Imatinib-TL, 100 mg capsules 120 pcs

Pharmacodynamics:

Proteintyrosine kinase inhibitor. Inhibits the enzyme Bcr-Abl-tyrosine kinase at the cellular level, in vitro and in vivo. It selectively suppresses proliferation and causes apoptosis of Bcr-Abl positive cell lines as well as young leukemia cells in Philadelphia chromosome positive chronic myeloleukemia and in acute lymphoblastic leukemia.

In colony transformation studies performed on peripheral blood and bone marrow samples, imatinib was shown to selectively inhibit Bcr-Abl-positive colonies obtained from chronic myeloleukemia patients.

In in vivo studies in animal models using Bcr-Abl-positive tumor cells, imatinib was shown to have antitumor activity with monotherapy.

In addition, imatinib is a tyrosine kinase receptor inhibitor for platelet-derived growth factor and stem cell factor and inhibits cellular responses mediated by these factors.

In vitro imatinib inhibits proliferation and induces apoptosis of GI stromal tumor cells expressing kit mutations.

Pharmacokinetics

Indications

Active ingredient

Composition

How to take, the dosage

Interaction

In concomitant use of imanitib with drugs that inhibit the CYP3A4 isoenzyme of cytochrome P450, such as viral protease inhibitors (indinavir, lopinavir, ritonavir, saquinavir, telaprevir, nelfinavir, boceprevir), antifungal drugs of the azole group (including ketoconazole, itraconazole, voriconazole).including ketoconazole, itraconazole, posaconazole, voriconazole), some macrolide antibiotics (erythromycin, clarithromycin, telithromycin), metabolism of imatinib may be slowed and its concentration in blood plasma may increase. Caution is required when using imatinib concomitantly with drugs with CYP3A4 isoenzyme inhibitors.

Special Instructions

The treatment with imatinib should only be performed under the supervision of a physician experienced in the use of antitumor drugs.

In cases of marked fluid retention have been reported with imatinib, regular monitoring of body weight is recommended. If there is a sudden rapid increase in body weight, an examination should be performed and, if necessary, imatinib therapy should be temporarily discontinued and/or diuretics should be started.

The development of neutropenia or thrombocytopenia has been noted with imatinib; these events have a clear relationship to the stage of the disease, with a higher incidence in patients with CML in the blast crisis or acceleration phase compared to patients with CML in the chronic phase. Temporary suspension of therapy or reduction of imatinib dose may be necessary.

When using imatinib it is recommended to perform regular clinical blood tests and monitor liver function (transaminases, bilirubin, ALP). When using in patients with liver disease, regular clinical blood tests should be performed and liver enzyme activity should be determined.

Imatinib and its metabolites are excreted by the kidneys to a small extent. Creatinine clearance decreases with age, and age has no significant effect on the pharmacokinetic parameters of imatinib. There is no correlation between imatinib exposure and renal function impairment in patients with renal impairment from mild (creatinine clearance 40-59 ml/min) to severe (creatinine clearance <20 ml/min) degrees of severity. However, the initial dose of imatinib should be reduced if intolerance is present in patients in this category.

There have been reports of hypothyroidism with imatinib in patients who have undergone thyroidectomy and are receiving levothyroxine sodium replacement therapy. Regular determination of thyrotropic hormone concentration in this category of patients should be performed.

Patients with cardiovascular diseases, risk factors for heart failure, and patients with a history of renal failure should be closely monitored. If signs or symptoms suggestive of these conditions are identified, the patient should be evaluated and appropriate treatment initiated.

In patients with myelodysplastic/myeloproliferative diseases and high eosinophil counts, serum cardiac-specific troponin concentrations should be measured. Prophylactic use of systemic GCS for 1-2 weeks concomitantly with imatinib should be considered if deviations from normal values are detected at the beginning of therapy.

There have been anecdotal reports of vascular ectasia of the gastric antrum (GAVE syndrome), a rare cause of gastrointestinal bleeding, reported in patients with CML and OLL and other conditions.

Gastrointestinal conditions in patients with metastatic malignant GVHD (abdominal pain, gastrointestinal bleeding, constipation and others) should be monitored at baseline and throughout therapy with imatinib. Discontinuation of imatinib therapy should be considered if necessary.

Because of the risk of tumor lysis syndrome, clinically significant dehydration and elevated uric acid concentrations should be corrected before use of imatinib, if necessary.

In patients who are carriers of hepatitis B virus, reactivation of this virus after therapy with BCR-ABL tyrosine kinase inhibitors such as imatinib is possible. In some cases during the use of this class of medications development of acute hepatic failure or fulminant hepatitis has been noted, leading to liver transplantation or death.

Before starting therapy with imatinib, all patients should be screened for hepatitis B virus. Patients who are carriers of hepatitis B virus should be closely monitored for signs and symptoms of active infection both during treatment with imatinib and for several months after therapy with imatinib.

Impact on driving and operating machinery

Some side effects, such as dizziness and blurred vision, may adversely affect the ability to drive and perform other potentially hazardous activities that require increased concentration and rapid psychomotor reactions. Therefore, patients should refrain from performing the above mentioned activities in case of manifestation of the described adverse effects.

Contraindications

Side effects

Infectious and parasitic diseases: infrequent – herpes zoster, herpes simplex, nasopharyngitis, pneumonia, sinusitis, subcutaneous tissue inflammation, upper respiratory tract infections, flu, urinary tract infections, gastroenteritis, sepsis; rarely – mycosis.

Hematopoietic system disorders: very common – neutropenia, thrombocytopenia, anemia; common – pancytopenia, febrile neutropenia; infrequent – thrombocythemia, lymphopenia, suppression of medullar hemopoiesis, eosinophilia, lymphadenopathy; rare – hemolytic anemia

Metabolism: very often – weight gain; often – anorexia, weight loss; infrequent – hypokalemia, increased appetite, hypophosphatemia, decreased appetite, dehydration, hyperuricemia, gout, hypercalcemia, hyperglycemia, hyponatremia; rarely – hyperkalemia, hypomagnesemia.

Psychiatric disorders: frequently – insomnia; infrequently – depression, decreased libido, anxiety; rarely – mental confusion.

Nervous system disorders: very commonly – headache; frequently – dizziness, paresthesia, taste disorder, hypoesthesia; infrequently – migraine, somnolence, syncope, peripheral neuropathy, memory disorders, sciatica, restless legs syndrome, tremor, hemorrhagic stroke; rarely – increased intracranial pressure, seizures, optic neuritis.

VIight organ disorders: often – eyelid edema, increased lacrimation, conjunctival hemorrhages, conjunctivitis, “dry eye” syndrome, blurred (hazy) vision; infrequent – eye irritation, eye pain, orbital edema, sclera hemorrhages, retinal hemorrhages, blepharitis, macular edema; rarely – cataract, optic disc edema, glaucoma.

Hearing and vestibular disorders: infrequent – vertigo, tinnitus, decreased hearing.

Cardiovascular system disorders: frequent – flushes, hemorrhage; infrequent – palpitations, tachycardia, chronic heart failure, pulmonary edema, increased or decreased BP, hematoma, subdural hematoma, cold extremities, Raynaud’s syndrome; rare – arrhythmia, atrial fibrillation, cardiac arrest, myocardial infarction, angina pectoris, pericardial effusion.

Respiratory system: frequently – nasal bleeding, dyspnea, cough; infrequently – pleural effusion, pain in the pharynx or larynx, pharyngitis; rarely – pleural pain, pulmonary fibrosis, pulmonary hypertension, pulmonary hemorrhage.

Digestive system disorders: very common – nausea, vomiting, diarrhea, dyspepsia, abdominal pain; common – abdominal bloating, flatulence, constipation, gastroesophageal reflux, dry mouth, gastritis; infrequent – stomatitis, ulceration of the oral mucosa, gastrointestinal bleeding, belching, melena, esophagitis, ascites, stomach ulcer, vomiting blood, cheilitis, dysphagia, pancreatitis; rare – colitis, paralytic/obstructive intestinal obstruction, inflammation of the colon.

Hepatic and biliary tract disorders: often – increased activity of liver transaminases; infrequent – jaundice, hepatitis, hyperbilirubinemia; rare – hepatic failure, liver necrosis.

Skin and subcutaneous tissue disorders: very common – periorbital edema, dermatitis, eczema, skin rash; common – skin itching, facial swelling, dry skin, erythema, alopecia, night sweating, photosensitization reactions; infrequent – pustular rash, petechiae, increased sweating, urticaria, ecchymosis, predisposition to formation of hematomas, hypotrichosis, hyperpigmentation/hypopigmentation of the skin, exfoliative dermatitis, nail damage, folliculitis, petechiae, psoriasis, purpura, bullous rash; rare – acute febrile neutrophilic dermatosis (Sweet’s syndrome), discoloration of nails, angioedema, vesicular rash, erythema multiforme, leukoplastic vasculitis, Stevens-Johnson syndrome, acute generalized pustular exanthema.

Muscular system disorders: very frequently – muscle spasms and cramps, musculoskeletal pain, including myalgia and arthralgia, bone pain; frequently – swelling of joints; infrequently – stiffness of muscles and joints; rarely – muscle weakness, arthritis.

Urinary system: infrequent – renal pain, hematuria, acute renal failure, frequent urination.

Reproductive system disorders: infrequent – gynecomastia, erectile dysfunction, menorrhagia, menstrual cycle disorders, sexual dysfunction, nipple pain, breast enlargement, scrotal edema.

Actually: very often – fluid retention, edema, increased fatigue; often – weakness, increased body temperature, anasarca, chills, shivering; infrequently – pain in the chest, general malaise.

Laboratory measures: infrequent – increase of creatinine concentration in blood, increased CPK activity in blood, increased ALP activity, LDH; rare – increase of amylase activity in plasma.

Overdose

Pregnancy use