Xeloda, 500 mg 120 pcs

Antitumor drug related to antimetabolites with a component capable of activating in tumor tissue and exerting a selective cytotoxic effect on it.

Indications

combination therapy with docetaxel for locally advanced or metastatic breast cancer, if chemotherapy including an anthracycline drug is ineffective;

monotherapy for locally advanced or metastatic breast cancer, if chemotherapy with taxanes or anthracyclines is ineffective, or if there are contraindications to therapy with anthracyclines;

Adjuvant therapy for colorectal cancer;

First-line therapy for metastatic colorectal cancer;

First-line therapy for advanced gastric cancer.

Active ingredient

Composition

1 tablet contains:

Active substances:

capecitabine 500 mg.

Associates:

Lactose – 52 mg,

Microcrystalline cellulose – 24 mg,

croscarmellose sodium – 20 mg,

hypromellose (3 mPa.c) – 15 mg,

magnesium stearate – 9 mg.

Shell contents:

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

There are 10 tablets in the blister.

There are 12 blisters in the carton pack.

How to take, the dosage

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

The standard dosing regimenIn monotherapy Xeloda® is administered in a dose of 2500 mg/m2 / (1250 mg/m2 2, in the morning and in the evening) for 2 weeks, followed by a 7-day break. In combination therapy with docetaxel Xeloda® is administered at a dose of 1250 mg/m2 2 times / for 2 weeks followed by a one-week break in combination with docetaxel at a dose of 75 mg/m2 once every 3 weeks.

Premedication is administered prior to administration of docetaxel according to the docetaxel administration instructions.

In combination therapy with cisplatin, Xeloda® is administered at 1000 mg/m2 2 for 2 weeks followed by a 1-week break in combination with cisplatin (80 mg/m2 once every 3 weeks, IV infusion for 2 h). The first dose of Xeloda® is given in the evening on day 1 of the therapy cycle and the last dose on the morning of day 15.

Interaction

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

Capecitabine increases the plasma concentration of phenytoin. It is thought to be based on inhibition of the CYP2C9 isoenzyme by capecitabine. In patients taking capecitabine concomitantly with phenytoin, it is recommended to monitor the plasma concentration of phenytoin regularly.

The antacids containing aluminum and magnesium hydroxide slightly increase plasma concentrations of capecitabine and one metabolite (5′-DFCT); the three major metabolites (5′-DFUR, 5-FU and FBAL) of capecitabine are not affected.

Calcium folinate (leucovorin) does not affect the pharmacokinetics of capecitabine and its metabolites; it may increase the toxic effect of capecitabine. When capecitabine is used concomitantly with sorivudine and its analogues, a fatal increase in fluoropyrimidine toxicity may potentially occur due to inhibition of dihydropyrimidine dehydrogenase by sorivudine.

Special Instructions

Careful medical monitoring of toxicity in patients treated with Xeloda® is necessary.

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

Diarrhea

The treatment with Xeloda® may cause diarrhea, sometimes severe. Patients with severe diarrhea should be monitored closely, and rehydration and reimbursement of electrolyte loss should be performed if dehydration develops. Standard antidiarrheals (e.g., loperamide) should be given as soon as medically necessary. The dose of Xeloda® should be reduced if necessary.

Dehydration

Dehydration should be prevented or managed at the onset. Dehydration can occur quickly in patients with anorexia, asthenia, nausea, vomiting, or diarrhea.

If dehydration of grade 2 or higher develops, treatment with Xeloda® should be stopped immediately and rehydration should be performed. Treatment should not be resumed until rehydration has been completed and the underlying factors have been eliminated or corrected. The dose of the drug should be modified according to the recommendations for adverse events that led to dehydration.

Toxicity

The spectrum of cardiotoxicity with treatment with capecitabine is similar to that with other fluoropyrimidines and includes myocardial infarction, angina pectoris, arrhythmias, cardiac arrest, heart failure and ECG changes. These adverse events are more common in patients with a history of CHD.

In rare cases, unexpected severe toxicities (e.g., stomatitis, diarrhea, neutropenia, and neurotoxicity) associated with 5-FU are due to insufficient activity of dihydropyrimidine dehydrogenase (DPD). Thus, a link between reduced DPD activity and the more pronounced, potentially lethal toxicity of 5-FU cannot be ruled out.

The manifestation of cutaneous toxicity of Xeloda® is the development of palmar-todermal syndrome (synonyms: palmar-todermal erythrodysesthesia or chemotherapy-induced acral erythema). The median time to development of manifestations of toxicity in patients treated with Xeloda® monotherapy is 79 days (range, 11 to 360 days), and the severity ranges from grade 1 to grade 3. Grade 1 palm plantar syndrome does not interfere with the daily activities of the patient and is manifested by numbness, dysesthesia/paresthesias, tingling or redness of the palms and/or soles, and discomfort. Grade 2 palm plantar syndrome is characterized by painful redness and swelling of the hands and/or feet, and the discomfort caused by these symptoms disrupts the patient’s daily activities. Grade 3 palm-todermal syndrome is defined as moist desquamation, ulceration, blistering and severe pain in the hands and/or feet, as well as severe discomfort that makes it impossible for the patient to perform any activities of daily living. If palmar-todermal syndrome of grade 2 or 3 occurs, therapy with Xeloda® should be interrupted until the symptoms disappear or are reduced to grade 1. If grade 3 syndrome occurs, subsequent doses of Xeloda should be reduced.

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

Hyperbilirubinemia

The drug Xeloda® may cause hyperbilirubinemia. If Xeloda® treatment causes hyperbilirubinemia >3 × HGH or increased hepatic aminotransferase activity (ALT, ACT) >2.5 × HGH, treatment should be discontinued.

The therapy can be resumed when bilirubin levels and hepatic aminotransferase activity decrease below these limits.

Simultaneous 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 anticoagulant dose should be adjusted accordingly.

The use of drug in elderly patients

The incidence of gastrointestinal toxic events in patients with colorectal cancer aged 60-79 years treated with Xeloda® monotherapy did not differ from that in general population of patients. In patients aged 80 years and older, reversible adverse GI events of grade 3 and 4, such as diarrhea, nausea, and vomiting, developed more frequently. In patients ≥65 years old who received combined therapy with capecitabine and other anticancer drugs, there was 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 old.

In an analysis of safety data in patients ≥60 years of age receiving combination therapy with Xeloda® and docetaxel, there was an increased incidence of therapy-related Grade 3 and 4 adverse events, serious adverse events, and early therapy withdrawal due to adverse events compared to those in patients less than 60 years of age.

Renal impairment

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

Hepatic impairment

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

Preliminary information

Handling of unused and expired drug. The release of the medication into the environment with waste should be kept to a minimum. The drug should not be disposed of with wastewater or with household waste. If possible, special systems should be used to dispose of medication.

Impact on the ability to drive vehicles and other mechanisms requiring high concentration

The drug Xeloda® has little or moderate effect on the ability to drive vehicles, mechanisms. Patients who have had such adverse events as dizziness, weakness or nausea should refrain from driving or operating machinery.

Contraindications

DPD (dihydropyrimidine dehydrogenase) deficiency is established, as for other fluoropyrimidines;

concomitant administration of sorivudine and its structural analogues like brivudine;

Heavy renal insufficiency (CK below 30 ml/min);

baseline neutrophil count < 1.5 × 109/L and/or platelets < 100 × 109/L;

if there are contraindications to one of the drugs in combination therapy, Xeloda® should not be administered; pregnancy;

breastfeeding period;

childhood (efficacy and safety of use not established);

hypersensitivity to capecitabine or any other component of the drug;

hypersensitivity to fluorouracil or a history of unexpected or severe adverse reactions to treatment with fluoropyrimidine derivatives.

With caution:

The drug should be administered in CHD, moderate renal failure, hepatic failure, concomitant use with oral coumarin-type anticoagulants, hereditary lactase deficiency, lactose intolerance, glucose-galactose malabsorption, patients aged over 60 years.

Side effects

Most common (10%): diarrhea, stomatitis, nausea, vomiting, palm syndrome, increased fatigue, weakness, lethargy, increased somnolence.

Digestive system disorders: diarrhea, vomiting, stomatitis (including ulcerative), lack of appetite, decreased appetite, abdominal pain, epigastric pain, constipation, dry mouth, dyspepsia, oral candidiasis; in less than 5% of cases – flatulence, esophagitis, gastritis, duodenitis, colitis, hiccups, gastrointestinal bleeding; in single cases – liver failure and cholestatic hepatitis; their causal relationship with capecitabine use is not established.

Dermatological reactions: Palmar and plantar syndrome (paresthesias, edema, hyperemia, skin flaking, blistering), dermatitis, dry skin, erythematous rash, erythema, alopecia, itching, focal skin flaking, hyperpigmentation of skin, nail structure and discoloration, onycholisis; less than 5% cases, photosensitization reactions, radiation dermatitis-like syndrome, skin cracking.

CNS and peripheral nervous system disorders: headache, sleep disturbance (marked somnolence, insomnia), paresthesia, dizziness, peripheral neuropathy; in less than 5% of cases – confusion, encephalopathy, cerebellar symptoms (ataxia, dysarthria, balance and coordination disorders), depression.

Sense organs: increased lacrimation, conjunctivitis, disorder of taste; very rarely – lacrimal-nasal canal stenosis.

Respiratory system disorders: sore throat, dyspnea, cough, nasal bleeding, dysphonia.

Musculoskeletal system: arthralgia, myalgia.

Cardiovascular system: edema of 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.

Hematopoietic system: anemia, neutropenia, granulocytopenia, lymphocytopenia, thrombocytopenia; in less than 5% of cases – pancytopenia.

Laboratory disorders: (regardless of their relation to capecitabine administration) – hyperbilirubinemia, elevated ALT/AST, hypercreatininemia, elevated ALP activity, hyperglycemia, hypo-/hypercalcemia, hypoalbuminemia, hyponatremia, hypokalemia.

As for the body in general: increased fatigue, fever, weakness, dehydration, weight loss, lethargy, back pain; in less than 5% of cases – infectious complications against myelosuppression, immunodeficiency and mucosal integrity disorders, local and systemic (bacterial, viral and fungal), possibly with fatal outcome, sepsis.

Overdose

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

Treatment: symptomatic therapy is carried out.

Pregnancy use

The drug is contraindicated in pregnancy and lactation.

A reliable contraceptive method should be used during therapy with Xeloda® and for at least 3 months after its completion.

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