Index of drugs

Treatment of 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. Treatment of children and adolescents with Ph + CML in the chronic phase when treatment with alpha Interferon is ineffective or in the accelerated phase of the disease or in the course of blast crisis. Treatment of adult patients with Ph + CML in blast crisis. Treatment of adult patients with newly diagnosed Philadelphia chromosome (Ph + ALL) acute lymphoblastic leukemia in combination with chemotherapy. Treatment of adult patients with recurrent or refractory Ph + ALL monotherapy. Treatment of adult patients with myelodysplastic / myeloproliferative syndromes (MDS / MPD) associated with the rearrangement of the platelet derived growth factor receptor (PDGFR) gene. Treatment of adult patients with advanced hypereosinophilic syndrome (HES) and / or chronic eosinophilic leukemia (CEL) with FIP1L1-PDGFRα rearrangement. Treatment of adult patients with inoperable dermatofibrosarcoma (DFSP) and adult patients with recurrent and / or metastatic DFSP who are not eligible for surgery.warning. The effect of imatinib on the effect of bone marrow transplantation was not determined. 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 rates in Ph + ALL, MDS / MPD, hematologic response rate in HES / CEL and based on an objective response rate in adult patients with inoperable and / or metastatic DFSP. 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 capsule contains 100 mg of imatinib as mesilate.

An anti-cancer drug - a protein-tyrosine kinase inhibitor.

Hypersensitivity to the active substance or to any of the excipients.

There are limited data on the use of imatinib in pregnant women; Animal studies have shown reproductive toxicity. Imatinib 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 potential should 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 of the infant to the drug is low (~ 10% of the treatment dose). However, because the effects of exposure to an infant on low doses of imatinib are unknown, women who take imatinib should not breast-feed.

Very common: neutropenia, thrombocytopenia, anemia, headache, nausea, diarrhea, vomiting, indigestion, abdominal pain, periorbital edema, dermatitis, eczema, rash, muscle spasms, musculoskeletal pain (including muscle, joint and bone pain) , fluid retention and swelling, fatigue, weight gain. Common: pancytopenia, febrile neutropenia, anorexia, insomnia, dizziness, paresthesia, taste disturbances, hypoaesthesia, eyelid edema, increased tearing, conjunctival haemorrhage, conjunctivitis, dry eye, blurred vision, facial flushing, bleeding, shortness of breath, nosebleed , cough, flatulence, 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, swelling of subcutaneous tissue, chills, stiff muscles, weight loss. Uncommon: virus infectionHerpes simplex, H. zoster, nasopharyngitis, pneumonia, sinusitis, cellulitis, upper respiratory tract infection, influenza, urinary tract infection, gastroenteritis, sepsis, thrombocytosis, lymphopenia, bone marrow suppression, eosinophilia, lymphadenopathy, hypokalaemia, increased appetite, hypophosphatemia, decreased appetite, dehydration, gout, hyperuricemia, hypercalcemia, hyperglycemia, hyponatremia, depression, decreased libido, anxiety, migraine, drowsiness, fainting, peripheral neuropathy, memory disorders, sciatica, restless legs syndrome, tremor, cerebral haemorrhage eye irritation, eye pain, orbital edema, scleral haemorrhage, retinal hemorrhage, blepharitis, macular edema, dizziness, tinnitus origin, tinnitus, hearing loss, palpitations, tachycardia, congestive heart failure, pulmonary edema, hypertension, hematoma, Subdural hematoma, cold toes and hands, hypotension, Raynaud's syndrome, pleural effusion, sore throat and larynx, pharyngitis, stomatitis, mouth ulcer, gastrointestinal haemorrhage, belching, tarry stools, esophagitis, ascites, gastric ulcer, bloody vomiting, inflammation lips, dysphagia, pancreatitis, hyperbilirubinemia, hepatitis, jaundice, pustular rash, bruising, increased sweating, urticaria, subcutaneous hemorrhage, increased tendency to bruise, sclerosis, discoloration of the skin, exfoliative dermatitis, nail fragility, folliculitis , ecchymosis, psoriasis, purpura, excessive skin pigmentation, blistering rashes, joint and muscle stiffness, kidney pain, hematuria, acute renal failure, frequent urination, gynecomastia, erectile dysfunction, menorrhagia, irregular menstrual bleeding, sexual dysfunction, nipple pain , enlarged breast, scrotal edema, chest pain, malaise, increased blood creatinine, increased CPK activity in the blood, increased LDH activity in the blood, increased ALP activity in the blood. Rarely: fungal infections, tumor lysis 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, inflammation of the large intestine, liver failure, hepatic necrosis, acute dermatosis with fever and neutrophilia (Sweet's syndrome), discolored nails, edema vasomotor, rash vesicle, erythema multiforme, leukoclastic vasculitis, Stevens-Johnson syndrome, acute generalized pustular exanthema (AGEP), muscle weakness, arthritis, rhabdomyolysis / myopathy, hemorrhagic yellow body / hemorrhagic ovarian cyst, increased activity blood amylase. Not known: tumor bleeding / tumor necrosis, anaphylactic shock, cerebral edema, intravitreal haemorrhage, pericarditis, cardiac tamponade, thrombosis / embolism, acute respiratory failure (there have been reports of deaths in patients with advanced disease, severe infections, severe neutropenia and other serious comorbidities), interstitial lung disease, intestinal obstruction, gastrointestinal perforation, diverticulitis, gastric widening of the gastric bypass (so-called watermelon stomach), hand-foot syndrome, lichenoid hyperplasia, lichen planus, toxic necrotic separation of the epidermis , drug rash with eosinophilia and systemic symptoms (DRESS), idle femoral necrosis / femoral head necrosis, growth retardation in children, chronic renal failure. Cases of necrotizing cholestatic hepatitis and hepatic failure have been reported; some of them ended in deaths, including the death of a patient after taking a high dose of paracetamol.

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 ≥30% or the presence of extramedullary outbreaks of the disease other than in the liver or spleen). In clinical trials, imatinib 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 have severe side effects and serious neutropenia or thrombocytopenia without leukemia, a dose increase from 600 mg to 800 mg (given in two doses of 400 mg) may be considered in the treatment of blast crisis in the following cases: disease progression (every step); 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.CML in children: dosage should be determined based on the body surface area (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 drug can be given as one dose per day or can be divided into two parts - one administered in the morning and the other in the evening. No experience in the treatment of children <2 years. In children who have no serious side effects and serious 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.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 imatinib 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.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.DFSP in adults: 800 mg / day.Dosage adjustment due to side effects. Non-haematological side effects. If serious 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 -neutropenia, thrombocytopenia. HES / CEL (initial dose 100 mg): ANC <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).HES / CEL (after 400 mg dose), MDS / MPD (initial dose 400 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. 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.CML in the blast crisis phase in adults, Ph + ALL (initial dose 600 mg)ANC <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 <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 (800 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. 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 liver failure: 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 insufficiency: 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; if the dose is tolerated, it can be increased if there is no efficacy.Elderly patients: no special dosage required.Children and youth. There is no experience in children with CML <2 years of age. The use experience in children and adolescents with Ph + ALL is limited. The experience of use in children and adolescents with MDS / MPD, DFSP, HES / CEL is very limited, there are no dosing recommendations.Way of giving. The drug should be taken with a meal, washed down with a large glass of water. The daily dose of 400 mg and 600 mg should be given once a day, while a daily dose of 800 mg should be given in two divided doses (400 mg in the morning and 400 mg in the evening). For patients who are unable to swallow the capsules, the contents of the capsules can be dissolved in a glass of non-carbonated water or apple juice. Due to the potential toxicity of imatinib for the human fetus, women of childbearing age who open the capsules should avoid contact of the powder with the skin, eyes and not inhale it.