At the advanced stage of malignant diseases, the evaluation of undesirable reactions (HP) of imatinib is difficult due to a number of symptoms,associated with multiple concomitant disorders, their progression and the intake of various medications. With prolonged daily intake in adults and children with XMJ1 imatinib in general, is well tolerated. Most HP were mild or moderate. HP were similar in almost all patients receiving imatinib for various indications. In patients with malignant GISO, myelosuppression is less likely, and intratumoral bleeding is characteristic only for this group. Most often, when taking imatinib, there was neutropenia, thrombocytopenia, anemia, headache, dyspepsia, swelling, weight gain, nausea, vomiting, diarrhea, myalgia, muscle cramps, skin rash, weakness, abdominal pain. The overall incidence of HP of varying severity (with the exception of edema) and the incidence of severe HP were similar in patients taking 400 mg and 800 mg per day. The most frequent edema was observed in patients with malignant GISO who received therapy at a dose of 800 mg. The incidence of adverse reactions is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0,01%,but less than 0.1%; very rarely (including isolated cases) - less than 0.01%.
Infectious and parasitic diseases: infrequent herpes zoster, herpes simplex, upper respiratory tract infection, nasopharyngitis, sinusitis, influenza, pneumonia1, infectious and inflammatory disease of subcutaneous tissue, infectious disease of the urinary tract, gastrointestinal tract infection (GI tract), gastroenteritis, sepsis; rarely fungal infection.
Benign, malignant and unspecified neoplasms (including cysts and polyps): rarely - tumor lysis syndrome.
From the side of the blood and lymphatic system: very often - neutropenia, thrombocytopenia, anemia; often pancytopenia, febrile neutropenia; infrequently - thrombocythemia, lymphopenia, oppression of bone marrow function, eosinophilia, lymphadenopathy; rarely hemolytic anemia. In the treatment of XMJ1 imatinib at a dose of more than 750 mg per day, the risk of developing neutropenia and thrombocytopenia increases.
From the side of metabolism and nutrition: often - anorexia; infrequently - hypokalemia, increase or decrease in appetite, hypophosphatemia, dehydration, gout, hypercalcemia, hyponatremia, hyperglycemia, hyperuricemia; rarely hyperkalemia, hypomagnesemia.
From the nervous system: very often headache; often - dizziness, paresthesia, taste disorder, hypoesthesia, insomnia; infrequently - depression, anxiety, migraine, drowsiness, syncope, peripheral neuropathy, memory impairment, tremor, lumboschialgia, restless leg syndrome, cerebral hemorrhage; rarely - confusion, increased intracranial pressure, convulsions, optic neuritis, cerebral edema.
From the side of the organ of vision: often - edema of the eyelids, hemorrhage under the conjunctiva, dry eye syndrome, increased tear, conjunctivitis, blurred vision; infrequently-eye irritation, eye pain, orbital edema, bleeding in the sclera of the eye, retinal hemorrhage, blepharitis, macular edema; rarely - cataract, edema of the optic nerve, glaucoma.
From the side of the hearing organ and labyrinthine disorders: infrequently - vertigo, noise in the ears, hearing loss.
From the cardiovascular system: often - "tides"2, bleeding2; infrequent - increase or decrease in blood pressure2, hematoma2, chilliness of the limbs2, Raynaud's syndrome2, palpitations, tachycardia, congestive heart failure3, pulmonary edema; rare-arrhythmias, atrial fibrillation, angina pectoris, infarction myocardium, pericardial effusion, sudden cardiac arrest.
From the respiratory system, chest and mediastinum: often shortness of breath, nosebleeds, cough; infrequently - pleural effusion5, pain in the pharynx or larynx, pharyngitis; rarely - pleural pain, pulmonary fibrosis, pulmonary hypertension, pulmonary hemorrhage. From the digestive tract: very often - nausea, vomiting, diarrhea, indigestion, abdominal pain; often - flatulence, gastroesophageal reflux, bloating, constipation, dry mouth, gastritis; infrequently - stomatitis, ulceration of the oral mucosa, gastrointestinal bleeding, melena, esophagitis, belching, ascites, stomach ulcer, cheilitis, vomiting of blood, dysphagia, pancreatitis; rarely - colitis, paralytic / obturation intestinal obstruction, inflammatory bowel disease.
From the liver and bile ducts: often - increased activity of "liver" transaminases; infrequently - hyperbilirubinemia, hepatitis, jaundice; rarely - liver failure, necrosis of the liver.
From the skin and subcutaneous tissues: very often - periorbital edema, dermatitis, eczema, skin rash; often-skin itch, puffiness of the face, dry skin, erythema, alopecia, night sweats, photosensitivity reactions; infrequently pustulous sychi, increased sweating, urticaria, ecchymosis, mild hematoma formation, hypotrichosis, hyperpigmentation / hypopigmentation of the skin, exfoliative dermatitis, nail damage, folliculitis, petechiae, psoriasis, purpura, bullous rash; rarely - a change in the color of the nails, vesicular sush, acute febrile neutrophilic dermatosis (Sweet syndrome), angioedema, erythema multiforme, leukoclastic vasculitis, Stevens-Johnson syndrome. From the musculoskeletal and connective tissue: very often muscle spasms and cramps, musculoskeletal pain (including myalgia, arthralgia, bone pain); often swelling of the joints; infrequently - stiffness of muscles and joints; rarely - muscle weakness, arthritis, rhabdomyolysis or myopathy.
From the urinary system: infrequent - pain in the kidney, hematuria, acute renal failure, frequent urination.
On the part of the reproductive system: infrequently - gynecomastia, erectile dysfunction, menorrhagia, menstrual disorder, sexual dysfunction, pain in the nipples, enlargement of the mammary glands, swelling of the scrotum. Other: very often - fluid retention, swelling, increased fatigue, weight gain; often - weakness, anasarca, chills, trembling, fever, loss of body weight; infrequently - chest pain, general malaise, increase in creatinine concentrations and activity of alkaline phosphatase (AF), creatine phosphokinase (CK), lactate dehydrogenase; rarely - increased activity of amylase in the blood plasma.
1 - Pneumonia was most frequently observed in patients with XMJI in the phase of acceleration, blast crisis and with inoperable and / or metastatic malignant GISOs.
2 - Headache is most often noted in patients with inoperable and / or metastatic GISO.
3 - "Tides" are most often observed in patients with inoperable and / or metastatic malignant GISOs; bleeding (hematoma, hemorrhage) is most often observed in patients with XML in the phase of acceleration, blast crisis and inoperable and / or metastatic malignant GIS.
4 - Adverse events from the heart, including congestive heart failure were more common in patients with XML in the phase of acceleration and blast crisis compared to patients with XML in the chronic phase (duration of follow-up was 1 year).
5 - Pleural effusion was more common in patients with XMJI in the accelerated phase and with blast crises compared to XMJI in the chronic phase (follow-up duration 1 year).
6/7 - Abdominal pain and gastrointestinal bleeding are most often noted in patients with inoperable and / or metastatic malignant GIS.
8 - Individual cases of hepatic insufficiency and liver necrosis have been reported.
9 - Musculoskeletal pain, including myalgia, arthralgia. Bone pain was more frequent in patients with XMJI than in patients with inoperable and / or metastatic malignant GISOs.
When imatinib was used in clinical practice and during additional studies, there were reports of adverse events, the relationship of which was not established with imatinib (the size of the patient population is unknown).
From the side of the nervous system: the frequency is not known - the swelling of the brain.
From the side of the organ of vision: the frequency is not known - hemorrhage into the vitreous.
From the cardiovascular system: infrequently - thrombosis / embolism; frequency is not known - pericarditis, cardiac tamponade.
Allergic reactions: the frequency is not known - anaphylactic shock.
On the part of the respiratory system, chest and mediastinum: the frequency is not known - acute respiratory failure, interstitial pneumonia.
From the gastrointestinal tract: frequency is not known - ileus / intestinal obstruction, bleeding from GISO / necrosis of GISO, gastrointestinal perforation, diverticulitis.
From the skin and subcutaneous tissues: the frequency is not known - palmar-plantar erythrodysesthesia, lichenoid keratosis, red flat lichen, toxic epidermal necrolysis.
From the side of the musculoskeletal and connective tissue: the frequency is not known - avascular necrosis / necrosis of the head of the femur.
1 - There are isolated reports of the development of severe acute respiratory failure with a fatal outcome in patients with severe infectious diseases, severe neutropenia and other concomitant diseases.
2 - There are reports of cases of development of gastrointestinal perforations with a lethal outcome.