Xeloda - a drug with antitumor action.
Release form and composition
Xeloda is produced in the form of film-coated tablets: oblong, biconvex, with the inscription "XELODA" on one side and "150" or "500" on the other:
- 150 mg: 60 pcs. in plastic bottles, 1 bottle in a carton box; on 10 pieces in blisters, 6 blisters in a carton box;
- 500 mg: 120 pcs. in plastic bottles, 1 bottle in a carton box; on 10 pieces in blisters, 12 blisters in a carton box).
The composition of 1 tablet includes:
- Active ingredient: capecitabine - 150 or 500 mg;
- Auxiliary components (respectively): lactose - 15.6 / 52 mg; microcrystalline cellulose - 7.2 / 24 mg; croscarmellose sodium - 6/20 mg; Hypromellose (3 mPa.s) - 4.5 / 15 mg, magnesium stearate - 2.7 / 9mg.
- 150 mg tablets (light milky pink): Opadry pink 03A14309 - 8.5 mg;
- Tablets of 500 mg (milky-pink): Opadry pink 03A14380 - 18 mg.
Indications for use
- Breast cancer: monotherapy with metastatic or locally advanced breast cancer, resistant to chemotherapy with taxanes or anthracycline drugs, or when contraindicated;
- Breast cancer: combined treatment with metastatic docetaxel or locally advanced breast cancer, with the ineffectiveness of chemotherapy, including anthracycline drugs;
- Stomach cancer: first line treatment of advanced stomach cancer;
- Colorectal cancer: adjuvant treatment of colon cancer stage III after surgical treatment;
- Colorectal cancer: treatment of metastatic colorectal cancer.
- The presence of contraindications to one of the drugs combination therapy;
- The initial content of neutrophils is less than 1.5 × 109 / l and / or platelet count is less than 100 × 109 / l;
- Renal failure severe (creatinine clearance below 30 ml per minute);
- Established dihydropyrimidine dehydrogenase (DPD) deficiency;
- Simultaneous administration with sorivudin and its structural analogues of the brivudin type;
- Children's age (safety and efficacy of the drug for this age group of patients have not been established);
- Pregnancy and lactation (breastfeeding);
- Hypersensitivity to the components of the drug, as well as to fluorouracil or in registered cases of severe or unexpected adverse reactions to the treatment with fluorinated pyrimidine derivatives in the anamnesis.
Xeloda should be prescribed with caution in patients over 60 years of age, as well as in patients with the following diseases / conditions:
- Liver failure;
- Moderate renal failure;
- Coronary heart disease;
- Simultaneous use with coumarin row oral anticoagulants;
- Hereditary lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
Dosing and Administration
Kseloda should be taken orally, drinking water, no later than 30 minutes after eating.
With monotherapy for colorectal cancer, colon cancer and breast cancer, Xeloda is usually prescribed 2 times a day (in the morning and in the evening) at 1,250 mg / m2 for 14 days, followed by a break for 7 days.
In the treatment of breast cancer, Xeloda, as part of a combination therapy, is prescribed according to the same scheme simultaneously with docetaxel, which is used 1 time in 3 weeks at a dose of 75 mg / m2 as an intravenous infusion for 1 hour. Premedication should be carried out before the introduction of docetaxel.
As part of a combination therapy for colorectal cancer and stomach cancer, a single dose of Xeloda should be reduced to 800-1000 mg / m2. The drug is used 2 times a day for 14 days followed by a seven-day break or continuously for 625 mg / m2 2 times a day. Adding immunobiological drugs to combination therapy does not affect the dose of Xeloda.
Antiemetics and premedication are prescribed before the administration of oxaliplatin and cisplatin according to the instructions for their use.
When conducting adjuvant treatment of colon cancer stage III, the recommended duration of Xeloda treatment is 6 months (i.e. 8 courses).
Xeloda in combination with cisplatin is usually prescribed 2 times a day at 1000 mg / m2 for 14 days, followed by a break of 7 days. Cisplatin is administered as an intravenous infusion over 2 hours 1 time every 3 weeks at 80 mg / m2 (the first infusion should be performed on the first day of the cycle).
In combination with bevacizumab and / or oxaliplatin, Xeloda is prescribed 2 times a day at 1000 mg / m2 for 14 days, followed by a seven-day break. The first dose of Xeloda should be taken in the evening on the first day of the therapy cycle, the last - in the morning on the 15th day. Bevacizumab is administered intravenously by infusion over a period of 30-90 minutes at a dose of 7.5 mg / kg every 3 weeks. The first infusion should be performed on the first day of the cycle. After bevacizumab, oxaliplatin in a dose of 130 mg / m2 is administered intravenously for 2 hours.
Simultaneously with epirubicin and a platinum-based drug, Xeloda is prescribed in a continuous mode of 625 mg / m2 2 times a day. Starting from the first day of the cycle, epirubicin is administered intravenously with a bolus of 1 every 3 weeks at 50 mg / m2. The drug based on platinum (oxaliplatin 130 mg / m2 or cisplatin 60 mg / m2) must be administered on the first day of the cycle as an intravenous infusion over 2 hours, then 1 time in 3 weeks.
Xeloda in combination with irinotecan is taken 2 times a day at 1000 mg / m2 for 14 days, followed by a seven-day break. Irinotecan is administered intravenously by infusion over 30 minutes at a dose of 250 mg / m2 once every 3 weeks. The first infusion is prescribed on the first day of the cycle.
Xeloda simultaneously with bevacizumab and irinotecan is prescribed 2 times a day at 800 mg / m2 for 14 days, followed by a seven-day break. Irinotecan is administered intravenously by infusion over 30 minutes at a dose of 200 mg / m2 1 time in 3 weeks. Bevacizumab is also administered intravenously by infusion over 30-90 minutes every 3 weeks at a dose of 7.5 mg / kg. The first infusion of bevacizumab and irinotecan is prescribed on the first day of the cycle.
Toxic effects of Xeloda can be eliminated by symptomatic treatment and / or correction of its dose (by reducing the dose of the drug or interrupting treatment). After lowering the dose, it can not be subsequently increased.
If, according to the doctor's assessment, the toxic effect of Xeloda is not serious or life threatening for the patient, the therapy can be continued in the initial dose without reducing or interrupting the therapy.
The patient should immediately inform the doctor about the appearance of undesirable symptoms. If, due to toxic effects, several methods of the drug were missed, they are not filled.
Therapy must be interrupted when there are signs of hematological toxicity of grade 3-4.
In patients with liver metastases and moderate or mild abnormal liver function, a change in the initial dose of Xeloda is not required. However, these patients must be carefully monitored.
Patients of elderly and senile age do not need to adjust the initial dose with monotherapy.
When using Xeloda as a monotherapy, the following disorders may develop:
- Nervous system: often - paresthesia, dizziness (except vertigo), headache, dysgeusia (taste perversion);
- Gastrointestinal tract: very often - vomiting, diarrhea, nausea, abdominal pain, stomatitis (including ulcerative); often - epigastric pain, constipation, dyspepsia;
- Organ of vision: often - conjunctivitis, increased tearing;
- Metabolism and nutrition: very often - anorexia; often - loss of appetite, dehydration;
- Laboratory indicators: often - hyperbilirubinemia;
- Skin and subcutaneous tissues: very often - dermatitis, palmar and plantar syndrome (edema, paresthesia, peeling of the skin, hyperemia, blistering); often - alopecia, rash, dry skin, erythema; skin cracks are also possible;
- General disorders: very often - drowsiness, fatigue; often - weakness, fever, asthenia.
The manifestations of toxicity known for treatment with fluoropyrimidines include:
- Nervous system: insomnia, taste disturbance, encephalopathy, confusion, cerebellar symptoms (dysarthria, ataxia, impaired coordination and balance);
- Cardiovascular system: cardialgia, including angina, edema of the lower extremities, myocardial ischemia, cardiomyopathy, ventricular extrasystoles, myocardial infarction, tachycardia, heart failure, supraventricular arrhythmias, including atrial fibrillation, sudden death;
- Musculoskeletal system and connective tissue: myalgia, arthralgia, back pain;
- Respiratory system: cough, shortness of breath;
- Gastrointestinal tract: flatulence, dry mouth, adverse reactions associated with inflammation / ulceration of mucous membranes (colitis, gastritis, esophagitis, duodenitis, gastrointestinal bleeding);
- Parasitic and infectious diseases: infectious complications associated with weakening of the immune system, myelosuppression and / or mucosal integrity (fatal and local systemic infections of fungal, viral or bacterial etiology) and sepsis;
- Mind: depression;
- Lymphatic system and blood: myelosuppression, anemia, pancytopenia;
- Skin and subcutaneous tissues: photosensitivity reactions, focal peeling of the skin, itching, nail changes, skin hyperpigmentation, a syndrome resembling radiation dermatitis;
- Organ vision: eye irritation;
- Disturbances at the injection site and common disorders: chest pain (non-cardiac etiology), pain in the extremities, asthenia, increased drowsiness.
When conducting a combined treatment, the following side effects may additionally occur:
- Cardiovascular system: very often - high blood pressure, thrombosis / embolism;
- Nervous system: very often - peripheral sensory neuropathy, peripheral neuropathy, dysesthesia;
- Respiratory system: very often - sore throat, pharyngeal dysesthesia; often - dysphonia, nasal bleeding, rhinorrhea;
- Infectious diseases: often - oral candidiasis;
- The musculoskeletal system and connective tissues: very often - pain in the jaw;
- Nutrition and metabolism: very often - weight loss;
- Lymphatic system and blood: very often - febrile neutropenia, leukopenia;
- Disorders at the injection site and general disorders: very often - temperature intolerance; often - fever, pain.
With simultaneous use of Xeloda with other chemotherapeutic drugs, there have been frequent reports of cases of hypersensitivity reactions and ischemia / myocardial infarction.
Changes in laboratory parameters during therapy may manifest as reduced hemoglobin, the numbers of granulocytes, neutrophils, platelets and lymphocytes, and hyperbilirubinemia, hypercreatininemia, activity increasing alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), hyperglycemia, hyponatremia, hypo- - / hypercalcemia, hypokalemia.
During the post-marketing study of Xeloda, the following undesirable reactions were identified: very rarely - stenosis of the lacrimal tubule unspecified; very rarely, liver failure and cholestatic hepatitis.
It is necessary to carefully monitor the manifestations of toxicity in patients using Xeloda.
As a rule, most adverse events are reversible and do not require complete drug withdrawal, although dose adjustment or temporary withdrawal of the drug may be necessary.
During therapy, diarrhea can occur, sometimes severe. Standard antidiarrheal drugs should be prescribed as soon as possible for medical reasons. If necessary, may reduce the dose of the drug Xeloda.
Dehydration should be prevented or eliminated at the first sign of its occurrence. It most often occurs in patients with asthenia, anorexia, nausea, diarrhea, or vomiting. With the development of dehydration grade 2 or above, treatment is immediately interrupted and rehydration is performed.
The spectrum of cardiotoxicity when using Xeloda is similar to that when using other fluoropyrimidines. Symptoms are more common in patients with a history of coronary artery disease, and include cardiac arrest, myocardial infarction, arrhythmias, angina, heart failure, and ECG changes.
A manifestation of Xeloda skin toxicity is palmar-plantar syndrome. With the development of up to 2-3 degrees of therapy should be interrupted until the disappearance of symptoms or to reduce them to the first degree. When combined treatment with cisplatin simultaneously, vitamin B6 is not recommended for symptomatic or secondary prophylactic treatment of the palm-plantar syndrome.
Treatment should be interrupted in cases of development of hyperbilirubinemia more than 3 × VGN or increased activity of liver aminotransferases (ALT, ACT) more than 2.5 × VGN. You can resume therapy by reducing the level of bilirubin and the activity of hepatic aminotransferases below the specified limits.
With the simultaneous use of Xeloda with oral anticoagulants - coumarin derivatives, it is necessary to monitor the indicators of clotting and on the basis of this, select the dose of anticoagulant.
Patients who have such undesirable effects as weakness, dizziness or nausea should refrain from driving or other mechanisms.
In patients taking Xeloda simultaneously with coumarin anticoagulants (fenprocumon and warfarin), a violation of blood clotting and / or bleeding is possible.
At the same time taking Xeloda with phenytoin may increase the concentration of the latter in the blood plasma.
Terms and conditions of storage
Keep out of reach of children at temperature up to 30 ° C.
Shelf life - 3 years.