Xeltabine

Xeltabine

capecitabine

Manufacturer:

Korea United Pharma

Distributor:

Qualimed
Full Prescribing Info
Contents
Capecitabine.
Description
Each Film-coated Tablet contains: Capecitabine, USP 500 mg.
Action
Pharmacotherapeutic group: cytostatic (antimetabolite). ATC code: L01BC06.
Pharmacology: Pharmacodynamics: Capecitabine is a non-cytotoxic fluoropyrimidine carbamate, which functions as an orally administered precursor of the cytotoxic moiety 5-fluorouracil (5-FU). Capecitabine is activated via several enzymatic steps. The enzyme involved in the final conversion to 5-FU, thymidine phosphorylase (ThyPase), is found in tumour tissues, but also in normal tissues, albeit usually at lower levels. In human cancer xenograft models capecitabine demonstrated a synergistic effect in combination with docetaxel, which may be related to the upregulation of thymidine phosphorylase by docetaxel.
There is evidence that the metabolism of 5-FU in the anabolic pathway blocks the methylation reaction of deoxyuridylic acid to thymidylic acid, thereby interfering with the synthesis of deoxyribonucleic acid (DNA). The incorporation of 5-FU also leads to inhibition of RNA and protein synthesis. Since DNA and RNA are essential for cell division and growth, the effect of 5-FU may be to create a thymidine deficiency that provokes unbalanced growth and death of a cell.
The effects of DNA and RNA deprivation are most marked on those cells which proliferate more rapidly and which metabolise 5-FU at a more rapid rate.
Pharmacokinetics: The pharmacokinetics of capecitabine have been evaluated over a dose range of 502-3514 mg/m2/day. The parameters of capecitabine, 5'-deoxy-5-fluorocytidine (5'-DFCR) and 5'-deoxy-5-fluorouridine (5'-DFUR) measured on days 1 and 14 were similar. The AUC of 5-FU was 30%-35% higher on day 14. Capecitabine dose reduction decreases systemic exposure to 5-FU more than dose-proportionally, due to non-linear pharmacokinetics for the active metabolite.
Absorption: after oral administration, capecitabine is rapidly and extensively absorbed, followed by extensive conversion to the metabolites, 5'-DFCR and 5'-DFUR. Administration with food decreases the rate of capecitabine absorption, but only results in a minor effect on the AUC of 5'-DFUR, and on the AUC of the subsequent metabolite 5-FU. At the dose of 1250 mg/m2 on day 14with administration after food intake, the peak plasma concentrations (Cmax in μg/ml) for capecitabine, 5'-DFCR, 5'-DFUR, 5-FU and FBAL were 4.67, 3.05, 12.1, 0.95 and 5.46 respectively. The time to peak plasma concentrations (Tmax in hours) were 1.50, 2.00, 2.00, 2.00 and 3.34. The AUC0-∞ values in μg•h/ml were 7.75, 7.24, 24.6, 2.03 and 36.3.
Distribution: in vitro human plasma studies have determined that capecitabine, 5'-DFCR, 5'-DFUR and 5-FU are 54%, 10%, 62% and 10% protein bound, mainly to albumin.
Biotransformation: capecitabine is first metabolised by hepatic carboxylesterase to 5'-DFCR, which is then converted to 5'-DFUR by cytidine deaminase, principally located in the liver and tumour tissues. Further catalytic activation of 5'-DFUR then occurs by thymidine phosphorylase (ThyPase). The enzymes involved in the catalytic activation are found in tumour tissues but alsoin normal tissues, albeit usually at lower levels. The sequential enzymatic biotransformation of capecitabine to 5-FU leads to higher concentrations within tumour tissues. In the case ofcolorectal tumours, 5-FU generation appears to be in large part localised in tumour stromal cells.
Following oral administration of capecitabine to patients with colorectal cancer, the ratio of 5-FU concentration in colorectal tumours to adjacent tissues was 3.2 (ranged from 0.9 to 8.0). The ratio of 5-FU concentration in tumour to plasma was 21.4 (ranged from 3.9 to 59.9, n=8) whereas the ratio in healthy tissues to plasma was 8.9 (ranged from 3.0 to 25.8, n=8). Thymidine phosphorylase activity was measured and found to be 4 times greater in primary colorectal tumour than in adjacent normal tissue. According to immunohistochemical studies, thymidine phosphorylase appears to be in large part localised in tumour stromal cells.
5-FU is further catabolised by the enzyme dihydropyrimidine dehydrogenase (DPD) to the much less toxic dihydro-5-fluorouracil (FUH2). Dihydropyrimidinase cleaves the pyrimidine ring to yield 5-fluoro-ureidopropionic acid (FUPA). Finally, β-ureido-propionase cleaves FUPA to α-fluoro-β-alanine (FBAL) which is cleared in the urine. Dihydropyrimidine dehydrogenase (DPD) activity is the rate limiting step. Deficiency of DPD may lead to increased toxicity of capecitabine.
Elimination: the elimination half-life (t1/2 in hours) of capecitabine, 5'-DFCR, 5'-DFUR, 5-FU and FBAL were 0.85, 1.11, 0.66, 0.76 and 3.23 respectively. Capecitabine and its metabolites are predominantly excreted in urine; 95.5% of administered capecitabine dose is recovered in urine.
Faecal excretion is minimal (2.6%). The major metabolite excreted in urine is FBAL, whichrepresents 57% of the administered dose. About 3% of the administered dose is excreted in urine as unchanged drug.
Combination therapy: Phase I studies evaluating the effect of capecitabine on the pharmacokinetics of either docetaxel or paclitaxel and vice versa showed no effect by capecitabine on the pharmacokinetics of docetaxel or paclitaxel (Cmax and AUC) and no effect by docetaxel or paclitaxel on the pharmacokinetics of 5'-DFUR.
Pharmacokinetics in special populations: A population pharmacokinetic analysis was carried out after capecitabine treatment of 505 patients with colorectal cancer dosed at 1250 mg/m2 twice daily. Gender, presence or absence of liver metastasis at baseline, Karnofsky Performance Status, total bilirubin, serum albumin, ASAT and ALAT had no statistically significant effect on the pharmacokinetics of 5'-DFUR, 5-FU and FBAL.
Patients with hepatic impairment due to liver metastases: According to a pharmacokinetic study in cancer patients with mild to moderate liver impairment due to liver metastases, the bioavailability of capecitabine and exposure to 5-FU may increase compared to patients with no liver impairment. There are no pharmacokinetic data on patients with severe hepatic impairment.
Patients with renal impairment: Based on a pharmacokinetic study in cancer patients with mild to severe renal impairment, there is no evidence for an effect of creatinine clearance on the pharmacokinetics of intact drug and 5-FU. Creatinine clearance was found to influence the systemic exposure to 5'-DFUR (35% increase in AUC when creatinine clearance decreases by 50%) and to FBAL (114% increase in AUC when creatinine clearance decreases by 50%). FBAL is a metabolite without antiproliferative activity.
Elderly: Based on the population pharmacokinetic analysis, which included patients with a widerange of ages (27 to 86 years) and included 234 (46%) patients greater or equal to 65, age has no influence on the pharmacokinetics of 5'-DFUR and 5-FU. The AUC of FBAL increased with age (20% increase in age results in a 15% increase in the AUC of FBAL). This increase is likely due to a change in renal function.
Ethnic factors: Following oral administration of 825 mg/m2 capecitabine twice daily for 14 days, Japanese patients (n=18) had about 36% lower Cmax and 24% lower AUC for capecitabine than Caucasian patients (n=22). Japanese patients had also about 25% lower Cmax and 34% lower AUC for FBAL than Caucasian patients. The clinical relevance of these differences is unknown.
No significant differences occurred in the exposure to other metabolites (5'-DFCR, 5'-DFUR, and 5-FU).
Indications/Uses
Capecitabine (Xeltabine) is given orally for the treatment of metastatic colorectal cancer and is also used for the adjuvant treatment of patients after surgery for Dukes C Colon Cancer.
It is also used in the treatment of metastatic breast cancer.
Dosage/Direction for Use
Colon, colorectal and breast cancer: The recommended dose of Capecitabine (Xeltabine) is 1250 mg/m2 administered orally twice daily (morning and evening; equivalent to 2500 mg/m2 total daily dose) for 2 weeks followed by a 1-week rest period given as 3-week cycles. Capecitabine (Xeltabine) tablets should be swallowed whole with water within 30 minutes after a meal.
In combination with docetaxel, the recommended dose of Capecitabine (Xeltabine) is 1250 mg/m2 twice daily for 2 weeks followed by a 1-week rest period, combined with docetaxel at 75 mg/m2 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 (Xeltabine) plus docetaxel combination.
Adjuvant treatment in patients with Dukes' C colon cancer is recommended for a total of 6 months [ie, Capecitabine (Xeltabine) 1250 mg/m2 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)].
In combination with oxaliplatin, the recommended dose of Capecitabine (Xeltabine) is 1000 mg/m2 twice daily for 2 weeks followed by a 1-week rest period combined with oxaliplatin at 130 mg/m2 intravenous infusion over 2-hours on day 1 every 3 weeks, as 3-week cycles for 24 weeks. Pre-medication, according to the oxaliplatin labeling, should be started with prior to oxaliplatin administration for patients receiving the Capecitabine (Xeltabine) plus oxaliplatin combination.
Gastric cancer: Advanced or colon gastric cancer which is inoperable: The recommended dose of Capecitabine (Xeltabine) is 1250 mg/m2 administered orally twice daily (morning and evening; equivalent to 2500 mg/m2 total daily dose) for 2 weeks followed by a 1-week rest period given as 3-week cycles. Capecitabine (Xeltabine) tablets should be swallowed whole with water within 30 minutes after a meal.
Capecitabine (Xeltabine) is indicated for first-line treatment of advanced gastric cancer in combination with a platinum-based regimen: The recommended starting dose of Capecitabine (Xeltabine) is 1000 mg/m2 when administered twice daily for 14 days followed by a 7-day rest period, or to 625 mg/m2 twice daily when administered continuously. Capecitabine (Xeltabine) tablets should be swallowed whole with water within 30 minutes after a meal. Premedication according to the cisplatin summary of product characteristics should be started prior to cisplatin administration for patients receiving the Capecitabine (Xeltabine) plus cisplatin combination.
In combination with cisplatin, the recommended dose of Capecitabine (Xeltabine) is 1000 mg/m2 twice daily for 2 weeks followed by a 1-week rest period, combined with cisplatin at 80 mg/m2 as a 2-hour intravenous infusion every 3 weeks.
In combination with cisplatin or epirubicin, the recommended dose of Capecitabine (Xeltabine) is 625 mg/m2 twice daily for 3 weeks continuously, combined with cisplatin at 60 mg/m2 as a 2-hour intravenous and epirubicin at 50 mg/m2 as a intravenous bolus infusion every 3 weeks.
Standard and reduced dose calculations according to body surface area: See Tables 1 and 2.

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Posology adjustments during treatment: Toxicity due to Capecitabine (Xeltabine) administration may be managed by symptomatic treatment and/or modification of the dose (treatment interruption or dose reduction). Once the dose has been reduced, it should not be increased at a later time. For those toxicities considered by the treating physician to be unlikely to become serious or life-threatening, e.g. alopecia, altered taste, nail changes, treatment can be continued at the same dose without reduction or interruption. Patients taking Capecitabine (Xeltabine) should be informed of the need to interrupt treatment immediately if moderate or severe toxicity occurs. (See Table 3.)

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Haematology: Patients with baseline neutrophil counts of <1.5 x 109/L and/or thrombocyte counts of <100 x 109/L should not be treated with Capecitabine (Xeltabine). If unscheduled laboratory assessments during a treatment cycle show that the neutrophil count drops below 1.0 x 109/L or that the platelet count drops below 75 x 109/L, treatment with Capecitabine (Xeltabine) should be interrupted.
Dose modifications for toxicity when Capecitabine (Xeltabine) is used as a 3 weekly cycle in combination with other agents: Dose modifications for toxicity when Capecitabine (Xeltabine) is used as a 3 weekly cycle in combination with other agents should be made according to Table 3 for Capecitabine (Xeltabine) and according to the appropriate summary of product characteristics for the other agent(s).
At the beginning of a treatment cycle, if a treatment delay is indicated for either Capecitabine (Xeltabine) or the other agent(s), then administration of all agents should be delayed until the requirements for restarting all drugs are met.
During a treatment cycle for those toxicities considered by the treating physician not to be related to Capecitabine (Xeltabine), Capecitabine (Xeltabine) should be continued and the dose of the other agent should be adjusted according to the appropriate Prescribing Information.
If the other agent(s) have to be discontinued permanently, Capecitabine (Xeltabine) treatment can be resumed when the requirements for restarting Capecitabine (Xeltabine) are met.
This advice is applicable to all indications and to all special populations.
Dose modifications for toxicity when Capecitabine (Xeltabine) is used continuously in combination with other agents: Dose modifications for toxicity when Capecitabine (Xeltabine) is used continuously in combination with other agents should be made according to Table 3 for Capecitabine (Xeltabine) and according to the appropriate summary of product characteristics for the other agent(s).
Posology adjustments for special populations: Hepatic impairment: Insufficient safety and efficacy data are available in patients with hepatic impairment to provide a dose adjustment recommendation. No information is available on hepatic impairment due to cirrhosis or hepatitis.
Renal impairment: Capecitabine (Xeltabine) is contraindicated in patients with severe renal impairment (creatinine clearance below 30 mL/min at baseline). The incidence of grade 3 or 4 adverse reactions in patients with moderate renal impairment (creatinine clearance 30-50 mL/min at baseline) is increased compared to the overall population. In patients with moderate renal impairment at baseline, a dose reduction to 75% for a starting dose of 1250 mg/m2 is recommended. In patients with moderate renal impairment at baseline, no dose reduction is required for a starting dose of 1000 mg/m2. In patients with mild renal impairment (creatinine clearance 51-80 mL/min at baseline) no adjustment of the starting dose is recommended. Careful monitoring and prompt treatment interruption is recommended if the patient develops a grade 2, 3 or 4 adverse event during treatment and subsequent dose adjustment as outlined in Capecitabine (Xeltabine) Dose Reduction Schedule. If the calculated creatinine clearance decreases during treatment to a value below 30 mL/min, Capecitabine (Xeltabine) should be discontinued. These dose adjustment recommendations for renal impairment apply both to monotherapy and combination use.
Children under 18: There is no administration experience in patient under 18 years.
Elderly: During Capecitabine (Xeltabine) monotherapy, no adjustment of the starting dose is needed. However, grade 3 or 4 treatment-related adverse reactions were more frequent in patients ≥60 years of age compared to younger patients.
When Capecitabine (Xeltabine) was used in combination with other agents, many elderly patients (≥65 years) experienced more grade 3 and grade 4 adverse drug reactions, including those leading to discontinuation. Careful monitoring of patients ≥60 years of age is advisable.
In combination with docetaxel: An increased incidence of grade 3 or 4 treatment-related adverse reactions and treatment-related serious adverse reactions were observed in patients 60 years of age or more. For patients 60 years of age or more, a starting dose reduction of Capecitabine (Xeltabine) to 75% (950 mg/m2 twice daily) is recommended. If no toxicity is observed in patients ≥60 years of age treated with a reduced Capecitabine (Xeltabine) starting dose in combination with docetaxel, the dose of Capecitabine (Xeltabine) may be cautiously escalated to 1250 mg/m2 twice daily.
Overdosage
Adverse reactions of overdose are not reported in Capecitabine (Xeltabine) trial test. Based on the experience of patient indicated the maximum tolerated dose (MTD) of Capecitabine (Xeltabine) (3514 mg/m2 per day) when Capecitabine (Xeltabine) was used alone, the expected manifestations of acute overdose would include nausea, vomiting, diarrhea, gastrointestinal irritation and bleeding, and bone marrow depression. When overdosing Capecitabine (Xeltabine), Symptomatic treatment is used at correcting the presenting clinical manifestations. Although no clinical experience using dialysis as a treatment for Capecitabine (Xeltabine) 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 (Xeltabine) 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/m2 basis).
Contraindications
The drug should not be administered in the following patients. Hypersensitivity to Capecitabine (Xeltabine) or to any of the excipients.
History of severe and unexpected reactions to fluoropyrimidine therapy.
During pregnancy and lactation.
In patients with severe renal impairment (creatinine clearance below 30 mL/min).
Treatment with sorivudine or its chemically related analogues, such as brivudine.
In patients with known dihydropyrimidine dehydrogenase (DPD) deficiency (unexpected, severe toxicity (eg, stomatitis, diarrhea, neutropenia and neurotoxicity) associated with fluorouracil can be occurred).
In patients with severe leucopenia, neutropenia, or thrombocytopenia.
In patients with severe hepatic impairment.
In taking a Tegafur, gimeracil, oteracil potassium complex or within seven days after interruption of administration.
As this medicinal product contains anhydrous lactose as an excipient, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Warnings
Diarrhea: Capecitabine (Xeltabine) can induce diarrhea, sometimes severe. Patients with severe diarrhea should be carefully monitored and given fluid and electrolyte replacement if they become dehydrated. The median time to first occurrence of grade 2 to 4 diarrhea was 31 days (range from 1 to 322 days).
National Cancer Institute of Canada Common Toxicity Criteria (NCIC CTC) defines diarrhea grades as follows.
Grade 2: An increase of 4 to 6 stools/day or nocturnal stools.
Grade 3: An increase of 7 to 9 stools/day incontinence and malabsorption.
Grade 4: 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 (Xeltabine) should be immediately interrupted until the diarrhea resolves or decreases in intensity to grade 1. Following a reoccurrence of grade 2 diarrhea or occurrence of any grade 3 or 4 diarrhea, subsequent doses of Capecitabine (Xeltabine) should be decreased (see Dosage & Administration). Standard antidiarrheal treatments (eg, loperamide) are recommended. Necrotizing enterocolitis (typhlitis) has been reported.
Dehydration: Dehydration should be prevented or corrected at the onset. Patients with anorexia, asthenia, nausea, vomiting or diarrhoea may rapidly become dehydrated. If Grade 2 (or higher) dehydration occurs, Capecitabine (Xeltabine) treatment should be immediately interrupted and the dehydration corrected. Treatment should not be restarted until the patient is rehydrated and any precipitating causes have been corrected or controlled. Dose modifications applied should be applied for the precipitating adverse event as necessary.
Hand-foot syndrome: Grade 1 hand-foot syndrome is defined as numbness, dysesthesia/paresthesia, tingling, painless swelling or erythema of the hands and/or feet and/or discomfort which does not disrupt the patient's normal activities. Grade 2 hand-foot syndrome is painful erythema and swelling of the hands and/or feet and/or discomfort affecting the patient's activities of daily living. Grade 3 hand-foot syndrome is moist desquamation, ulceration, blistering and severe pain of the hands and/or feet and/or severe discomfort that causes the patient to be unable to work or perform activities of daily living. If grade 2 or 3 hand-foot syndrome occurs, administration of Capecitabine (Xeltabine) should be interrupted until the event resolves or decreases in intensity to grade 1. Following grade 3 hand-foot syndrome, subsequent doses of Capecitabine (Xeltabine) should be decreased. When Capecitabine (Xeltabine) and cisplatin are used in combination, the use of vitamin B6 (pyridoxine) is not advised for symptomatic or secondary prophylactic treatment of hand-foot syndrome, because of published reports that it may decrease the efficacy of cisplatin.
Cardiotoxicity: Cardiotoxicity has been associated with fluoropyrimidine therapy, including myocardial infarction, angina, arrhythmia, cardiogenic shock, dysrhythmias, cardioplegia, heart failure, sudden death and electrocardiographic changes. These adverse reactions may be more common in patients with a prior history of coronary artery disease. Cardiac arrhythmia, angina pectoris, myocardial infarction, heart failure and cardiomyopathy have been reported in patients receiving Capecitabine (Xeltabine). Caution must be exercised in patients with history of significant cardiac disease, arrhythmias and angina pectoris.
Hypo- or hypercalcaemia: Hypo- or hypercalcaemia has been reported during Capecitabine (Xeltabine) treatment. Caution must be exercised in patients with pre-existing hypo- or hypercalcaemia.
Central or peripheral nervous system disease: Caution must be exercised in patients with central or peripheral nervous system disease, e.g. brain metastasis or neuropathy.
Diabetes mellitus or electrolyte disturbances: Caution must be exercised in patients with diabetes mellitus or electrolyte disturbances, as these may be aggravated during Capecitabine (Xeltabine) treatment.
Coumarin-derivative anticoagulation: In a drug interaction study with single-dose warfarin administration, there was a significant increase in the mean AUC (+57%) of S-warfarin. These results suggest an interaction, probably due to an inhibition of the cytochrome P450 2C9 isoenzyme system by Capecitabine (Xeltabine). Patients receiving concomitant Capecitabine (Xeltabine) and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored closely and the anticoagulant dose adjusted accordingly.
Hepatic impairment: In the absence of safety and efficacy data in patients with hepatic impairment, Capecitabine (Xeltabine) use should be carefully monitored in patients with mild to moderate liver dysfunction, regardless of the presence or absence of liver metastasis. Administration of Capecitabine (Xeltabine) should be interrupted if treatment-related elevations in bilirubin of >3.0 x ULN or treatment-related elevations in hepatic aminotransferases (ALT, AST) of >2.5 x ULN occur. Treatment with Capecitabine (Xeltabine) monotherapy may be resumed when bilirubin decreases to ≤3.0 x ULN or hepatic aminotransferases decrease to ≤2.5 x ULN.
Renal impairment: The incidence of grade 3 or 4 adverse reactions in patients with moderate renal impairment (creatinine clearance 30-50 mL/min) is increased compared to the overall population.
Special Precautions
The drug should be administered with caution in the following patients: In patients with severe renal impairment; In patients hepatic insufficiency; In patients with history of Hypo- or hypercalcaemia; In patients with history of central or peripheral nervous system disease, e.g. brain metastasis or neuropathy; Patients with history of diabetes mellitus or electrolyte disturbances; Elderly patients (see Elderly under Dosage & Administration); Patients with history of coronary disease (myocardiopathy can be occurred); Patients with myelosuppression ( myelosuppression can be aggaravated); Patients with gastrointestinal tract ulcer or gastrointestinal tract bleeding.
General: Capecitabine (Xeltabine) should only be prescribed by a qualified physician experienced in the utilisation of anti-neoplastic agents. Most adverse reactions are reversible and do not require permanent discontinuation of therapy, although doses may need to be withheld or reduced. (See Dosage & Administration).
In clinical trial of Capecitabine (Xeltabine) in patients with metastatic colorectal cancer, a survival benefit over 5-FU/LV has not been demonstrated with Capecitabine (Xeltabine) monotherapy. Use of Capecitabine (Xeltabine) instead of 5-FU/LV in combinations has not been adequately studied to assure safety or preservation of the survival advantage.
A single agent for adjuvant treatment in patients with Stage III (Dukes' C) colon cancer who have undergone complete resection of the primary tumor: as adjuvant treatment for patients with stage III (Dukes' C) colon cancer who have undergone surgery, Capecitabine (Xeltabine) was approved by reason of being non-inferior to 5-fluorouracil and leucovorin (5-FU/LV) for disease-free survival (DFS); as adjuvant treatment for patients with stage III (Dukes' C) colon cancer who have undergone surgery, in the primary analysis for DFS in the ITT population, Capecitabine (Xeltabine) was shown to be significantly superior to 5-FU/LV. But after median observation time of 57 months, the analysis for the secondary endpoint of overall survival was not shown to be significant statistically.
Capecitabine (Xeltabine) monotherapy for gastric cancer is approved by reaction rate. And there is no trial result to prove clinical significance like improvement to symptoms or increase of overall survival.
Capecitabine (Xeltabine) is generally administrated in home, patients should be informed of available adverse reactions and what have to do in the case adverse reaction occurring. Patients should be carefully monitored for toxicity.
Hyperbilirubinemia: In 875 patients with either metastatic breast or colorectal cancer who received at least one dose of Capecitabine (Xeltabine) 1250 mg/m2 twice daily as monotherapy for 2 weeks followed by a 1-week rest period, grade 3 (1.5-3 x ULN) hyperbilirubinemia occurred in 15.2% (n=133) of patients and grade 4 (>3 x ULN) hyperbilirubinemia occurred in 3.9% (n=34) of patients. Of 566 patients who had hepatic metastases at baseline and 309 patients without hepatic metastases at baseline, grade 3 or 4 hyperbilirubinemia occurred in 22.8% and 12.3%, respectively. Of the 167 patients with grade 3 or 4 hyperbilirubinemia, 18.6% (n=31) also had postbaseline elevations (grades 1 to 4, without elevations at baseline) in alkaline phophatase and 27.5% (n=46) had postbaseline elevations in transaminases at any time (not necessarily concurrent). The majority of these patients, 64.5% (n=20) and 71.7% (n=33), had liver metastases at baseline. In addition, 57.5% (n=96) and 35.3% (n=59) of the 167 patients had elevations (grades 1 to 4) at both prebaseline and postbaseline in alkaline phosphatase or transaminases, respectively. Only 7.8% (n=13) and 3.0% (n=5) had grade 3 or 4 elevations in alkaline phosphatase or transaminases.
In the 596 patients treated with Capecitabine (Xeltabine) as first-line therapy for metastatic colorectal cancer, the incidence of grade 3 or 4 hyperbilirubinemia was similar to the overall clinical trial safety database of Capecitabine (Xeltabine) monotherapy. The median time to onset for grade 3 or 4 hyperbilirubinemia in the colorectal cancer population was 64 days and median total bilirubin increased from 8 μm/L at baseline to 13 μm/L during treatment with Capecitabine (Xeltabine). Of the 136 colorectal cancer patients with grade 3 or 4 hyperbilirubinemia, 49 patients had grade 3 or 4 hyperbilirubinemia as their last measured value, of which 46 had liver metastases at baseline.
In 251 patients with metastatic breast cancer who received a combination of Capecitabine (Xeltabine) and docetaxel, grade 3 (1.5 to 3 x ULN) hyperbilirubinemia occurred in 7% (n=17) and grade 4 (>3 x ULN) hyperbilirubinemia occurred in 2% (n=5).
If drug-related grade 2 to 4 elevations in bilirubin occur, administration of Capecitabine (Xeltabine) should be immediately interrupted until the hyperbilirubinemia resolves or the hyperbilirubinemia decreases to grade 1. NCIC CTC grade 2 hyperbilirubinemia is defined as an 1.5 times of normal, grade 3 hyperbilirubinemia is defined as 1.5~3 times of normal and grade 4 hyperbilirubinemia is defined as more than 3 times of normal (see recommended dose modifications under Dosage & Administration).
Hematologic: In 875 patients with either metastatic breast or colorectal cancer who received a dose of 1250 mg/m2 administered twice daily as monotherapy for 2 weeks followed by a 1-week rest period, 3.2%, 1.7%, and 2.4% of patients had grade 3 or 4 neutropenia, thrombocytopenia or decreases in hemoglobin. In 251 patients with metastatic breast cancer who received a dose of Capecitabine (Xeltabine) in combination with docetaxel, 68% had grade 3 or 4 neutropenia, 2.8% had grade 3 or 4 thrombocytopenia, and 9.6% had grade 3 or 4 anemia.
Rarely, unexpected, severe toxicity (eg, stomatitis, diarrhea, neutropenia and neurotoxicity) associated with 5-fluorouracil has been attributed to a deficiency of dihydropyrimidine dehydrogenase (DPD) activity. A link between decreased levels of DPD and increased, potentially fatal toxic effects of 5-fluorouracil therefore cannot be excluded.
Effects on Ability to Drive and Use Machine: Capecitabine (Xeltabine) has minor or moderate influence on the ability to drive and use machines. Capecitabine (Xeltabine) may cause dizziness, fatigue and nausea.
Use in Children: There is no experience in children under 18 years.
Use in Elderly: When Capecitabine (Xeltabine) was used elderly patients (≥65 years) experienced more adverse drug reactions compared to younger patients. Careful monitoring of patients ≥65 years of age is advisable.
There is no study between age and Capecitabine (Xeltabine) or its metabolites. elderly patients ≥80 years can experienced more grade 3 and grade 4 adverse drug reactions in gastrointestinal tract compared to younger patients.
As elderly patients can be more sensitive to 5-FU toxicity pharmacologically, careful monitoring to indicate Capecitabine (Xeltabine) of patients ≥60 years of age of is advisable.
Use In Pregnancy & Lactation
There are no studies in pregnant women using Capecitabine (Xeltabine).
In reproductive toxicity studies in animals, Capecitabine (Xeltabine) administration caused embryolethality and teratogenicity. These findings are expected effects of fluoropyrimidine derivatives. As taking Capecitabine (Xeltabine) during pregnancy can damage fetus, Capecitabine (Xeltabine) should be considered as possible inducer of teratogenicity. Therefore Capecitabine (Xeltabine) is contraindicated during pregnancy. If this drug is used during pregnancy, or if a patient becomes pregnant while receiving Capecitabine (Xeltabine), the patient should be apprised of the potential hazard to the fetus.
Men and women should use birth control while taking Xeltabine.
It is not known whether Capecitabine (Xeltabine) is excreted in human breast milk. In lactating mice, considerable amounts of Capecitabine (Xeltabine) and its metabolites were found in milk. Breast-feeding should be discontinued while receiving treatment with Capecitabine (Xeltabine).
Adverse Reactions
The overall safety profile of Capecitabine (Xeltabine) is based on data from over 3000 patients treated with Capecitabine (Xeltabine) as monotherapy or Capecitabine (Xeltabine) in combination with different chemotherapy regimens in multiple indications. The safety profiles of Capecitabine (Xeltabine) monotherapy for the metastatic breast cancer, metastatic colorectal cancer and adjuvant colon cancer populations are comparable. The most commonly reported and/or clinically relevant treatment-related adverse drug reactions (ADRs) were gastrointestinal disorders (especially diarrhoea, nausea, vomiting, abdominal pain, stomatitis), hand-foot syndrome (palmar-plantar erythrodysesthesia), fatigue, asthenia, anorexia, cardiotoxicity, increased renal dysfunction on those with preexisting compromised renal function, and thrombosis/embolism.
Summary of Safety Profile: ADRs considered by the investigator to be possibly, probably, or remotely related to the administration of Xeltabine are listed in following tables. The following headings are used to rank the ADRs by frequency: very common (≥1/10), common (≥1/100, <1/10) and uncommon (≥1/1,000, <1/100). Within each frequency grouping, ADRs are presented in order of decreasing seriousness.
Capecitabine (Xeltabine) Monotherapy: Table 4 lists ADRs associated with the use of Capecitabine (Xeltabine) monotherapy based on a pooled analysis of safety data from three major studies including over 1900 patients (studies M66001, SO14695, and SO14796). ADRs are added to the appropriate frequency grouping according to the overall incidence from the pooled analysis. (See Table 4.)

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Capecitabine (Xeltabine) in combination therapy: Table 5 lists ADRs associated with the use of Capecitabine (Xeltabine) in combination with different chemotherapy regimens in multiple indications based on safety data from over 3000 patients. ADRs are added to the appropriate frequency grouping (Very common or Common) according to the highest incidence seen in any of the major clinical trials and are only added when they were seen in addition to those seen with Capecitabine (Xeltabine) monotherapy or seen at a higher frequency grouping compared to Capecitabine (Xeltabine) monotherapy. Uncommon ADRs reported for Capecitabine (Xeltabine) in combination therapy are consistent with the ADRs reported for Capecitabine (Xeltabine) monotherapy or reported for monotherapy with the combination agent. Some of the ADRs are reactions commonly seen with the combination agent (e.g. peripheral sensory neuropathy with docetaxel or oxaliplatin, hypertension seen with bevacizumab); however an exacerbation by Capecitabine (Xeltabine) therapy can not be excluded. (See Table 5.)

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Post-Marketing Experience in Abroad: The following additional serious adverse reactions have been identified during post-marketing exposure: Very rare: Lacrimal duct stenosis.
Very rare: Hepatic failure and cholestatic hepatitis have been reported during clinical trials and post-marketing exposure.
Description of Selected Adverse Reactions: Hand-foot syndrome: For the Capecitabine (Xeltabine) dose of 1250 mg/m2 twice daily on days 1 to 14 every 3 weeks, a frequency of 53% to 60% of all-grades HFS was observed in Capecitabine (Xeltabine) monotherapy trials (comprising studies in adjuvant therapy in colon cancer, treatment of metastatic colorectal cancer, and treatment of breast cancer) and a frequency of 63% was observed in the Capecitabine (Xeltabine)/docetaxel arm for the treatment of metastatic breast cancer. For the Capecitabine (Xeltabine) dose of 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks, a frequency of 22% to 30% of all-grade HFS was observed in Capecitabine (Xeltabine) combination therapy.
A meta-analysis of 13 clinical trials with data from over 3800 patients treated with Capecitabine (Xeltabine) monotherapy or Capecitabine (Xeltabine) in combination with different chemotherapy regimens in multiple indications showed that HFS (all grades) occurred in 1788 (47%) patients after a median time of 155 [95% CI 135, 187] days after starting treatment with Capecitabine (Xeltabine). In all studies combined, the following covariates were statistically significantly associated with an increased risk of developing HFS: increasing Capecitabine (Xeltabine) starting dose (gram), increasing cumulative Capecitabine (Xeltabine) dose (0.1 *kg), increasing relative dose intensity in the first six weeks, increasing duration of study treatment (weeks), increasing age (by 10 year increments), female gender, and good ECOG performance status at baseline (0 versus ≥1).
Diarrhoea: Capecitabine (Xeltabine) can induce the occurrence of diarrhoea, which has been observed in up to 50% of patients.
The results of a meta-analysis of 13 clinical trials with data from over 3800 patients treated with Capecitabine (Xeltabine) showed that in all studies combined, the following covariates were statistically significantly associated with an increased risk of developing diarrhea: increasing Capecitabine (Xeltabine) starting dose (gram), increasing duration of study treatment (weeks), increasing age (by 10 year increments), and female gender. The following covariates were statistically significantly associated with a decreased risk of developing diarrhea: increasing cumulative Capecitabine (Xeltabine) dose (0.1 *kg) and increasing relative dose intensity in the first six weeks.
Cardiotoxicity: In addition to the ADRs described in Tables 4 and 5, the following ADRs with an incidence of less than 0.1% were associated with the use of Capecitabine (Xeltabine) monotherapy based on a pooled analysis from clinical safety data from 7 clinical trials including 949 patients (2 phase III and 5 phase II clinical trials in metastatic colorectal cancer and metastatic breast cancer): cardiomyopathy, cardiac failure, sudden death, and ventricular extrasystoles.
Encephalopathy: In addition to the ADRs described in Tables 4 and 5, and based on the above pooled analysis from clinical safety data from 7 clinical trials, encephalopathy was also associated with the use of Capecitabine (Xeltabine) monotherapy with an incidence of less than 0.1%.
Capecitabine (Xeltabine) Monotherapy of Gastric Cancer: In clinical trial in patients with advanced and metastatic gastric cancer, dose of Capecitabine (Xeltabine) is 1250 mg/m2 administered orally twice daily (morning and evening; equivalent to 2500 mg/m2 total daily dose) for 2 weeks followed by a 1-week rest period given as 3-week cycles. ADRs considered by the study, related to the administration of Xeltabine are listed in Table 6. (See Table 6.)

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Result of Domestic Post-Marketing Surveillance: As a result of domestic post marketing surveillance of colorectal cancer for 4 years regardless of causality between Capecitabine (Xeltabine) and the result, ADRs of total 646 patients and 1,381 cases out of 1,272 patients are reported and a frequency of 50.79% is observed. Hand-foot syndrome is occurred most frequently in 28.46%, skin discoloration, alopecia, diarrhea, nausea, vomiting, abdominal pain, stomatitis, anorexia, constipation, asthenia, paresthesia, agranulocytosis is occurred in ≥1% and <10%. The others occurred in <1% are sorted into each organ as follows.
Skin & Subcutan.: dermatitis exfoliativa, hand-foot-and-mouth disease, rash, pruritus, dermatitis, nail disease, keratosis, herpes simplex, hives, hand macule, nail discoloration, sclerema, skin damage, skin fissure, erythema (polymorphic).
Gastrointestinal: ispepsia, mucositis, thirst, abdominal inflation, gastrointestinal tract disease, proctodynia, bloody excrement, gas, protorrhagia, ulcer, abdominal displeasure, esophagitis, gastritis.
General & Metabolic disorder: pain, fever, fatigue, edema, increase in body weight, modififcation in bodyweight, abdominal pain, pleurodynia, chill, decrease in body weight, increase in alkali phosphatase.
Central and peripheral nervous system: vertigo, neuropathy, headache.
Respiratory: dyspnoea, cough, pharyngitis, epistaxis, pain in the nose.
Hematoscopio: leucopenia, thrombopenia, hematocitopenia, anemia, neutropenia.
Musculoskeletal: muscle pain, arthralgia, omarthralgia, femoral pain.
Urethral & Reproductive: dysuria, pollakiuria, face edema, hematuria, urinary tract infection, urethralgia, colporrhagia.
Others: insommia, hepatosis, billirubinemia, moniliasis, herpes zoster, tachycardia, diet disorder.
As a result of domestic post marketing surveillance of breast cancer for 6 years regardless of causality between Capecitabine (Xeltabine) and the result, ADRs of total 630 patients and 1,499 cases out of 1,009 patients are reported and a frequency of 62.4% is observed.
Hand-foot syndrome is occurred most frequently in 26.07%, nausea is occurred in 11.30%, stomatitis, diarrhea, vomiting, abdominal pain/epigastralgia, constipation, dyspepsia, skin discoloration, pain, asthenia, fever, fatigue, edema (face, peripheral, legs and arms), melagia, headache, paresthesia, neuropathy, vertigo, lumbago, arthralgia, muscle pain, cough, dyspnea, anorexia & appetite.
Decreased, leucopenia, neutropenia, thrombopenia isoccurred in ≥1% and <10%. the others occurred in < 1% are sorted into each organ as follows.
Skin & Subcutan.: pruritus, skin disease, nail disease, skin hypertrophy, dermatitis, erythema, rash, shingles, alopecia, genitals spot, exfoliative dermatitis, skin fissure, xeroderma.
Gastrointestinal: flatulence, thirst, glossitis, gastritis, hemoptysis, abdominal inflation.
General & Metabolic disorder: ascites, hypothermia, jaundice, stiffen (chill), decrease of body weight, increase of calcium.
Central and peripheral nervous system: change of voice/ husky voice, convulsion, paralysis (unilateral anesthesia, hemiparalysis), dysphagia, dizziness, hands and feet pain, peripheral neuropathy, benum bed hands and feet, insomnia, hand tremor, anxiety.
Respiratory: pleural effusion, chest pain, throat discomfort, upper respiratory tract infection, rhinorrhea, sputum, allergic coryza, pneumonia.
Hematoscopio: anemia, increase SGOT, increase SGPT, hyperbilirubinemia, oligochromemia, agranulocytosis, increase alkaline phosphatase, hypocytosis, abnormal blood test result (CBC).
Cardiovascular: palpitation, tachycardia, SVC syndrome.
Urethral & Reproductive: leucorrhea, colporrhagia, dysuria.
Others: Infection, septicemia, chest tightness, abnormalities of visual field, increase tear.
As a result of domestic post marketing surveillance of gastric cancer for 4 years regardless of causality between Capecitabine (Xeltabine) and the result, ADRs of total 607 patients and out of 1,145 patients are reported and a frequency of 53.0% is observed. Anemia (18.9%), hand-foot syndrome (13.6%), nausea/vomiting (13.3%), abnormal neutrophils/neutrophilia (10.6%) is occurred frequently, anorexia/appetite decreased, blood sugar disorder/increase, leukocyte disorder/leukopenia, abnormal result of liver function test, debility, hyperbiliubinemia, hypoalbuminemia, fatigue, muscle pain, lumbago, polyneuropathy, insomnia, paresthesia, fever and chills, edema, nail disorder, alopecia is occurred in ≥1% and <10%. The others occurred in <1% are sorted into each organ as follows.
Skin & Subcutan.: urtication, shingles, folliculitis, rash, hyperpigmentation, phlegmon, exfoliative dermatitis, chromodermatosis, angitis.
Gastrointestinal: thirst, hiccup, abdominal displeasure, ascites, upper abdominal pain, epigastralgia, indigestion, heartburn, disphagia, intestinal obstruction and gastritis, hermapeces and hermatemesis/hermoptysis.
General & Metabolic disorder: hands and feet pain, enfermedad, narcoleptic, pain, chest pain, hypoglycaemia, decrease in body weight, increase in body weight, increase ALP, decrease HCT, hyperuricacidemia, lymphocytopenia, recessive neutropenia, hyponatremia, hypocalcemia, oligocythemia, azotemia, hypocytosis, increase serum creatinine.
Central and peripheral nervous system: paresthesia, headache, vertigo/dizziness.
Respiratory: cold.cough, sputum, abnormal pharvnx function, sore throat, rhinorrhea,dyspnea.
Hematoscopio: blood coagulation defect.
Others: infection.
Drug Interactions
Coumarin-derivative anticoagulants: Patients taking coumarin-derivative anticoagulants concomitantly with Capecitabine (Xeltabine) should be monitored regularly for alterations in their coagulation parameters (PT or INR) and the anti-coagulant dose adjusted accordingly. Altered coagulation parameters and/or bleeding have been reported in patients taking Capecitabine (Xeltabine) concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon. These reactions occurred within several days and up to several months after initiating Capecitabine (Xeltabine) therapy and, in a few cases, within one month after stopping Capecitabine (Xeltabine). In a clinical pharmacokinetic interaction study, after a single 20 mg dose of warfarin, Capecitabine (Xeltabine) treatment increased the AUC of S-warfarin by 57% with a 91% increase in INR value. Since metabolism of R-warfarin was not affected, these results indicate that Capecitabine (Xeltabine) down-regulates isozyme 2C9, but has no effect on isozymes 1A2 and 3A4.
Antacid: The effect of an aluminum hydroxide and magnesium hydroxide-containing antacid on the pharmacokinetics of Capecitabine (Xeltabine) was investigated. There was a small increase in plasma concentrations of Capecitabine (Xeltabine) and one metabolite (5'-DFCR); there was no effect on the 3 major metabolites (5'-DFUR, 5-FU and FBAL).
Allopurinol: Interactions with allopurinol have been observed for 5-FU. Concomitant use of allopurinol with Capecitabine (Xeltabine) should be avoided.
Paclitaxel: Phase I studies with cancer patients evaluating the effect of Capecitabine (Xeltabine) on the pharmacokinetics of paclitaxel and vice versa showed no effect by Capecitabine (Xeltabine) on the pharmacokinetics of paclitaxel (Cmax, AUC) and no significant effect by paclitaxel on the pharmacokinetics clinically.
Sorivudine and analogues: A clinically significant drug-drug interaction between sorivudine and 5-FU, resulting from the inhibition of dihydropyrimidine dehydrogenase by sorivudine, has been described. This interaction, which leads to increased fluoropyrimidine toxicity, is potentially fatal. Therefore, Capecitabine (Xeltabine) must not be administered concomitantly with sorivudine or its chemically related analogues, such as brivudine. There must be at least a 4-week waiting period between end of treatment with sorivudine or its chemically related analogues such as brivudine and start of Capecitabine (Xeltabine) therapy.
Phenytoin: Increased phenytoin plasma concentrations resulting in symptoms of phenytoin intoxication in single cases have been reported during concomitant use of Capecitabine (Xeltabine) with phenytoin. Patients taking phenytoin concomitantly with Capecitabine (Xeltabine) should be regularly monitored for increased phenytoin plasma concentrations.
Plasma proteins: Capecitabine (Xeltabine) has low plasma protein binding rate (54%). Therefore interaction resulting from replacement procedure to drug with high plasma protein binding rate is not in concern.
Cytochrome P-450: See Coumarin-derivative anticoagulation for interaction isoenzyme 1A2, 2C9 and 3A4 on previous text.
Interferon alpha: The maximum tolerated dose (MTD) of Capecitabine (Xeltabine) was 2000 mg/m2 per day when combined with interferon alpha-2a (3 MIU/m2 per day) compared to 3000 mg/m2 per day when Capecitabine (Xeltabine) was used alone.
Radiotherapy: The maximum tolerated dose (MTD) of Capecitabine (Xeltabine) alone using the intermittent regimen is 3000 mg/m2 per day, whereas, when combined with radiotherapy for rectal cancer, the maximum tolerated dose (MTD) of Capecitabine (Xeltabine) is 2000 mg/m2 per day (using either a continuous schedule or given daily Monday through Friday during a 6-week course of radiotherapy).
Folinic acid: A combination study with Capecitabine (Xeltabine) and folinic acid indicated that folinic acid has no major effect on the pharmacokinetics of Capecitabine (Xeltabine) and its metabolites. However, folinic acid has an effect on the pharmacodynamics of Capecitabine (Xeltabine) and its toxicity may be enhanced by folinic acid: the maximum tolerated dose (MTD) of Capecitabine (Xeltabine) alone using the intermittent regimen is 3000 mg/m2 per day whereas it is only 2000 mg/m2 per day when Capecitabine (Xeltabine) was combined with folinic acid (30 mg orally twice daily).
Taking a tegafur, gimeracil, oteracil potassium complex combined with Capecitabine (Xeltabine) or taking the complex within seven days after interruption of Capecitabine (Xeltabine) administration is contraindicated. Blood fluorouracil contents increased remarkably due to gimeracil inhibiting metabolism of fluorouracil cause gastrointestinal disorder like severe blood disorder, diarrhea or stomatitis etc.
Oxaliplatin: No clinically significant differences in exposure to Capecitabine (Xeltabine) or its metabolites, free platinum or total platinum occurred when Capecitabine (Xeltabine) was administered in combination with oxaliplatin or in combination with oxaliplatin and bevacizumab.
Storage
Store at room temperature not exceeding 30°C.
Patient Counseling Information
Information for patient: Patients and patients' caregivers should be informed of the expected adverse effects of Capecitabine (Xeltabine), particularly nausea, vomiting, diarrhea, and hand-and-foot syndrome, and should be made aware that patient-specific dose adaptations during therapy are expected and necessary (see Dosage & Administration). Patients should be encouraged to recognize the common grade 2 toxicities associated with Capecitabine (Xeltabine) treatment.
Diarrhea: Patients experiencing grade 2 diarrhea (an increase of 4 to 6 stools/day or nocturnal stools) or greater should be instructed to stop taking Capecitabine (Xeltabine) immediately. Standard antidiarrheal treatments (eg, loperamide) are recommended.
Nausea: Patients experiencing grade 2 nausea (food intake significantly decreased but able to eat intermittently) or greater should be instructed to stop taking Capecitabine (Xeltabine) immediately. Initiation of symtomatic treatment is recommended.
Vomiting: Patients experiencing grade 2 vomiting (2 to 5 episodes in a 24-hour period) or greater should be instructed to stop taking Capecitabine (Xeltabine) immediately. Initiation of symptomatic treatment is recommended.
Hand-and-Foot Syndrome: 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 should be instructed to stop taking Capecitabine (Xeltabine) immediately.
Stomatitis: Patients experiencing grade 2 stomatitis (painful erythema, edema or ulcers of the mouth or tongue, but able to eat) or greater should be instructed to stop taking Capecitabine (Xeltabine) immediately. Initiation of symptomatic treatment is recommended (see Dosage & Administration).
Patients who develop a fever of 38°C or greater or other evidence of potential infection should be instructed to call their physician.
Drug-food interaction: In all clinical trials, patients were instructed to administer Capecitabine (Xeltabine) within 30 minutes after a meal. Since current safety and efficacy data are based upon administration with food, it is recommended that Capecitabine (Xeltabine) be administered with food (see Dosage & Administration).
In studies of fertility and general reproductive performance in male mice, this dose caused degenerative testicle changes in the testes, including decreases in the weight of testicle and epididymis, the number of spermatocytes and spermatids. In females, oral Capecitabine (Xeltabine) doses of 760 mg/kg/day (about 2300 mg/m2/day) disturbed estrus and consequently caused a decrease in fertility. In mice that became pregnant, no fetuses survived this dose.
Capecitabine (Xeltabine) at doses of 198 mg/kg/day during organogenesis caused malformations and embryo death in mice. Malformations in mice included cleft palate, anophthalmia, microphthalmia, polydactyly, syndactyly, kinky tail and dilation of cerebral ventricles. In separate pharmacokinetic studies, this dose in mice produced 5'-DFUR AUC values about 0.2 times the corresponding values in patients administered the recommended daily dose.
At doses of 90 mg/kg/day, Capecitabine (Xeltabine) given to pregnant monkeys during organogenesis caused fetal death. This dose produced 5'-DFUR AUC values about 0.6 times the corresponding values in patients administered the recommended daily dose.
Biological test result shows Capecitabine (Xeltabine) is to decrease the immune functions.
Pre-clinical test result shows significant structural anomaly of chromosome statistically when metabolic activation system doesn't exist in chromosome aberration test using peripheral blood lymphocytes of human.
ATC Classification
L01BC06 - capecitabine ; Belongs to the class of antimetabolites, pyrimidine analogues. Used in the treatment of cancer.
Presentation/Packing
FC tab 500 mg (peach, oblong, biconvex, engraved with "UT" on one side and "500" on the other side) x 120's.
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