Xeloda pills 150mg №60

Packaging

60 pcs.

Mechanism of action

Xeloda is an anticancer drug for oral administration, a fluoropyrimidine carbamate derivative.
In vitro, Capecitabine does not have a cytotoxic effect. In vivo is activated in the tumor tissue and, turning into 5-fluorouracil (5-FU), has a selective cytotoxic effect. The formation of 5-FU occurs in the tumor tissue under the action of a tumor angiogenic factor — thymidine phosphorylase, which thus minimizes the systemic effect of 5-FU on the healthy tissues of the body. As a result of selective activation, the content of 5-FU in the tumor significantly exceeds its levels in healthy tissues.
To study the selective conversion of capecitabine into a tumor, a pharmacokinetic study was conducted comparing the concentrations of capecitabine in the tumor, healthy tissue, and plasma of patients with cancer of the rectum and rectum. After taking capecitabine orally (at a dose of 1255 mg / m² 2 times / day for 5-7 days before surgery) the concentration of 5-FU in the primary tumor was significantly higher than in the surrounding healthy tissues and in the plasma. Thymidine phosphorylase activity in the primary tumor is 4 times higher than in healthy tissue.Human tumors, such as cancer of the breast, stomach, cross-rectum and rectum, cervix and ovary, contain much more thymidine phosphorylase capable of converting 5-DFUR (5'-deoxy-5-fluorouridine) in 5-FU than in healthy tissues.
Efficacy in colon cancer. Data from 2 multicenter, randomized, controlled phase III studies conducted according to one plan confirm the possibility of using Xeloda as a drug of choice for metastatic cancer of the colon (colon and rectum). In these studies, 603 patients were randomly assigned to Xeloda treatment groups at a dose of 2510 mg / m²/ day for 2 weeks followed by a week-long break (three-week cycles), and the other 604 patients - for the treatment of 5-FU and leucovorin (Mayo scheme). The overall incidence of objective remission was 25.7% with Xeloda and 16.7% with Mayo treatment (p <0.0002). The median time to disease progression was 140 days with Xeloda and 144 days with the Mayo scheme, the median survival was 392 and 391 days, respectively.
Efficacy in breast cancer. The antitumor activity of Xeloda was evaluated in patients with stage IV breast cancer who had already received massive therapy and refractory to the previously conducted treatment with Paclitaxel. In addition, 41% of patients were resistant, and 26% had no effect from previous anthracycline therapy; 82% of patients have already received 5-FU. The primary criterion for the effectiveness of the study was an objective reduction in the size of the tumor (where they could be determined).Remission was considered to be a reduction in the amount of mutually perpendicular tumor diameters of not less than 50% for at least 1 month. Xeloda was administered at a daily dose of 2510 mg / m² for 2 weeks, then a week-long break was taken and the drug was again administered in three-week cycles.
The total frequency of objective remission in the analysis of all included patients (135 people) was 20% (27 remissions, including 3 complete ones). The median time to disease progression was 93 days, the median duration of remission was 241 days, and the median life expectancy was 384 days.
A prospectively calculated clinical response score (pain, need for analgesics, and Karnofsky general condition) was used to evaluate the effect of treatment. The total clinical response was 20% (29 patients). Of those patients in whom the initial pain syndrome was assessed on a visual analogue scale as exceeding 20 mm, 47% showed a positive dynamics of pain intensity (a decrease of 50% or more).

Indications and usage

- locally advanced or metastatic breast cancer with the ineffectiveness of Chemotherapy, including paclitaxel and anthracycline drug, or if there are contraindications to anthracycline therapy;
- first line metastatic colon cancer therapy.

Contraindications

Hypersensitivity to capecitabine or any other components of the drug.
Hypersensitivity to Fluorouracil or in cases of unexpected or severe adverse reactions to the treatment with a history of fluoropyrimidine derivatives.
Determined deficiency of DPD (dihydropyrimidine dehydrogenase), as well as for other fluoropyrimidines.
Simultaneous reception of sarivudin or its structural analogs of type brivudin.
Severe renal failure (creatinine clearance below 30 ml / min).
The original content of neutrophils <1.5 x 109 / l and / or platelet <100 x 109 / l.
If there are contraindications to one of the combination therapy drugs, it should not be used.
Pregnancy and lactation period.
Children's age (efficacy and safety have not been established).

Pregnancy and Breastfeeding

Do not use Xeloda during pregnancy. If the drug must be prescribed during pregnancy or if the pregnancy occurs in a patient who is already taking this drug, it should be warned about the possible danger to the fetus.
There are no clinical studies on the use of Xeloda during pregnancy, however, based on the pharmacological and toxicological characteristics, it can be assumed that Xeloda may have a damaging effect on the fetus.
Women of childbearing age should be advised to avoid pregnancy during treatment with Xeloda.
It is not known whether capecitabine and its metabolites are excreted in breast milk. Because of possible adverse reactions in infants, the use of a nursing mother should be avoided, unless the benefits of therapy for the mother exceed the potential risk to the baby.
ATexperimental studies Reproductiveness in animals: Capecitabine administration was accompanied by an increase in the death of embryos and teratogenic effects, which is the expected effect of fluoropyrimidine derivatives. Capecitabine should be considered potentially teratogenic for humans.
In a study with a single oral administration of Xeloda to lactating mice, a significant amount of capecitabine metabolites was found in their milk.

Inside, 30 minutes after a meal, in a daily dose of 2.5 g / sq.m / day (for 2 doses) for 2 weeks, followed by a break for 1 week. Calculation of the total daily dose depending on the surface of the body: less than 1.24 sq.m - 3 g, 1.25-1.36 sq.m - 3.3 g, 1.37-1.51 sq.m - 3.6 g, 1.52-1.64 sq.m - 4 g, 1.65 -1.76 m2 - 4.3 g, 1.77-1.91 m2 - 4.6 g, 1.92-2.04 m2 - 5 g, 2.05-2.17 m2 - 5.3 g, more than 2.18 m2 - 5.6. Manifestations of toxicity during treatment, symptomatic therapy and / or dose reduction can be eliminated. Changing the dose depending on the degree of toxic effects (Canadian classification of cytotoxicity): I Art. - Do not change the dose; II st. - at the first appearance of signs of toxicity, it is necessary to discontinue therapy until they disappear or diminish to I st. Treatment is resumed with 100% of the recommended dose; at the second appearance of signs of toxicity - from 75%, at the third appearance - from 50%; at the fourth appearance of signs of toxicity, the drug is canceled; III Art. - at the first appearance of signs of toxicity, it is necessary to discontinue therapy until they disappear or diminish to stage I. Treatment is resumed with 75% of the recommended dose; at the second appearance of signs of toxicity - from 50%; at the third appearance of signs of toxicity, the drug is canceled; IV Art. - the drug is canceled.

Adverse reactions

The incidence of adverse reactions is set out according to the following gradation: very often ≥1 / 10, often from ≥1 / 100 to <1/10, infrequently from ≥1 / 1000 to <1/100 and less than 5% of cases.
Metabolism: very often - anorexia; often - dehydration, loss of appetite.
Nervous system: often - headache, dizziness (except vertigo), paresthesia, dysgeusia (taste perversion).
On the part of the organ of vision: often - increased tearing, conjunctivitis.
From the digestive system: very often - diarrhea, vomiting, nausea, stomatitis (including ulcerative), abdominal pain; often - constipation, epigastric pain, dyspepsia.
From the skin: very often - palmar and plantar syndrome (paresthesia, edema, hyperemia, peeling of the skin, blistering), dermatitis; often - rash, alopecia, erythema, dry skin. In less than 2% of patients in 7 completed clinical studies (N = 949), skin cracks were reported, at least supposedly related to therapy with Xeloda.
Changes in laboratory parameters: often - hyperbilirubinemia.
Other: very often - increased fatigue, increased drowsiness; often - fever, weakness, asthenia.

Patients receiving Xeloda should be carefully monitored for toxicity. Most adverse events are reversible and do not require constant discontinuation of the drug, although it may be necessary to reduce its dose or temporarily interrupt the administration.
The spectrum of cardiotoxicity in the treatment of Xeloda is similar to that of other fluoropyrimidines, and includes ECG changes, myocardial infarction, angina pectoris, arrhythmias, cardiac arrest and heart failure. These adverse events are more common in patients with coronary artery disease.
In rare cases, unexpectedly severe toxic effects associated with 5-FU in the form of stomatitis, diarrhea, neutropenia and neurotoxicity due to insufficient dihydropyrimidine dehydrogenase (DPD) activity are observed.
In patients with moderately severe renal insufficiency (creatinine clearance 30-50 ml / min), as in the treatment of 5-FU, the incidence of adverse events 3 and 4 severity is higher, therefore, in the appointment of Xeloda such patients should be careful.
Treatment with Xeloda can cause diarrhea, sometimes severe. The median time to the first signs of diarrhea 2-4 degrees was 31 days. Patients with severe diarrhea should be carefully monitored, taking them to replace fluids and electrolytes in the event of dehydration. When diarrhea of ​​grade 2, 3 and 4 occurs, Xeloda should be discontinued until diarrhea disappears or its intensity decreases to grade 1.In case of diarrhea grade 3 and 4, treatment with Xeloda should be resumed with a decrease in dose. It is recommended to prescribe standard antidiarrheal drugs (for example, loperamide).
The frequency of toxic effects of the gastrointestinal tract in patients aged 60-79 years was the same as in the general population of patients. In patients 80 years and older, reversible gastrointestinal disorders of grade 3 and 4, such as diarrhea, nausea and stomatitis, developed more frequently.
Xeloda can cause the development of hand-plantar syndrome (syn. - palmar-plantar erythrodestestosis, or acral erythema caused by chemotherapy), which is a manifestation of skin toxicity (median time to development - 79 days, range from 11 to 360 days), severity which varies from 1 to 3. In case of 2 or 3 degrees of palmar and plantar syndrome, the use of Xeloda should be interrupted until the symptoms disappear or their reduction to 1 degree; in grade 3 syndrome, subsequent doses of Xeloda should be reduced.
With an increase in the level of bilirubin in serum 2-4 degrees, Xeloda should be immediately discontinued until hyperbilirubinemia disappears or decreases to 1 degree.
Patients with impaired liver function should be carefully monitored. The impact of liver damage, not caused by metastases to the liver, as well as severe liver failure on the distribution of Xeloda has not been studied. In patients taking coumarin anticoagulants and capitsetabin, it is necessary to regularly monitor clotting parameters.
Use in pediatrics
The safety and effectiveness of Xeloda in children has not been studied.

Xeloda has a low potential for pharmacokinetic interactions, because it binds poorly to serum proteins, and neither capecitabine nor its metabolites suppress or stimulate the activity of isoenzymes P₄₅₀ in vitro and in vivo in animals.
With the simultaneous use of capecitabine with indirect anticoagulants (such as Warfarin and fenprocoumon), a violation of coagulation and bleeding indices is described. They occurred within a few days - a few months from the start of therapy with capecitabine, and in one case - a month after its completion.
With simultaneous use of capitsetabin and phenytoin, an increase in the concentration of phenytoin in plasma is described, as a result of which regular monitoring of the latter is recommended.
With the combined use of Xeloda with antacids containing aluminum and Magnesium hydroxides, there was a slight increase in the concentrations of capecitabine and one metabolite (5'-DFCR) in plasma; they did not affect the three main metabolites (5'-DFUR, 5-FU and FBA).
With simultaneous use of leucovorin does not affect the pharmacokinetics of capecitabine and its metabolites.
When combined, capecitabine does not affect the pharmacokinetics of paclitaxel, and paclitaxel does not have a clinically significant effect on the pharmacokinetics of capecitabine.
The literature describes a clinically significant interaction between sorivudine and 5-FU, arising from the suppression of dihydropyrimidine dehydrogenase sorivudine.This leads to increased toxicity of fluoropyrimidines, potentially fatal. Therefore, Xeloda should not be prescribed with sorivudin or its chemical analogues, such as brivudin.

In clinical studies, there were no cases of Xeloda overdose.
Symptoms Given the experience of prescribing the maximum tolerated dose (3514 mg / m²/ day), it can be expected that acute overdose will be manifested by nausea, vomiting, diarrhea, bleeding, as well as bone marrow suppression.
Treatment: conduct supportive symptomatic therapy. It is possible to lower the concentration of 5'-DFUR, a low-molecular metabolite of the drug, using dialysis.

The drug should be stored at a temperature not exceeding 30 ° C out of the reach of children.

2 years.