Capecitabine

When ATH:
L01BC06

Characteristic.

Antimetaʙolit, fluoropyrimidine carbamate derivative, molecular weight 359,35, растворимость в воде — 26 mg/ml at 20° c.

Pharmacological action.
Antitumor.

Application.

Mammary cancer (Locally advanced or metastatic). Monotherapy — the ineffectiveness of chemotherapy drugs from the Group taksanov (paclitaxel) or anthracyclines, or with contraindications to chemotherapy with anthracyclines. Combination therapy with Docetaxel is the ineffectiveness of chemotherapy, including drugs anthracyclines. Colon cancer (metastasizing).

Contraindications.

Hypersensitivity (incl. to fluorouracil or other fluoropyrimidines history), severe renal insufficiency (Cl creatinine below 30 ml / min), dihydropyrimidine dehydrogenase deficiency; combined treatment with docetaxel should be considered a contraindication to the use of docetaxel.

Restrictions apply.

CHD, giperʙiliruʙinemija, liver metastases in violation of its function, the elderly or children's age (to 18 years).

Pregnancy and breast-feeding.

Contraindicated in pregnancy.

Category actions result in FDA - D. (There is evidence of the risk of adverse effects of drugs on the human fetus, obtained in research or practice, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk, if the drug is needed in life-threatening situations or severe disease, when safer agents should not be used or are ineffective.)

At the time of treatment should stop breastfeeding.

Side effects.

From the nervous system and sensory organs: more than 2% patients-fatigue, headache, paresthesia, weakness, asthenia, dizziness, taste disturbance, peripheral neuropathy, insomnia, drowsiness, increased lacrimation, conjunctivitis, eye irritation; less than 2% -confusion, encephalopathy, cerebellar symptoms (ataxia, dysarthria, impaired balance and coordination).

Cardio-vascular system (hematopoiesis, hemostasis): more than 2% patients-anemia; less than 2% patients — cardialgia, cardiomyopathy, angina, myocardial ischemia, myocardial infarction, heart failure, sudden death, tachycardia, supraventricular arrhythmia (including atrial fibrillation), ventricular premature beats, Hypo- or hypertension, tromboflebit, phlebitis; bone marrow depression, pancytopenia.

From the respiratory system: more than 2% patients is shortness of breath, cough, sore throat; rarely, bronchospasm, dyspnoea, respiratory distress syndrome, embolism pulmonary vascular.

From the digestive tract: more than 2% patients-diarrhoea, nausea, vomiting, stomatitis, abdominal pain, epigastric, constipation, anorexia, decreased appetite, dyspepsia, dry mouth, flatulence, violation of stool consistency (upholstered chairs), oral candidiasis, giperʙiliruʙinemija; less than 2% patients-ulcerous defeat of inflammatory mucous membranes (esophagitis, gastritis, duodenitis, colitis, gastrointestinal bleeding). There are cases of hepatic failure and cholestatic hepatitis (their causal relationship to the use of capecitabine is not installed).

On the part of the musculoskeletal system: more than 2% monotherapy patients and more than 5% patients in the treatment in combination with Docetaxel is a pain in the limbs, myalgia, arthralgia, lower back pain, lower extremity edema.

For the skin: more than 2% patients-Palmar-Plantar syndrome (numbness, paraesthesia, pricking, swelling, redness, peeling, blistering and a sharp pain), dermatitis, xerosis, erythematous rash, alopecia, itch, patchy peeling, giperpigmentatsiya, nail infections; less than 2% patients-cracked skin, photosensitivity, syndrome, reminiscent of radiation dermatitis, onixolizis, brittleness, obestsvechivanie dystrophy and nogtey.

Other: less than 2% patients-infection amid mielosupression, weakening of the immune system and compromising the integrity of the mucous membranes (Bacterial, viral and fungal; local and systemic, fatal), sepsis; chest pain, changes in the level of ALT, IS, giperglikemiâ; more than 5% patients in the treatment in combination with docetaxel-dehydration, weight loss; very rarely is a nasolacrimal Canal stenosis, nose bleed.

Cooperation.

In combination with cyclophosphamide may increase cytotoxicity (in tumor tissue is increased thymidine phosphorylase activity). In simultaneous reception with anti kumarinovyh (warfarin and phenprocoumon) indicators of possible violations of clotting and bleeding (occurred within a few days to several months after initiation of therapy with capecitabine, in one case, a month after its completion). Increasing the concentration of phenytoin plasma. Antacids, hydroxides containing aluminum and magnesium, increase the concentration of capecitabine and 5′-DFCR plasma. Sorivudin and increase the toxicity of fluoropyrimidine analogs (inhibit dihydropyrimidine dehydrogenase). Calcium folinate, paclitaxel, docetaxel does not affect the pharmacokinetic properties of capecitabine and its metabolites.

Overdose.

Symptoms: nausea, vomiting, diarrhea, mukozit, gastrointestinal irritation and bleeding, suppression of bone marrow function.

Treatment: symptomatic.

Dosing and Administration.

Inside, drinking water, through 30 min after meal (not later than). The average daily intake is 2500 mg / m², in 2 admission (in the morning and in the evening), during 2 Sun. After a week break, repeat the course. In combination with Docetaxel is on 1250 mg / m² 2 twice a day for 2 Sun, break 1 Sun (Docetaxel — I / infuzionno within 1 h dose 75 mg / m² 1 once every 3 Sun).

The daily dose of capecitabine is calculated on a body surface area. When body surface area of ​​less than 1,26 m² total daily dose is 3000 mg; 1,27-1.38 M² - 3300 mg; 1,39-1.52 M² - 3600 mg; 1,53-1.66 M² - 4000 mg; 1,67-1.78 M² - 4300 mg; 1,79-1.92 M² - 4600 mg; 1,93-2.06 M² - 5000 mg; 2,07-2.18 M² - 5300 mg; more 2,19 m² - 5600 mg. In patients with mild renal insufficiency (CL creatinine is 30-50 mL/min) or manifestations of toxicity reduce the dose 75 and 50% as the initial monotherapy, and combination therapy.

Precautions.

During treatment requires careful medical supervision for timely detection of signs of toxicity (diarrhea, nausea, stomatitis, neutropenia, and others.). If you have any toxic symptoms, depending on their severity, perhaps symptomatic therapy, dose reduction, a break in treatment or elimination. Toxicity I level includes a small clinical manifestation of side effects; (II) extent of diarrhea (4-6 Times a day or a night chair), the appearance of painful reddening, swelling of the hands and / or feet in violation of the patient's activities of daily living, hyperbilirubinemia 1,5 times the upper limit of normal; 3rd degree-diarrhea (7-9 Times per day, fecal incontinence, or malabsorption syndrome), moist desquamation, izayazvlenie, blistering, sharp pains in the hands and / or feet, dramatically reducing daily activity and performance of the patient, hyperbilirubinemia 1.5-3 times upper limit of normal; 4th degree-diarrhea (more 10 once a day, the presence of blood in the stool, the need for parenteral therapy), hyperbilirubinemia 3 or more times the upper limit of normal.

When alone in the development of I degree of toxicity dose adjustment is required either in the current, nor subsequent therapy cycles. When the toxicity of II degree capecitabine should be interrupted until reducing the severity of adverse events to the extent I; resume treatment at a dose of 100, 75 and 50% recommended during the first, the second and third signs of toxicity of this degree, respectively. When the fourth appearance — therapy ceased and will not resume. With the development of signs of toxicity level III treatment is interrupted; while reducing the side effects to the extent I welcome resumed at a dose of, component 75% previous; the second appearance of signs of toxicity is 50% the recommended dose; in the third appearance — therapy overturned. If signs of toxicity grade IV treatment should be discontinued; while reducing the side effects to the extent I welcome resumed at a dose of, component 50% previous. If the dose was reduced, can not subsequently increase it, When I miss a reception — dose not filled.

In the case of toxicity in combination therapy adjust the dose of capecitabine and docetaxel is carried out on the general principles. If any toxic effects are not serious or life-threatening (alopecia, change in taste, nail changes), Treatment can be continued at the same dose. At the beginning of each cycle of therapy, if the expected delay in the introduction of docetaxel or capecitabine, you need to postpone the introduction until, until you can resume therapy with both drugs. If you have to cancel docetaxel, capecitabine treatment can be continued in accordance with the requirements for the resumption of capecitabine.

In patients with mild to moderate hepatic impairment, induced liver metastases, with mild renal insufficiency (Creatinine CL 51-80 mL/min) correction of the initial dose is required.

Against the background of ischemic heart disease during treatment should be carefully monitored, aimed at identifying signs of cardiotoxicity (manifested ECG changes, possible myocardial infarction, angina, arrhythmia, cardiogenic shock, cardiac arrest, heart failure). Patients with liver metastases require laboratory monitoring of its functions. It will be appreciated, that increases with age sensitivity to the toxic effects of 5-FU.

It should refrain from the use in pediatric practice, because the safety and efficacy of the use of children to be determined.

Women of childbearing age during treatment should use reliable methods of contraception. If pregnancy occurs during treatment, the patient should be warned of the possible danger to the fetus.

Be wary appoint patients with renal insufficiency. In patients with moderate renal insufficiency (CL creatinine 30-50 mL/min) the incidence of adverse side effects III-IV severity above.

To use caution in patients, engage in potentially hazardous activities, requiring concentration and speed of psychomotor reactions.

Patients, at the same time receiving Capecitabine and oral anticoagulants-coumarin derivatives, you must carefully monitor the performance of bleeding (prothrombin time) and adjust the dose of anticoagulant.

Cautions.

In combination therapy with docetaxel in the treatment of hematologic toxicity symptoms can be resumed only after the, as the neutrophil count exceeds 1500 / l (grade 0-I). The dose of docetaxel should be reduced 75 to 55 mg / m² in patients with neutropenia grade IV (less 500 cells 1 l) of more than 1 Sun or febrilynoy neytropeniey. If neutropenia IV degree or neutropenia develops during treatment with docetaxel in a dose 55 mg / m², it should be abolished. Patients with baseline neutrophil count of less than 1,500 cells / mm or with a platelet count less than 100,000 / ml should not be treated with combination therapy with capecitabine and docetaxel. With the development of severe hypersensitivity reactions to stop the use of drugs and prescribe appropriate therapy. The first signs of peripheral neuropathy (II) toxicity the dose reduced to docetaksela 55 mg / m², when a degree of toxicity III docetaxel cancel. It is necessary to carefully monitor such heavy (III или IV степени) toxicity effects, possibly related to docetaxel, as the pleural or pericardial effusion or ascites. When they appear docetaxel should be abolished, capecitabine treatment can be continued without dose modification. Docetaxel should not be administered to patients with bilirubin levels, exceeds the upper limit of normal. The dose of docetaxel is corrected by increasing the activity of ALT, IS Gospel ЩF.

Degidrataciю (can quickly develop in patients with anorexia, asthenia, toshnotoy, vomiting or diarrhea) should prevent or eliminate at source. With the development of dehydration of II degree or higher capecitabine treatment should be immediately interrupted and rehydration hold. Treatment can not reopen until the completion of rehydration and removal or correction factors to cause it.

Cooperation