Symptoms: neutropenia and diarrhea.
Treatment: symptomatic. In case of overdose, the patient should be hospitalized and the function of vital organs should be carefully monitored. The specific antidote of irinotecan is unknown.
hypersensitivity to irinotecan or other components of the drug,
chronic inflammatory bowel diseases and / or intestinal obstruction,
pronounced suppression of bone marrow hematopoiesis,
the level of bilirubin in the blood serum, more than 1.5 times higher than the upper limit of the norm (VGN),
the general condition of the patient, evaluated on the WHO scale of more than two,
pregnancy,
breastfeeding period,
children's age (data on safety and efficacy in children are not available).
With caution:
radiation therapy for the abdominal or pelvic area in the anamnesis,
leukocytosis,
in female patients (increased risk of diarrhea).
Since irinotecan has anticholinesterase activity, it is possible to increase the duration of neuromuscular blockade when combined with suxamethonium and antagonistic interaction with neuromuscular blockade when combined with non-depolarizing muscle relaxants.
Biotecan (Irinotecan) should not be mixed with other drugs in the same bottle.
From the side of the hematopoietic organs: neutropenia is observed on average in 80% of patients, including half of them have a decrease in neutrophils to <1000 cells/µl. Recovery of the neutrophil count is usually observed after 7-20 days from the start of treatment. Anemia of varying severity occurs on average in 60% of patients, thrombocytopenia-in 7% of patients. One case of thrombocytopenia with the formation of antiplatelet antibodies was described.
From the digestive system: late diarrhea that occurs more than 24 hours (on average, 5 days) after administration of the drug is a dose-limiting toxic manifestation and is observed in approximately 87% of patients, of which 38% are severe. Nausea and vomiting usually occur on the first day of administration or after 24 hours in 85% of patients. Dehydration has been reported with vomiting and diarrhea, very rarely with the development of renal failure, hypotension, and heart failure. Possible abdominal pain, anorexia, mucositis, constipation.
Acute cholinergic syndrome It is observed in 9% of patients within the first 24 hours after administration of the drug and is manifested by diarrhea, abdominal pain, increased sweating, miosis, vision disorder, lacrimation, salivation, decreased blood pressure, dizziness, chills and general malaise.
From the central nervous system: involuntary muscle twitching or convulsions, paresthesia, asthenia.
Allergic reactions: rarely-skin rash and very rarely-the development of anaphylactic shock.
Other: shortness of breath, alopecia, fever, local reactions.
Locally advanced or metastatic cancer of the colon and rectum:
- in combination with 5-fluorouracil and calcium folinate in patients who have not previously received chemotherapy,
- monotherapy or in combination with capecitabine in patients with disease progression after conventional treatment.
Irinotecan-a semisynthetic derivative of camptothecin-is a specific inhibitor of the cellular enzyme topoisomerase I. In the tissues, the drug is metabolized to form the active metabolite SN-38, which is superior in its activity to irinotecan. Irinotecan and SN-38 stabilize the topoisomerase I complex with DNA, which prevents the latter from replicating.
The pharmacokinetic profile of irinotecan is dose-independent.
The maximum plasma concentration of irinotecan and SN-38 was reached by the end of the intravenous infusion at the recommended dose of 350 mg / m2.
The binding to plasma proteins for irinotecan is approximately 65%, for its active metabolite — SN-38 — 95%.
The distribution of the drug in the plasma is two-or three-phase.
It is mainly metabolized in the liver under the action of the enzyme carboxylesterase to the active metabolite-SN-38.
Average T1/2 the drug in the first phase is 12 minutes, in the second — 2.5 hours and in the last — 14.2 hours.
It is excreted in the urine for 24 hours as an unchanged drug (20%) and as SN-38 (0.25%). About 30% of the drug is excreted in the bile, both in unchanged form and in the form of glucuronide SN-38.
5-fluorouracil and calcium folinate do not affect the pharmacokinetics of irinotecan.
Biotecan (Irinotecan)
Irinotecan
V/v.
The drug is intended for adults only.
Biotecan (Irinotecan) is administered as an intravenous infusion lasting at least 30 minutes and no more than 90 minutes.
When choosing the dose and mode of administration in each individual case, you should refer to the special literature.
In monotherapy mode: at a dose of 350 mg / m2 every 3 weeks.
As part of combined chemotherapy:
- with 5-fluorouracil (continuous infusion) and calcium folinate with weekly administration-at a dose of 80 mg / m2,
- when administered with calcium folinate and prolonged infusion of 5-fluorouracil 1 time in 2 weeks-180 mg/m2,
- in combination with a jet injection of 5-fluorouracil and calcium folinate-125 mg / m2 weekly.
The doses and administration regimen of 5-fluorouracil and calcium folinate are described in detail in the literature.
The introduction of Biotecan (Irinotecan)a should not be carried out until the number of neutrophils in the peripheral blood exceeds 1500 cells/µl, and until such complications as nausea, vomiting and especially diarrhea are completely stopped. The administration of the drug before the resolution of all side effects can be postponed for 1-2 weeks.
With the development of severe inhibition of bone marrow hematopoiesis (neutrophil count <500 cells/µl, and/or white blood cell count <1000 cells/µl, and/or platelet count <100,000 cells/µl), febrile neutropenia (neutrophil count <1000 cells/µl of blood in combination with an increase in body temperature of more than 38 °C), infectious complications, severe diarrhea or other non-hematological toxicity of 3-4 degrees, subsequent doses of Biotecan (Irinotecan)a and, if necessary, 5-fluorouracil should be reduced by 15-20%.
Patients with impaired liver function. When the level of bilirubin in the blood serum exceeds the upper limit of the norm by no more than 1.5 times, due to the increased risk of developing severe neutropenia, the patient's blood parameters should be carefully monitored. With an increase in bilirubin levels of more than 1.5 times-treatment with Biotecan (Irinotecan)om should be stopped.
Patients with impaired renal function. Treatment of Biotecan (Irinotecan)om is not recommended, because data on the use of irinotecan in this category of patients are not available.
Elderly patients. There are no special instructions for the use of irinotecan in the elderly. The dose of the drug in each specific case should be selected with caution.
Instructions for preparing the infusion solution
Dilute the required amount of the drug in 250 ml of 0.5% dextrose solution or 0.9% sodium chloride solution and mix the resulting solution by rotating the bottle. Before administration, the solution should be visually examined for transparency. If a precipitate is found, the preparation must be destroyed.
The solution should be used immediately after dilution.
If the dilution is carried out in accordance with the rules of asepsis (for example, in a laminar air flow unit), Biotecan (Irinotecan) a solution can be used if stored at room temperature for 12 hours (including infusion time) and if stored at a temperature of 2-8 °C for 24 hours after opening the concentrate bottle.
