Gleevec - a protein tyrosine kinase inhibitor, an antineoplastic agent.
release form and composition
- opaque capsules: size №3 - labeled «NVR SH» red ink, from orange-yellow to light yellow in color or size №1 - labeled «NVR SI»from orange to gray shade to orange;contents of capsules - powder white with a yellow tint (№3 size: 10 pieces in blister packs in a cardboard unit 3 blisters; №1 size: 12 pieces in blister packs in a cardboard unit 2, 3, 4, 8, 10..blisters or 15);
- Coated tablets: brownish orange to dark yellow, biconvex, beveled: round - on one side marked «NVR», on the other - «S» and «A» on both sides of the separation risks or oval- marking on one side "400", on the other - «SL» and «SL» on both sides of the risk (10 pieces in blister packs in a cardboard bundle: 100 mg - 2 or 6 blisters with 400 mg - 1.or 3 blisters).
The active substance of Glivec - imatinib mesylate:
- 1 capsule (size №3 / size №1) - 59,75 mg / 119.5 mg, which is equivalent to the content of imatin
ib 50 mg / 100 mg;
- 1 tablet (round / oval) - 119.5 mg / 478 mg, which is equivalent to the content of imatinib 100 mg / 400 mg.
- capsules: titanium dioxide, microcrystalline cellulose, colloidal anhydrous silica, crospovidone, magnesium stearate, iron oxide yellow dye, gelatin;
- Tablets: crospovidone, microcrystalline cellulose, hypromellose, magnesium stearate, colloidal silicon dioxide, macrogol 4000, iron oxide yellow, red iron oxide, talc.
Additionally, the composition of capsules: ink - soy lecithin, iron oxide red dye (E172), shellac.
The use of Glivec is indicated for the treatment of oncological pathologies in adult patients:
- monotherapy in recurrent or refractory PH-positive acute lymphoblastic leukemia (ALL);
- combination with chemotherapy in newly diagnosed Philadelphia chromosome-positive (Ph +) ALL;
- Myeloproliferative and myelodysplastic diseases caused by gene rearrangements factor receptor platelet growth;Systemic mastocytosis
- the lack D816V c-Kit mutation or unknown mutation status c-Kit;
- Chronic eosinophilic leukemia and / or hypereosinophilic syndrome with positive or negative anomalous FIP1L1-PDGRF alpha tyrosine kinase;
- Gastrointestinal stromal malignancies positive for c-Kit (CD 117) in metastatic or unresectable stage;
- dermatofibrosarcoma protuberans in metastatic, recurrent, and / or unresectable stage;
- Gastrointestinal stromal tumors positive for c-Kit (CD 117) for adjuvant therapy.
addition, Glivec is prescribed for adults and children:
- Philadelphia chromosome-positive (Ph +) chronic myeloid leukemia (CML) revealed for the first time;
- PH-positive chronic myeloid leukemia in step with no effect of the prior treatment with interferon alpha, as well as blast crisis phase or acceleration.
- Pregnancy and breast-feeding;
- age of 2 years;
- hypersensitivity to the drug.
Precautions recommended for Glivec in patients with severe renal dysfunction, regular hemodialysis treatments, severe liver disease, cardiovascular disease or risk factors for heart failure.
Dosage and Administration
Glivec is taken orally with meals, abundantly (at least 1 cup) with water.
If necessary, tablets or capsules, the content can be dissolved in water or apple juice to form a slurry.The suspension was prepared immediately before taking a proportion of 50 ml liquid formulation or 100 mg per 100 ml - 400 mg.
dose and treatment period determined by a physician based on clinical indications.
Purpose of 400 and 600 mg taken once a day 1, 800 mg - 2 divided doses (morning and evening) 400 mg.
- Chronic myeloid leukemia: chronic phase - 400 mg per day, in accelerated phase and blast crisis - 600 mg per day.With good tolerability and absence of neutropenia, thrombocytopenia or other unwanted effects, showing increasing doses up to 800 mg in the progression of any stage CML absence after 3 months of therapy satisfactory hematological or 12 months - cytogenetic response and, in case of loss of the previously reached hematological and / orcytogenetic indices.For children (2 years of age), the dose determined on the basis of body surface area - 340 mg per 1 m2 but not more than 600 mg per day.The calculated dose the child can be taken once or in equal parts, 2 times a day;
- PH-positive acute lymphoblastic leukemia: 600 mg per day;
- Myeloproliferative and myelodysplastic disease: 400 mg per day;
- metastatic and / or unresectable malignant gastrointestinal stromal tumors gastrointestinal tract (GIT): 400 mg per day, in low clinical effect and the absence of side reactions the dose may be increased to 600 or 800 mg.Patients with evidence of progression of disease receiving Glivec should be abolished;
- Adjuvant therapy of gastrointestinal stromal tumor: 400 mg per day for 36 months or more;
- dermatofibrosarcoma protuberans (inoperable, recurrent and / or metastatic): 800 mg per day;Systemic mastocytosis
- absence D816V c-Kit mutations: 400 mg.Patients with unknown mutation status and with little effect of the previous treatment - 400 mg per day;
- Systemic mastocytosis due to abnormal FIP1L1-PDGFR alpha fusion tyrosine kinase genes in the background Fip like1 and PDGFR: initial dose - 100 mg per day, with a possible increase to 400 mg per day;
- hypereosinophilic syndrome and / or chronic eosinophilic leukemia (HES / CEL): adult patients - 400 mg per day.When HES / HAL from the anomalous FIP1L1-PDGFR-alpha kinase - initial dose should be 100 mg per day, and to increase the efficiency in the absence of serious adverse effects, the dose can be increased to 400 mg per day.
Receiving Imatinib lasts until the termination of the clinical effect.
patients with mild, moderate or severe form of the functional liver disorder drug administered in a daily dose of no more than 400 mg.With the development of toxic side effects, the dose should be reduced.Particular caution should be exercised when administering the drug to patients with severe hepatic insufficiency.
If the kidney function, including severe or systematic hemodialysis initial dose is 400 mg 1 time per day.
Patients with poorly tolerated imatinib starting dose may be reduced at low efficiency - increase.
correction dosing regimen for elderly patients is not required.
In case of serious non-hematologic adverse events in patients receiving Glivec treatment should be repealed before the elimination of the symptoms of disorders of the patient.
drug overturned by increasing the concentration of bilirubin in 3 times, liver transaminases in blood serum - 5 times higher than in congenital adrenal hyperplasia (CAH).After the restoration of the bilirubin concentration (less than 1.5 × ULN) and the liver transaminases (less than 2.5 × ULN) the drug is resumed.Treatment continues by lowering the initial daily dose: 800 mg to 600 mg, from 600 mg to 400 mg, from 400 mg to 300 mg;in children - from 340 to 260 mg per 1 m2.
Temporary cancellation of therapy or dose reduction is required for the appearance of neutropenia and thrombocytopenia.
for systemic mastocytosis and HES / CEL (caused by abnormal FIP1L1-PDGFR alpha-tyrosine kinase), chronic phase CML (adults and children), malignant stromal gastrointestinal tumors, myelodysplastic or myeloproliferative pathologies, systemic mastocytosis and HES / CEL after reaching an absolute neutrophil count1500 / l and platelet count more than 75,000 / microliter shown resumption of treatment in the initial dose.In case of repeated reduction in the number of neutrophils and platelets after another cancellation treatment should be initiated at a dose: adults - 300 mg, children - 260 mg per 1 m2.
patients with an absolute neutrophil count less than 500 / l and / or platelet count less than 10,000 / microliter patients with PH-positive acute lymphoblastic leukemia and CML in accelerated phase and blast crisis (children and adults) after one or more months of therapy, make surethat is not associated with cytopenia leukemia.If cytopenia is not due to leukemia dose of Glivec is reduced to 400 mg in adults and up to 260 mg per 1 m2 in children, while maintaining cytopenia after 2 weeks of therapy dose should be again reduced to 300 mg and 200 mg per 1 m2, respectively.If no effect after 4 weeks of drug therapy to restore the overturned absolute neutrophil count to 1000 / mm and more platelets 20,000 / ul.Adults begin receiving a dose of 300 mg, children - 260 mg per 1 m2.
When dermatofibrosarcoma protuberans in unresectable, recurrent and / or metastatic after discontinuation resume treatment at a dose of 600 mg, with repeated decrease in the number of neutrophils and / or platelet count - 400 mg after recovery state.
In clinical studies, the use of Glivec in patients with unresectable and / or metastatic stromal malignant neoplasms of the gastrointestinal tract and CML following side effects observed:
- Infectious diseases: rare - sinusitis, herpes zoster, nasopharyngitis, herpes simplex, pneumonia,cellulitis, influenza, infections of the upper respiratory tract, gastroenteritis, septicemia, urinary tract infection;rarely - fungal infections;
- malignant, and unspecified Benign tumors, including polyps and cysts: rare - cider tumor lysis;
- hemopoietic system: very often - thrombocytopenia, neutropenia, anemia;often - febrile neutropenia, pancytopenia;infrequently - lymphopenia, thrombocythemia, inhibition of bone marrow hematopoiesis, lymphadenopathy, eosinophilia;rarely - hemolytic anemia;
- Metabolism: often - anorexia;rarely - a violation of appetite, hypokalemia, hypophosphatemia, hyperuricemia, hyponatremia, dehydration, gout, hyperglycemia, hypercalcemia;rarely - hypomagnesemia, hyperkalemia;
- nervous system: very often - headache;often - taste disturbance, insomnia, dizziness, hypoesthesia, paresthesia;rarely - hemorrhagic stroke, peripheral neuropathy, syncope, somnolence, memory impairment, migraine, sciatica, tremor, restless legs syndrome, depression, decreased libido, anxiety;rarely - increased intracranial pressure, optic neuritis, seizures, confusion;
- sensory organs: often - increase lacrimation, eyelid edema, conjunctival hemorrhage, dry eye, blurred vision, conjunctivitis;infrequently - eye pain, eye irritation, orbital edema, macular edema, retinal hemorrhage, bleeding in the sclera of the eye, blepharitis, tinnitus, vertigo, hearing loss;rare - swelling of the optic nerve, cataract, glaucoma;
- Cardiovascular system: Infrequent - hot flashes, palpitations, tachycardia, congestive heart failure, hemorrhage, pulmonary edema;rarely - angina, arrhythmias, lowering blood pressure, pericardial effusion, atrial fibrillation, myocardial infarction, sudden cardiac arrest, hypertension, cold extremities, bruises, Raynaud's syndrome, hypotension;
- Respiratory system: often - shortness of breath, nosebleeds, cough;rarely - pain in the throat or larynx, pleural effusion, pharyngitis;rarely - pulmonary fibrosis, pleural pain, pulmonary hemorrhage, pulmonary hypertension;
- digestive system: very often - indigestion, nausea, vomiting, abdominal pain, diarrhea;often - dry mouth, flatulence, constipation, bloating, gastro-oesophageal reflux, gastritis, elevated liver enzymes;infrequently - regurgitation, stomatitis, gastrointestinal bleeding, ulceration of the mucous membranes of the mouth, melena, ascites, esophagitis, gastric ulcer, cheilitis, vomiting blood, pancreatitis, dysphagia, hyperbilirubinemia, hepatitis, jaundice;rarely - paralytic or obstructive ileus, colitis, inflammatory bowel disease, hepatic necrosis, hepatic failure;
- Dermatological reactions: very often - skin rash, dermatitis, periorbital edema, eczema;often - dry skin, itching, swelling of the face, erythema, night sweats, photosensitivity reaction, alopecia;infrequently - bruises, pustular rash, increased sweating, ecchymosis, urticaria, increased susceptibility to bruise, skin hyperpigmentation or hypopigmentation, exfoliative dermatitis, hypotrichosis, nail damage, petechiae, folliculitis, psoriasis, bullous rash, purpura;rarely - acute febrile neutrophilic dermatosis (Sweet's syndrome), nail changes color, angioedema, leykoklastichesky vasculitis, Stevens-Johnson syndrome, erythema multiforme, acute generalized pustular rash;
- Musculoskeletal system: very often - myalgia, arthralgia, muscle cramps and spasms, bone pain and other musculoskeletal pain;often - swelling of the joints;infrequently - stiffness of joints and muscles;rarely - arthritis, muscle weakness;the frequency is unknown - slowing of growth in children;
- Urinary system: rare - frequent urination, hematuria, kidney pain, acute renal failure;
- reproductive system: rarely - erectile dysfunction, gynaecomastia, menorrhagia, sexual dysfunction, menstrual disorders, pain in the nipples, scrotal edema, breast enlargement;
- General reactions: often - edema, fluid retention, weight gain, fatigue;often - fever, fatigue, anasarca, shaking, shivering, reduction in body weight;infrequently - malaise, chest pain;
- Laboratory indicators: rarely - increased activity of alkaline phosphatase, creatine kinase, lactate dehydrogenase, and creatinine level in blood serum;rarely - increased activity of amylase in the blood plasma.
addition, when additional clinical studies were observed adverse reactions, the appearance of which with taking Glivec is not installed:
- Cardiovascular system: rarely - thrombosis or embolism;rarely - cardiac tamponade, pericardial effusion;very rarely - anaphylactic shock;
- Digestive system: Infrequent - paralytic or obstructive ileus, gastrointestinal tumor necrosis, bleeding from the gastrointestinal tract tumor, perforation of the gastrointestinal tract;rarely - diverticulitis;
- Respiratory system: rare - interstitial pneumonia, acute respiratory failure;
- organ of vision: rarely - a hemorrhage in the vitreous;
- nervous system: rarely - swelling of the brain;
- Musculoskeletal System: rare - avascular necrosis of the femoral head necrosis, myopathy or rhabdomyolysis;
- reproductive system: very rarely - bleeding from the corpus luteum or ovarian cysts (women);
- Allergic reactions: very rarely - anaphylactic shock;
- Dermatological reactions: seldom - palmar-plantar eritrodizesteziya;rarely - lichen planus, lichenoid keratosis, toxic epidermal necrolysis.
Avoid contact with Glivec powder on the skin, the respiratory tract, eyes.
Treatment is carried out only under the supervision of oncologist.
The drug is recommended to accompany the scheduled clinical studies peripheral blood, kidney and liver functioning, careful observation of patients with heart disease.
Due to the risk of fluid pronounced delay is necessary to control the body weight of patients, especially in elderly patients with cardiovascular disease.If necessary, it is recommended to temporarily stop taking the drug.Keep away from children.
Shelf life - 3 years.