The safety profile of imatinib has been well studied. Most patients experience certain adverse reactions when using the drug. The most common side effects (> 10%) associated with taking imatinib were: neutropenia, thrombocytopenia, anemia, headache, dyspepsia, swelling, weight gain, nausea, vomiting, diarrhea, myalgia, muscle cramps, rash, weakness, abdominal pain. Often marked peripheral edema mainly in the periorbital area and swelling of the lower extremities. In general, the adverse reactions were mild or moderate. Only 2-5% of patients stopped imatinib therapy because of the development of side effects associated with the use of the drug.
The types of adverse reactions and the frequency of their development are similar when taking imatinib by adults and children with leukemia.
Myelosuppression, unwanted reactions from the gastrointestinal tract (GIT), edema and rash occur when imatinib is used as indicated by CML, and for malignant stromal tumors of the gastrointestinal tract. In patients with CML, myelosuppression develops more often, and in patients with malignant stromal tumors of the gastrointestinal tract, gastrointestinal and intracutaneous hemorrhages often occur. Other disorders of the gastrointestinal tract, such as gastrointestinal obstruction, perforation and ulceration, occur more often with stromal GI tract. Other serious adverse reactions with imatinib are hepatotoxicity, acute renal failure, hypophosphatemia, respiratory system disorders, tumor lysis syndrome and growth retardation in children. Possible correction of the dose of imatinib, depending on the severity of unwanted reactions, up to the withdrawal of the drug.
In clinical trials in patients with CML and with inoperable and / or metastatic malignant stromal tumors of the gastrointestinal tract, the following undesirable reactions listed below for organs and systems with the frequency of their occurrence were noted: very often (more than 10%), often (1-10% ), infrequently (0.1-1%), rarely (0.01-0.1%), very rarely (less than 0.01%), including individual reports.
Infectious and parasitic diseases: infrequent herpes zoster, herpes simplex, nasopharyngitis, pneumonia1, sinusitis, inflammation of the subcutaneous tissue, upper respiratory tract infections, influenza, urinary tract infections, gastroenteritis, sepsis; rarely - mycosis; frequency unknown - reactivation of hepatitis B virus.
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 hematopoiesis, eosinophilia. lymphadenopathy; rarely - hemolytic anemia.
From the side of metabolism and nutrition: often - anorexia; infrequently - hypokalemia. increased or decreased appetite, hypophosphatemia, dehydration, hyperuricemia, gout, hypercalcemia, hyperglycemia, hyponatremia; rarely - hyperkalemia, hypomagnesemia.
Disorders of the psyche: often - insomnia; infrequently - depression, anxiety, decreased libido; rarely confusion.
From the nervous system: very often - headache2; often - dizziness, paresthesia, taste disorder, hypoesthesia; infrequently - migraine, drowsiness, fainting, peripheral neuropathy, memory impairment, sciatica, restless legs syndrome, tremor, hemorrhagic stroke; rarely - increased intracranial pressure, convulsions, optic neuritis.
From the side of the organ of vision: often - swelling of the eyelids, increased lacrimation, conjunctival hemorrhage, conjunctivitis, dry eye syndrome, blurred vision: infrequent - 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 heart: infrequent - sensation of palpitations, chronic3 heart failure, pulmonary edema, tachycardia, rarely - arrhythmia, atrial fibrillation, sudden cardiac arrest; myocardial infarction, stenocardia, pericardial effusion.
From the side of the vessels: often - hemorrhages4; infrequently - "tides"4; rarely - increased blood pressure (BP), hematoma,subdural hematoma, cold extremities, decreased blood pressure, Raynaud's syndrome.
From the respiratory system, organs of the thorax. mediastinum: often - epistaxis, shortness of breath, cough: infrequent - pleural effusion5, pain in the pharynx or larynx, pharyngitis; rarely - pleural pain, pulmonary fibrosis, pulmonary hypertension, pulmonary hemorrhage.
From the digestive system: very often - nausea, vomiting, diarrhea, dyspepsia, abdominal pain6, often - bloating, flatulence, constipation, gastroesophageal reflux, dry mouth, gastritis; infrequently - stomatitis, ulceration of the mucous membrane of the oral cavity, gastrointestinal bleeding7, belching, melena, esophagitis, ascites, stomach ulcer, vomiting of blood, cheilitis, dysphagia, pancreatitis; rarely - colitis, paralytic / obturation intestinal obstruction, inflammation of the intestine.
From the liver and bile ducts: often - increased activity of "liver" transaminases, infrequently - jaundice, hepatitis, hyperbilirubinemia; rarely - liver failure8, necrosis of the liver9.
From the skin and subcutaneous tissues: very often - periorbital edema, dermatitis, eczema, skin rash; often puffiness of the face,skin itching, dry skin, erythema, alopecia, night sweats, photosensitivity reactions; infrequently - pustular rash, petechiae, increased sweating, urticaria, ecchymosis, predisposition to the formation of hematomas, hypotrichosis, hyperpigmentation / hypopigmentation of the skin, exfoliative dermatitis, nail damage, folliculitis, psoriasis, purpura, bullous rash; rarely acute febrile neutrophilic dermatosis (Sweet syndrome), discoloration of the nails, angioedema, erythema multiforme, leukocytoclastic vasculitis, Stevens-Johnson syndrome, acute generalized pustular exanthema.
From the side of the musculoskeletal and connective tissue: very often - muscle spasms and cramps, musculoskeletal pain, including myalgia, arthralgia, bone pain10; often swelling of the joints; infrequent - stiffness of muscles and joints, rarely - muscle weakness, arthritis; frequency is unknown - growth retardation in children.
From the side of the kidneys and urinary tract: infrequently - pain in the nights, hematuria, acute renal failure, frequent urination.
From the genitals and mammary glands: infrequently - gynecomastia, erectile dysfunction, menorrhagia, menstrual disorder, sexual dysfunction, pain in the nipples, enlargement of the mammary glands, swelling of the scrotum.
General disorders and disorders at the site of administration: very often - fluid retention and swelling, increased fatigue, weight gain; often - weakness, fever, anasarca, chills, trembling, weight loss; infrequently - chest pain, general malaise.
Laboratory and instrumental research: infrequently, an increase in the activity of alkaline phosphatase (FA), creatine phosphokinase (CK), lactate dehydrogenase, and serum creatinine concentration; rarely - increased activity of amylase in the blood plasma.
1 - the development of pneumonia was most often reported in patients with CML in the phase of acceleration, blast crisis and with inoperable and / or metastatic gastrointestinal malignant stromal tumors (CLL)
2 - The headache was most often observed in patients with inoperable and / or metastatic malignant COX
3- unwanted reactions from the heart, including chronic heart failure,were more often observed in patients with CML in the phase of acceleration and with blast crisis compared with patients with CML in the chronic phase (duration of follow-up is 1 year)
4 - a sensation of blood rush was most often observed in patients with inoperable and / or metastatic malignant CLL; bleeding (haematomas, hemorrhages) - most often in patients with CML in the phase of acceleration, blast crisis and with inoperable and / or metastatic malignant COOL
5 - Pleural swelling was more often reported in patients with CML in the phase of acceleration and blast crisis compared to patients with CML in the chronic phase (duration of follow-up is 1 year)
6/7 - abdominal pain and gastrointestinal hemorrhage were most often observed in patients with inoperable and / or metastatic malignant COX
8/9 - reported on individual cases of hepatic insufficiency and liver necrosis
10 - pain in muscles and bones and similar reactions were more often observed in patients with CML than in patients with inoperable and / or metastatic malignant LIVE
When imatinib was used in clinical practice and in the course of additional studies, there were reports of side effects,the relationship of which is not established with imatinib (the size of the patient population is unknown).
From the nervous system: infrequently - edema of the brain.
From the side of the organ of vision: rarely - vitreous hemorrhage.
From the side of the heart and blood vessels: infrequently - thrombosis / embolism; rarely - pericarditis, cardiac tamponade.
From the immune system: very rarely - anaphylactic shock.
From the respiratory system, organs of the thorax, mediastinum: infrequent acute respiratory failure1, interstitial pneumonia.
From the digestive tract: infrequently - ileus (intestinal obstruction), bleeding from the tumor of the digestive tract, necrosis of the tumor of the gastrointestinal tract, perforation of the gastrointestinal tract2; rarely - diverticulitis, vascular ectasia of the antrum of the stomach (GAVE-syndrome).
From the skin and subcutaneous tissues: infrequently - palmar-plantar erythrodysesthesia; rarely - lichenoid keratosis, red flat lichen; very rarely - toxic epidermal necrolysis; frequency unknown - drug rash with eosinophilia and systemic symptoms (DRESS).
From the side of musculoskeletal and connective tissue: rarely - avascular necrosis / necrosis of the head of the femur, rhabdomyolysis / myopathy.
From the genitals and mammary glands: very rarely - women bleed from the cyst of the yellow body / ovary.
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 perforations of the gastrointestinal tract with a lethal outcome.