Capecitabine (lat. Capecitabinum ) is a substance that is a derivative of fluoropyrimidine carbamate. It belongs to the group of antimetabolites - special compounds that can inhibit the growth of malignant tumors. Interest in such substances arose in 1960. First, positive data were obtained through studies on laboratory mice. After some time, their effectiveness in the treatment of certain human oncological diseases was discovered.
To date, many anticancer drugs contain capecitabine as the active substance. Reviews of many patients indicate the success of the use of such drugs in anti-cancer therapy.
Pharmacological group and properties
The formula for capecitabine is 5'-deoxy-5-fluoro-N - [(pentyloxy) carbonyl] cytidine. The chemical group of antimetabolites is represented by a number of substances that are similar in nature to the products of human metabolism (metabolism). They are able to enter into metabolic reactions, correct them and inhibit some biochemical processes. In this case, the normal functioning of the tumor cells is disturbed and their growth is inhibited when using preparations based on the substance capecitabine. Reviews of people speak of a decrease in the size of neoplasms. This mechanism of action is called cytostatic.
Such properties of antimetabolite substances allow their use in antitumor therapy. Their effectiveness against malignant neoplasms of the gastrointestinal tract and mammary glands has been proven. Moreover, both monotherapy and combination with other agents give a good result. To date, more than 800 drugs have been created based on antimetabolites, but the search for new groups of compounds is still ongoing.
Mechanism of action
Activation of capecitabine occurs in the tissues of the tumor itself, after which it begins to exert a toxic effect on its cells (cytotoxic mechanism). This substance is involved in the metabolic reaction and leads to the fact that both healthy and tumor cells will be converted to cytotoxic analogues. In this case, there is a violation of the production of the substance necessary for the synthesis of DNA and, accordingly, the division process.
So the cells stop increasing their numbers. According to another scenario, there is a “substitution” of one substance for another, resulting in impaired protein synthesis when taking drugs based on the capecitabine compound. The manual describes this process in detail.
The mechanism of this transformation minimizes the possibility of damage to healthy cells. Capecitabine is more concentrated in the tumor itself than in the surrounding tissues. This feature is less harmful to the body when a person is treated with a drug based on the substance capecitabine. The instruction for use recommends taking the drug in strictly prescribed doses, which are determined by the attending physician.
Stay in the body
After taking capecitabine, it is rapidly absorbed in the gastrointestinal tract. If you eat at this time, the process will slow down. Therefore, taking drugs based on antimetabolites is carried out after a meal. Further transformations of the substance occur in the liver, a certain amount of capecitabine and its metabolites binds to proteins (for example, blood albumin). Peak plasma levels are reached after 1.5 -3 hours after drug administration. This is indicated by the preparation "Capecitabine" instruction. Analogs have similar pharmacokinetics.
Most of the substance is excreted in the urine, the smaller - with feces. Moreover, the body leaves not only capecitabine unchanged (about 3%), but also its derivatives. Some of them are metabolized to less active compounds. The presence and conversion of capecitabine in the body is not affected by gender, age, or race.
When is it prescribed?
Capecitabine in the form of various drugs is prescribed for patients with breast cancer, including at the stage of metastasis. In this case, the substance is used as part of monotherapy, or combination treatment in the presence of contraindications or the lack of effectiveness of chemotherapy. Most often, capecitabine is combined with docetaxel.
Also prescribed to patients with cancer of the colon, esophagus, stomach, pancreas, colorectal cancer, both in the stage of local distribution and during metastasis. In the treatment of colon cancer , Capecitabine is also prescribed. Instructions for use recommend that you carefully observe the dosage and adhere to the advice of your doctor.
Interaction with other means
If chemotherapy courses have been ineffective, an oncologist may prescribe a combination treatment where Capecitabine will be used. Instructions for use provide a list of means with which a successful combination is possible.
For example, with "Docetaxel" - a cytotoxic type of drug of plant origin. It is able to persist for a long time in cells in high concentrations. However, this combination of drugs is contraindicated in people with platelet and neutrophil counts of 100,000 / μl and 1,500 / μl, respectively. Also, "Docetaxel" is not used for patients with an increased rate of bilirubin. In this case, unpleasant consequences are possible. If Docetaxel for some reason “drops out” of the treatment regimen, continue with “Capecitabine” therapy, but in reduced doses.
If a hypersensitivity reaction occurs, treatment with "Capecitabine" and "Docetaxel" is stopped and the symptoms that have arisen are eliminated. The combined drug regimen is developed by a competent oncologist. If toxic effects occur, this regimen is adjusted.
"Capecitabine" is not prescribed simultaneously with "Sorivudine" - an antiviral agent. This combination may increase the toxicity of the first drug. Joint use with the antiepileptic drug "Phenytoin" increases the concentration of the latter in blood plasma. It is also possible a violation of blood coagulability when consuming coumarin anticoagulants and drugs, where the main component is capecitabine. Instructions for use warns of possible consequences, so you must first familiarize yourself with it.
Who is contraindicated in?
The reasons why the drug is contraindicated or limited may be:
- High sensitivity (hypersensitivity reaction).
- The presence of severe renal and hepatic insufficiency.
- Various stages of pregnancy (the drug acts on the fetus), with the exception of cases where the life of the mother is given priority;
- Breastfeeding a newborn.
Also, capecitabine is limited for people with coronary heart disease (CHD), with a state of increased concentration of bilirubin in the blood, liver damage with metastases with a violation of its basic functions. For minor children and elderly people, the drug is not recommended. This confirms the instructions for the drug "Capecitabine". Patient reviews speak of a variety of side effects and toxic effects during treatment. Therefore, capecitabine therapy is under the strict supervision of an oncologist.
Are there any side effects?
After taking the drug, headache, a state of rapid fatigue, apathy, and weakness are possible. Insomnia may occur, or, conversely, drowsiness. In rare cases - a violation of coordination and balance, confusion.
An adverse effect on the cardiovascular system is anemia (anemia). To a lesser extent, the appearance of angina pectoris, myocardial ischemia, heart attack, heart failure and others is possible. If the respiratory system is involved, shortness of breath, a feeling of sore throat, and coughing may appear. Very rarely - pulmonary embolism, spasm of the lungs.
When used as part of monotherapy or combination treatment, a negative effect on the musculoskeletal system is possible. It manifests itself in pain in the limbs and lower back, the occurrence of muscle hypertonicity (myalgia), joint pain (arthralgia).
The skin can also be affected. The appearance of dermatitis, erythema, excessive dryness of the skin, redness, tingling, numbness, peeling, itching, increased pigmentation, damage to the nails. In rare cases, skin cracks, increased sensitivity to ultraviolet radiation, exfoliation and increased fragility of the nail plates occur.
Among other side effects, infectious processes can occur against the background of a decrease in the body's defenses. After all, drug therapy causes a decrease in platelet and white blood cell counts. Such manifestations are described for the capecitabine medication by the instructions for use. Analogs give the same effects.
Taking the drug
Capecitabine is exclusively for internal use. Usually it is washed down with water half an hour after eating, but not later.
The daily dose is determined by the attending oncologist, depending on the size of the neoplasm, stage of development and the total surface area of the body. It is advisable that the specialist already had the skills to work with this drug. Most often, a double appointment is prescribed - morning and evening. Moreover, the entire course lasts two weeks, then a break for seven days, followed by a repeat of treatment.
For patients with renal failure, daily doses are reduced. With a decrease in the number of leukocytes (leukopenia) and neutrophilic granulocytes (neutropenia) in the blood, the drug is continued to be taken. So it recommends instructions for use for the capecitabine. Synonyms or analogues are prescribed at the initiative of the attending physician.
Degree of toxicity
There are several degrees according to which the toxic effect of the drug "Capecitabine" develops (instructions for use). The reviews of many people suggest that this process is purely individual.
There are several degrees of toxicity:
- 1 degree. Minor side effects appear.
- 2 degree. Intense diarrhea (up to 4 times a day) accompanied by swelling of the extremities, redness, impaired activity, a sharp increase in bilirubin. At this stage, capecitabine is interrupted until signs of toxicity of stage 1 appear.
- 3 degree. Diarrhea increases up to 9 times per day. There is a violation of absorption (malabsorption syndrome). At the same time, severe peeling of the skin, redness, the appearance of ulcers and blisters are observed. There are sharp pains in the limbs, decreased performance. Bilirubin rises 3 times. At this stage, treatment is interrupted, and if 1 degree of toxicity is manifested, the drug is continued to be taken in a reduced dose.
- 4 degree. More frequent diarrhea - up to 10 times per day. Feces mixed with blood. There is a need for the introduction of drugs, bypassing the gastrointestinal tract. When signs of this degree appear, treatment is discontinued and is no longer resumed.
What precautions should be followed?
The course of treatment should take place under close medical supervision. The specialist must identify toxic manifestations in time - be it nausea, diarrhea, etc. If these signs are detected, the treatment is adjusted. If necessary, eliminate the symptoms, reduce the daily dose, take a break. Treatment is continued if signs of toxicity are not life threatening.
For people with coronary heart disease, specialist supervision should be especially thorough. In this case, it is necessary to identify the negative impact on the cardiovascular system in time and take the necessary measures in time.
Specialists refrain from using the substance in the practice of pediatrics. The effectiveness of its use for children has not been established. If a woman of childbearing age is treated, she should be warned about the effect of capecitabine on the fetus. During treatment, she should use reliable contraceptives.
Preparations and analogues
There are several capecitabine-based agents available. On the Russian market there are 7 trade names of drugs produced by several domestic and foreign companies. For instance:
- Capecitabine
- "Capecitabine-TL".
- Tutabin.
- Xeloda.
- Cabecin.
- "Capecitover."
- "Capamethin FS".
Since the basis of all these agents is the same active substance - capecitabine, the instructions for them will be similar. Usually, it indicates a dosage calculation table taking into account body weight and a treatment correction scheme when signs of toxicity of varying degrees occur.
It is important to understand that the first thing to read when it was prescribed, for example, "Capecitabine TL" - instructions. The information contained in it is not suitable for the independent use of funds! All calculations related to setting the dose and treatment regimen are performed by the attending physician - an oncologist, who has sufficient competence in this matter. Self-administration of anticancer drugs causes irreparable harm to the body.
Let us consider in more detail some of the drugs.
Description of drugs
- Capecitabine-TL is produced by the Russian company Technology of Medicines LLC. The key component is capecitabine. Instructions for use, release form are of interest to many. Let's consider in more detail. These are film-coated tablets. The content of the active substance is 150 or 500 mg. Auxiliary components: cellulose, lactose, croscarmellose sodium, hypromellose, magnesium stearate. In one package there can be 60 or 120 tablets, depending on the dosage of Capecitabine-TL. The instruction necessarily contains detailed information on the use of the tool.
- "Capecitabine" is a domestic drug with the same active substance. Its description is similar to the tool above. The release form of the drug "Capecitabine" is tablets. Instructions for use are also included in the package.
- Cabecin is a Russian-made antitumor drug (Deco Company LLC). The release form is film-coated tablets of 150 or 500 mg of the active substance. Minor components: microcrystalline cellulose, crospovidone, starch, magnesium stearate. Leave from pharmacies only on prescription.
- Capecitover is a product of the Russian company Veropharm OJSC. This antitumor drug is available in tablets of 150 or 500 mg in an amount of 60 - 120 pieces. In addition to capecitabine, the composition of the drug includes lactose, cellulose, croscarmellose sodium, sodium stearate and hypromellose.
- "Capamethin FS" - produced by the Russian company "Nativa" - an active participant in the program of import substitution of medicines. "Capamethin FS" is produced with a dosage of 150 - 500 mg, the active substance is capecitabine. Instructions for use (the manufacturer is also indicated in it) will tell you how many tablets are in the package - 60 or 120.
- "Tutabin" is a foreign drug based on capecitabine. It is produced by the Argentinean company Laboratorio VARIFARMA SA, which is also the registrar of funds. "Tutabin" is produced in the form of tablets with an active substance content of 500 mg. Packaging - a cardboard box with the attached instructions.
- Xeloda is an antitumor agent. It is produced in Switzerland by F. Hoffman La Roche, as well as its subsidiaries and representative offices in other countries - Mexico and the USA. On the Russian market there are 5 drugs with this trade name. Release form - tablets (150 - 500 mg) in 60 or 120 pcs. in one package.
Reviews
Reviews on the work of drugs based on capecitabine are very diverse. Most of them are positive, but there are also negative reviews. However, this does not characterize these funds as good or bad, because you should always consider the factor of the individual organism of each individual person. Taking the same remedy by different people never gives the same result. Of great importance is which particular organ was affected by the neoplasm and how long this has been happening.
People taking the drug report a strong toxic effect after several days of administration. However, many note a significant improvement in their condition and even entry into the period of remission. An important condition for the drug to work as well as possible for a single person is the consultation of an oncologist and strict adherence to his instructions regarding treatment.