Capecitabine-Vista tablets are prescribed for the following indications:
Colon cancer, colorectal cancer:
- colon cancer, in adjuvant therapy after surgical treatment of stage III cancer (Duke stage C);
- metastatic colorectal cancer.
Stomach cancer:
- a drug for the first line treatment of advanced gastric cancer, in combination with platinum-based drugs.
Mammary cancer:
- local advanced or metastatic breast cancer, in combination with docetaxel after ineffective chemotherapy including anthracycline drugs;
- local advanced or metastatic breast cancer, as monotherapy if chemotherapy, including taxanes and anthracycline drugs, is ineffective, or if there is a contraindication to anthracycline therapy.
Compound
Active ingredient: capecitabine.
1 film-coated tablet contains 150 mg or 500 mg capecitabine.
Excipients: croscarmellose sodium, microcrystalline cellulose PH 101, microcrystalline cellulose PH 200, hypromellose 5cP, colloidal silicon (E 551), magnesium stearate (E 470b);
Shell composition: hypromellose 5cP, titanium dioxide (E 171), talc (E 553b), macrogol 400, red iron oxide (E172), yellow iron oxide (E 172).
Contraindications
History of severe, including unexpected reactions to treatment with fluoropyrimidines. Hypersensitivity to capecitabine or any component of the drug, or fluorouracil. Known complete absence of dihydropyrimidine dehydrogenase (DPD) activity.
During pregnancy and breastfeeding.
Severe leukopenia, neutropenia, thrombocytopenia.
Severe liver dysfunction.
Severe renal failure (creatinine clearance <30 ml/min).
Recent or concomitant treatment with brivudine.
Contraindications to the use of any drug used in combination.
CAPECITABINE
Side effects
The frequency of adverse reactions is presented according to WHO recommendations: very often (> 10%), often (> 1% and < 10%), infrequently (> 0.1% and < 1%), rarely (> 0.01% and < 0.1%), very rare (<0.01%).
The most common side effects associated with capecitabine were gastrointestinal (GIT) disorders (diarrhea, nausea, vomiting, abdominal pain, stomatitis), hand-foot syndrome, fatigue, asthenia, anorexia, cardiotoxicity, increased renal function. failure in patients with a history of renal impairment, as well as thrombosis/embolism.
Side effects reported in patients taking capecitabine as monotherapy
Infectious and parasitic diseases
: often - herpes viral infection, nasopharyngitis, lower respiratory tract infection; uncommon - sepsis, urinary tract infection, cellulitis, tonsillitis, pharyngitis, candidiasis of the oral mucosa, influenza, gastroenteritis, fungal infections, infections, tooth abscess.
Benign, malignant and unspecified neoplasms
: uncommon - lipoma.
Blood and lymphatic system disorders
: often - neutropenia; uncommon - febrile neutropenia, granulocytopenia, thrombocytopenia, leukopenia, hemolytic anemia, increase in international normalized ratio, prolongation of prothrombin time.
Immune system disorders
: uncommon - hypersensitivity. Metabolic and nutritional disorders: very often - anorexia; often - dehydration, weight loss; uncommon - diabetes mellitus, hypokalemia, indigestion, hypertriglyceridemia.
Mental disorders
: uncommon - panic attacks, depressed mood, decreased libido.
Nervous system disorders
: often - headache, dizziness (except vertigo), lethargy, paresthesia, dysgeusia (taste perversion): infrequently - aphasia, memory impairment, fainting, imbalance, loss of sensitivity, peripheral neuropathy.
Visual disorders
: often - increased lacrimation, conjunctivitis; infrequently - decreased visual acuity, diplopia.
Hearing and labyrinth disorders
: uncommon - vertigo, ear pain.
Heart disorders
: uncommon - angina, including unstable, arrhythmia, sinus tachycardia, palpitations.
Vascular disorders
: often - thrombophlebitis; uncommon - deep vein thrombosis, increased blood pressure, petechiae, decreased blood pressure, hot flashes, coldness of the distal extremities.
Respiratory, thoracic and mediastinal disorders
: often - nosebleeds, rhinorrhea; uncommon - pneumothorax, hemoptysis, bronchial asthma, shortness of breath on exertion.
Gastrointestinal disorders
: very often - diarrhea, vomiting, nausea, stomatitis (including ulcerative), abdominal pain;
often - constipation, epigastric pain, dyspepsia; uncommon - intestinal obstruction, ascites, enteritis, dysphagia, lower abdominal pain, abdominal discomfort, gastroesophageal reflux disease, blood in the stool. Disorders of the liver and biliary tract
: often - changes in liver function tests; infrequently - jaundice.
Skin and subcutaneous tissue disorders
: very often - palmar-plantar syndrome (paresthesia, swelling, hyperemia, skin peeling, blistering), dermatitis; often - skin hyperpigmentation, macular rash, rash, alopecia, erythema, dry skin; Uncommon: blister, skin ulcers, urticaria, palmar erythema, facial edema, purpura. Skin cracks at least thought to be related to capecitabine therapy were reported in less than 2% of patients in 7 completed clinical studies (N=949).
Musculoskeletal and connective tissue disorders
: often - pain in the limbs, back pain; Uncommon: joint swelling, bone pain, facial pain, stiffness, muscle weakness.
Renal and urinary tract disorders
: uncommon - hydronephrosis, urinary incontinence, hematuria, nocturia, increased plasma creatinine.
Genital and breast disorders
: uncommon - vaginal bleeding.
General and administration site disorders
: very often - fatigue, drowsiness; often - peripheral edema, malaise, chest pain, fever, weakness, asthenia; infrequently - swelling, chills, flu-like syndrome, trembling, increased body temperature.
Impact on the results of laboratory and instrumental studies: often - hyperbilirubinemia.
The following adverse reactions are toxicities known to occur with fluoropyrimidine therapy; At least an indirect association between the development of such reactions and the use of capecitabine was reported in less than 5% of patients participating in 7 completed clinical studies (N=949):
gastrointestinal disorders
: dry mouth, flatulence, adverse reactions associated with inflammation/ulceration of the mucous membranes, such as esophagitis, gastritis, duodenitis, colitis, gastrointestinal bleeding;
disorders of the cardiovascular system
: edema of the lower extremities, cardialgia, including angina pectoris, cardiomyopathy, myocardial ischemia, myocardial infarction, heart failure, sudden death, tachycardia, supraventricular arrhythmias, including atrial fibrillation, ventricular extrasystoles;
nervous system disorders
: taste disturbance, insomnia, confusion, encephalopathy, symptoms of cerebellar disorders (ataxia, dysarthria, impaired balance and coordination);
mental disorders
: depression;
infectious and parasitic diseases
: infectious complications associated with myelosuppression, immunosuppression and/or mucositis, such as local and fatal systemic infections (bacterial, viral or fungal etiology) and sepsis;
disorders of the blood and lymphatic system
: anemia, myelosuppression/pancytopenia;
disorders of the skin and subcutaneous tissues
: itching, focal peeling of the skin, skin hyperpigmentation, nail changes, photosensitivity reactions, radiation dermatitis;
visual impairment
: eye irritation;
disorders of the respiratory system, chest and mediastinal organs
: shortness of breath, cough;
Musculoskeletal and connective tissue disorders
: arthralgia, myalgia, back pain;
general disorders and disorders at the injection site
: chest pain (non-cardiac etiology), pain in the extremities.
Use of capecitabine in combination therapy
The safety profile did not differ between indications and combinations, but the adverse reactions listed with monotherapy may occur with greater frequency when capecitabine is used in combination therapy.
The following are undesirable reactions that were observed in addition to those with monotherapy:
Infectious and parasitic diseases
: often - candidiasis of the oral mucosa, herpes zoster, urinary tract infections, upper respiratory tract infections, rhinitis, influenza, infection, oral herpes;
Blood and lymphatic system disorders
: very often - neutropenia, anemia, thrombocytopenia, leukopenia, febrile neutropenia; often - myelosuppression;
Immune system disorders
: often - increased sensitivity;
Metabolic and nutritional disorders
: very often - weight loss, loss of appetite; often - hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia, hyperglycemia;
Mental disorders
: often - sleep disorders, anxiety;
Nervous system disorders
: very often - paresthesia, dysgeusia, headache, peripheral neuropathy, peripheral sensory neuropathy, dysesthesia; often - neurotoxicity, tremor, neuralgia, hypoesthesia;
Visual disorders
: very often - lacrimation; often - visual disturbances, dry eyes, eye pain, blurred vision;
Hearing and labyrinth disorders
: often - ringing in the ears, hearing loss;
Heart disorders
: often - atrial fibrillation;
Vascular disorders
: very often - thrombosis/embolism, increased blood pressure (BP), swelling of the lower extremities; often - hyperemia, decreased blood pressure, hypertensive crisis, hot flashes, phlebitis;
Respiratory system disorders
, organs of the chest and mediastinum: very often - pharyngeal dysesthesia, sore throat; often - nosebleeds, dysphonia, rhinorrhea, hiccups, pain in the pharynx and larynx;
Gastrointestinal disorders
: very often - constipation, dyspepsia; often - bleeding from the upper gastrointestinal tract, oral ulcers, gastritis, bloating, gastroesophageal reflux disease, oral pain, dysphagia, rectal bleeding, lower abdominal pain, dysesthesia, paresthesia and hypoesthesia in the mouth, abdominal discomfort;
Disorders of the liver and biliary tract
: often - liver dysfunction;
Skin and subcutaneous tissue disorders
: very often - alopecia, changes in nails; often - hyperhidrosis, erythematous rash, urticaria, night sweats;
Musculoskeletal and connective tissue disorders
: very often - myalgia, arthralgia, pain in the extremities; often - jaw pain, muscle spasms, trismus, muscle weakness;
Renal and urinary tract disorders:
often - hematuria, proteinuria, decreased creatinine clearance, dysuria;
General and administration site disorders
: very often - weakness, lethargy, increased sensitivity to high and low temperatures; often - fever, pain, inflammation of the mucous membrane, chills, chest pain, flu-like syndrome, contusion.
Cases of liver failure and cholestatic hepatitis have been reported both in and outside of clinical studies. A cause-and-effect relationship with capecitabine has not been established.
Hypersensitivity reactions (2%) and myocardial ischemia/infarction (3%) have been reported frequently (but in less than 5% of patients) during capecitabine therapy in combination with other chemotherapy drugs.
Laboratory and instrumental data:
The following are laboratory changes observed in clinical trials in patients undergoing adjuvant therapy for colon cancer and in patients undergoing treatment for metastatic breast cancer and metastatic colorectal cancer, regardless of their relationship to capecitabine: neutropenia, granulocytopenia, lymphocytopenia, thrombocytopenia, anemia, hyperbilirubinemia, increased activity of ALT, AST, alkaline phosphatase, hypercreatininemia, hyperglycemia, hypo-/hypercalcemia, hyponatremia, hypokalemia.
Post-registration experience with capecitabine
rarely - acute renal failure as a result of dehydration, including fatal outcome, punctate keratitis, ventricular fibrillation, prolongation of the QT interval, ventricular tachysystolic arrhythmia "pirouette", bradycardia, vasospasm; very rarely - cutaneous lupus erythematosus, severe skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, unspecified lacrimal duct stenosis, corneal damage, including keratitis; very rarely, in clinical studies and outside of their framework, cases of liver failure and cholestatic hepatitis were recorded.
Diarrhea
Diarrhea was observed in 50% of patients during capecitabine therapy. A meta-analysis of 14 clinical trials involving more than 4,700 patients treated with capecitabine identified covariates that were statistically associated with an increased risk of developing diarrhea: increasing the initial dose of capecitabine (in grams), increasing the study period of treatment (in weeks), increasing patient age (every 10 years), female gender. Covariates statistically associated with a reduced risk of diarrhea: increasing the cumulative dose of capecitabine (0.1 - kg) and increasing the relative dose intensity in the first 6 weeks of treatment.
Patients with severe diarrhea should be closely monitored with rehydration and restoration of fluid and electrolyte balance if dehydration occurs. According to indications, it is recommended to take standard antidiarrheal drugs (for example, loperamide) as early as possible.
Cardiotoxicity
In addition to the side effects presented in Tables 4 and 5, the following adverse reactions were observed with capecitabine monotherapy with an incidence of less than 0.1%: cardiomyopathy, heart failure, sudden death and ventricular extrasystoles.
Encephalopathy
During monotherapy with capecitabine, the development of encephalopathy was observed with an incidence of less than 0.1%.
Adverse reactions in special patient groups
Elderly patients
Elderly patients aged >60 years receiving capecitabine alone or in combination with docetaxel experienced an increased incidence of grade 3, 4 and serious adverse reactions compared with patients aged <60 years. The majority of patients aged >60 years receiving combination therapy with docetaxel experienced earlier discontinuation of treatment due to adverse reactions compared with patients aged <60 years. A meta-analysis of 14 clinical studies involving more than 4,700 patients treated with capecitabine found that as the patient's age increases (every 10 years), the risk of developing hand-foot syndrome and diarrhea increases, while the risk of developing neutropenia, on the contrary, increases , was decreasing.
Floor
In female patients, there is a statistically significant increase in the risk of developing hand-foot syndrome and diarrhea; the risk of developing neutropenia is reduced.
Patients with impaired renal function
Patients with pre-treatment renal impairment who received capecitabine monotherapy experienced an increased incidence of treatment-related grade 3 and 4 adverse reactions compared with patients with normal renal function (36% in patients without renal impairment, 41% in patients without renal impairment). with mild renal failure and 54% with moderate renal failure). Patients with moderate renal impairment were more likely to require dose reductions (44%) compared with 33% and 32% of patients without renal impairment with mild renal impairment, respectively, and were more likely to have premature treatment discontinuation.
Mode of application
Capecitabine-Vista should only be prescribed by a qualified physician experienced in the use of antineoplastic drugs. Close monitoring is recommended for all patients during the first cycle of treatment.
Treatment should be discontinued if disease progression or unacceptable toxicity develops.
Take Capecitabine-Vista tablets whole orally, no later than 30 minutes after a meal, with water. Capecitabine-Vista tablets should not be crushed or cut.
Use of the drug Capecitabine
Orally 30 minutes after meals at a daily dose of 2.5 g/m2/day (in 2 doses) for 2 weeks, followed by a break for 1 week. Calculation of the total daily dose depending on the body surface: less than 1.24 m2 - 3 g, 1.25-1.36 m2 - 3.3 g, 1.37-1.51 m2 - 3.6 g, 1.52 –1.64 m2 – 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 g. Manifestations of toxicity during the treatment period can be eliminated by symptomatic therapy and/or dose reduction. Changing the dose depending on the degree of toxicity (Canadian classification of cytotoxicity): Grade I - do not change the dose; Grade II - at the first appearance of signs of toxicity, it is necessary to discontinue therapy until they disappear or decrease to grade I. Treatment is resumed at 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 discontinued; Grade III - at the first appearance of signs of toxicity, it is necessary to stop therapy until they disappear or decrease to grade 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 discontinued; IV degree - the drug is discontinued.
Interaction
Because available safety and efficacy data are based on the administration of capecitabine with food, it is recommended that Capecitabine-Vista be administered with food. Taking Capecitabine-Vista with food results in a slower rate of absorption of capecitabine.
An interaction has been observed between allopurinol and 5-fluorouracil, with a possible decrease in the effectiveness of 5-fluorouracil. In this regard, the simultaneous use of capecitabine and allopurinol should be avoided.
Pharmacological properties of the drug Capecitabine
Antitumor agent, antimetabolite. It is a prodrug that turns into a cytotoxic compound - fluorouracil. The formation of fluorouracil occurs in tumor tissue under the influence of the tumor angiogenic factor - thymidine phosphorylase, as a result of which the systemic effect of fluorouracil on healthy tissues of the body is minimal. Consistent enzymatic metabolism into fluorouracil creates high concentrations of the latter in tumor cells (thymidine phosphorylase activity in the primary tumor is 4 times higher than in healthy tissue). Absorption is high (food reduces absorption). Metabolized in the liver by carboxylesterase to the metabolite 5-deoxy-5-fluorocytidine (5-DFCT), which is then transformed into 5-deoxy-5-fluorouridine (5-DFUR) by cytidine deaminase in the liver and tumor tissues. Further transformation to the active cytotoxic metabolite fluorouracil occurs in the tumor under the influence of thymidine phosphorylase. The content of fluorouracil and its active phosphorylated derivative in the tumor significantly exceeds the levels in healthy tissues, which ensures the relative selectivity of the cytotoxic effect. For capecitabine, 5-DFCT, 5-DFUR and fluorouracil, the binding to plasma proteins is 54, 10 and 62 and 10%, respectively, AUC - 7.4 mg/h/ml, 5.21 mg/h/ml, 21.7 mg/h/ml, for fluorouracil - 1.63 mg/h/ml. Maximum concentrations in blood plasma are determined 2 hours after administration. Then the concentrations decrease exponentially, the half-life is 0.7–1.14 hours. α-Fluoro-β-alanine, a breakdown product of fluorouracil, reaches its maximum concentration in the blood plasma after 3 hours and has a half-life of 3–4 hours. Excreted mainly by the kidneys (84% of the dose), including 57% in the form of α-fluoro-β-alanine. In patients with renal failure, when creatinine clearance decreases by 50%, the concentration of α-fluoro-β-alanine increases by 45%.
Note!
Description of the drug Capecitabine-Vista table. p/o 500 mg No. 120 on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.
Special instructions for the use of capecitabine
Women of reproductive age should be treated only if they are using reliable contraception. The drug should be prescribed with caution to patients with mild to moderate liver dysfunction caused by liver metastases and the elderly. If hyperbilirubinemia develops, capecitabine should be discontinued until bilirubin levels normalize. Currently, the safety of use in patients with renal failure has not been established. Prescribe with caution to patients whose activities require increased concentration and speed of psychomotor reactions. Prescription of coumarin anticoagulants is possible no earlier than 1 month after the end of capecitabine therapy due to the high risk of blood clotting disorders and bleeding.
