The incidence of adverse reactions is as follows: very often (≥1 / 10 cases), often (≥1 / 100 and <1/10 cases) infrequently (≥1 / 1000 and <1/100 cases), rarely (≥1 / 10000 and <1/1000 cases) and very rarely (<1/10000 cases).
Adverse reactions listed in the "frequently" group occurred with a frequency below 3%, except for nausea and diarrhea. In each frequency group, undesirable drug reactions are listed in order of decreasing significance.
Infectious and parasitic diseases: often - fungal superinfections.
On the part of the hematopoiesis system: infrequently - anemia, leukopenia, neutropenia, thrombocytopenia, thrombocythemia, lengthening of the porphyrin time / increase in the international normalized ratio (INR); rarely - a change in the concentration of tromboplastin; very rarely - an increase in the concentration of the protozoa / decrease in INR.
From the immune system: infrequently - allergic reactions, itching, rashes, urticaria, eosinophilia; rarely anaphylactic / anaphylactoid reactions, angioedema, including laryngeal edema (potentially life-threatening); very rarely - anaphylactic / anaphylactoid shock (including potentially life-threatening).
From the side of metabolism: infrequently hyperlipidemia; rarely hyperglycemia, hyperuricemia.
Mental disorders: infrequently - anxiety, psychomotor hyperactivity / agitation; rarely - emotional lability, depression (in very rare cases, behavior with a tendency to self-harm, such as suicidal thoughts or suicidal attempts), hallucinations; very rarely - depersonalization,psychotic reactions (potentially manifested in behavior with a tendency to self-harm, such as suicidal thoughts and suicidal attempts).
From the nervous system: often - headache, dizziness; infrequently paresthesia / dysesthesia, disorders of taste sensitivity (including very rare cases of agevia), confusion and disorientation, sleep disorders, tremor, vertigo, drowsiness; rarely - hypoesthesia, olfactory impairment (including anosmia), atypical dreams, impaired coordination (including dizziness or vertigo gait disturbance, very rarely leading to trauma from falling, especially in elderly patients), seizures with different clinical manifestations (including including "grand mal" seizures), attention disorders, speech disorders, amnesia, peripheral neuropathy and polyneuropathy; very rarely hyperesthesia.
From the side of the organ of vision: infrequently - visual impairment (especially with CNS reactions); very rarely - transient loss of vision (especially against the background of reactions from the central nervous system).
From the side of the hearing organ and labyrinthine disorders: rarely - noise in the ears, hearing impairment, including deafness (usually reversible).
From the cardiovascular system: often - prolongation of the QT interval in patients with concomitant hypokalemia, infrequent - prolongation of the QT interval, palpitation, tachycardia, vasodilation; rarely - ventricular tachyarrhythmias, fainting, increased blood pressure, lower blood pressure; very rarely - nonspecific arrhythmias, polymorphic ventricular tachycardia (Torsade de Pointes), cardiac arrest (mainly in persons with predisposing to arrhythmias, such as clinically significant bradycardia, acute myocardial ischemia).
From the respiratory system, chest and mediastinum: infrequently - shortness of breath (including asthmatic condition).
From the gastrointestinal tract: often - nausea, vomiting, abdominal pain, diarrhea; infrequent - reduced appetite and reduced food intake, constipation, dyspepsia, flatulence, gastroenteritis (other than erosive gastroenteritis), increased amylase activity; rarely - dysphagia, stomatitis, pseudomembranous colitis (in very rare cases associated with life-threatening complications).
Disorders from the liver and bile ducts: often - increased activity of "liver" transaminases,infrequent liver function disorders (including increased lactate dehydrogenase activity), increased bilirubin concentration, increased activity of gamma-glutamyl transferase, increased alkaline phosphatase activity in blood; rarely - jaundice, hepatitis (mostly cholestatic); very rarely - fulminant hepatitis, potentially leading to life-threatening liver failure (including fatal cases).
From the skin and soft tissues: very rarely - bullous skin reactions, for example, Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening).
From the side of the musculoskeletal and connective tissue: infrequently - arthralgia, myalgia; rarely - tendonitis, increased muscle tone and cramps, muscle weakness; very rarely - tendon ruptures, arthritis, gait disturbance due to damage to the musculoskeletal system, increased symptoms of myasthenia gravis.
From the side of the kidneys and urinary tract: infrequently - dehydration (caused by diarrhea or decreased fluid intake); rarely - renal dysfunction, renal failure (as a result of dehydration, which can lead to kidney damage, especially in elderly patients with pre-existing impairment of kidney function.
The frequency of development of the following adverse reactions was higher in the group receiving stepwise therapy: often - increased activity of gamma-glutamyltransferase; infrequently, ventricular tachyarrhythmias, lowering blood pressure, swelling, pseudomembranous colitis (in very rare cases associated with life-threatening complications), seizures with various clinical manifestations (including "grand mal" seizures), hallucinations, impaired renal function, renal insufficiency as a result of dehydration, which can lead to kidney damage, especially in elderly patients with pre-existing impaired renal function).