shell composition: hypromellose 5cP, titanium dioxide (E 171), talc (E 553b), macrogol 400, red iron oxide (E 172), yellow iron oxide (E 172).
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated tablets, oval-shaped, light peach in color, engraved with "150" on one side. Approximate dimensions 11.4 mm x 5.9 mm;
Film-coated tablets, oblong, peach-coloured, engraved with "500" on one side. Approximate dimensions 17.1 mm x 8.1 mm.
Capecitabine is a non-cytotoxic fluoropyrimidine carbamate derivative, an oral precursor of the cytotoxic compound 5-fluorouracil (5-FU). Capecitabine is activated in several enzymatic steps. Final conversion to 5-FU occurs under the action of thymidine phosphorylase in tumor tissue, as well as in healthy tissues of the body, but, as a rule, at low levels. In human cancer xenograft models, capecitabine has demonstrated a synergistic effect in combination with docetaxel, which may be due to an increase in thymidine phosphorylase activity by docetaxel.
Evidence suggests that 5-FU metabolism anabolically blocks the methylation reaction of deoxyuridylic acid to thymidylic acid, thereby inhibiting the synthesis of deoxyribonucleic acid (DNA). Incorporation of 5-FU also inhibits RNA and protein synthesis. Because DNA and RNA are essential for cell division and growth, 5-FU can cause thymidine deficiency, which contributes to unbalanced cell growth and death. The effects on DNA and RNA are more pronounced in cells with more rapid proliferation and higher levels of 5-FU metabolism.
Pharmacokinetics
The pharmacokinetics of capecitabine were determined over a dose range of 502-3514 mg/m2/day. Capecitabine, 5'-deoxy-5-fluorocytidine (5'-DFCT) and 5'-deoxy-5-fluorouridine (5'-DFUR) parameters were similar on days 1 and 14. On day 14, the AUC of 5-FU was 30-35% higher. Reducing the capecitabine dose resulted in a greater than dose-proportional decrease in 5-FU exposure due to the non-linear pharmacokinetics of the active metabolite.
Absorption
After oral administration, capecitabine is rapidly and completely absorbed, followed by biotransformation to the metabolites 5'-deoxy-5-fluorocytidine (5'-DFCT) and 5'-DFUR. Food intake reduces the rate of absorption of capecitabine, but has no significant effect on the area under the concentration-time curve (AUC) of 5'-DFUR and the subsequent metabolite 5-FU. When administered at a dose of 1250 mg/m2 after food on day 14, the maximum concentrations of capecitabine, 5'-DFCR, 5'-DFUR, 5-FU and FBAL were 4.67, 3.05, 12.1, 0.95 and 5.46 μg/ml, respectively. The time to reach the maximum concentration Tmax is 1.50, 2.00, 2.00, 2.00 and 3.34 hours, and AUC is 7.75, 7.24, 24.6, 2.03 and 36.3 μg × h/ml, respectively.
Distribution
In vitro studies in human plasma have demonstrated that for capecitabine, 5'-DFCT, 5'-DFUR and 5-FU, protein binding (mainly to albumin) is 54%, 10%, 62% and 10%, respectively.
Metabolism
It is metabolized in the liver by carboxylesterase to the metabolite 5'-DFCT, which is then transformed into 5'-DFUR by cytidine deaminase, which is mainly found in the liver and tumor tissues. Further catalytic activation of 5'-DFUR occurs due to thymidine phosphorylase. The enzymes involved in catalytic activation are found in both tumor tissues and normal tissues, but usually at lower levels. Further enzymatic biotransformation of capecitabine to 5-FU leads to higher concentrations in tumor tissues. In the case of colorectal tumors, a significant part of 5-FU is localized in tumor stromal cells. After oral administration of capecitabine to patients with colorectal cancer, the ratio of 5-FU concentration in colorectal tumors to the concentration in adjacent tissues was 3.2 (range 0.9 to 8.0). The ratio of 5-FU concentration in the tumor to the concentration in the blood plasma was 21.4 (range 3.9 to 59.9, N=8), while the ratio of the concentration in healthy tissues to the concentration in the blood plasma was 8.9 (range 3.0 to 25.8, N=8). When measured, the activity of thymidine phosphorylase was 4-fold higher in the primary colorectal tumor compared with the adjacent normal tissues. According to immunohistochemical studies, the majority of thymidine phosphorylase is localized in the stromal cells of the tumor.
5-FU is then catabolized by dihydropyrimidine dehydrogenase (DPD) to form the less toxic dihydro-5-fluorouracil (FUN2). Dihydropyrimidinease cleaves the pyrimidine ring to form 5-fluoroureidopropionic acid (FUPA). The final reaction is the cleavage of FUPA by β-ureidopropionase to α-fluoro-β-alanine (FBA), which is detected in the urine. Dihydropyrimidine dehydrogenase activity is rate-limiting. DPD deficiency may lead to increased toxicity of capecitabine.
The elimination half-lives (T1/2) of capecitabine, 5'-DFCR, 5'-DFUR, 5-FU and FBAL are 0.85, 1.11, 0.66, 0.76 and 3.23 hours, respectively. Capecitabine and metabolites of capecitabine are mainly excreted in the urine. Excretion in the urine is 95.5%, in the feces - 2.6%. The main metabolite in the urine is FBAL, which accounts for 57% of the administered dose. Approximately 3% of the administered dose is excreted in the urine unchanged.
Combination therapy
There was no effect of capecitabine on the pharmacokinetics of docetaxel and paclitaxel (Cmax and AUC) and no effect of docetaxel and paclitaxel on the pharmacokinetics of capecitabine and 5'-DFUR.
Pharmacokinetics in special clinical groups
A population pharmacokinetic analysis was performed after treatment with capecitabine at a dose of 1250 mg/m2 twice daily in 505 patients with colorectal cancer. Gender, presence or absence of liver metastases at the start of treatment, Karnowski performance status, total bilirubin, serum albumin, ALT and ACT activity had no significant effect on the pharmacokinetics of 5'-DFUR, 5-FU and FBAL.
Patients with metastatic liver disease: Pharmacokinetic studies suggest that capecitabine bioavailability and 5-FU exposure may be increased in patients with mild to moderate hepatic impairment due to metastases compared to patients without hepatic impairment. Pharmacokinetic data are not available in patients with severe hepatic impairment.
Patients with renal impairment. In patients with varying degrees of renal insufficiency (from mild to severe) in cancer patients, the pharmacokinetics of the unchanged drug and 5-FU do not depend on creatinine clearance (CC). CC affects the AUC of 5'-DFUR (increase in AUC by 35% - with a decrease in CC by 50%) and FBAL (increase in AUC by 114% with a decrease in CC by 50%). FBAL is a metabolite that does not have antiproliferative activity.
Elderly: Based on a population pharmacokinetic analysis that included patients with a wide age range (27–86 years), of whom 234 patients (46%) were 65 years or older, age did not affect the pharmacokinetics of 5'-DFUR and 5-FU. The AUC of FBAL increased with age (a 20% increase in age was accompanied by a 15% increase in the AUC of FBAL), which is likely due to changes in renal function.
Ethnic factors. After oral administration of 825 mg/m2 capecitabine twice daily for 14 days in Japanese patients (N=18), capecitabine Cmax was 36% lower and AUC was 24% lower compared to Caucasian patients (N=22). Also for FBAL, Japanese patients had a 25% lower capecitabine Cmax and 34% lower AUC compared to Caucasian patients. The clinical significance of this difference is unknown. No significant difference in exposure of other metabolites (5'-DPCT,
5'-DFUR and 5-FU).
Indication
Colon cancer, colorectal cancer:
– colon cancer, in adjuvant therapy after surgical treatment of stage III cancer (Duke stage C);
– metastatic colorectal cancer.
Stomach cancer:
– a drug for the first-line treatment of advanced stomach cancer, in combination with platinum-based drugs.
Breast cancer:
– locally advanced or metastatic breast cancer, in combination with docetaxel after ineffective chemotherapy, including anthracyclines;
– locally advanced or metastatic breast cancer, as monotherapy after ineffective chemotherapy, including taxanes and anthracyclines, or in the presence of contraindications to anthracycline therapy.
Contraindication
History of severe, including unexpected, reactions to fluoropyrimidine treatment. Hypersensitivity to capecitabine or to any component of the drug, or to fluorouracil. Known complete lack of dihydropyrimidine dehydrogenase (DPD) activity (see section "Special warnings and precautions for use").
Pregnancy or breastfeeding.
Severe leukopenia, neutropenia, thrombocytopenia.
Severe liver dysfunction.
Severe renal impairment (creatinine clearance
Recent or concomitant treatment with brivudine (see sections “Special warnings and precautions for use” and “Interaction with other medicinal products and other forms of interaction” for interactions with other medicinal products).
Contraindications for the use of any medicinal product used in combination.
Special safety measures.
Disposal of unused and expired medicinal products: Release of medicinal products into the environment should be minimised. The medicinal product should not be disposed of via wastewater or household waste. For disposal, use a so-called “waste collection system” if available.
Interaction with other medicinal products and other types of interactions
Interaction studies have only been performed in adult patients.
Interaction with other drugs
A clinically significant interaction has been described between brivudine and fluoropyrimidines (e.g. capecitabine, 5-fluorouracil, tegafur) as a result of inhibition of dihydropyrimidine dehydrogenase by brivudine. This interaction, which leads to increased fluoropyrimidine toxicity, can potentially be fatal. Therefore, brivudine should not be used concomitantly with capecitabine (see sections 4.3 and 4.4). There should be a waiting period of at least 4 weeks between the end of brivudine treatment and the start of capecitabine therapy. Brivudine treatment can be started 24 hours after the last dose of capecitabine.
Cytochrome P450 2C9 substrates.
Interaction studies with capecitabine and other drugs metabolized by the cytochrome P450 2C9 isoenzyme, except warfarin, have not been conducted. Caution should be exercised when prescribing capecitabine with these drugs (e.g. phenytoin).
Coumarin anticoagulants.
Capecitabine enhances the effects of indirect anticoagulants (warfarin and phenprocoumon), which can lead to impaired coagulation and bleeding several days or months after the start of capecitabine therapy, and in some cases within 1 month after the end of capecitabine treatment. In a clinical pharmacokinetic interaction study after a single administration of S-warfarin at a dose of 20 mg, treatment with Capecitabine-Vista led to an increase in warfarin AUC by 57% and MHO by 91%. Since the metabolism of R-warfarin was not impaired, this indicates that capecitabine inhibits the 2C9 isoenzyme and does not affect the 1A2 and 3A4 isoenzymes. In patients receiving capecitabine and oral anticoagulants – coumarin derivatives, it is necessary to conduct detailed monitoring of blood coagulation parameters (international normalized ratio or prothrombin time) and adjust the dose of the anticoagulant.
Phenytoin.
Isolated cases of increased phenytoin plasma concentrations, accompanied by symptoms of phenytoin intoxication, have been reported with concomitant use of Capecitabine-Vista and phenytoin. It is recommended that phenytoin plasma concentrations be monitored regularly in patients receiving capecitabine and phenytoin concomitantly.
Folinic acid/folic acid.
Folinic acid does not significantly affect the pharmacokinetics of capecitabine and its metabolites. However, folinic acid affects the pharmacodynamics of Capecitabine-Vista, which may lead to increased toxicity of capecitabine: the maximum tolerated dose of capecitabine in monotherapy with an intermittent dosing regimen is 3000 mg/m2 per day, and in combination with folinic acid (30 mg orally twice a day) - only 2000 mg/m2 per day. Increased toxicity is possible when switching from 5-FU/LV to a capecitabine regimen. This may also be observed when folic acid is used to correct folic acid deficiency due to the similarity between folinic and folic acids.
Antacids.
The effect of antacids containing aluminum and magnesium hydroxide on the pharmacokinetics of capecitabine was studied. Antacids containing aluminum and magnesium hydroxide slightly increase the plasma concentrations of capecitabine and one of its metabolites (5'-DFPR); they do not affect the three major metabolites (5'-DFPR, 5-FU and FBA) of capecitabine.
Allopurinol.
An interaction between allopurinol and 5-fluorouracil has been observed, with a possible reduction in the efficacy of 5-fluorouracil. Therefore, the concomitant use of capecitabine and allopurinol should be avoided.
Interferon alpha.
The maximum tolerated dose of Capecitabine-Vista is 2000 mg/m2 per day when used in combination with interferon alfa-2a (3 million IU/m2 per day) compared to 3000 mg/m2 per day when capecitabine is used as monotherapy.
Radiation therapy.
The maximum tolerated dose of capecitabine in monotherapy with an intermittent dosing regimen is 3000 mg/m2 per day, when combined with radiotherapy for rectal cancer - 2000 mg/m2 per day with a continuous course of radiotherapy or a daily 6-week course of radiotherapy from Monday to Friday.
Oxaliplatin.
When capecitabine and oxaliplatin were combined with or without bevacizumab, there was no clinically significant difference in the exposure of capecitabine or its metabolites, free platinum, and total platinum.
Bevacizumab.
There was no clinically significant effect of bevacizumab on the pharmacokinetic parameters of capecitabine and its metabolites in the presence of oxaliplatin.
Drug-food interaction
Since the available safety and efficacy data are based on the use of capecitabine with food, it is recommended that Capecitabine-Vista be taken with food. Taking Capecitabine-Vista with food slows down the rate of absorption of capecitabine.
Application features
Toxic effect, depending on the dose.
Diarrhea. Patients with severe diarrhea should be closely monitored for rehydration and electrolyte replacement in case of dehydration. Standard antidiarrheal agents (e.g. loperamide) may be administered. Grade II diarrhea according to the National Cancer Institute of Canada (NCIC CTS, version 2) criteria is defined as an increase in the number of bowel movements to 4–6 times per day or bowel movements at night; grade III diarrhea is defined as an increase in the number of bowel movements to 7–9 times per day or fecal incontinence and malabsorption. Grade 4 diarrhea is defined as an increase in the number of bowel movements ≥10/day or massive diarrhea with blood, or the need for parenteral infusions. If necessary, the dose of the drug should be reduced (see section “Method of administration and dosage”).
Dehydration. Dehydration should be prevented and corrected if it occurs. Dehydration may develop rapidly in patients with anorexia, asthenia, nausea, vomiting or diarrhoea. Dehydration may lead to acute renal failure, especially in patients with pre-existing renal impairment or when capecitabine is administered concomitantly with medicinal products known to be nephrotoxic. Acute renal failure resulting from dehydration may be potentially fatal. If grade II (or higher) dehydration occurs, capecitabine therapy should be discontinued immediately and dehydration should be corrected. Treatment may be resumed with adequate correction of dehydration and correction/control of precipitating causes (see section 4.2). Dose adjustments should be made for precipitating adverse events as necessary.
Palmar-plantar syndrome
Palmoplantar syndrome is also known as palmoplantar skin reactions or palmoplantar erythrodysesthesia, or chemotherapy-induced peripheral erythema. Grade I palmoplantar syndrome does not interfere with the patient's daily activities and presents with numbness, paresthesias, dysesthesias, tingling, painless swelling or redness of the palms and/or soles, and/or discomfort.
Grade II palmar-plantar syndrome is manifested by painful redness and swelling of the hands and/or soles; the discomfort caused by these manifestations disrupts the patient's daily activities.
Grade III palmoplantar syndrome is defined as moist desquamation, ulceration, blistering and acute pain of the palms and/or soles, and/or severe discomfort that prevents patients from working or engaging in daily activities. Persistent or severe palmoplantar syndrome (grade 2 or higher) may eventually lead to loss of fingerprints, which may affect patient identification. In the event of grade II or III palmoplantar syndrome, capecitabine should be discontinued until symptoms resolve or improve to grade I; if grade III syndrome recurs, the capecitabine dose should be reduced. Vitamin B6 (pyridoxine) is not recommended for symptomatic or secondary prophylaxis of palmoplantar syndrome in patients receiving capecitabine and cisplatin concomitantly, as published data suggest that it may reduce the efficacy of cisplatin. Some evidence suggests that dexpanthenol is effective in preventing palmar-plantar syndrome in patients treated with capecitabine.
Cardiotoxicity.
The spectrum of cardiotoxicity with capecitabine is similar to that seen with other fluoropyrimidines and includes myocardial infarction, angina pectoris, arrhythmias, cardiogenic shock, sudden death, cardiac arrest, cardiac failure and ECG changes (including very rare cases of QT prolongation). These adverse events are more common in patients with coronary artery disease. Cardiac arrhythmias (including ventricular fibrillation, torsades de pointes, bradycardia), angina pectoris, myocardial infarction, heart failure and cardiomyopathy have been reported with capecitabine. Caution should be exercised when prescribing capecitabine to patients with clinically significant cardiac disease, arrhythmias and angina pectoris.
Hypo- or hypercalcemia.
Hypo- or hypercalcemia has been reported during treatment with capecitabine.
Diseases of the central or peripheral nervous system.
Caution should be exercised when prescribing Capecitabine-Vista to patients with central or peripheral nervous system disease, such as brain metastases or neuropathy.
Diabetes or electrolyte imbalance.
Caution should be exercised when prescribing Capecitabine-Vista to patients with diabetes mellitus or electrolyte disturbances, as the use of capecitabine may worsen their condition.
In a single-dose warfarin interaction study, a significant increase in the mean area under the concentration-time curve (AUC) of S-warfarin (by 57%) was observed, indicating an interaction likely due to inhibition of the cytochrome P450 2C9 isoenzyme by capecitabine. In patients receiving capecitabine and oral coumarin anticoagulants, close monitoring of blood coagulation parameters (international normalized ratio or prothrombin time) and adjustment of the anticoagulant dose are necessary.
Brivudin
Brivudine should not be used concomitantly with capecitabine. Fatalities have been reported following this drug interaction. There should be a waiting period of at least 4 weeks between the end of brivudine treatment and the start of capecitabine therapy. Brivudine treatment can be started 24 hours after the last dose of capecitabine (see sections “Contraindications” and “Interaction with other medicinal products and other forms of interaction”).
In case of accidental ingestion of brivudine in patients receiving capecitabine treatment, effective measures should be taken to reduce capecitabine toxicity. Immediate hospitalization is recommended. All necessary measures should be initiated to prevent systemic infections and dehydration.
Liver dysfunction.
Due to the lack of safety and efficacy data in patients with hepatic impairment, capecitabine should be carefully monitored in patients with mild to moderate hepatic impairment, regardless of the presence or absence of liver metastases. If capecitabine treatment results in hyperbilirubinemia exceeding the upper limit of normal by more than 3 times or an increase in the activity of hepatic aminotransferases (ALT, ACT) exceeding 2.5 times the upper limit of normal, capecitabine should be discontinued. Capecitabine monotherapy can be resumed when bilirubin and hepatic transaminases decrease below the specified limits.
Kidney dysfunction.
The incidence of grade III and IV adverse reactions in patients with moderate renal impairment (creatinine clearance 30–50 mL/min) is increased compared to the general patient population.
Dihydropyrimidine dehydrogenase (DPD) deficiency.
Unexpected severe toxicity (e.g. stomatitis, diarrhoea, mucosal inflammation, neutropenia and neurotoxicity) associated with 5-fluorouracil (5-FU) has occasionally been observed due to deficiency in DPD activity.
Patients with low or absent DPD activity, the enzyme involved in the breakdown of fluorouracil, are at increased risk of severe, life-threatening or fatal adverse reactions caused by fluorouracil. Although DPD deficiency cannot be precisely defined, it is known that patients with certain homozygous or some compound heterozygous mutations in the DPYD genetic locus (e.g. DPYD*2A, c. 1679T>G, c. 2846A>T and c. 1236G>A/HapB3 variations), which may result in complete or near complete absence of DPD enzymatic activity (as determined by laboratory tests), are at highest risk of life-threatening or fatal toxicity and should not be treated with capecitabine (see section 4.3). There is no proven safe dose for patients with complete absence of DPD activity.
It has been demonstrated that patients with known heterozygous DPYD variations (specifically, DPYD*2A, c. 1679T>G, c. 2846A>T and c. 1236G>A/HapB3 variations) are at increased risk of severe toxicity when treated with capecitabine.
The frequency of heterozygous DPYD*2A genotype in the DPYD gene in Caucasian patients is approximately 1%, 1.1% for c. 2846A>T, 2.6–6.3% for c. 1236G>A/HapB3 variations and 0.07–0.1% for c. 1679T>G. Genotyping of these alleles is recommended to identify patients at increased risk of severe toxicity. Data on the frequency of these DPYD variations in different Caucasian populations are limited. It cannot be excluded that other rare variations may also be associated with an increased risk of severe toxicity.
Patients with partial DPD deficiency (including heterozygous mutations in the DPYD gene) and if the physician considers that the benefits of capecitabine outweigh the risks (taking into account the feasibility of prescribing alternative non-fluoropyrimidine-based chemotherapy regimens), should be treated with extreme caution and frequent monitoring with dose adjustments based on toxicity. A reduced starting dose should be considered for these patients to avoid serious toxicity. There are insufficient data to recommend a specific dose for patients with partial DPD activity based on specific test results. The DPYD*2A, c. 1679T>G variation has been reported to result in a greater reduction in enzyme activity with a higher risk of adverse reactions among other types of variation. The effect of dose reduction on efficacy is currently unknown. Therefore, in the absence of serious toxicity, the dose may be increased with careful monitoring of the patient.
Patients with unrecognized DPYD deficiency treated with capecitabine, as well as patients who test negative for specific DPYD variations, may experience life-threatening toxicities similar to those seen in acute overdose (see section 4.8). In the event of acute toxicity of Grade II to IV, treatment should be discontinued immediately. Permanent discontinuation of treatment should be considered based on clinical assessment of the onset, duration, and severity of the observed toxicity.
Ophthalmological complications.
Patients should be closely monitored for ophthalmic complications such as keratitis or corneal disorders, especially if there is a history of visual impairment. Treatment of visual impairment should be initiated as clinically indicated.
Severe skin reactions.
Capecitabine-Vista can cause severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Capecitabine should be permanently discontinued in patients who develop severe skin reactions while taking the drug.
Capecitabine-Vista tablets should not be crushed or cut. Adverse reactions may occur if the patient or caregiver comes into contact with crushed or cut Capecitabine-Vista tablets (see section 4.8).
Pancreatitis.
There are reports in the literature of cases of pancreatitis following the use of capecitabine.
Use during pregnancy or breastfeeding
Women of reproductive age/contraception in men and women
Women of childbearing potential should be advised to avoid pregnancy during treatment with capecitabine. If pregnancy occurs during treatment, the patient should be informed of the potential adverse effects on the fetus. Effective methods of contraception should be used during treatment and for 6 months after the last dose of capecitabine.
Given the results of genotoxicity studies, male patients with female partners of reproductive age should use effective contraception during treatment and for 3 months after the last dose of capecitabine.
Pregnancy
Capecitabine has not been studied in pregnant women, but it is expected that Capecitabine-Vista may cause fetal harm when administered to pregnant women. In animal reproductive toxicity studies, capecitabine caused embryolethality and teratogenicity, which are expected effects of fluoropyrimidine derivatives. Capecitabine-Vista should not be used during pregnancy.
Breastfeeding period
It is not known whether capecitabine is excreted in human milk. Studies on the effects of capecitabine on lactation or the presence of capecitabine in human milk have not been conducted. Significant amounts of capecitabine and its metabolites have been detected in the milk of lactating mice. Because the potential harm to breast-fed infants is unknown, breast-feeding should be discontinued during treatment with capecitabine and for 2 weeks after the last dose.
Fertility
There are no data on the effects of capecitabine on fertility. The pivotal studies of capecitabine-Vista included only women of reproductive age and men who agreed to use acceptable methods of birth control to prevent pregnancy during the study and for an appropriate period thereafter. Effects on fertility were observed in animal studies.
Ability to influence reaction speed when driving vehicles or other mechanisms
The drug has minor or moderate influence on the ability to drive and use machines. Capecitabine-Vista may cause dizziness, weakness and nausea.
Method of administration and doses
Capecitabine-Vista should only be prescribed by a qualified physician experienced in the use of antineoplastic agents. Careful monitoring is recommended for all patients during the first cycle of treatment.
Treatment should be discontinued if disease progression or unacceptable toxicity occurs.
Capecitabine-Vista tablets should be taken orally whole, no later than 30 minutes after a meal, with water. Capecitabine-Vista tablets should not be crushed or cut.
Special precautions for disposal and other handling of the drug
Safe handling procedures for cytotoxic drugs should be followed.
Monotherapy
Colon cancer, colorectal cancer and breast cancer. The recommended initial daily dose of Capecitabine-Vista as adjuvant therapy is 2500 mg/m2 body surface area. Administer in 3-week cycles: take daily for 2 weeks, followed by a 1-week rest period. The total daily dose of capecitabine should be divided into 2 doses (1250 mg/m2 body surface area in the morning and evening). The recommended total duration of adjuvant therapy in patients with stage III colon cancer is 6 months.
Breast cancer: In combination with docetaxel, the recommended starting dose for the treatment of metastatic breast cancer is 1250 mg/m2 twice daily for 2 weeks followed by a 1-week rest period (in combination with docetaxel 75 mg/m2 once every 3 weeks as an intravenous infusion). Premedication with oral corticosteroids, such as dexamethasone, should be administered prior to docetaxel administration in accordance with the docetaxel prescribing information for patients receiving capecitabine plus docetaxel.
Colon cancer, colorectal cancer, gastric cancer. In the combination regimen, the initial dose of capecitabine should be reduced to 800–1000 mg/m2 twice daily for 2 weeks followed by a weekly rest period or to 625 mg/m2 twice daily for continuous use. In combination with irinotecan (200 mg/m2 on day 1), the recommended initial dose is 800 mg/m2 twice daily for 2 weeks followed by a weekly rest period. The inclusion of bevacizumab in the combination regimen does not affect the initial dose of capecitabine.
Antiemetics and premedication to ensure adequate hydration should be administered to patients receiving capecitabine therapy in combination with cisplatin or oxaliplatin prior to cisplatin administration according to the cisplatin and oxaliplatin prescribing information. The total recommended duration of adjuvant therapy in patients with stage III colon cancer is 6 months.
The dose of Capecitabine-Vista should be calculated based on body surface area.
Tables 1 and 2 show calculations of the standard and reduced (see “Dose adjustment during treatment”) initial dose of Capecitabine-Vista 1250 mg/m2 or 1000 mg/m2.
Calculations of the standard and reduced starting dose of Capecitabine-Vista 1250 mg/m2 depending on body surface area
Table 1
Dose 1250 mg/m2 (twice daily)
Body surface area, m2
Full dose
1250 mg/m2
Number of tablets 150 mg and/or 500 mg per dose
(morning and evening)
Reduced dose
(75%)
950 mg/m2
Reduced dose
(50%)
625 mg/m2
Dose per 1 dose, mg
150 mg
500 mg
Dose per 1 dose, mg
Dose per 1 dose, mg
≤1.26
1500
-
3
1150
800
1.27–1.38
1650
1
3
1300
800
1.39–1.52
1800
2
3
1450
950
1.53–1.66
2000
-
4
1500
1000
1.67–1.78
2150
1
4
1650
1000
1.79–1.92
2300
2
4
1800
1150
1.93–2.06
2500
-
5
1950
1300
2.07–2.18
2650
1
5
2000
1300
≥2.19
2800
2
5
2150
1450
Calculations of the standard and reduced starting dose of Capecitabine-Vista 1000 mg/m2 depending on body surface area
Table 2
Body surface area, m2
Dose 1000 mg/m2 (2 times daily)
Full dose
1000 mg/m2
Number of tablets 150 mg and/or 500 mg per dose
(morning and evening)
Reduced dose
(75%)
750 mg/m2
Reduced dose
(50%)
500 mg/m2
Dose per 1 dose, mg
150 mg
500 mg
Dose per 1 dose, mg
Dose per 1 dose, mg
≤1.26
1150
1
2
800
600
1.27–1.38
1300
2
2
1000
600
1.39–1.52
1450
3
2
1100
750
1.53–1.66
1600
4
2
1200
800
1.67–1.78
1750
5
2
1300
800
1.79–1.92
1800
2
3
1400
900
1.93–2.06
2000
-
4
1500
1000
2.07–2.18
2150
1
4
1600
Specifications
Characteristics
Active ingredient
Capecitabine
Adults
Can
Country of manufacture
Cyprus
Diabetics
With caution
Dosage
150 мг
Drivers
With caution, weakness and dizziness are possible.
For allergies
With caution
For children
It is impossible.
Form
Film-coated tablets
Method of application
Inside, solid
Nursing
It is impossible.
Pregnant
It is impossible.
Primary packaging
blister
Producer
Mistral Capital Management
Quantity per package
60 pcs
Trade name
Kapevista
Vacation conditions
By prescription
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