; CAP) is a recently developed oral antineoplastic prodrug of 5-fluorouracil (5-FU) with enhanced tumor selectivity. Previous studies have shown that CAP activation follows a pathway with three enzymatic steps and two intermediary metabolites, 5'-deoxy-5-fluorocytidine (5'-DFCR) and 5'-deoxy-5-fluorouridine (5'-DFUR), to form 5-FU preferentially in tumor tissues. In the present work, all fluorinated compounds present in liver, bile, and perfusate medium of isolated perfused rat liver (IPRL) and in liver, plasma, kidneys, bile, and urine of healthy rats /were investigated/. Moreover, data obtained from rat urine were compared with those from mice and human urine. According to a low cytidine deaminase activity in rats, 5'-DFCR was by far the main product in perfusate medium from IPRL and plasma and urine from rats. Liver and circulating 5'-DFCR in perfusate and plasma equilibrated at the same concentration value in the range 25 to 400 microM, which supports the involvement of es-type nucleoside transporter in the liver. 5'-DFUR and alpha-fluoro-beta-ureidopropionic acid (FUPA) + alpha-fluoro-beta-alanine (FBAL) were the main products in urine of mice, making up 23 to 30% of the administered dose versus 3 to 4% in rat. In human urine, FUPA + FBAL represented 50% of the administered dose, 5'-DFCR 10%, and 5'-DFUR 7%. Since fluorine-19 nuclear magnetic resonance spectroscopy gives an overview of all the fluorinated compounds present in a sample, we observed the following unreported metabolites of CAP: 1) 5-fluorocytosine and its hydroxylated metabolite, 5-fluoro-6-hydroxycytosine, 2) fluoride ion, 3) 2-fluoro-3-hydroxypropionic acid and fluoroacetate, and 4) a glucuroconjugate of 5'-DFCR.|Fluorouracil is catabolized to dihydrofluorouracil (FUH2), a much less toxic metabolite, by dihydropyrimidine dehydrogenase. Dihydropyrimidinase cleaves the pyrimidine ring of dihydrofluorouracil, yielding 5-fluoro-ureido-propionic acid (FUPA), which is then cleaved by beta-ureido-propionase to form alpha-fluoro-beta-alanine (FBAL).

45-60 minutes for capecitabine and its metabolites.|The plasma elimination half-life of capecitabine and its metabolites, including the active drug, fluorouracil, is about 45-60 minutes, except for alpha-fluoro-beta-alanine (FBAL), a catabolite of fluorouracil, which has an initial half-life of about 3 hours.

Capecitabine is a prodrug that is selectively tumour-activated to its cytotoxic moiety, fluorouracil, by thymidine phosphorylase, an enzyme found in higher concentrations in many tumors compared to normal tissues or plasma. Fluorouracil is further metabolized to two active metabolites, 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP), within normal and tumour cells. These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N5-10-methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex. This binding inhibits the formation of thymidylate from 2'-deaxyuridylate. Thymidylate is the necessary precursor of thymidine triphosphate, which is essential for the synthesis of DNA, therefore a deficiency of this compound can inhibit cell division. Secondly, 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 through the production of fraudulent RNA.|Capecitabine is a prodrug and has little pharmacologic activity until it is converted to fluorouracil, an antimetabolite. Because capecitabine is converted to fluorouracil by enzymes that are expressed at higher concentrations in many tumors than in adjacent normal tissues or plasma, it is thought that high tumor concentrations of the active drug may be achieved with less systemic toxicity. Fluorouracil is metabolized in both normal and tumor cells to 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). Although the precise mechanisms of action of fluorouracil have not been fully elucidated, the main mechanism is thought to be the binding of the deoxyribonucleotide of the drug (FdUMP) and the folate cofactor (N5-10-methylenetetrahydrofolate) to thymidylate synthase (TS) to form a covalently bound ternary complex, which inhibits the formation of thymidylate from 2'-deoxyuridylate, thereby interfering with DNA synthesis. In addition, FUTP can be incorporated into RNA in place of uridine triphosphate (UTP), producing a fraudulent RNA and interfering with RNA processing and protein synthesis. Capecitabine has been shown to be active in xenograft tumors that are resistant to fluorouracil indicating incomplete cross-resistance between the drugs.|In this report, /the authors/ investigated whether apoptosis induced by capecitabine was mediated by the Fas/FasL system. To achieve this goal, a specific in vitro coculture model mixing hepatoma and human colorectal cell line was used. A bystander effect was observed between HepG2 and LS174T cells treated with capecitabine. Besides this, Xeloda showed a 7-fold higher cytotoxicity and markedly stronger apoptotic potential in thymidine phosphorylase (TP)-transfected LS174T-c2 cells. The striking enhancement of thymidylate synthase inhibition that we observed in cells with high TP activity was most probably at the origin of the potentiation of capecitabine antiproliferative efficacy. In addition, this increase of sensitivity was accompanied by a strong overexpression of the CD95-Fas receptor on the cell surface. Both Fas and FasL mRNA expression were triggered after exposing TP+ cells to the drug. This implication of Fas in Xeloda-induced apoptosis was next confirmed by using antagonistic anti-Fas and anti-FasL antibodies that proved to reverse capecitabine antiproliferative activity, thus highlighting the key role that Fas could play in the optimization of an antitumor response to fluoropyrimidine drugs. /The/ data, therefore, show that TP plays a key role in the capecitabine activity and that the Fas/FasL system could be considered as a new determinant for Xeloda efficacy.

2',3'-di-O-acetyl-5'-deoxy-5-fluorocytidine; 5'-deoxy-5-fluoro-N4-(2-methyl-1-butyloxycarbonyl)cytidine; 5'-deoxy-5-fluoro-N4-(3-methyl-1-butyloxycarbonyl)cytidine; [1-[5-deoxy-3-O-(5-deoxy-beta-D-ribofuranosyl)-beta-D-ribofuranosyl]-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]-carbamic acid pentyl ester; [1-[5-deoxy-2-O-(5-deoxy-beta-D-ribofuranosyl)-beta-D-ribofuranosyl]-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]-carbamic acid pentyl ester; [1-[5-deoxy-3-O-(5-deoxy-alpha-D-ribofuranosyl)-beta-D-ribofuranosyl]-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl]-carbamic acid pentyl ester; 2',3'-di-O-acetyl-5'-deoxy-5-fluoro-N4-(pentyloxycarbonyl)cytidine

Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotension, and arrhythmias if they occur. Treat nausea and vomiting with metoclopramide and fluid loss caused by gastroenteritis with intravenous crystalloid fluids. Bone marrow depression should be treated with the assistance of an experienced hematologist or oncologist. Extravasation: Immediately stop the infusion and withdraw as much fluid as possible by negative pressure on the syringe. ... /For/ decontamination administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. Because of the rapid intracellular incorporation of these agents, dialysis and other extracorporeal removal procedures are generally not effective.|Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ .../Investigators/ performed a retrospective evaluation of hypokalemia in 77 patients, who received capecitabine for gastrointestinal malignancies between April 2002 and November 2004. Hypokalemia was defined as K(+) level <3.2 mEq/L. Patients with documented >/=grade 2 vomiting or diarrhea, diuretics, hypomagnesemia, hypokalemia, renal insufficiency, endocrine dysfunction (thyroid, adrenal, diabetic) were excluded. Hypokalemic patients were graded as: mild (grade 1: 3.0-3.2 mEq/L), moderate (grade 3: 2.5-2.9 mEq/L) and severe (grade 4: <2.5 mEq/L). /Investigators/ also reviewed the literature. Fifty-four patients met the above criteria. The most common cause of exclusion was >/= grade 2 diarrhea (23 patients; 30%). Overall, hypokalemia was encountered in 11 patients (20.4%). Among hypokalemic patients, 8 patients (73%) presented with mild/grade 1 hypokalemia (3.0-3.2 mEq/L), 2 patients (18.18%) with moderate/grade 3 hypokalemia (2.5-2.9 mEq/L) and 1 patient (9.09%) with severe/grade 4 hypokalemia (<2.5 mEq/L) 8 (73%). Dose of capecitabine ranged between 1000-2000 mg/sq m. Hypokalemia occurred after an average of 83.7 days of capecitabine administration. No cardiac or neuromuscular complications were noticed. Replacement of K(+) was required in 6 patients (2 intravenous and 4 oral), while 2 patients (3.7%) required oral supplements >4 weeks. No patient had to stop capecitabine due to hypokalemia. One patient had persistent hypokalemia even after stopping capecitabine. Normalization of K(+) levels was achieved in 91% of patients. Four patients were on K(+) sparing diuretics for ascites and never presented with hypokalemia. Mean urine K(+) was 28 mEq/L. Only 5.5% patients had >/=grade 3 hypokalemia in our study compared with 2% and 14% in two other studies. ...|/HUMAN EXPOSURE STUDIES/ Macrocytosis has not been previously reported in association with capecitabine therapy. /Investigators/ performed a retrospective review of consecutive metastatic breast cancer (MBC) patients receiving standard 21-day cycles of oral capecitabine therapy at a single center during the year 2000. Patients were assessed prior to each cycle with clinical examinations and complete blood counts. Seventy-six women (median age 52 years, median follow-up 273 days) met inclusion criteria for the study. Prior to treatment, the average mean corpuscular volume (MCV) was 91.6 fl (normal range 80-100 fl). During chemotherapy, MCV increased in a dose-dependent and time-dependent manner. Fifty-seven percent of study patients developed macrocytosis (MCV > 100 fl) while on capecitabine therapy; 85% of women who received at least nine cycles of therapy exhibited macrocytosis. Development of macrocytosis was independent of anemia, thrombocytopenia, neutropenia, liver metastasis, and hepatic dysfunction; however, increases in MCV were more pronounced in 5-FU-naive patients. Alternative causes of macrocytosis were not identified in patients without coexisting anemia. /The authors/ conclude that capecitabine therapy produces time-dependent and dose-dependent macrocytosis in MBC patients. However, macrocytosis was not associated with anemia or overt myelosuppression. ...|/SIGNS AND SYMPTOMS/ Overdosage of capecitabine would be expected to cause nausea, vomiting, diarrhea, GI irritation and bleeding, and bone marrow depression. Patients receiving capecitabine 1657 mg/sq m daily (as 2 divided doses) in a continuous daily regimen for at least 6 weeks experienced severe palmar-plantar erythrodysesthesia, mucositis, and diarrhea.|/CASE REPORTS/ ... A 65-year-old white woman with stage IV colorectal cancer with liver metastasis was started on a chemotherapy regimen of capecitabine, oxaliplatin, and bevacizumab, given every three weeks. She tolerated the first two treatment cycles fairly well without major toxicities. The capecitabine dosage was started at 2000 mg daily for 14 days during the first cycle and increased to 2500 and 3000 mg daily during the second and the third cycles, respectively. On day 5 of the third cycle, the patient reported increased nausea, fatigue, and sleepiness, and the dosage of capecitabine was subsequently reduced to 2500 mg daily. On day 12 of the fourth treatment cycle, she reported ongoing lightheadedness and progressive gait disturbance with worsening ataxia over the past 3 days. Her capecitabine dosage was further reduced to 2000 mg daily, and the time between treatment intervals was increased to four weeks. The patient continued to experience intermittent, but less severe, ataxia during the fifth treatment cycle. On the day before the seventh cycle was to begin, she had ataxic gait and could not walk without assistance. Subsequent magnetic resonance imaging of the brain revealed no evidence of brain metastasis or cerebellar abnormality. The chemotherapy was postponed for a total of six weeks until the ataxia completely resolved. Her chemotherapy was ultimately discontinued due to disease progression. Her neurologic symptoms did not recur. ...|For more Human Toxicity Excerpts (Complete) data for CAPECITABINE (25 total), please visit the HSDB record page.

capecitabine

Formulations: Oral tablets, 150 mg and 500 mg Capecitabine (Xeloda) /by/ Roche

... a prodrug that is selectively tumor-activated to its cytotoxic moiety, fluorouracil by thymidine phosphorylase.

Analyte: capecitabine; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: capecitabine; matrix: chemical identification; procedure: retention time of the major peak of the liquid chromatogram with comparison to standards|Analyte: capecitabine; matrix: chemical purity; procedure: liquid chromatography with ultraviolet detection at 250 nm with comparison to standards|Analyte: capecitabine; matrix: pharmaceutical preparation (tablet); procedure: infrared absorption spectrophotometry with comparison to standards (chemical identification)|For more Analytic Laboratory Methods (Complete) data for CAPECITABINE (6 total), please visit the HSDB record page.

Analyte: capecitabine; matrix: blood (plasma); procedure: high-performance liquid chromatography with mass spectrometric detection; limit of quantitation: 1.4 ng/mL|Analyte: capecitabine; matrix: blood (plasma); procedure: high-performance liquid chromatography with ultraviolet detection at 310 nm; limit of quantitation: 50 ng/mL

Human drugs -> Capecitabine Medac -> EMA Drug Category|Antineoplastic agents -> Human pharmacotherapeutic group|Human drugs -> Capecitabine Accord -> EMA Drug Category|Human drugs -> Ecansya (previously Capecitabine Krka) -> EMA Drug Category|Human drugs -> Capecitabine Teva -> EMA Drug Category|Human drugs -> Xeloda -> EMA Drug Category|Human drugs -> Capecitabine SUN -> EMA Drug Category|capecitabine -> Human pharmacotherapeutic group|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals -> Cytostatics