Index of drugs

Treatment: children and adolescents with newly diagnosed chronic myeloid leukemia (CML) with Philadelphia chromosome (Bcr-Abl, Ph +) who are not eligible for bone marrow transplantation as first-line treatment; children and adolescents with Ph + CML in the chronic phase when alpha-interferon therapy is ineffective or in the accelerated phase of the disease or in the course of blast crisis; adult patients with Ph + CML in the course of blast crisis; adult patients with newly diagnosed Philadelphia chromosome acute lymphoblastic leukemia (Ph + ALL) in combination with chemotherapy; adult patients with recurrent or refractory Ph + ALL monotherapy; adult patients with myelodysplastic / myeloproliferative syndromes (MDS / MPD) associated with the rearrangement of the platelet derived growth factor receptor (PDGFR) gene; adult patients with advanced hypereosinophilic syndrome (HES) and / or chronic eosinophilic leukemia (CEL) with FIP1L1-PDGFRα rearrangement. The effects of imatinib on the outcome of bone marrow transplantation have not been evaluated. Treatment of adult Kit patients (CD 117) with positive inoperable and / or metastatic, gastrointestinal stromal tumor (GIST); adjuvant treatment of adult patients with a significant risk of recurrence after the removal of Kit (CD 117) - positive gastrointestinal stromal tumors (GIST). Patients with low or very low risk of relapse should not receive adjuvant treatment. Treatment of adult patients with inoperable dermatofibrosarcoma (DFSP) and adult patients with recurrent and / or metastatic DFSP who are not eligible for surgery.warning. In adult patients as well as children and adolescents, the efficacy of imatinib was assessed based on the overall hematology and cytogenetic response rate and disease-free survival in CML, hematologic and cytogenetic response rate in Ph + ALL, MDS / MPD, hematologic response rate in HES / CEL and on the basis of the objective response rate in adult patients with inoperable and / or metastatic GIST and DFSP and on the basis of survival without recurrence in adjuvant GIST. The experience with the use of imatinib in patients with MDS / MPD associated with PDGFR gene rearrangement is very limited. There are no controlled clinical trials showing a clinical benefit or increased survival in these indications.

1 tabl coated contains 400 mg of imatinib as mesilate.

Hypersensitivity to the components of the preparation.

Animal studies have shown reproductive toxicity. It should not be used during pregnancy unless clearly necessary (in such cases, the patient must be informed of the potential risk to the fetus). Women of childbearing age must be informed about the need to use effective contraception during treatment with the preparation. Imatinib and its active metabolite can pass into breast milk. Considering the combined concentration of imatinib and metabolite and the maximum daily intake of milk by infants, the total predicted exposure is low (~ 10% of the treatment dose). Because the effects of exposure of an infant to low-dose imatinib are unknown, imatinib women should not breast-feed.

Very common: neutropenia, thrombocytopenia, anemia, headache (most commonly in patients with GIST), nausea, vomiting, diarrhea, indigestion, abdominal pain (abdominal pain and gastrointestinal haemorrhage were most commonly observed in patients with GIST), periorbital edema, inflammation skin, eczema, rash, muscle spasms, musculoskeletal pain (including muscle, joint and bone pain, more frequent in patients with CML compared with patients with GIST), fluid retention and edema, fatigue, weight gain.Common: pancytopenia, febrile neutropenia, anorexia, insomnia, dizziness, paresthesia, disturbance of taste, hypoaesthesia, eyelid edema, increased tearing, conjunctival haemorrhage, conjunctivitis, dry eye, blurred vision, facial flushing, bleeding (facial redness most commonly patients with GIST, and bleeding was most commonly observed in patients with GIST and in patients with CML after transformation - CML-AP and CML-BC), dyspnea, nosebleed, cough, bloating, abdominal distension, gastro-oesophageal reflux, constipation, dry mouth, gastritis, increased liver enzymes, pruritus, facial edema, dry skin, erythema, alopecia, night sweats, photosensitivity reaction, swollen joints, weakness, fever, subcutaneous edema, chills, muscle stiffness, weight loss body. Uncommon: virus infectionHerpes simplex, H. zoster, nasopharyngitis, pneumonia (most commonly in patients with transformed CML and patients with GIST), sinusitis, cellulitis, upper respiratory tract inflammation, influenza, urinary tract inflammation, gastroenteritis, sepsis, thrombocytosis, lymphopenia, inhibition bone marrow function, eosinophilia, enlarged lymph nodes, hypokalemia, increased appetite, hypophosphatemia, decreased appetite, dehydration, gout, hyperuricemia, hypercalcemia, hyperglycemia, hyponatremia, depression, decreased libido, anxiety, migraine, drowsiness, syncope, peripheral neuropathy, memory, sciatica, restless legs syndrome, tremor, cerebral hemorrhage, eye irritation, eye pain, orbital edema, scleral haemorrhage, retinal hemorrhage, blepharitis, macular edema, dizziness, tinnitus, hearing loss, palpitation, tachycardia, congestive heart failure (more frequently seen in patients with C ML after transformation than in patients with CML in the chronic phase), pulmonary edema, hypertension, hematoma, cold fingers and toes, hypotension, Raynaud's syndrome, pleural effusion (more often in patients with GIST and in patients with CML after transformation - CML-AP and CML-BC than in patients with chronic phase CML), sore throat and laryngitis, pharyngitis, stomatitis, mouth ulcer, gastrointestinal haemorrhage, belching, tarry stools, esophagitis, ascites, gastric ulcer, bloody vomiting, inflammation of the lips, dysphagia, pancreatitis, hyperbilirubinaemia, hepatitis, jaundice, pustular rash, bruising, severe sweating, urticaria, subcutaneous hemorrhage, increased tendency to bruise, scant hair, skin discoloration, exfoliative dermatitis, nails fragility, inflammation of the hair follicles, petechiae, psoriasis, purpura, excessive skin pigmentation, blistering rashes, stiffness joints and muscles, kidney pain, hematuria, acute renal failure, frequent urination, gynecomastia, erectile dysfunction, menorrhagia, irregular menstruation, sexual dysfunction, nipple pain, breast enlargement, scrotal edema, chest pain, malaise, increased creatinine and creatine phosphokinase, lactate dehydrogenase and alkaline phosphatase in the blood. Rarely: fungal infections, tumor decay syndrome, hemolytic anemia, hyperkalemia, hypomagnesaemia, confusion, increased intracranial pressure, seizures, optic neuritis, cataracts, glaucoma, congestive disc, arrhythmia, atrial fibrillation, cardiac arrest, myocardial infarction, angina pectoris , pericardial effusion, pain associated with pleurisy, pulmonary fibrosis, pulmonary hypertension, pulmonary haemorrhage, colitis, ileus, colitis, liver failure, hepatic necrosis (including deaths), acute dermatosis with fever and neutrophilia (Sweet's syndrome) ), nail discoloration, angioneurotic edema, follicular rash, erythema multiforme, leukoclastic vasculitis, Stevens-Johnson syndrome, acute generalized pustular exanthema (AGEP), muscle weakness, arthritis, rhabdomyolysis / myopathy, hemorrhagic yellow body / hemorrhagic ovarian cyst, blood amylase activity.After marketing, tumor haemorrhage / tumor necrosis, anaphylactic shock, cerebral edema, intravitreal haemorrhage, pericarditis, cardiac tamponade, thrombosis / embolism, acute respiratory failure (deaths were reported in patients with advanced disease, severe infections, severe neutropenia and other serious comorbidities), interstitial lung disease, intestinal obstruction, gastrointestinal perforation, diverticulitis, palm-plantar erythrodysaesthesia, lichenoid hypersecretion, lichen planus, toxic necrotic epidermal separation, sterile osteonecrosis of the femur / femoral head necrosis , growth retardation in children.

Orally. Treatment should be carried out by a doctor who has experience in the treatment of patients with hematologic malignancies and sarcoma.CML in adults: in the course of blast crisis, 600 mg / day (blast crisis is defined as a condition in which the number of blasts in the blood or bone marrow is ≥30% or the presence of extramedullary outbreaks of the disease other than in the liver or spleen). In clinical trials, treatment was continued until the disease progressed. The effect of cessation of treatment after full cytogenetic response has not been studied. In patients who do not experience severe adverse reactions and severe neutropenia or thrombocytopenia without leukemia, a dose increase from 600 mg to 800 mg may be considered for the treatment of blast crisis in the following cases: disease progression (at each stage); no satisfactory haematological response after at least 3 months of treatment; no cytogenetic response after 12 months of treatment; loss of a previously achieved hematological and / or cytogenetic response. After dose increase, patients should be carefully observed as it may increase the severity of side effects.CML in children: dosage should be determined based on the body surface area (mg / m² pc.). A dose of 340 mg / m is recommended for children with chronic CML and advanced CML phases² pc. daily (do not use a total dose greater than 800 mg). The preparation can be given in one dose per day or the daily dose can be divided into two parts - one administered in the morning and the other in the evening. Dosage recommendations are based on the use of a small number of children and adolescents. No experience in the treatment of children <2 years. In children who have no serious side effects and severe neutropenia or thrombocytopenia without leukemia, a dose increase of 340 mg / m² pc. up to 570 mg / m² pc. daily (do not use a total dose greater than 800 mg) in the following cases: disease progression (at each stage); no satisfactory haematological response after at least 3 months of treatment; no cytogenetic response after 12 months of treatment; loss of a previously achieved hematological and / or cytogenetic response. After dose increase, patients should be carefully observed as it may increase the severity of side effects.Ph + ALL in adults: 600 mg / day in combination with chemotherapy during induction, consolidation and maintenance treatment. The duration of treatment may vary depending on the treatment program chosen, but in general longer exposure to the preparation gave better results. For patients with relapsed or refractory Ph + ALL, monotherapy with 600 mg / day imatinib is safe, effective and can be used until the disease progresses. In all phases of treatment, it is necessary to supervise haematologists experienced in managing patients with this disease.MDS / MPD in adults: 400 mg / day. Duration of treatment: in the only clinical study conducted so far, treatment continued until progression of the disease. At the time of the analysis, the median duration of treatment was 47 months (24 days - 60 months).HES / CEL in adults: 100 mg / day. An increase in the 100 mg to 400 mg dose may be considered in the absence of side effects if the studies show an inadequate response to treatment. Treatment should be continued for as long as the patient benefits from it.GIST in adults. Non-surgical and non-surgical GISTs (or) with metastases: 400 mg / day.Data on the increase in the dose of 400 mg to 600 mg or 800 mg in patients with progression at the lower dose are limited. Duration of treatment: in clinical trials in patients with GIST, the drug was administered until disease progression. At the time of data analysis, the median duration of treatment was 7 months (from 7 days to 13 months). The effect of stopping treatment after reaching a response to treatment has not been examined. Adjuvant treatment after GIST resection: 400 mg / day. The optimal duration of treatment has not yet been determined. The duration of treatment in this indication in the clinical trial was 12 months.DFSP in adults: 800 mg / day.Dosage adjustment due to side effects. Non-haematological side effects. If severe side effects occur, treatment with imatinib should be discontinued until resolution. Then, depending on the initial severity of the adverse event, appropriate treatment can be resumed. If the bilirubin concentration exceeds the upper limit of normal (ULN) by 3 times or hepatic transaminase levels exceed 5-fold ULN, the drug should be discontinued until the bilirubin concentration <1.5 times the GGN value and transaminases <2.5 -GGN value. Treatment can be continued with reduced daily doses. In adults, the dose should be reduced from 400 mg to 300 mg or 600 mg to 400 mg or 800 mg to 600 mg, and in children with 340 mg / m² pc. up to 260 mg / m² pc. per day.Hematologic side effects - thrombocytopenia, neutropenia. HES / CEL (initial dose100 mg): ANC absolute neutrophil count <1.0 x 10⁹/ l and / or platelets <50 x 10⁹/ l - 1. discontinue the drug until ANC ≥ 1.5 x 10⁹/ l and platelets ≥75 x 10⁹/ L; 2. restart treatment at the previously used dose (ie before the onset of a serious side effect). MDS / MPD and GIST (initial dose 400 mg), HES / CEL (after 400 mg dose): ANC <1.0 x 10⁹/ l and / or platelets <50 x 10⁹/ l - 1. discontinue treatment until ANC ≥ 1.5 x 10⁹/ l and platelets ≥75 x 10⁹/ L; 2. restart treatment at the previously used dose (i.e. before the onset of a serious side effect); 3. if the ANC is again decreased <1.0 x 10⁹/ l and / or platelets <50 x 10⁹/ l, repeat the procedure given in point 1, and then return to administration of the drug in a dose reduced to 300 mg.CML in the chronic phase in children and adolescents (after a dose of 340 mg / m² pc.): ANC <1.0 x 10⁹/ l and / or platelets <50 x 10⁹/ l - 1. discontinue treatment until ANC ≥ 1.5 x 10⁹/ l and platelets ≥75 x 10⁹/ L; 2. restart treatment at the previously used dose (i.e. before the onset of a serious side effect); 3. if the ANC is again decreased <1.0 x 10⁹/ l and / or platelets <50 x 10⁹/ l, repeat the procedure given in point 1, and then return to administration of the drug at a dose reduced to 260 mg / m² pc.Blast crisis and Ph + ALL (initial dose 600 mg): ANC after at least 1 month of treatment <0.5 x 10⁹/ l and / or platelets <10 x 10⁹/ l - 1. check if blood cell deficiency is caused by leukemia (bone marrow aspiration or biopsy); 2. if the blood cell deficiency is not related to leukemia, reduce the dose of imatinib up to 400 mg; 3. if the blood cell deficiency persists for 2 weeks, reduce the dose to 300 mg; 4. if the blood cell deficiency persists for 4 weeks and is still not due to leukemia, discontinue treatment until ANC ≥ 1 x 10⁹/ l and platelets ≥ 20 x 10⁹/ l, then resume treatment with a 300 mg dose.CML in the acceleration and blast crisis phase in children and adolescents (initial dose of 340 mg / m² pc.): ANC after at least 1 month of treatment <0.5 x 10⁹/ l and / or platelets <10 x 10⁹/ l - 1. check if blood cell deficiency is caused by leukemia (bone marrow aspiration or biopsy); 2. if the lack of blood cells is not related to leukemia, reduce the dose to 260 mg / m² pc .; 3. if the blood cell deficiency persists for 2 weeks, reduce the dose to 200 mg / m² pc .; 4. if the blood cell deficiency persists for 4 weeks and is still not caused by leukemia, discontinue treatment until ANC ≥ 1 x 10⁹/ l and platelets ≥20 x 10⁹/ l, then resume treatment at a dose of 200 mg / m² pc.DFSP (at a dose of 800 mg): ANC <1.0 x 10⁹/ l and / or platelets <50 x 10⁹/ l - 1.discontinue treatment until ANC ≥ 1.5 x 10⁹/ l and platelets ≥75 x 10⁹/ L; 2. resume treatment at a dose of 600 mg; 3. if the ANC is reduced again <1.0 x 10⁹/ l and / or platelets <50 x 10⁹/ l, repeat the procedure given in point 1, and then return to administration of the drug at a dose reduced to 400 mg.Special groups of patients. Patients with mild, moderate or severe hepatic impairment should receive the minimum recommended dose of 400 mg / day; this dose can be reduced if you are intolerant. Patients with renal impairment or dialysis should receive the minimum recommended dose of 400 mg / day as the starting dose; the dose may be reduced in the case of intolerance; the dose may be increased in the absence of efficacy. There is no need for special dosing in elderly patients.Wayapplication. The tablet can be divided into equal doses. The tablets should be taken with a large glass of water during a meal. Doses of 400 mg and 600 mg should be administered once daily, while a daily dose of 800 mg should be given in two doses of 400 mg in the morning and in the evening. For patients who are unable to swallow tablets, you can suspend the tablets in a glass of non-carbonated water or apple juice (about 200 ml on a 400 mg tablet) and mix. The suspension should be administered after complete disintegration of the tablet.