Xeloda, pills 500mg, 120pcs

Composition

1 tablet contains:

Active ingredients:

capecitabine 500 mg.

Auxiliary substances:

lactose – 52 mg,

microcrystalline cellulose-24 mg,

croscarmellose sodium-20 mg,

hypromellose (3 MPa. c) – 15 mg,

magnesium stearate-9 mg.

Shell composition:

opadray pink 03A14380 (hypromellose (6 MPa. c), talc, titanium dioxide (E171), iron oxide yellow dye (E172), iron oxide red dye (E172)) – 18 mg.

The blister contains 10 tablets.

There are 12 blisters in a cardboard box.

Pharmacological action

antitumor drug related 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.

Indications

combination therapy with docetaxel for locally advanced or metastatic breast cancer after failure of chemotherapy involving the drug antratsiklinovogo series;

monotherapy for locally advanced or metastatic breast cancer after failure of chemotherapy taxonomy or drugs antratziklinovogo number, or with contraindications to therapy with anthracyclines;

adjuvant therapy of colon cancer;

first-line therapy for metastatic colorectal cancer,

first-line therapy gastric cancer.

Use during pregnancy and lactation

The drug is contraindicated for use during pregnancy and lactation.

Reliable methods of contraception should be used during Xeloda therapy and for at least 3 months after it ends.

If pregnancy occurs during therapy, the patient should be aware of the potential threat to the fetus.

Contraindications

Set DPD deficiency (of digidropirimidindegidrogenazy), as for other torpedinidae;

simultaneous reception of sorivudine and its structural analogues of the type of brivudine;

renal failure severe (CC below 30 ml/min);

the initial contents of neutrophils < 1,5 × 109/l and/or platelets < 100 × 109/l;

in the presence of contraindications to one of the drugs combination therapy should not be prescribed the drug xeloda®; pregnancy;

the period of breastfeeding;

children’s age (efficacy and safety not established);

hypersensitivity to capecitabine or any other component of product;

hypersensitivity to fluorouracil or the registered cases of unexpected or severe adverse reactions to the treatment of derivatives of torpedinidae in history.

With caution:

the drug should be prescribed for CHD, moderate renal failure, hepatic insufficiency, concomitant use with coumarin-type oral anticoagulants, hereditary lactase deficiency, lactose intolerance, glucose-galactose malabsorption, and patients over the age of 60 years.

Side effects

Most common (10%): diarrhea, stomatitis, nausea, vomiting, palmar-plantar syndrome, increased fatigue, weakness, lethargy, increased drowsiness.

From the digestive system: diarrhea, vomiting, stomatitis (including ulcerative), lack of appetite, decreased appetite, abdominal pain, epigastric pain, constipation, dry mouth, dyspepsia, candidiasis of the oral cavity; in less than 5% of cases – flatulence, esophagitis, gastritis, duodenitis, colitis, hiccups, gastrointestinal bleeding; in isolated cases-liver failure and cholestatic hepatitis; their symptoms include: A causal relationship with the use of capecitabine has not been established.

Dermatological reactions: palmar-plantar syndrome (paresthesia, edema, hyperemia, peeling of the skin, blistering), dermatitis, dry skin, erythematous rash, erythema, alopecia, pruritus, focal peeling, hyperpigmentation of the skin, violation of the structure and discoloration of the nails, onycholysis; in less than 5% of cases – photosensitization reactions, a syndrome resembling radiation dermatitis, skin cracks.

From the central nervous system and peripheral nervous system: headache, sleep disorders (severe drowsiness, insomnia), paresthesia, dizziness, peripheral neuropathy; in less than 5% of cases – confusion, encephalopathy, cerebellar symptoms (ataxia, dysarthria, balance and coordination disorders), depression.

From the sensory organs: increased lacrimation, conjunctivitis, taste disorders; very rarely-stenosis of the lacrimal-nasal canal.

From the respiratory system: sore throat, shortness of breath, cough, nosebleeds, dysphonia.

Musculoskeletal disorders: arthralgia, myalgia.

From the cardiovascular system: edema of the lower extremities; in less than 5% of cases – cardialgia, angina pectoris, cardiomyopathy, myocardial ischemia, myocardial infarction, heart failure, sudden death, tachycardia, supraventricular arrhythmias, including atrial fibrillation, ventricular extrasystoles.

From the hematopoietic system: anemia, neutropenia, granulocytopenia, lymphocytopenia, thrombocytopenia; less than 5% of cases – pancytopenia.

From the laboratory parameters: (regardless of their association with capecitabine) – hyperbilirubinemia, increased ALT/AST activity, hypercreatininemia, increased alkaline phosphatase activity, hyperglycemia, hypo- / hypercalcemia, hypoalbuminemia, hyponatremia, hypokalemia.

From the body as a whole: fatigue, fever, weakness, dehydration, weight loss, lethargy, pain in the back; less than 5% of cases of infectious complications against the background of myelosuppression, weakening of immunity and the violation of the integrity of the mucous membranes, local and systemic (bacterial, viral and fungal), possibly with fatal sepsis.

Interaction

Capecitabine increases the effects of indirect anticoagulants, which can lead to clotting disorders and bleeding several days or months after the start of capecitabine therapy, and in one case-a month after its completion. Increases the AUC of warfarin by 57% and INR by 91%. Studies on the interaction of capecitabine and other drugs metabolized by the CYP2C9 isoenzyme have not been conducted. Caution should be exercised when prescribing capecitabine with these medications.

Capecitabine increases the concentration of phenytoin in plasma. It is assumed that it is based on the suppression of the CYP2C9 isoenzyme under the influence of capecitabine. In patients taking capecitabine concomitantly with phenytoin, it is recommended to regularly monitor the concentration of phenytoin in plasma.

Antacids containing aluminum and magnesium hydroxide slightly increase the concentrations of capecitabine and one metabolite (5′ – DFTT) in plasma; they do not affect the three main metabolites (5′-DFUR,5-FU and FBAL) of capecitabine.

Calcium folinate (leucovorin) does not affect the pharmacokinetics of capecitabine and its metabolites, and may increase the toxic effect of capecitabine. When capecitabine is co-administered with sorivudine and its analogues, a potentially fatal increase in fluoropyrimidine toxicity can occur due to the suppression of dihydropyrimidine dehydrogenase by sorivudine.

How to take, course of use and dosage

The drug is taken orally, washed down with water, no later than 30 minutes after a meal.

Standard dosage regimen When conducting monotherapy, Xeloda® is prescribed at a dose of 2500 mg / m2/ (1250 mg/m2 2, morning and evening) for 2 weeks, followed by a seven-day break. In combination therapy with docetaxel, Xeloda® is prescribed 1250 mg / m2 2 times / for 2 weeks, followed by a weekly break in combination with docetaxel at a dose of 75 mg/m2 1 time in 3 weeks.

Premedication is performed before use of docetaxel in accordance with the instructions for use of docetaxel.

In combination therapy with cisplatin, Xeloda® is prescribed at 1000 mg / m2 2 for 2 weeks, followed by a weekly break in combination with cisplatin (80 mg/m2 1 every 3 weeks, intravenous infusion for 2 hours). The first dose of Xeloda® is prescribed in the evening on the 1st day of the therapy cycle, the last-in the morning on the 15th day.

Overdose

Symptoms: nausea, vomiting, diarrhea, mucositis, gastrointestinal irritation and bleeding, and bone marrow suppression.

Treatment: perform symptomatic therapy.

Special instructions

Careful medical monitoring of toxicity should be performed in patients receiving Xeloda®therapy.

Most adverse events are reversible and do not require complete discontinuation of the drug, although it may be necessary to adjust the dose or temporarily discontinue the drug.

Diarrhea

Treatment with Xeloda may cause diarrhea, sometimes severe. Patients with severe diarrhea should be carefully monitored, and if dehydration develops, rehydration and replacement of electrolyte losses should be performed. Standard antidiarrheal medications (such as loperamide) should be prescribed as early as possible for medical reasons. If necessary, reduce the dose of Xeloda®.

Dehydration

Dehydration should be prevented or eliminated at the very beginning of its occurrence. Dehydration can quickly develop in patients with anorexia, asthenia, nausea, vomiting, or diarrhea.

If grade 2 or higher dehydration occurs, treatment with Xeloda® should be discontinued immediately and rehydration should be performed. Treatment should not be resumed until rehydration is complete and the underlying factors have been eliminated or corrected. The dose of the drug should be modified in accordance with the recommendations for adverse events leading to dehydration.

Toxicity

The cardiotoxicity spectrum of 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 a history of coronary artery disease.

In rare cases, unexpected severe toxicity events (e. g. stomatitis, diarrhea, neutropenia, and neurotoxicity) associated with 5-FU are due to insufficient dihydropyrimidine dehydrogenase (DPD) activity. Thus, it is impossible to exclude a link between reduced DPD activity and more pronounced, potentially fatal toxicity of 5-FU.

Skin toxicity of Xeloda® is manifested by the development of palmar-plantar syndrome (synonyms-palmar-plantar erythrodysesthesia or acral erythema caused by chemotherapy). The median time to development of toxicity in patients receiving Xeloda ® monotherapy is 79 days (ranging from 11 to 360 days), and the severity varies from grade 1 to grade 3. Palmar-plantar syndrome of the 1st degree does not interfere with the patient’s daily activity and is manifested by numbness, dysesthesia/paresthesia, tingling or redness of the palms and / or soles, discomfort. Palmar-plantar 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. Palmar-plantar syndrome of the 3rd degree is defined as wet desquamation, ulceration, blistering and sharp pain in the hands and / or feet, as well as severe discomfort that makes it impossible for the patient to perform any daily activities. If palmar-plantar syndrome of the 2nd or 3rd degree occurs, Xeloda® therapy should be interrupted until symptoms disappear or decrease to the 1st degree. If grade 3 syndrome occurs, subsequent doses of Xeloda should be reduced.

Vitamin B6 (pyridoxine) is not recommended for the symptomatic or secondary prophylactic treatment of palmar-plantar syndrome when Xeloda® is prescribed in combination with cisplatin, as it may reduce the effectiveness of cisplatin.

Hyperbilirubinemia

Xeloda may cause hyperbilirubinemia. If hyperbilirubinemia > 3x ULN or increased activity of hepatic aminotransferases (ALT, ACT) >>2.5 x ULN is observed in connection with treatment with Xeloda®, treatment should be discontinued.

Therapy can be resumed if the level of bilirubin and the activity of hepatic aminotransferases decreases below the specified limits.

Concomitant use with coumarin anticoagulants

In patients taking Xeloda® and coumarin – derived oral anticoagulants at the same time, coagulation parameters (prothrombin time or MHO) should be monitored and the dose of the anticoagulant adjusted accordingly.

Use of the drug in elderly and senile patients

The incidence of gastrointestinal toxicity in patients with colorectal cancer aged 60-79 years who received Xeloda ® monotherapy did not differ from that in the general patient population. Reversible gastrointestinal adverse events of grade 3 and 4, such as diarrhea, nausea, and vomiting, were more common in patients 80 years of age and older. Patients ≥ 65 years of age receiving combined therapy with capecitabine and other antitumor drugs showed an increase in the frequency of grade 3 and 4 adverse reactions and adverse events that led to discontinuation of therapy compared to patients younger than 65 years of age.

When analyzing safety data in patients ≥60 years of age who received combined therapy with Xeloda® and docetaxel, there was an increase in the frequency of treatment-related adverse events of 3rd and 4th severity, serious adverse events and early withdrawal of therapy due to adverse events compared to those in patients younger than 60 years.

Kidney failure

Caution should be exercised when prescribing Xeloda to patients with moderate renal insufficiency. As with treatment with fluorouracil, the incidence of treatment-related grade 3 and 4 adverse events was higher in patients with moderate renal insufficiency (creatinine clearance 30-50 ml / min).

Liver failure

Patients with hepatic insufficiency during therapy with Xeloda® should be under close medical supervision. The effect of impaired liver function, not due to metastatic liver damage or severe hepatic insufficiency, on the distribution of Xeloda® is unknown.

Additional information

Handling of an unused product or an expired product. The release of the medicinal product together with waste products into the environment should be kept to a minimum. Do not dispose of the product using waste water or together with household waste. If possible, it is necessary to use special systems for disposing of medicines.

Influence on the ability to drive vehicles and other mechanisms that require increased concentration of attention

Xeloda ® has a small or moderate effect on the ability to drive vehicles and mechanisms. Patients who have experienced such adverse events as dizziness, weakness or nausea should refrain from driving vehicles or mechanisms.

Form of production

Film-coated tablets.

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

3 years

Active ingredient

Capecitabine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets