Irinotecan for infusions 20 mg/ml. 25 ml. /500 mg. vial

Description

Irinotecan 500 mg Storage
active substance: irinotecan;

1 ml of concentrate contains 20 mg of irinotecan hydrochloride trihydrate;

Excipients: sorbitol (E 420), lactic acid, sodium hydroxide, dilute hydrochloric acid, water for injections.

Irinotecan 500 mg Dosage form
Concentrate for solution for infusion.

Main physical and chemical properties: clear, colorless or slightly yellowish solution.

Irinotecan 500 mg Pharmacotherapeutic group
Antineoplastic agents. Irinotecan. ATX code L01X X19.

Pharmacological properties

Pharmacodynamics

Irinotecan is an antineoplastic agent, a semi-synthetic derivative of camptothecin, an alkaloid of Camptotheca acuminata, a specific topoisomerase I inhibitor.

Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent replication of these single-stranded sequences. Recent studies have shown that the cytotoxicity of irinotecan is associated with damage to double-stranded DNA during its synthesis, when the replication enzyme interacts with the Quaternary complex formed by topoisomerase I, DNA and irinotecan or SN-38.

Irinotecan is a water-soluble precursor of the lipophilic metabolite SN-38. SN-38 is formed from irinotecan by carboxylesterase-mediated carbonate binding between camptothecin and the dipiperidine side chain. As an inhibitor of topoisomerase I isolated from human and rodent tumor lines, SN-38 is approximately 1000 times more potent than irinotecan. In vitro cytotoxicity analysis shows that the potency of SN-38 compared to irinotecan varies from 2 to 2000. However, the area under the concentration-time curve (AUC) in plasma for SN-38 is 2-8% of that for irinotecan. Both irinotecan and SN-38 exist in active lactone and inactive hydroxyl anionic form. There is a pH-dependent equilibrium between these forms. The acidic pH accelerates the formation of lactone, while the alkaline pH accelerates the formation of the hydroxyl anionic form.

Indication
Treatment of patients with advanced colorectal cancer:

in combination with 5-fluorouracil (5-FU) and folinic acid (FC) in patients who have not received prior chemotherapy to treat a common disease;
monotherapy for patients in whom 5-fluorouracil treatment was ineffective.
Irinotecan in combination with cetuximab is indicated for the treatment of patients with metastatic colorectal cancer with wild-type KRAS gene, accompanied by increased expression of epidermal growth factor receptor (REFR), who have not previously received chemotherapy, or after ineffective cytotoxic therapy, which included

Irinotecan in combination with 5-fluorouracil, folinic acid and bevacizumab is indicated for the treatment of metastatic colorectal cancer as first-line therapy.

In combination with capecitabine (with or without bevacizumab), irinotecan should be used as first-line therapy in patients with metastatic colorectal cancer.

Contraindication
Chronic inflammatory bowel disease and / or intestinal obstruction (see section “Special warnings and precautions for use”);
hypersensitivity to irinotecan hydrochloride or to other ingredients of the drug;
breastfeeding period;
hyperbilirubinemia (the level of bilirubin in the blood is 3 times higher than the upper limit of normal);
severe inhibition of bone marrow hematopoiesis;
general condition of the patient> 2 (according to the WHO classification);
severe neutropenia (less than 1.5 × 109 / l);
joint use with preparations of St. John’s wort perforated;
live attenuated vaccines.
In the case of combination treatment with cetuximab, bevacizumab or capecitabine – additional contraindications to use are given in the instructions for medical use of appropriate drugs.