Antitumor drug referring to antimetabolites and having in its composition a component that can be activated in the tumor tissue and have a selective cytotoxic effect on it. Combination therapy with docetaxeloma of localized or metastatic breast cancer in case of ineffectiveness of chemotherapy including the preparation of anthracycline type; Localized or metastatic breast cancer monotherapy, ineffective chemotherapy with taxanas or anthracyclines, or contraindications to the treatment with anthracyclines; adjuvant therapy for colon cancer; first-line metastatic colorectal cancer therapy; first-line treatment of common stomach cancer. The drug is contraindicated for use during pregnancy and lactation. Reliable methods of contraception should be used during Kselodic therapy and for at least 3 months after its completion. If the pregnancy occurs during the period of therapy, the patient should be aware of the potential threat to the fetus.
The established deficit of DPD (dihydropyrimidine dehydrogenase), as well as for other fluoropyrimidines; simultaneous administration of sorivudine and its structural analogues such as bryvudine; severe renal failure (QC below 30 ml/min); initial content of neutrophils in the presence of contraindications to one of the drugs of combined therapy should not prescribe a drug Kseloda ®; pregnancy; breastfeeding period; childhood (efficacy and safety of use are not established); hypersensitivity to capecitabine or any other components of the drug; hypersensitivity to fluororacil or in reported cases of development of unexpected or severe adverse reactions to treatment by fluoropyrimidine derivatives in the history. Caution: It is necessary to prescribe the drug in case of CHD, renal insufficiency of medium severity, hepatic insufficiency, concomitant use with oral anticoagulants of coumarin type, hereditary deficiency of lactase, lactose intolerance, glucose-galactosis malabsorption, patients over 60 years old.
The drug is taken inside, drinking water no later than 30 minutes after a meal. Standard mode of dosingThe monotherapy drug Kseloda is prescribed in a dose of 2500 mg/m2 / (1250 mg/m2 2, in the morning and evening) for 2 weeks, followed by a seven-day break. In combination therapy with docetaxel Kselodoux is prescribed 1250 mg/m2 2 times / for 2 weeks followed by a weekly break in combination with docetaxel in a dose of 75 mg/m2 1 time in 3 weeks. In combination therapy with cisplatinum, Kselodoux is prescribed 1000 mg/m2 2 for 2 weeks, followed by a weekly break in combination with cisplatinum (80 mg/m2 once every 3 weeks, infusion for 2 hours). The first dose of Kseloda is administered in the evening on the 1st day of the therapy cycle, the last dose is administered in the morning on the 15th day.
Kapecitabine enhances the effects of indirect anticoagulants, which can lead to impaired coagulation and bleeding a few days or months after the start of capecitabine therapy, and in one case - a month after its completion. Increases AUC warfarin by 57% and INR by 91%. Studies on the interaction of capecitabine and other drugs metabolized by CYP2C9 isoenzyme have not been conducted. Care should be taken when prescribing capecitabine with these drugs. Kapecitabine increases the concentration of phenytoin in plasma. It is supposed to be based on suppression of CYP2C9 isoenzyme under the influence of capecitabine. In patients taking capecitabine at the same time as phenytoin, it is recommended to regularly monitor the concentration of phenytoin in plasma. Antacids containing aluminum and magnesium hydroxide slightly increase the concentration of capecitabine and one metabolite (5'-DPCT) in plasma; they do not affect the three main metabolites (5'-DPFUR, 5'-PH and FBAL) of capecitabine. Calcium folinate (leukovorine) does not affect the pharmacokinetics of capecitabine and its metabolites, may increase the toxic effect of capecitabine. Simultaneous use of capecitabine with sorivudine and its analogues may potentially lead to fatal increase in fluoropyrimidine toxicity due to suppression of dihydropyrimidine dehydrogenase by sorivudine.
There should be careful medical monitoring of toxicity in patients receiving Kselodic therapy. Most adverse events are reversible and do not require complete withdrawal of the drug, although it may be necessary to correct the dose or temporarily cancel the drug. Treatment with Kseloda may cause diarrhea, sometimes severe. Patients with severe diarrhoea should be monitored closely and rehydration and electrolyte loss compensation should be provided when dehydration develops. Standard antidiarrhoeal drugs (e.g. loperamide) should be prescribed as soon as possible for medical reasons. If necessary, the dose of Kcelloda should be reduced. Dehydration should be prevented or eliminated at the very beginning of its occurrence. Dehydration can develop rapidly in patients with anorexia, asthenia, nausea, vomiting or diarrhoea. If dehydration of the 2nd degree or higher develops, Kcelloda treatment should be immediately interrupted and rehydration performed. Treatment cannot be resumed until rehydration is complete and the factors that caused it have been eliminated or corrected. The dose of the drug should be modified according to the recommendations for adverse events leading to dehydration. The spectrum of cardiotoxicity in capecitabine treatment is similar to that of other fluoropyrimidines and includes myocardial infarction, angina, arrhythmias, cardiac arrest, heart failure and ECG changes. These adverse events are more common in patients with history of CHD. In rare cases, unexpected severe toxicity events (e.g., stomatitis, diarrhoea, neutropenia and neurotoxicity) associated with 5-FI are due to insufficient activity of dihydropyrimidine dehydrogenase (DHA). Thus, the association between decreased activity of DPD and more pronounced, potentially lethal toxicity of 5-FI cannot be excluded. The development of palm-solar syndrome (synonyms - palm-solar erythrodysesthesia or acral erythema caused by chemotherapy) is a manifestation of skin toxicity of Kseloda drug. The median of time before the development of toxicity in patients receiving monotherapy with Kseloda is 79 days (in the range from 11 to 360 days), and the degree of severity varies from the 1st degree to the 3rd degree. Palm-solar syndrome of the 1st degree does not disrupt the daily activity of the patient and is manifested by numbness, dysesthesia/paresthesia, tingling or redness of the palms and/or soles, discomfort. Palm-solar syndrome of the 2nd degree is characterized by painful redness and swelling of the hands and/or feet, and the discomfort caused by these symptoms disrupts the daily activity of the patient. Palm-solar syndrome, 3rd degree, is defined as wet desquamation, ulceration, bubble formation and severe pain in the hands and/or feet, as well as severe discomfort that makes it impossible for the patient to carry out any daily activities. In the case of palm-solar syndrome of the 2nd or 3rd degree, Kseloda therapy should be discontinued until the symptoms disappear or are reduced to the 1st degree. Subsequent doses of Kcelloda should be reduced if third-degree syndrome occurs. Vitamin B6 (pyridoxine) is not recommended for symptomatic or secondary prophylactic treatment of the palm-solar syndrome when administered Kseloda in combination with cisplatinum, as it may reduce the effectiveness of cisplatinum. Hyperbilirubinemia Treatment can be resumed when bilirubin levels and liver aminotransferase activity are below these limits. Simultaneous administration with coumarin anticoagulants Patients taking Kseloda and oral anticoagulants (coumarin derivatives) at the same time should be monitored for clotting (prothrombin time or MHO) and a dose of the anticoagulant should be selected accordingly. Administration of the drug in elderly and senile patients Frequency of toxic phenomena on the part of gastrointestinal tract in patients with colorectal cancer at the age of 60-79 years, who received monotherapy with Kseloda®, did not differ from that in the general population of patients. In patients 80 years old and older reversible undesirable effects of gastrointestinal tract of the 3rd and 4th degree, such as diarrhoea, nausea and vomiting, developed more often. Patients ≥ 65 years of age who received combined therapy with capecitabine and other antitumor drugs showed an increase in the frequency of adverse reactions of the 3rd and 4th degree of severity and adverse events, which led to the termination of treatment compared to patients under 65 years of age. Safety data analysis of patients ≥60 years of age who received combined therapy with Kseloda and docetaxel showed an increase in the frequency of adverse events associated with therapy of the 3rd and 4th degree of severity, serious adverse events, and early cancellation of therapy due to adverse events compared to those of young patients