Clinical and pharmacological group: & nbsp

Antitumor agents of vegetable origin

Included in the formulation
  • Irenax®
    concentrate d / infusion 
    Sandoz d.     Slovenia
  • Irynotekan
    concentrate d / infusion 
    BIOCAD, CJSC     Russia
  • Irynotekan
    concentrate d / infusion 
    AKTAVIS GROUP, AO     Iceland
  • Irynotekan medak
    concentrate d / infusion 
    medac GmbH     Germany
  • Irinotecan Pliva-Lahema
    concentrate d / infusion 
  • Irinotecan-Teva
    concentrate d / infusion 
  • Irinotecan-Filaxis
    concentrate d / infusion 
  • Irinotel
    concentrate d / infusion 
  • Iriten
    concentrate d / infusion 
    LENS-PHARM, LLC     Russia
  • Irnokam®
    concentrate d / infusion 
  • Kampeter
    concentrate d / infusion 
  • Campto® CA
    concentrate d / infusion 
  • Kolotekan
    concentrate d / infusion 
  • Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

    VED

    АТХ:

    L.01.X.X.19   Irynotekan

    Pharmacodynamics:

    Antitumor agent.

    Irinotecan and its active metabolite SN-38 inhibit topoisomerase I - an enzyme that reversibly breaks the primary structure of DNA during its replication, which leads to cell death.The drug acts predominantly in the S-phase of the cell cycle. SN-38 is about 1000 times stronger than irinotecan, inhibits the activity of topoisomerase I, isolated from the cell lines of human tumors or rodents. Metabolite has a much higher connection with proteins and a low area under the concentration-time curve, rather than irinotecan. The cytotoxic activity is time-dependent and specific for the S-phase.

    Pharmacokinetics:

    With intravenous infusion irinotecan mis metabolized mainly in the liver by the action of the carboxyesterase enzyme to the active metabolite SN-38. The average amount of excretion of irinotecan with urine in 24 hours is 19.9%, and the metabolite SN-38 - 0.25%.

    The kinetic profile of irinotecan is dose independent. After intravenous infusion, the irinotecan elimination curve from plasma has a multi-exponential character, half-life in the terminal phase - 6-12 hours. The terminal elimination half-life for metabolite SN-38 is 10-20 hours.

    Indications:Local distributionMetastatic or metastatic cancer of the colon or rectum - in combination with fluorouracil and calcium folinate in patients who have not previously received chemotherapy, or in monotherapy in patients with progressionm disease after conventional treatment.

    II.C15-C26.C18   Malignant neoplasm of colon

    II.C15-C26.C20   Malignant neoplasm of rectum

    II.C15-C26.C21   Malignant neoplasm of anus [anus] and anal canal

    Contraindications:Hypersensitivitychronic inflammatory bowel disease, intestinal obstruction, hyperbilirubinemia(the level of bilirubin is 1.5 or more times higher than normal), severe inhibition of bone marrow hematopoiesis, severe neutropenia (less than 1.5×109 / l), pregnancy, breast-feeding, children's age (safety and efficacy of the application are not determined).
    Carefully:Caution is used in patients who received previous radiation therapy on the abdominal or pelvic area, with previously noted hyperleukocytosis, and also with the Karnovsky index (reflecting the general condition) of less than 50%, in female patients (the risk of diarrhea increases).
    Pregnancy and lactation:

    Contraindicated in pregnancy and lactation (breastfeeding).

    The action category for the fetus by FDA is D.

    Patients of childbearing age should use reliable methods of contraception during the treatment period and within 3 months after its termination.

    Dosing and Administration:The dosage regimen is set individually, depending on the indications, the status of the hematopoietic system, the chemotherapy regimen. Enter intravenously drip, within 30-90 minutes. The average dose in the monotherapy regime is 350 mg / m2 (previously required volume of the initial solution is diluted with 250 ml of 0.9% sodium chloride solution or 5% glucose solution and mixed thoroughly), injected once every 3 weeks.
    Side effects:

    On the part of the hematopoiesis system: neutropenia (reversible), anemia, thrombocytopenia.

    From the digestive system: diarrhea, nausea, vomiting; possible - pain in the abdomen, stomatitis, constipation.

    Acute cholinergic syndrome: early diarrhea, abdominal pain, conjunctivitis, rhinitis, arterial hypotension, vasodilation, sweating, chills, general malaise, dizziness, visual impairment, increased tear and salivation (during or within the first 24 hours after administration).

    Dermatological reactions: reversible alopecia is possible.

    Allergic reactions: rarely - skin rash.

    Other: shortness of breath, involuntary muscle contractions, seizures, paresthesia, asthenia, fever (in the absence of infection and severe neutropenia).

    Overdose:

    Symptoms: diarrhea, neutropenia, leukopenia, neutropenic fever is possible.

    Treatment: hospitalization, careful monitoring of vital functions, symptomatic therapy. The specific antidote is unknown. With severe myelosuppression, transfusion of blood components may be required, with leukopenia and neutropenia - the use of colony-stimulating factors, with febrile neutropenia - empirical antibiotic therapy with broad-spectrum antibacterial drugs, sensitivity determination of the causative agent, symptomatic therapy to prevent dehydration in severe diarrhea.

    Interaction:

    Dexamethasone - when prescribed before the application of irinotecan as a means of preventing nausea and vomiting can cause hyperglycemia (especially in the presence of diabetes mellitus or a violation of glucose tolerance in the anamnesis) and increase the incidence of lymphocytopenia.

    Diuretics - it is possible to increase the dehydration caused by vomiting and diarrhea as a result of the appointment of irinotecan. It is recommended to carefully monitor the patient and cancel the use of diuretics during the period of active diarrhea and vomiting.

    Radiation therapy is a significant increase in the risk of developing severe myelosuppression in patients who have previously received radiation therapy for the pelvic or abdominal region; Combination of irinotecan with radiation therapy has not been studied and is not recommended.

    Immunosuppressants (azathioprine, glucocorticoids, mercaptopurine, mycophenolate mofetil, muromonab-CD3, tacrolimus, chlorambucil, cyclophosphamide, ciclosporin) - it is possible to increase the risk of infections in parallel application.

    Prochlorperazine is an increase in the incidence of akathisia when administered on a single day with irinotecan during the weekly administration of the latter.

    Laxatives - may increase the risk of severe diarrhea in parallel use; Do not combine with irinotecan.

    Fluorouracil is an increase in the incidence of severe diarrhea, neutropenia, sepsis, dehydration, and deaths when combining irinotecan with fluorouracil and calcium folinate (Mayo Clinic regimen). The administration of fluorouracil after 48 hours or more after irinotecan is associated with lower toxicity than the use of irinotecan after fluorouracil.Combination of irinotecan with the mode of the Mayo Clinic is not recommended.

    As irinotecan has anticholinesterase activity, it is possible to increase the duration of neuromuscular blockade when combined with suxamethonium salts and antagonistic interaction with neuromuscular blockade when combined with nondepolarizing muscle relaxants.

    In the joint application of irinotecan with herbal preparations based on St. John's wort (Hypericum perforatum), as well as with antiepileptic drugs inducers CYP3A (carbamazepine, phenobarbital and phenytoin) the concentration in the plasma of the active metabolite SN-38 is reduced.

    The simultaneous administration of irinotecan with atazanavir, the inhibitor of the enzymes CYP3A4 and UGT1A1, as well as with ketoconazole may cause an increase in the concentration of the active metabolite SN-38 in the blood plasma.

    Irinotecan should not be mixed with other medicines.

    Special instructions:

    It is necessary to have equipment and medicines in the department to stop possible adverse reactions, and in the institution - intensive care units.

    Irinotecan is administered only by intravenous drip. It is necessary to avoid extravasation.

    Before intravenous injection, the contents of the 20 mg / ml vial are diluted with 5% dextrose solution or 0.9% sodium chloride solution (at least 250 ml) to a concentration of 0.12-2.8 mg / ml.

    With weekly use, it is possible to increase the dose to 150 mg /m2 and a decrease to 50 mg /m2 with a step of 25-50 mg /m2 (depending on the portability).

    The modification of irinotecan dose when used in monotherapy during the next cycle depends on the severity of the toxicity. At a toxicity of II degree it is necessary to lower a dose on 25 mg /m2. If in the subsequent cycles there is a complete restoration of the body, then you can return to the original dose. At toxicity of III degree the next introduction postpone before the sanction of toxicity up to II degree and more low; with subsequent treatment, the dose is reduced by 25-50 mg /m2 and do not increase it with further therapy. With toxicity of IV degree, it is necessary to postpone the next administration until toxicity is resolved to grade II or less; with subsequent treatment, the dose is reduced by 50 mg /m2 and do not increase with further therapy.

    With the development of toxicity against the background of the use of the drug every 3 weeks, it is necessary to postpone the administration or reduce the dose by 50 mg /m2.

    When combined with fluorouracil and calcium folinate and development of grade II toxicity, it is necessary to reduce the dose by 25 mg /m2, III-IV degree - postpone the next administration until the toxicity is restored to grade II and below and resume treatment at a dose reduced by 50 mg /m2.

    With the development of diarrhea after the first cycle of treatment with a weekly regimen, the next administration is postponed until its complete regression. With the development of late diarrhea II-IV degree, a reduction in the dose of irinotecan is necessary.

    For the prevention of nausea and vomiting, it is recommended that premedication be carried out with anti-emetics 30 minutes before the administration of irinotecan: a combination of dexamethasone (10 mg) and a serotonin 5-HT3 receptor antagonist (ondansetron or granisetron). Other antiemetics (eg, prochlorperazine) can be used, if necessary, to stop nausea and vomiting that occur after the infusion.

    Preventive administration of loperamide with a view to reducing the frequency and severity of late diarrhea is not recommended.

    With the development of severe (grade III-IV) diarrhea or other toxicity, further treatment should be postponed until its complete regression (usually within 1-2 weeks) and later resume therapy in reduced doses.With the progression of toxicity for 2 weeks or more, consideration should be given to discontinuing treatment with irinotecan.

    Possible long-term treatment with irinotecan, depending on the duration of response or stabilization of the process, provided that the drug is well tolerated.

    It is not recommended to combine the use of irinotecan with the mode of the Mayo Clinic (fluorouracil and calcium folinate for 4-5 consecutive days every 4 weeks), except in cases of clinical trials due to the high incidence of severe toxicity and increased lethality.

    The maximum dose for a weekly administration is 150 mg /m2, in combination with fluorouracil and calcium folinate - 125 mg /m2.

    When extravasation is necessary, wash the place of its occurrence with sterile water and put ice on it.

    In patients over the age of 65, there may be an increased risk of late diarrhea. Careful observation of patients is recommended. When treating patients over the age of 70, it is necessary to reduce the starting dose in the mode of administration once every 3 weeks. With a weekly dose adjustment is not required.

    If you get on the skin of a solution of irinotecan, immediately wash it off with soap and water, and on mucous membranes with water.

    After diluting with 5% dextrose solution, the resulting solution is stable for 48 hours at a temperature of 2-8 ° C and stored in a dark place or for 24 hours at room temperature and illuminated with fluorescent lamps. A dosage form that does not contain preservatives should be used for 6 hours at room temperature or for 24 hours when stored in a refrigerator.

    After diluting with 0.9% sodium chloride solution, the resulting solution is stable for 24 hours at room temperature and illuminated with fluorescent lamps. A dosage form that does not contain preservatives should be used for 6 hours at room temperature. A solution of irinotecan in a 0.9% solution of sodium chloride should not be stored in the refrigerator due to the possible occurrence of precipitation.

    Vials with a volume of 2 ml and 5 ml are intended for single use. Unused residue is to be disposed of.

    Impact on the ability to drive vehicles and manage mechanisms

    During treatment, especially within 24 hours after the administration of irinotecan, it is not recommended to engage in potentially dangerous activities associated with the need for concentration of attention and high speed of psychomotor reactions.

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