The expressed renal failures and/or a liver;
Hematologic frustration, including a marrow hypoplasia, a leukopenia, thrombocytopenia, anemia;
Acute form of infectious diseases;
Immunodeficiency syndrome;
Period of pregnancy and breastfeeding;
Age up to 3 years;
Hypersensitivity to drug components.

With care patients are recommended to appoint the Methotrexate with a peptic ulcer of a stomach and duodenum, ulcer colitis, infectious diseases of bacterial, virus or fungal genesis, at an exudate in a pleural cavity, ascites, dehydration, a nephrolithiasis or gout in the anamnesis; against the background of carried out earlier beam or chemotherapy.

Route of administration and dosage

Pill is taken orally.

The doctor appoints a dose and the period of treatment on the basis of clinical indications individually taking into account the scheme of chemotherapy.

The recommended dosing:

Trophoblastic tumors: on 15-30 mg of 1 times a day within 5 days. The course of treatment is repeated by from 3 to 5 times with a break in one or more weeks (taking into account toxicity signs). Besides, perhaps alternative appointment on 50 mg of 1 times in 5 days with a break 1 month and more, a course provides reception of 300-400 mg of drug;
Nekhodzhkinsky lymphoma (as a part of complex therapy): on 15-20 mg on 1 ^sq.m of a body surface of the patient of 1 times a day 2 times a week or on 7,5 mg on 1 ^sq.m of 1 times a day within 5 days;
Acute lymphoblastoid leukosis (as a part of complex therapy): from calculation for 3,3 mg on 1 ^sq.m in combination with Prednisolonum. After achievement of remission the mode of dosing can make on 15 mg on 1 ^sq.m 2 times a week or 2,5 mg on 1 kg of weight of the patient each 14 days;
Psoriasis: on 10-25 mg a week, the dose should be raised gradually, after achievement of optimum clinical effect it begins to be reduced to the level of the smallest effective dose;
Fungoid mycosis: the initial dose – on 25 mg 2 times a week, depending on reaction of the patient and hematologic indicators is made a dose decline or drug withdrawal;
Pseudorheumatism: an initial dose – 7,5 mg once a week once or in 3 receptions at an interval of 12 hours. For the purpose of achievement of optimum clinical effect increase in a week dose to 20 mg is allowed. After achievement of desirable result the dose is recommended to be reduced to the level of the lowest effective dose gradually. Duration of therapy is defined individually. To children at juvenile chronic arthritis the dose is determined from calculation for 10-30 mg on 1 ^sq.m of a body surface of the child once a week or by 0,3-1 mg on 1 kg of weight.

Side effects

System of a hemopoiesis: thrombocytopenia, anemia (including aplastic), leukopenia, agranulocytosis, neutropenia, eosinophilia, limfoproliferativny diseases, lymphadenopathy, pancytopenia, hypogammaglobulinemia;
Cardiovascular system: pericardiac exudate, pericardis, decrease in the ABP, thromboembolism (thrombosis of cerebral vessels, arterial thrombosis, deep vein thrombosis, thrombophlebitis, retina vein thrombosis, pulmonary embolism);
Alimentary system: nausea, vomiting, anorexia, stomatitis, pharyngitis, an ulitis, enteritis, erosive cankers and bleeding from digestive tract (including a melena, a hematemesis), pancreatitis, a hepatotoxic (increase in activity of liver enzymes, a liver failure, an acute hepatitis, cirrhosis and fibrosis of a liver, a hypoalbuminemia);
Nervous system: drowsiness, dizziness, headache, hemiparesis, dysarthtia, paresis, aphasia, spasms; against the background of high doses – emotional lability, tranzitorny disorder of cognitive functions, encephalopathy (including a leukoencephalopathy), unusual cranial sensitivity;
Organ of sight: a vision disorder (including a passing blindness), conjunctivitis;
Respiratory system: seldom – respiratory insufficiency, a pneumosclerosis, an alveolitis, the chronic obstructive pulmonary disease (COPD), an intersticial pneumonitis (including with a fatal outcome), symptoms of intersticial pneumonia (potentially dangerous) – an otdyshka, dry cough, fever;
Integument: skin itch, erythematic rash, small tortoiseshell, pigmentation disturbance, photosensitivity, alopecia, telangiectasia, ecchymomas, exfoliative dermatitis, furunculosis, eels, multiformny erythema (Stephens-Johnson's syndrome), necrosis and ulceration of skin, toxic epidermal necrolysis; at psoriasis – burning of skin, painful erosive plaques on skin;
Urinogenital system: cystitis, renal failure or heavy nephropathy, proteinuria, azotemia, hamaturia, disturbance ovo-and spermatogenesis, decrease libido, tranzitorny oligospermatism, impotence, vaginal allocations, dysmenorrhea, gynecomastia, abortion, defects of fetation, death of a fruit, infertility;
Musculoskeletal system: mialgiya, arthralgia, osteoporosis, fractures, osteonecrosis;
New growths: lymphoma, including reversible;
Others: the increased perspiration, a diabetes mellitus, allergic reactions (including an acute anaphylaxis), an allergic vasculitis, a necrosis of soft tissues, a syndrome of a lysis of a tumor, sudden death, opportunistic infections, life-threatening (including pneumocystic pneumonia), a Cytomegaloviral (TsMV) infection (including TsMV-pneumonia), histoplasmosis, a nocardiosis, a cryptococcosis, sepsis (including fatal), shingles, the simple and disseminated herpes.

Special instructions

Cytotoxicity of drug demands the careful treatment of him. Only the experienced specialist can make purpose of drug. Considering properties and features of action of the Methotrexate, the doctor has to inform the patient on ability of drug to cause heavy, and at times and fatal side effects and about need of observance of a high security of therapy for their minimization.

Use of drug should be accompanied with careful medical observation for early detection of signs of toxic action, their assessment, and acceptance of adequate measures.

Appointment has to be made on the basis of full general blood test with determination of content of thrombocytes, biochemical analysis of blood with establishment of activity of enzymes of a liver, a seralbumin, bilirubin, a research of function of kidneys, a thorax X-ray analysis, if necessary – tests for hepatitis and tuberculosis.

Reception of the Methotrexate has to take place in conditions of regular control of a condition of peripheral blood regarding the maintenance of number of leukocytes and thrombocytes. Within the first month of therapy the analysis is carried out at first every other day, then at an interval of 3-5 days. During the subsequent period – 1 time in 7-10 days, at remission – 1 time in 1-2 weeks. Before each administration of drug on existence of ulcerations the mucous surface of a mouth and throat is inspected. It is necessary to check: systematically – activity of hepatic transaminases, function of kidneys (clearance of creatinine, an urea nitrogen), the level of concentration of uric acid in blood; periodically – roentgenoscopic researches of bodies of a thorax. The condition of a marrowy hemopoiesis is checked three times (prior to therapy, during treatment, after end of a course).

Effect of drug can cause an acute or chronic hepatotoxic, including fibrosis and cirrhosis. A chronic hepatotoxic can turn out to be consequence of reception of the general cumulative dose of 1,5 g or long (2 and more years) therapies by a methotrexate and to lead to a fatal outcome.

Considering toxic impact of a methotrexate on the patient's organism, it is necessary to avoid co-administration of other hepatotoxic means, except cases of obvious need.

Degree of toxic effect of drug can be caused by the burdening concurrent factors, such as obesity, alcoholism, diabetes mellitus and advanced age of the patient.

For objective assessment of function of a liver except biochemical parameters it is recommended to use these biopsies of a liver received prior to the beginning of or after 2-4 months of treatment.

In case of moderate fibrosis of a liver or existence of symptoms of cirrhosis the methotrexate should be cancelled, when diagnosing an easy form of fibrosis repeated carrying out a biopsy in 6 months is recommended. At minor histologic changes of a liver (an easy portal inflammation, fatty changes) it is necessary to observe extra care at further use of drug.

At a stomacace and diarrhea it is necessary to interrupt therapy with a methotrexate because of big risk of development of hemorrhagic enteritis and a perforation of a wall of intestines.

Patients should avoid influence of direct sunshine and ultra-violet radiation not to allow development of reaction of a photosensitization.

It is necessary to consider influence of drug on immune system when conducting immunoassays and possible deterioration in reaction to vaccination. Therefore during 3-12 months after drug withdrawal immunization is not shown to the patient (except the cases recommended by the doctor), the persons living with the patient should cancel immunization against poliomyelitis. The patient needs to be masked to avoid contact with the people receiving a vaccine against poliomyelitis.

During treatment patients of childbearing age need to apply reliable methods of contraception, and also after the end of therapy – to men within 3 months, to women – throughout not less after one ovulyatsionny cycle.

For reduction of toxicity of high doses of a methotrexate after a course of treatment reception of calcium of a folinat is shown to the patient.

In view of influence of drug on the central nervous system (dizzinesses, feeling of fatigue), patients need to refrain from control of vehicles or mechanisms during therapy.

Medicinal interaction

As drug is cytotoxic, the concomitant use of any medicines has to be coordinated with the attending physician. Considering properties and features of the Methotrexate, a condition of the patient and medicinal interaction of drugs, the doctor will make the recommendations allowing to avoid emergence of heavy side effects.