Imatinib-TL

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Imatinib-TL: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Imatinib-TL

ATX code: L01XE01

Active ingredient: Imatinib (Imatinib)

Manufacturer: TECHNOLOGY DRUGS LLC (Russia)

Description and photo update: 18.10.2018

Imatinib-TL is an anticancer drug that inhibits protein tyrosine kinase.

Release form and composition

Dosage form Imatinib-TL - capsules: hard gelatinous, filled with powder from white to yellow (with a possible brown tint); dosage 50 mg - size No. 3, white body and orange cap, dosage 100 mg - size No. 1, yellow body and lid (10 or 12 pcs. in cell contour packs, or 60, 100 or 120 pcs. in cans from polymer, in a cardboard box, 6, 10 or 12 packs, or 1 can).

The composition of 1 capsule Imatinib-TL includes:

active substance: imatinib mesylate - 59.75 or 119.5 mg (corresponds to the content of imatinib - 50 or 100 mg);
auxiliary ingredients: crospovidone, aerosil (colloidal silicon dioxide), microcrystalline cellulose, magnesium stearate.

Shell composition:

capsule No. 3: gelatin, titanium dioxide, azorubin dye (E122), sunset yellow dye (E110);
capsule number 1: gelatin, titanium dioxide, iron oxide yellow dye.

Pharmacological properties

Pharmacodynamics

According to the instructions, Imatinib has the following pharmacodynamic effects:

selectively inhibits the enzyme Bcr-Abl-tyrosine kinase, which is formed during the fusion of the protooncogene Abl (Abelson) and the Bcr gene region (breakpoint cluster region), at the cellular level, selectively suppressing proliferation and causing apoptosis of cell lines expressing Bcr-Abl-tyrosine kinase, in m h and immature leukemic cells, which are formed in Philadelphia chromosome-positive patients with acute lymphoblastic leukemia and CML (chronic myeloid leukemia);
selectively inhibits the growth of Bcr-Abl-positive colonies obtained from blood cells of patients with CML;
triggers apoptosis and inhibits mitosis of stromal tumor cells of the gastrointestinal tract (gastrointestinal tract), expressing tyrosine kinase with a mutation of the c-Kit receptor.

Activation of receptors for growth factors of the Abl-fragment of tyrosine kinase or platelets can cause the development of both myelodysplastic (MDS) and / or myeloproliferative (MPD) diseases, and hypereosinophilic syndrome, bulging dermatofibrosarcoma, chronic eosinophilic leukemia. Systemic mastocytosis may be based on the activation of the c-Kit receptor for tyrosine kinase, as well as receptors for platelet growth factors. Imatinib inhibits cell proliferation and signaling in cells, which are formed as a result of a malfunction of the regulation of the activity of platelet and stem cell growth factors, the c-Kit receptor and the Abl fragment of tyrosine kinase.

Pharmacokinetics

absorption: oral bioavailability of the drug is ~ 98%, AUC (area under the concentration-time curve coefficient) is from 40 to 60%; taking the drug on an empty stomach, in comparison with the simultaneous intake of food containing a large amount of fat, slightly increases the degree of absorption of the substance and slows down the rate of the process;
distribution: in studies of the use of imatinib in clinically significant doses in vitro, it was found that it binds up to 95% to blood plasma proteins (mainly albumin and acidic α-glycoprotein, in a small amount - with lipoprotein);
metabolism: the main metabolite of imatinib circulating in the bloodstream is an N-demethylated piperazine derivative, which has in vitro pharmacological action similar to that of the unchanged parent substance. The AUC value for the metabolite is only 16% of the AUC of imatinib, and the plasma protein binding of the metabolite is similar to that of imatinib;
excretion: it was experimentally determined that in 1 week up to 68% of the administered dose is excreted by the intestines, 13% by the kidneys. In this case, up to 25% is excreted unchanged (20% - by the intestines, 5% - by the kidneys), the remaining 75% are excreted in the form of metabolites. The half-life (T½) in healthy volunteers is about 18 hours. In the dose range of 25–1000 mg, there is a direct linear dependence of AUC on the dose. The use of repeated doses once a day does not change the pharmacokinetics of imatinib. The equilibrium concentration indicator (C _ss) exceeds the initial concentration by 1.5–2.5 times.

Indications for use

positive for the Philadelphia chromosome (Ph +) newly diagnosed chronic myeloid leukemia (CML) in adults and children;
Ph + XML in the chronic course in case of unsuccessful previous treatment with interferon alpha or in the phase of acceleration / blast crisis in adults and children;
Ph + newly diagnosed acute lymphoblastic leukemia (ALL) in combination with chemotherapy in adult patients;
Ph + ALL recurrent or refractory as monotherapy in adult patients;
MDS / MPZ diseases associated with gene rearrangements of the platelet growth factor receptor in adult patients;
systemic mastocytosis (CM) with no D816V c-Kit mutation or with unknown c-Kit mutation status in adult patients;
hypereosinophilic syndrome (HES) / chronic eosinophilic leukemia (CEL) with positive or negative abnormal FIP1L1-PDGFR α-tyrosine kinase in adult patients;
inoperable, recurrent / metastatic bulging dermatofibrosarcoma in adult patients.

Contraindications

Absolute:

the period of pregnancy and lactation (breastfeeding);
age up to 2 years;
hypersensitivity to imatinib or excipients of the drug.

Relative:

severe hepatic / renal impairment;
cardiovascular disease and / or the presence of risk factors for the development of heart failure;
regular hemodialysis.

Instructions for the use of Imatinib-TL: method and dosage

Imatinib-TL capsules are taken orally, during meals, with a large amount (up to 200 ml) of water.

The daily dose of imatinib 400 and 600 mg should be taken at one time; 800 mg is divided into 2 doses (400 mg each in the morning and evening).

If it is impossible to swallow the capsule whole (for example, for children), dilute its contents with water or apple juice. The contents of the capsule in the required dose are placed in a glass and filled with liquid in a volume of ~ 50 ml for a 100 mg capsule and stirred until a homogeneous suspension is formed. Immediately after preparation, the suspension must be taken orally.

Recommended doses of Imatinib-TL:

XML: chronic phase - 400 mg per day; the acceleration phase and blast crisis - 600 mg per day, the entire dose is taken at one time, the therapy is carried out until the clinical effect is observed. In the absence of pronounced adverse reactions (not associated with leukemia, neutropenia or thrombocytopenia), or, if necessary, in the chronic phase, the dose is increased from 400 to 600 or 800 mg per day, in the acceleration phase or in a blast crisis - from 600 to 800 mg per day … Such an increase may also be necessary in case of progression at any stage of CML, if there is no satisfactory hematological response after 3 months of therapy, cytogenetic response - after 12 months, or if a previously achieved hematological / cytogenetic response is lost. For children over 2 years of age, the dosage regimen is determined based on body surface area,so in the chronic phase of XMJI and the acceleration phase, the recommended dose is 340 mg / m² per day, the maximum daily dose for children is 600 mg. The daily dose can be taken at the same time or divided into 2 equal doses - morning and evening;
Ph + OLL: 600 mg per day;
MDS / MPZ of the disease: 400 mg per day (in case of signs of disease progression, imatinib should be discontinued);
inoperable, recurrent and / or metastatic bulging dermatofibrosarcoma: 800 mg per day;
CM in the absence of D816V c-Kit mutation, as well as in unknown mutation status and insufficient effectiveness of previous therapy: 400 mg per day;
SM caused by abnormal FIP1L1-PDGFR α-tyrosine kinase, formed as a result of the fusion of the Fip likel and PDGFR genes: the initial dose is 100 mg per day, in case of insufficient efficacy and in the absence of pronounced adverse reactions, the dose may be increased to 400 mg per day;
HES / HEL with positive or negative abnormal FIP1L1-PDGFR α-tyrosine kinase in adult patients: the initial dose is 100 mg per day, in case of insufficient efficacy and in the absence of pronounced adverse reactions, the dose may be increased to 400 mg per day.

Correction of the imatinib dosing regimen is necessary in the following cases:

the development of non-hematological side effects;
an increase in the concentration of bilirubin in the blood serum by 3 times, an increase in the activity of hepatic transaminases by 5 times or more from the upper limit of normal (UHN);
the development of serious adverse reactions from the blood and lymph system (severe thrombocytopenia and neutropenia).

Side effects

Long-term daily intake of Imatinib-TL capsules is generally well tolerated by adults and children with CML, most of the adverse reactions are mild to moderate. When receiving imatinib for various indications, the side effects are similar in almost all patients.

Most often, due to taking the drug, the following were recorded: anemia, thrombocytopenia, neutropenia, headache, edema, dyspepsia, weight gain, nausea / vomiting, diarrhea, muscle cramps, myalgia, rash, abdominal pain, weakness. All these side effects were easily controlled.

Adverse events observed in clinical trials of imatinib:

infections: infrequently - herpes simplex or herpes zoster, inflammation of the hypodermis, nasopharyngitis, sinusitis, pneumonia, upper respiratory tract infections, influenza, urinary tract infections, sepsis, gastroenteritis; sometimes - mycoses;
benign, malignant, unspecified neoplasms (including polyps and cysts): sometimes - tumor lysis syndrome;
circulatory and lymphatic systems: very often - thrombocytopenia, neutropenia, anemia; often - pancytopenia, neutropenic fever; infrequently - lymphopenia, thrombocythemia, inhibition of bone marrow hematopoiesis, lymphadenopathy, eosinophilia; sometimes - hemolytic anemia;
metabolism and nutrition: often - anorexia; infrequently - increased or decreased appetite, hyperglycemia, hypokalemia, hypophosphatemia, hyperuricemia, dehydration, gout, hypercalcemia, hyponatremia; sometimes - hyperkalemia, hypomagnesemia;
psyche: often - insomnia; infrequently - anxiety, depression, decreased libido; sometimes - confusion of consciousness;
nervous system: very often - headache; often - dizziness, taste disturbance, hypesthesia, paresthesia; infrequently - drowsiness, migraine, fainting, peripheral neuropathy, sciatica, memory impairment, tremor, restless legs syndrome, hemorrhagic stroke, cerebral edema; sometimes - convulsions, increased intracranial pressure, optic neuritis;
organ of vision: often - increased tearing, blurred vision, eyelid edema, conjunctivitis, conjunctival hemorrhage, dry eye syndrome; infrequently - pain and irritation in the eyes, hemorrhages in the sclera, orbital edema, blepharitis, retinal hemorrhages, macular edema; sometimes - edema of the optic nerve head, vitreous hemorrhage, cataract, glaucoma;
hearing organ and labyrinthine disorders: infrequently - tinnitus, vertigo, hearing loss;
cardiovascular system: infrequently - tachycardia, palpitations, CHF (chronic heart failure), pulmonary edema, hot flashes, thrombosis / embolism, hemorrhage; sometimes - atrial fibrillation, arrhythmias, sudden cardiac arrest, angina pectoris, myocardial infarction, pericardial effusion, increase / decrease in blood pressure, cold extremities, hematomas and subdural hematomas, Raynaud's syndrome, cardiac tamponade, pericarditis; isolated cases - anaphylactic shock;
respiratory system, chest and mediastinal organs: often - shortness of breath, cough, nosebleeds; infrequently - pain in the pharynx or larynx, pharyngitis, acute respiratory failure, pleural effusion, interstitial pneumonia; sometimes - pleural pain, pulmonary hypertension, pulmonary fibrosis, pulmonary hemorrhage;
digestive system: very often - nausea / vomiting, dyspepsia, diarrhea, abdominal pain; often - dry mouth, flatulence, bloating, constipation, gastritis, gastroesophageal reflux; infrequently - ulceration of the oral mucosa, stomatitis, gastrointestinal bleeding, melena, belching, esophagitis, stomach ulcer, ascites, vomiting of blood, dysphagia, cheilitis, pancreatitis, gastrointestinal perforation, bleeding / necrosis of gastrointestinal tumor; sometimes - colitis, intestinal inflammation, paralytic or obstructive intestinal obstruction, diverticulitis;
hepatobiliary system: often - increased activity of hepatic transaminases; infrequently - hyperbilirubinemia, jaundice, hepatitis; sometimes - liver failure, liver necrosis;
dermatological reactions: very often - dermatitis, eczema, periorbital edema, skin rashes; often - itching, facial swelling, erythema, dry skin, photosensitivity reactions, night sweats, alopecia; infrequently - pustular rash, hyperhidrosis, urticaria, bruises, increased predisposition to hematoma formation, hypotrichosis, exfoliative dermatitis, ecchymosis, hyper- or hypopigmentation of the skin, nail damage, petechiae, folliculitis, psoriasis, bullous rash, purpura; sometimes - discoloration of nails, Sweet syndrome, Stevens-Johnson syndrome, erythema multiforme, leucoclastic vasculitis, acute generalized pustular exanthema, lichenoid keratosis, palmar-plantar erythrodysesthesia, lichen planus, Lyell's syndrome, angioedema;
musculoskeletal and connective tissue: very often - musculoskeletal pain (including arthralgia, myalgia, bone pain), muscle spasms and cramps; often - joint swelling; infrequently - stiffness in muscles and joints; sometimes - arthritis, muscle weakness; frequency unknown - avascular necrosis / necrosis of the femoral head, growth retardation in children, myopathy / rhabdomyolysis;
kidneys and urinary system: infrequently - hematuria, pain in the kidneys, acute renal failure, frequent urination;
endocrine system, genitals, mammary gland: infrequently - erectile dysfunction, menstrual irregularities, gynecomastia, menorrhagia, sexual dysfunction, breast enlargement, nipple pain, scrotal edema; isolated cases - bleeding from the cyst of the corpus luteum / ovary;
other reactions: very often - fluid retention, edema, weight gain, increased fatigue; often - fever, weakness, anasarca, trembling, chills, weight loss; infrequently - general malaise, chest pain, increased serum creatinine and the activity of creatine phosphokinase, alkaline phosphatase, lactate dehydrogenase; sometimes - an increase in the activity of amylase in plasma.

Overdose

There have been isolated cases of imatinib overdose.

Dosage-related reactions to imatinib overdose in adult patients:

1200-1600 mg in a course of 1 to 10 days: increased fatigue, headache, rash, nausea / vomiting, diarrhea, edema, erythema, facial swelling, muscle spasms, pancytopenia, thrombocytopenia, loss of appetite, abdominal pain;
1800–3200 mg in a course of 1 to 10 days: weakness, myalgia, increased blood creatine phosphokinase activity, bilirubin concentration, gastrointestinal pain;
6400 mg one time: nausea / vomiting, abdominal pain, facial edema, hyperthermia, decreased platelet count and increased activity of liver enzymes;
8000-10,000 mg one time: vomiting, gastrointestinal pain.

Reaction to imatinib overdose in children 3 years of age: taking a single dose of 400 mg - vomiting, diarrhea, anorexia; at a dose of 980 mg - diarrhea, a decrease in the number of leukocytes.

There is no data on the antidote of imatinib; in case of an overdose, medical supervision of the patient and symptomatic treatment are recommended.

special instructions

Imatinib-TL should only be taken under the supervision of a physician with experience in the use of anticancer drugs.

Avoid getting the contents of the capsules on the skin, in the eyes and in the respiratory tract.

During therapy, it is recommended to conduct regular clinical studies of peripheral blood and monitor liver function (bilirubin, transaminases, alkaline phosphatase).

Patients with heart disease and impaired renal function must be carefully monitored.

Since 1–2% of patients experience severe fluid retention due to imatinib use, regular monitoring of body weight is desirable. In the event of an unexpected rapid weight gain, the patient is examined and, if necessary, diuretics are prescribed and / or imatinib therapy is temporarily discontinued. Most often, the development of fluid retention is noted in old age with concomitant cardiovascular diseases. In the case of severe fluid retention, the likelihood of a severe course of pathology with a fatal outcome cannot be excluded.

Given the availability of information on the development of hypothyroidism during the use of imatinib in patients after thyroidectomy, receiving replacement therapy with levothyroxine, they need regular monitoring of the level of thyroid-stimulating hormone.

In MDS / MPZ with a high level of eosinophils, an electrocardiographic (ECG) study should be performed and the concentration of cardiospecific troponin in the blood serum should be determined. If at the beginning of therapy deviations of these parameters from the norm are detected, the possibility of using systemic glucocorticosteroids (for prophylaxis) simultaneously with imatinib at a dose of 1-2 mg / kg for 1-2 weeks is considered.

At the beginning of imatinib therapy in patients with heart disease and hypereosinophilic syndrome, isolated cases of cardiogenic shock and / or left ventricular failure were recorded. Such conditions, after the introduction of systemic glucocorticosteroids, are stopped by measures aimed at maintaining blood circulation, and the temporary discontinuation of the drug.

In patients with malignant gastrointestinal stromal tumors, gastrointestinal bleeding and bleeding of metastatic foci were observed. Bleeding opened depending on the localization of tumor foci both in the abdominal organs and in the liver.

Influence on the ability to drive vehicles and complex mechanisms

If side effects such as blurred vision and dizziness occur, you should refrain from engaging in potentially hazardous activities, including driving.

Application during pregnancy and lactation

There are no data on the use of imatinib in pregnant women. But animal studies have shown that imatinib has a toxic effect on reproductive function. The potential risk to the fetus is currently unknown, therefore the use of Imatinib-TL during pregnancy is contraindicated. Women of childbearing age should use reliable contraception during the course of treatment and for at least 3 months afterwards.

There is no data on the excretion of imatinib in breastfeeding mothers in breast milk. According to studies carried out on animals, it was revealed that in significant quantities imatinib in unchanged form and / or its metabolites are excreted in milk. If it is necessary to take Imatinib-TL during lactation, women need to stop breastfeeding.

Pediatric use

The experience of treating CML with imatinib in children under 2 years of age is limited; there is insufficient data on the safety and efficacy of using Imatinib-TL for other indications in patients under 18 years of age. Careful monitoring of the condition of children using imatinib is required, as there are reports of stunted growth.

With impaired renal function

The kidneys do not play a significant role in the elimination of imatinib and its metabolites. Patients with impaired renal function or with systematic hemodialysis are recommended to begin therapy with caution, with a minimum effective daily dose of 400 mg. In case of drug intolerance, the initial daily dose may be reduced, and in case of insufficient effectiveness, increase.

For violations of liver function

Patients with hepatic impairment need regular monitoring of the clinical blood test and the activity of liver enzymes.

Due to the fact that imatinib is mainly metabolized in the liver, patients with impaired liver function are prescribed the drug in a minimum daily dose of 400 mg. In the event of the development of undesirable toxic reactions, the dose should be further reduced, since its effect is likely to increase.

Use in the elderly

Elderly patients do not need to correct the dosage regimen of Imatinib-TL.

Drug interactions

inhibitors of the isoenzyme CYP3A4 (including ketoconazole): an increase in the plasma concentration of imatinib is possible;
inducers of the isoenzyme CYP3A4 (including dexamethasone): it is possible to increase the metabolism of imatinib and decrease its plasma concentration;
simvastatin: the C _max and 3.5 times the AUC of simvastatin increase by 2 times due to inhibition of the CYP3A4 isoenzyme by imatinib;
drugs that are substrates of CYP3A4 and have a narrow range of therapeutic concentration, drugs containing paracetamol: it is recommended to be careful with this combination;
drugs that are substrates of the isoenzyme CYP2D6: it is possible to enhance the effect when combined with imatinib.

Analogs

Analogues of Imatinib-TL are: Imagliv, Genfatinib, Imatib, Glivec, Imatinib, Imatinib Medak, Imatinib Grindeks, Imatinib-Teva, Imatinib-Alvogen, Filachromin FS, Neopax, etc.

Terms and conditions of storage

Store in a dark place at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Imatinib-TL

Reviews of Imatinib-TL are quite diverse, since it is the drug of choice for the treatment of chronic myeloid leukemia and is included in the list of drugs that are prescribed by the decision of the medical commission of medical institutions and are used in a large number of patients. In addition, the active substance of the drug, imatinib, has many side effects, and therefore there are both positive and negative reviews.

The provision of such drugs on prescription is carried out in accordance with standards of medical care free of charge. Previously, the original drug Gleevec was used for this purpose, today it is being replaced by a variety of generics, including Imatinib-TL. According to experts, replacing Gleevek with generics does not affect the quality of therapy, the only difference is in the form of release - capsules or tablets.

Price for Imatinib-TL in pharmacies

The approximate price for Imatinib-TL capsules in a dosage of 100 mg (120 pieces per package) is 28,000 rubles.

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!