According to the information in the instructions, "Methotrexate" is a drug for fighting tumors. The name of the drug was due to the active component of methotrexate. On average, one package costs from 200 rubles or more. Metotrexate is produced by the Austrian pharmaceutical company Ebeve Pharma. On pharmacy shelves, the product is represented by cardboard boxes containing Metotrexate tablets and instructions. In one pack - one can of plastic, in it - fifty tablets. Each instance contains 2.5 mg of active compound. In addition, Methotrexate is formulated as an injectable substance.
Pharmacological features
"Methotrexate" belongs to the class of antitumor drugs with the effect of cytostatics. The drug belongs to the class of antimetabolites, it is able to inhibit dihydrofolate reductase, which is involved in the chemical reactions of dihydrofolate. Consequently, the amount of tetrahydrofolate acid generated is controlled in the body, which is capable of transporting the carbon enzymes involved in the generation of purine nucleotides, the products of their interaction with other substances.
The manufacturer in the instructions to "Methotrexate" indicates that shortly after the active compound enters the body, mitosis is inhibited at the cellular level. There is a definite effect on DNA (production, repair). The greatest effect of Methotrexate is relatively prone to active proliferation of tissues. Studies have shown that these are:
- epithelium of the oral mucosa;
- intestinal membranes;
- bladder tissue;
- atypical malignant cells;
- embryonic structures;
- bone marrow elements.
The instructions of "Methotrexate" mention that the drug belongs to the category of not only antitumor, but also immunosuppressive drugs. This must be taken into account when prescribing it to patients as part of a therapeutic course, especially a long one.
Kinetics of the substance
Instructions for use of "Methotrexate" states that the body's ability to perceive the active compound is determined by the dosage of the drug. If 30 mg is used at the same time, then the absorbability is quite good, and the bioavailability reaches 60%.
If Methotrexate is used to treat children who have leukemia, absorption is estimated at 23-95%.
In the instructions for use of "Methotrexate", the manufacturer draws attention: the highest concentrations of the active compound in the circulatory system are achievable not earlier than 40 minutes after the tablets are ingested, but not later than four hours from the time of administration. If you take pills during the meal, the absorption rate decreases, the maximum concentration in the circulatory system decreases.
The ability to associate with blood protein structures (albumin) is estimated at 50%. Soon after absorption, the substance is distributed to organs and tissues. The highest indicators of accumulation are characteristic:
In this case, transformation into polyglutamates occurs.
The instructions for use of "Methotrexate" indicate the possibility of a cumulative effect in these organs, and the substance can accumulate for weeks and months.
If you use the medication in the dosage recommended by the manufacturer, methotrexate practically does not leak through the brain barrier. Tests have shown that the substance passes into breast milk.
Features of biological reactions
In the instructions for the use of Methotrexate, the manufacturer warns that when the drug is used orally, the metabolic process is partially due to the microflora of the intestinal tract, but the main reaction is in the liver. Localization (liver) does not depend on the form of methotrexate administration into the patient's body.
The main metabolite of the active compound is the polyglutamine form. This substance has pharmacological activity, inhibits dihydrofolate reductase, prevents the formation of thymidine.
If the medicine is prescribed in a dosage of up to 30 mg / m 2 , the half-life is estimated at 2-4 hours for the initial phase, but the final one requires several large time intervals - up to ten hours, if the dose is small, five hours more if Methotrexate appointed in high dosage.
The half-life, as indicated in the instructions for use of Methotrexate (injections, tablets), can significantly increase if the patient suffers from kidney failure. The main route of excretion is tubular, glomerular filtration. The substance leaves the body with urine. Approximately one tenth of the total volume is excreted by bile, a process of reabsorption takes place in the intestinal tract. If renal dysfunction, ascites, transudate in a pronounced form are detected, elimination is slowed down. Reuse of Methotrexate provokes a cumulative effect. Accumulation occurs in the form of metabolites - polyglutamates.
When to use?
The instructions for "Methotrexate" (injections, tablets) indicate that the medicine can improve the condition of patients who are diagnosed with:
- leukemia;
- severe psoriasis;
- fungal mycosis (late stages);
- rheumatoid arthritis (with the ineffectiveness of alternative treatment methods);
- non-Hodgkin lymphoma;
- trophoblastic pathological formations.
It is impossible!
Instructions for the use of tablets "Methotrexate" contains a reference to the impossibility of using the composition if severe, pronounced impaired liver and kidney function are detected. It can not be used if the diagnosis contains mention of:
- bone marrow hypoplasia;
- blood diseases
- leuko-, thrombocytopenia;
- anemia
- infection in the acute stage.
The instruction for the Methotrexate tablets is forbidden to use the medication if the patient suffers from increased susceptibility, sensitivity to any compound used in the manufacture of the medicine. A similar condition applies to the release form for injective administration.
"Methotrexate" is allowed for patients strictly older than three years of age. The drug should not be used during pregnancy and lactation. It is not allowed to use the drug if immunodeficiency syndrome is detected.
Special occasion
The need for particularly careful monitoring of the condition of patients suffering from a stomach or intestinal ulcer is indicated in the Methotrexate instructions. Ampoules containing the active compound, tablets based on it, are allowed for use with ulcerative colitis, but only if it is possible to provide an appropriate level of medical care. The manufacturer indicates the need for careful attention, if the patient has:
- infection with bacteria, viruses, pathological fungi;
- ascites;
- lack of water in the body;
- the presence of effusion in the pleural cavity;
- gout, nephrolithiasis, mentioned in the medical history.
You can use "Methotrexate" according to the instructions for rheumatoid arthritis, tumor processes, if the patient has previously undergone chemo-radiation therapy, but such anamnesis also requires extremely careful monitoring of the patient's condition.
Tablets: rules of admission
According to those who took the drug in their reviews of Methotrexate, the instructions for use give a clear explanation of the rules for using the drug, so it is easy to follow the established program. The tablets are intended for oral administration, and the doctor selects the duration of the course and dosage, evaluating the individual characteristics of the client's condition. This takes into account whether the patient is undergoing chemotherapy, what diagnosis caused the appointment of Methotrexate (the instructions for use in rheumatoid arthritis are slightly different from the rules for treating the tumor), what are the individual characteristics of the reaction to the medication.
If the basis for prescribing the tablets was trophoblastic disease, then it is recommended to use from 15 mg to twice as much per day. The entire volume is taken at a time. The duration of the course is five days. If necessary, the program is repeated, keeping a week break between sets or a little more. The manufacturer indicates the possibility of repeating the course with this diagnosis 3-5 times. Features of treatment will depend on the severity of the toxic effect.
Another method of combating trophoblastic tumors is taking 50 mg daily for five days in a row, after which they take a month or longer break. As part of the course, 300-400 mg of active compound is used in food.
Diagnoses and rules
According to reviews and instructions for use, Methotrexate is effective if non-Hodgkin's lymphoma is detected. The drug is used as an element of a comprehensive program. For each square meter of the body surface, 15 to 20 mg of the active compound is prescribed. The medicine is taken at a time, twice a week. An alternative is 7.5 mg / m 2 per day for five days in a row.
The reviews and instructions for "Methotrexate" contain a reference to the effectiveness of the drug in some forms of leukemia, but the drug is used only as one of the points of complex treatment, since monotherapy will not show a pronounced effect. In the acute form of lymphoblastic leukemia, 3.3 mg / m 2 is indicated. The medication is combined with drugs containing prednisone. Having achieved remission, the drug in question can be used in an amount of 15 mg / m 2 twice a week. Alternative: 2.5 mg / kg once every two weeks.
Other diseases
Most often, users are interested, as can be seen from the questions and reviews, the instructions for “Methotrexate” for rheumatoid arthritis, but this disease is far from the only non-oncological class in which the pills and injections in question are effective. In particular, the practice of using the drug against psoriasis is widespread. Dosage for a week - from 10 to 25 mg. Gradually, the doctor increases the volume by monitoring the response of the patient. The decrease begins when it is possible to achieve a pronounced clinical effect. The main task is to identify the minimum amount of medicine that allows you to get the desired result.
With fungal mycosis, the drug is prescribed first 25 mg twice a week, then adjusts the volumes based on the reaction of the body. Assess the quality of the circulatory system, side effects, pathology response. There are two options: reduction of the used volumes of the drug or its complete abolition.
The greatest interest among many is the instructions for the use of Methotrexate for rheumatoid arthritis. The drug begins to be used with a dose of 7.5 mg. This volume is used once a week or in three doses, keeping between them twelve-hour time intervals. To obtain a pronounced, persistent clinical effect, the volumes used can be increased to 20 mg. The instructions for the use of Methotrexate for arthritis are recommended in the minimum effective dosage, the choice of which is carried out, first achieving the effect, then starting to reduce the doses of the medicine used by the patient. The doctor’s task is to be able to choose such volumes when Methotrexate is effective, and its toxic effects for the patient’s body are minimal.
If arthritis in a chronic form has developed in a child, adolescent, the dosage is calculated as follows: 10-30 mg / m 2 or 0.3-1 mg / kg. Obtained in such calculations, the volume of the drug must be consumed once a week. The tool is used at a time.
Side effects
Like many other similar analogue drugs, Methotrexate (reviews, instructions for use confirm this) can provoke a wide variety of negative reactions due to increased toxicity of the components. The manufacturer indicates the following possible negative consequences of using the composition:
- thrombo-, neutro-, pancyto-, leukopenia;
- anemia;
- agranulocytosis;
- eosinophilia;
- effusion into the pericardial region;
- pressure reduction;
- blood clots
- vomiting, nausea;
- weight loss;
- erosion, ulcers, bleeding in the digestive tract;
- pancreatitis
- activation of liver enzymes;
- hepatitis;
- encephalopathy;
- craving for sleep;
- sore and dizzy;
- paresis;
- visual impairment;
- pulmonary fibrosis;
- COPD
- signs of interstitial pneumonia;
- skin reactions;
- necrotic processes;
- nephropathy;
- the presence in urine of protein structures, nitrogen and blood inclusions;
- sexual dysfunction, fertility;
- dysmenorrhea;
- myalgia;
- allergy;
- diabetes;
- lymphoma
- cytomegalovirus infection;
- vasculitis;
- shingles;
- herpes.
The doctor warns about possible negative reactions before starting the course. The doctor evaluates the patient’s condition and analyzes which negative answers are most likely, immediately gives instructions, explains what to do if the condition worsens when using Methotrexate.
Too much!
Clinical observations have shown that no specific symptoms when using an excessively large volume of Methotrexate do not occur. To identify the fact of an excess, it is necessary to take blood samples for laboratory analysis and determination of the concentration parameters of active compounds in the liquid.
The most effective measure to stabilize the patient's condition and prevent the severe consequences of an overdose is to use a specific antidote. Currently, calcium folinate is used as such a substance. It is advisable to use it as soon as possible after the intake of an excessive amount of Methotrexate. The procedure will show the best effect if the antidote is taken within the first hour after the main drug. Dosage of calcium folinate - equal to the amount of Methotrexate used in food or more.
After establishing the fact of taking too much of the drug, it is necessary to establish control over the patient's condition. From time to time, serum samples are taken to detect the concentration of methotrexate, based on these data, they decide on the repeated use of the antidote. To speed up the withdrawal of the drug from the body, you should drink more, take measures to increase the alkalinity of urine. To reduce the likelihood of nephropathy provoked by precipitation of the active compound, urine should be additionally tested for alkalinity before administration, repeated tests should be done at six-hour intervals when using an antidote. Calcium folinate is used until it is possible to achieve a concentration of methotrexate in the blood plasma of up to 0.05 μmol / L. At the same time, alkalinity should exceed seven units.
Special conditions
Cytological toxicity of "Methotrexate" forces the use of the drug very carefully. The drug is prescribed only by experienced, highly qualified doctors. The actions of the medication are quite specific, so a professional introduces the patient to the course of the possibility of negative reactions, including severe ones. Pay attention that "Methotrexate" can provoke fatal, irreversible negative effects. To minimize risks, you must strictly follow the instructions and the developed therapeutic program.
To use Methotrexate as safe as possible, it is important to take the course under the supervision of a doctor. Medical observation will allow you to understand in time that the toxic effect is severe, take measures to improve the patient's condition. Before prescribing Methotrexate, the doctor directs the patient for blood tests to determine the platelet counts, liver enzyme activity, bilirubin, and albumin. Additionally, an x-ray of the chest is prescribed, the efficiency of the kidneys is studied, and in some cases tests are done to check for the presence of tuberculosis and hepatitis. It is strictly forbidden to use "Methotrexate" at one’s own discretion - this will cause serious consequences (up to death).
Reception: Nuances
If the patient is prescribed Methotrexate, he will have to undergo regular tests to monitor the quality of the peripheral circulatory system and blood-forming organs. Doctors control the concentration of platelets, leukocytes, on the basis of the data obtained from the analyzes, decide on the need to cancel the program if the medicine is difficult to tolerate.
The first month of using the medication requires blood tests every other day, then the intervals are extended to three, sometimes five days. With a long course, systematic blood control is carried out at ten-day intervals, and during remission, two-week intervals.
Before using Methotrexate, the patient should be examined by a doctor. The doctor will check the condition of the pharynx, mucous membranes of the oral cavity.From time to time, tests are done to detect the activity of liver enzymes, creatinine clearance and the content of nitrogen in urine, and uric acid in the blood. The patient is shown chest x-ray. Three times (before the start of the course, during its passage and upon completion), the work of the blood-forming organs is checked.
"Methotrexate": effect on the liver
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If Methotrexate caused diarrhea, stomatitis complicated by ulcers, treatment is stopped because the symptoms indicate an increased risk of hemorrhagic enteritis. In addition, a high probability of perforation of the intestinal wall.
During the course of treatment, it is reasonable to avoid ultraviolet radiation, direct exposure to sunlight, since there is a likelihood of increased sensitivity to light.
"Methotrexate" affects the patient's immunity. Doctors should take this into account when assigning tests to determine the functioning of the immune system. Under the influence of the active components of the drug, an atypical response to the vaccine is possible. After the cancellation of Methotrexate from three months to a year, immunization should be avoided unless the case is directly recommended by the doctor. All people living with the patient for this period should refuse vaccination against polio. To avoid accidental contact with people who have received such a vaccine, you must always wear a protective mask.
Lifestyle & Treatment
When taking Methotrexate, patients of reproductive age should use reliable methods to prevent conception. At the end of the program, men should use contraceptives for at least three months, and women should use one ovulatory cycle.
To make the toxicity of the components of Methotrexate less pronounced, calcium folinate should be used during the course.
"Methotrexate" acts on the central nervous system, provokes lethargy, fatigue, and sometimes causes dizziness. This imposes restrictions on the ability to control vehicles, work with precise mechanisms.
"Methotrexate": analogues
Instructions for use of the drug indicate that the active compound is called "methotrexate", it was because of it that the name was given to the drug. The drugs are based on the same compound:
- "Metortrite."
- Zeksat.
- Evetrex.
As you can conclude from the instructions, the analogues of Methotrexate are the Metodzhekt and Trexan drugs. If it is not possible to purchase the option prescribed by the doctor, the choice of replacement should be agreed with the attending physician, otherwise the results of the treatment course will be unpredictable. It is necessary to remember the toxicity of the active substance on which all these medicines are based. It is unacceptable to use it of your own choice - the consequences can be the most severe.