Irinotecan
When ATH:
L01XX19
Characteristic.
Semi-synthetic derivative of camptothecin (alkaloid, isolated from the plant Camptotheca pointed). Irinotecan hydrochloride - pale yellow or yellow crystalline powder. Sparingly soluble in water and organic solvents. Molecular weight 677,19.
Pharmacological action.
Antitumor, cytostatic.
Application.
Locally advanced or metastatic cancer of the colon or rectum - in combination with fluorouracil and calcium Valium at patients, not previously treated with chemotherapy, or as monotherapy in patients with disease progression after standard treatment.
Contraindications.
Hypersensitivity, chronic inflammatory bowel disease, ileus, giperʙiliruʙinemija (bilirubin 1,5 or more times higher than normal), pronounced inhibition of bone marrow hematopoiesis, severe neutropenia (less than 1.5 109/l), pregnancy, lactation, childhood (Safety and efficacy have not been determined).
Pregnancy and breast-feeding.
Contraindicated in pregnancy (adequate and well-controlled studies of the safety of use in pregnant women were not conducted, possible adverse effects on the fetus).
Unknown, whether irinotecan penetrates into breast milk of nursing women, but it is found in the milk of rats. Because many drugs are excreted in the milk of women and the potential for serious adverse reactions in infants, breastfed, It recommended to stop breast-feeding during treatment with irinotecan.
Side effects.
Cardio-vascular system and blood (hematopoiesis, hemostasis): myelosuppression - reversible neutropenia, anemia, thrombocytopenia (cm. Precautions).
From the digestive tract: nausea and vomiting, diarrhea (cm. Precautions), abdominal pain, anorexia, mukozit, stomatitis, constipation. Reported cases of pseudomembranous colitis, bowel obstruction, bleeding from the gastrointestinal tract, intestinal perforation, raising the level of amylase and lipase.
From the nervous system and sensory organs: involuntary muscle twitches, convulsions, paraesthesia, asthenia.
Other: Acute cholinergic syndrome (Early diarrhea, rhinitis, hyperptyalism, mioz, lacrimation, increased perspiration, vasodilation, increased intestinal peristalsis, spastic abdominal pain - see. Precautions), alopecia; fever (in the absence of infection and severe neutropenia); breathlessness; transient increase in transaminases, Alkaline phosphatase, bilirubin and creatinine in blood serum; in rare cases - renal dysfunction and acute renal failure, hypotension or circulatory failure, usually in patients, after an episode of dehydration, associated with severe vomiting and / or diarrhea, or in patients with sepsis; allergic reactions (incl. skin rash), injection site reactions.
Cooperation.
In a joint application with suxamethonium may increase the duration of neuromuscular blockade. When combined with the non-depolarizing muscle relaxants - antagonistic interaction against neuromuscular blockade.
Overdose.
Symptoms: neutropenia, diarrhea.
Treatment: hospitalization, Careful monitoring of vital functions, simptomaticheskaya therapy. Spetsificheskiy antidote unknown.
Dosing and Administration.
The mode set individually, depending on the evidence, the state of the hematopoietic system, regimens. Misleading I / drop, for 30-90 min. The average dose in monotherapy - 350 mg / m2 (previously required volume of the stock solution is diluted 250 ml 0,9% sodium chloride solution or 5% glucose solution and thoroughly stirred), introduced 1 once every 3 Sun.
Precautions.
Treatment should be carried out in specialized chemotherapy wards, under the supervision of a qualified oncologist.
During treatment it is necessary to monitor weekly the peripheral blood and monitor liver function.
In order to prevent nausea and vomiting before each cycle of therapy is recommended prophylactic antiemetics.
Caution must be exercised in / in the introduction and to avoid extravasation.
During treatment, at least 3 months after cessation of therapy, Patients of childbearing age should use adequate contraceptive measures.
Diarrhea. Irinotecan can cause early and late forms of diarrhea, which are caused by different mechanisms.
Early diarrhea, developing within 24 hours after the administration of irinotecan, a cholinergic nature. Normally it is transient, very rarely - severe and may be accompanied by other symptoms of acute cholinergic syndrome. Acute cholinergic syndrome develops during infusion or for a short period of time after it, often at high doses of irinotecan. Patients with a history of information about acute cholinergic syndrome, incl. severe, Before the appointment of irinotecan, as well as in the development of this syndrome after administration of irinotecan, recommended atropine sulfate (the absence of clinical contraindications).
Diarrhea, appearing in more than 24 hours after treatment (delayed diarrhea), It is a consequence of cytostatic effect and dose-limiting toxic effect of irinotecan. This form of diarrhea can be life-threatening, tk. It may be prolonged (to 3 days) and lead to dehydration, disruption of electrolyte balance and sepsis. The average time until the first liquid stool after the infusion - 5 days. When the first episode of loose stool should be the appointment of a large amount of liquid, electrolytes containing, and the immediate holding of antidiarrheal therapy, comprising receiving high doses of loperamide. Loperamide should not be given prophylactically, incl. sick, whose diarrhea was observed during previous administrations of irinotecan.
Antidiarrheal therapy is continued for at least 12 hours after the last episode of loose stool, but not more 48 h because of the possibility of paresis of the small intestine. If you develop diarrhea as severe (more 6 episodes of liquid stools within days or severe tenesmus), and if it is accompanied by vomiting or fever, the patient should be urgently hospitalized for complex treatment, comprising the administration of broad spectrum antibiotics. In moderate or mild diarrhea (less 6 episodes of loose stool during the day and moderate tenesmus), which is not stopped during the first 48 no, you must start taking broad-spectrum antibiotics inside, while the patient is recommended to be hospitalized.
The patient should be forewarned about the possibility of his delayed diarrhea. Patients should immediately inform their physician of the occurrence of diarrhea and start appropriate therapy immediately. With inadequate treatment of diarrhea may develop the condition, threatening the life of the patient, especially if the diarrhea has developed against the background of neutropenia.
With the development of diarrhea on the background of neutropenia treatment broad-spectrum antibiotics begin immediately.
Neutropenia
Reported fatalities, due to sepsis on a background of severe neutropenia, patients, irinotecan. Irinotecan therapy should be temporarily discontinued in febrile neutropenia with an absolute neutrophil count less than 0.5 109/l and can be resumed when the number of neutrophils is restored to 0.5 109/l.
Patients with febrile neutropenia (body temperature ≥38 °C and neutrophil count less than 0.5 109/l) It must be started without delay introduction of broad-spectrum antibiotics in the hospital.
Caution should be exercised when using the drug in patients with bronchial asthma. The drug should be used with caution in patients, received prior radiation therapy to the abdomen or pelvis, female patients, Seniors (senior 65 years), patients, who earlier celebrated hyperleukocytosis, and the, whose Karnofsky Index (reflecting the general state) is less than 50% - In these cases increases the risk of diarrhea.
Patients should be warned of the possibility of occurrence during treatment with irinotecan dizziness and visual disturbances, which develop over 24 hours after infusion. If you experience these symptoms, patients are advised to refrain from driving and other mechanisms.
