In connection with the characteristics of the underlying disease and a large number of drugs used simultaneously after transplantation, the profile of undesirable phenomena of immunosuppressants is difficult to pinpoint.
Many of the undesirable reactions presented below are reversible and / or reduced with a lower dose. Oral reception is associated with a lower risk of adverse reactions compared with intravenous administration of tacrolimus.Within each frequency group, undesirable phenomena are presented in descending order of gravity.
Undesirable phenomena classified by organs and systems are listed below in order of decreasing frequency of detection: very often (> 1/10), often (> 1/100 to <1/10), infrequently (> 1/1000 to <1 / 100), rarely (from> 1/10 000 to <1/1 000), very rarely (<1/10 000), the frequency is unknown (to establish the frequency of which the data is insufficient).
Heart Disease:
often: ischemic coronary disorders, tachycardia;
infrequently: ventricular arrhythmias and cardiac arrest, heart failure, cardiomyopathies, ventricular hypertrophy, supraventricular arrhythmias, palpitations, abnormal ECG, disturbances in rhythm and heart rate and heart rate; rarely: pericardial effusion;
very rarely: pathological changes on the echocardiogram, lengthening of the interval QT on an electrocardiogram, a disturbance of the rhythm of the heart such as "pirouette" (bidirectional spindle-shaped ventricular tachycardia).
Violations from sides of blood vessels:
very often: arterial hypertension;
often: bleeding, thromboembolic and ischemic complications, peripheral circulatory disorders, vascular hypotension;
infrequently: a heart attack, deep vein thrombosis of the extremities, shock.
Violations of the blood and lymphatic system:
often: anemia, leukopenia, thrombocytopenia, leukocytosis, a decrease or increase in hemoglobin and / or hematocrit, deviations in the analysis of erythrocytes; infrequently: coagulopathy, abnormalities in coagulogram, pancytopenia, neutropenia;
rarely: thrombotic thrombocytopenic purpura, hypothrombinemia;
frequency unknown: partial red cell aplasia, agranulocytosis, hemolytic anemia.
Disturbances from the nervous system:
very often: tremor, headache;
often: convulsions, impaired consciousness, paresthesia and dysesthesia, peripheral neuropathies, dizziness, violation of writing, nervous system disorders;
infrequently: coma, hemorrhages in the central nervous system and cerebral circulatory disorders, paralysis and paresis, encephalopathy, speech and articulation disorders, amnesia;
rarely: increased muscle tone; very rarely: myasthenia gravis.
Disturbances on the part of the organ of sight:
often: blurred vision, photophobia, eye diseases, visual impairment;
infrequently: cataract;
rarely: blindness.
Hearing disorders and labyrinthine disorders:
often: noise (ringing) in the ears;
infrequently: hearing loss;
rarely: sensorineal deafness;
very rarely: hearing impairment.
Onrespiratory system, thoracic and mediastinal disorders:
often: dyspnea, pulmonary parenchymal disorders, pleural effusion, pharyngitis, cough, nasal congestion, rhinitis;
infrequent: respiratory failure, respiratory tract disorders, asthma;
rarely: acute respiratory distress syndrome.
Disorders from the gastrointestinal tract:
very often: diarrhea, nausea;
often: inflammatory diseases of the gastrointestinal tract, gastrointestinal ulcers and perforations, gastrointestinal bleeding, stomatitis and ulceration of the oral mucosa, ascites, vomiting, gastrointestinal and abdominal pain, dyspepsia, constipation, flatulence, sensations of bloating and swelling in the abdomen, loose stool, symptoms of disorders of the gastrointestinal tract;
infrequent: paralytic intestinal obstruction (paralytic ileus), peritonitis, acute and chronic pancreatitis, increased levels of amylase in the blood,gastroesophageal reflux disease, a violation of the evacuation function of the stomach;
rarely: subileus, pancreatic pseudocysts.
Disorders from the kidneys and urinary tract:
very often: impaired renal function;
often: renal failure, acute renal failuretatality, oliguria, acute tubular necrosis, toxic nephropathy, urinary syndrome, disorders of the bladder and urethra;
infrequently: anuria, hemolytic uremic syndrome; very rarely: nephropathy, hemorrhagic cystitis.
Disturbances from the skin and subcutaneous tissues:
often: itching, rashes, alopecia, acne, hyperhidrosis;
infrequently: dermatitis, photosensitivity;
rarely: toxic epidermal necrolysis (Lyell's syndrome);
very rarely: Stevens-Johnson syndrome.
Disturbances from musculoskeletal and connective tissue:
often: arthralgia, muscle cramps, pain in the limbs, back pain;
infrequently: articular disorders.
Disorders from the endocrine system:
rarely: hirsutism.
Disorders from the metabolism and nutrition:
very often: hyperglycemia, diabetes, hyperkalemia;
often: hypomagnesemia, hypophosphatemia, hypokalemia, hypocalcemia, hyponatremia, hypervolemia, hyperuricemia, decreased appetite, anorexia, metabolic acidosis, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, electrolyte disturbances;
infrequently: dehydration, hypoproteinemia, hyperphosphataemia, hypoglycemia.
Immune system disorders: in patients taking tacrolimus, allergic and anaphylactic reactions were observed.
Infectious and parasitic diseases: against the background of tacrolimus therapy, as well as other immunosuppressants, the risk of local and generalized infectious diseases (viral, bacterial, fungal, protozoal) increases. The course of previously diagnosed infectious diseases may worsen. Cases of nephropathy associated with BV virus, as well as progressive multifocal leukoencephalopathy (PML) associated with the JC virus, were observed against immunosuppressive therapy, including tacrolimus therapy.
Trauma, intoxication and complications of manipulation:
often: primary transplant dysfunction.
In practice, there were errors in the use of tacrolimus preparations, including unreasonable, unintentional or uncontrolled transfer of patients from one tacrolimus dosage form (standard or prolonged) to another, and also recorded cases of graft rejection (according to available data, the frequency can not be estimated).
Benign, malignant and unspecified neoplasms (including cysts and polyps): patients receiving immunosuppressive therapy have a higher risk of developing malignant tumors. When tacrolimus was used, both benign and malignant neoplasms appeared, including the Epstein-Barr virus (EBV) - associated lymphoproliferative diseases and skin cancer.
General disorders and disorders at the site of administration:
often: asthenia, febrile conditions, swelling, pain and discomfort, enhancementalkaline phosphatase in the blood, increased body weight, impaired body temperature perception;
infrequently: multiple organ failure, influenza-like syndrome, impaired perception of environmental temperature,a feeling of squeezing in the chest, a sense of anxiety, worsening of well-being, an increase in lactate dehydrogenase activity in the blood, a decrease in body weight;
rarely: thirst, loss of balance (falling), a feeling of stiffness in the chest, obstruction of movement, ulcer;
very rarely: an increase in the mass of adipose tissue.
Disturbances from the liver and bile ducts:
often: increased levels of hepatic enzymes, impaired liver function, pathological changes in functional liver tests, cholestasis and jaundice, liver cell damage and hepatitis, cholangitis;
rarely: thrombosis of the hepatic artery, obliterating endophlebitis of the hepatic veins; very rarely: hepatic insufficiency, stenosis of the bile duct.
Violations of the genitals and mammary gland:
infrequently: dysmenorrhea and uterine bleeding.
Disorders of the psyche:
very often: insomnia;
often: anxiety, confusion and disorientation, depression, depressed mood, affective disorders, nightmares, hallucinations, mental disorders;
infrequently: psychotic disorders.