Very likely - agranulocytosis, nausea, vomiting, increased activity of aspartate aminotransferase and alanine aminotransferase, anemia, weakness, decreased platelet count, complete lack of appetite, diarrhea.
Occasionally, the development of side effects led to the death of patients - with monotherapy by Yondelis (1.9% of cases), with complex therapy (0.9%). Lethal outcome usually comes from a combination of undesirable effects of the drug, incl. A sharp decrease in erythrocytes, leukocytes, platelets, febrile agranulocytosis (sometimes with septicemia), hepatic, renal or multi-organ dysfunction and muscle necrosis.
Next comes a list of side effects attributed to the probable in connection with the use of this drug and observed at least 1% of cases.
To compare the frequency of side effects:
- a high probability (very often) - at least 0.1%,
- often (often) - at least 0.01 to 0.1%,
- infrequently - at least 0,001% to 0,01%.
Deviations from the norm of laboratory test indices: a large percentage of cases of increased activity of serum creatinine phosphokinase (III-IV, 4%), increased creatinine density, decreased albumin density; very often - weight loss; in about a quarter of cases, the level of creatine kinase increases in different degrees, less than 1% of them - in combination with muscle necrosis.
Deviations from the norm of the functions of the hematopoiesis: a high probability of agranulocytosis, a decrease in the number of platelets, erythrocytes, leukocytes, anemia; often - febrile agranulocytosis.
Agranulocytosis most often manifests hematologic intoxication, this symptom of III and IV century. Was traced in 19% and 8% of the Yondelis courses, respectively. Agranulocytosis was reversible, with little or no fever and / or endemia.
The decrease in the number of platelets was traced in 3% and less than 1% of the courses, respectively. Manifestations of hemorrhage, which have arisen because of this, were less than in 1% of patients with therapy only by Yondelis.
Reduction of hemoglobin - with therapy only Yondelis and in a complex in 93% and 94% of patients, respectively. This symptom of III and IV st. Was traced in 3% and 1% of courses, respectively.
Deviations from the norm of the functions of the digestive organs: a high likelihood of nausea (III-IV st. - 6%), vomiting (III-IV st. - 6.5%), constipation (III-IV st. - less than 1%); often - diarrhea (III-IV st. - less than 1%), stomatitis (III-IV st. - less than 1%), abdominal and epigastric pain, indigestion.
Abnormal hepatobiliary system functions: a high probability of raising the level of bilirubin (III v - 1%.), Increased alanine aminotransferase activity (III v - 38%, IV v - 3%..), Aspartate aminotransferase (III st.- 44%, IV 7%), deviation from the norm of alkaline phosphatase and gamma-glutamyltransferase.
The bilirubin index rose to a maximum in about a week, another week was enough to normalize it. Part of the undesirable consequences in the form of jaundice, increased liver and pain in her area, as well as part of the deceased due to violations of the patients' hepatic activity, did not exceed 1%.
Temporal increase in the intensity of alanine aminotransferase and aspartate aminotransferase III st. Was found in 12% and 20% of courses, and IV in 1% and 2% in courses, respectively. The half-period of reaching the highest index was five days. In most cases, the activity index of these enzymes decreased approximately to two weeks to Ist. Or up to the norm, in less than 2% of the cycles - the normalization process slightly exceeded three weeks. An increase in the number of infusions in the patient contributed to a trend towards the normalization of enzyme activity.
Deviations from the norm of the functions of the nervous system: a greater likelihood of a headache; often - sensory polyneuropathy, parrerexia, dizziness, paresthesia, insomnia.
Deviations from the norm of the functions of the cardiovascular system: a high probability of hypotension, tides of blood.
Deviations from the norm of the functions of the respiratory system: a high probability of dyspnea (III-IV st. - 2%), cough.
Deviations from the norm of skin functions: high probability of hair loss (with monotherapy - 3%).
Deviations from the norm of the functions of the musculoskeletal system: frequent pain in the lower back, as well as joint and muscular.
Deviations from the norm of metabolic functions: a high probability of lack of appetite (III-IV st. - less than 1%); often dehydration, a decrease in the content of potassium in the blood.
Other side effects: a high likelihood of weakness (III-IV st. - 9%), increased fatigue (III-IV st. - 1%); often - the addition of secondary infections, fever, peripheral edema, local reactions to the administration of trabektidine.
According to the results of post-registration studies, there were few episodes of the drug getting into the tissue with their necroticization and the need for surgical removal of these tissue sites.
Occasionally, there was a manifestation of acute liver dysfunction (including lethal cases) in patients on the background of a severe accompanying clinic with infusions of trabecadine.
Risk factors, possibly contributing to the marked increase in toxic properties of trabectidine noted in these situations:
- dosage of the drug did not meet the recommended;
- the reaction with competitive biomes of the CYP3A4 isoenzyme or its inhibitors is likely;
- There was no prophylactic therapy (dexamethasone).