Irinotecan
Irinotecan: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Irinotecan
ATX code: L01XX19
Active ingredient: irinotecan (Irinotecan)
Manufacturer: Biocad CJSC (Russia); S. K. Sindan-Pharma S.r.l. (SC Sindan-Pharma SrL) (Romania); Actavis Italy S.p. A. (Actavis Italy SpA) (Italy)
Description and photo update: 2019-05-03
Prices in pharmacies: from 1909 rubles.
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Irinotecan is an anticancer drug from the group of alkaloids.
Release form and composition
The drug is produced in the form of a concentrate for the preparation of a solution for infusion: transparent, from pale yellow to yellow, with a possible greenish tint (2 or 5 ml in a bottle, in a cardboard box 1 bottle; 2 ml in a bottle, in a blister strip1 bottle, in a cardboard box 1 package and instructions for the use of Irinotecan).
1 ml of solution contains:
- active substance: irinotecan hydrochloride trihydrate - 20 mg;
- additional components: sorbitol or D-sorbitol (depending on the manufacturer), sodium hydroxide, lactic acid, water for injection.
Pharmacological properties
Pharmacodynamics
Irinotecan is a semi-synthetic derivative of camptothecin and belongs to specific inhibitors of the cellular enzyme topoisomerase I. In tissues, the substance is metabolized by the enzyme carboxylesterase to form the metabolite SN-38, the activity of which exceeds that of the parent substance.
Irinotecan and its metabolite stabilize the complex of topoisomerase I with DNA, leading to linear DNA damage, which prevents its replication.
In the course of experiments in vivo, it was found that irinotecan also exhibits activity against tumors expressing P-glycoprotein of multiple drug resistance (vincristine and doxorubicin-resistant leukemias P388). Another significant pharmacological effect of the active ingredient is its ability to inhibit acetylcholinesterase.
Pharmacokinetics
The pharmacokinetics of irinotecan and its active metabolite SN-38 was studied with a 30-minute intravenous (IV) infusion of the drug at a dose of 100–750 mg / m². The dosage regimen had no effect on the pharmacokinetic profile of the substance. Its distribution in plasma is two- or three-phase, the volume of distribution (V d) was 157 l / m². Against the background of intravenous infusion at the recommended dose of 350 mg / m2 of body surface, the maximum concentration (C max) of irinotecan and SN-38 in plasma was observed by the end of the procedure and amounted to 7.7 μg / ml and 56 ng / ml, respectively, and the value area under the pharmacokinetic curve (AUC) - 34 μg / h / ml and 451 ng / h / ml.
In blood plasma, the active substance is determined mainly unchanged. For irinotecan, the bond with plasma proteins is approximately 65%, for SN-38 this figure reaches about 95%.
The metabolic transformation of the active substance occurs in the liver in 2 ways: with the participation of carboxylesterase to the SN-38 metabolite, and further glucuronidation by means of the CYP3A4 isoenzyme with the formation of aminopentanoic acid derivatives and amines. Only SN-38 has significant cytotoxic activity. The average half-life (T 1/2) of the drug in plasma in the first phase of the three-phase model is 12 minutes, in the second phase this figure is 2.5 hours, in the last phase - 14.2 hours.
The average plasma clearance is 15 l / h / m². The drug is excreted by the kidneys unchanged - about 19.9%, and in the form of SN-38 - 0.25%. About 30% of the drug is excreted in the bile, both unchanged and in the form of SN-38 glucuronide.
According to the results of clinical studies, fluorouracil and calcium folinate do not affect the pharmacokinetics of irinotecan. Elimination of the drug is reduced by an average of 40% in patients with bilirubin levels exceeding the upper limit of normal (UHN) by 1.5-3 times.
Indications for use
Irinotecan is recommended for the treatment of locally advanced or metastatic cancer of the colon and rectum in the following cases:
- treatment of patients who have not previously received chemotherapy in combination with calcium folinate and fluorouracil;
- treatment of patients with disease progression after standard antitumor treatment (in monotherapy mode).
Contraindications
Absolute:
- pronounced inhibition of bone marrow hematopoiesis;
- chronic bowel disease, inflammatory, and / or intestinal obstruction;
- serum concentration of bilirubin in the blood exceeding more than 1.5 or 3 times (depending on the manufacturer) VGN;
- the general condition of patients, assessed on a WHO scale of more than 2;
- pregnancy and lactation;
- age up to 18 years;
- renal failure;
- simultaneous use with yellow fever vaccine (depending on the manufacturer);
- hypersensitivity to any of the constituents of the drug.
Relative (use irinotecan with caution):
- leukocytosis;
- radiation therapy (in history) to the pelvic or abdominal region;
- elderly age;
- belonging to the female sex (due to the increased risk of diarrhea).
Additional relative contraindications depending on the manufacturer:
- the general condition of the patient on the scale of the World Health Organization (WHO) equal to 2;
- functional disorders of the liver;
- hypovolemia;
- predisposition to thrombosis and thromboembolism;
- simultaneous use of pneumotoxic drugs;
- therapy with colony-stimulating factors.
Irinotecan, instructions for use: method and dosage
Irinotecan is intended only for intravenous infusion, lasting at least 30 and no more than 90 minutes. The drug can be used both as monotherapy and in combination with calcium folinate and fluorouracil.
Recommended dosage regimen:
- monotherapy: at a dose of 125 mg / m² once a week as a 90-minute intravenous infusion for 4 weeks with a break of 2 weeks, as well as at a dose of 350 mg / m² as a 60-minute infusion every 3 weeks;
- combined chemotherapy: with calcium folinate and fluorouracil at a dose of 125 mg / m² once a week, by long-term infusion at a dose of 180 mg / m² once every 2 weeks; a detailed description of the doses and administration of calcium folinate and fluorouracil is given in the specialized literature.
In the case of previous extensive radiation therapy, an indicator of the patient's general condition on the WHO scale equal to 2, an increased level of bilirubin in the blood, or when the patient is 65 years of age or older, a decrease in the initial dose of Irinotecan may be recommended: in monotherapy mode - from 125 to 100 mg / m² and from 350 to 300 mg / m²; in combination therapy mode - from 125 to 100 mg / m² and from 180 to 150 mg / m².
You should not start treatment with the drug until such undesirable effects as vomiting, nausea, and especially diarrhea have been completely stopped, and until the number of neutrophils in the peripheral blood does not exceed 1500 cells / μl of blood. Until the removal of all adverse reactions, you can postpone the use of Irinotecan for 1–2 weeks.
In case of detection during therapy of pronounced inhibition of bone marrow hematopoiesis (platelet count below 100,000 / μl and / or leukocyte count less than 1000 / μl, and / or neutrophil count less than 500 / μl), infectious complications, severe diarrhea, febrile neutropenia (neutrophil count 1000 / μl and below against the background of an increase in body temperature of more than 38 ° C) or other non-hematological toxicity of III – IV degree, the dose of Irinotecan should be reduced by 15–20%, and, if necessary, fluorouracil.
If the appearance of signs of progression of a tumor disease or the development of unacceptable toxic manifestations is recorded, treatment with the drug must be discontinued.
Irinotecan solution must be prepared under aseptic conditions. It is recommended to dilute the required dose of the concentrate in 250 ml of 0.9% sodium chloride solution or 0.5% dextrose solution and then, gently rotating the bottle, mix the resulting liquid. If a precipitate is found in the prepared solution, the drug must be disposed of.
The solution must be injected immediately after dissolving the concentrate. If the dilution was carried out in compliance with the rules of asepsis (in particular, in the installation of a laminar air flow), it is allowed to use the product after opening the vial with the concentrate for 12 hours (including the infusion period) if stored at room temperature, and for 24 hours - at a storage temperature of 2–8 ° C.
Side effects
- hematopoietic system: very often - anemia, leukopenia, neutropenia; often - febrile neutropenia, thrombocytopenia when using the drug in monotherapy; extremely rare - the formation of antiplatelet antibodies;
- nervous system: rarely - asthenia, headache, involuntary muscle twitching or cramps, paresthesia, gait disturbance, confusion; extremely rarely - transient speech impairment;
- digestive system: very often - late diarrhea; often - hiccups, nausea, constipation, vomiting, candidiasis of the gastrointestinal tract (GIT); sometimes - pseudomembranous colitis (in the only case, C. difficile was found), gastrointestinal bleeding, intestinal obstruction; rarely - abdominal pain, anorexia, inflammation of the mucous membranes, colitis, including typhlitis; intestinal perforation, ischemic and ulcerative colitis, pancreatitis;
- autonomic nervous system: acute cholinergic syndrome - manifestations of this complication may be - abdominal pain, increased intestinal motility, early diarrhea, increased sweating, conjunctivitis, rhinitis, malaise, chills, lacrimation, miosis, visual disturbances, dizziness, decreased blood pressure (BP), vasodilation, bradycardia; salivation was recorded in 9 and 1.4% of patients who received irinotecan as monotherapy and as part of combined chemotherapy, respectively; all these symptoms were relieved after the administration of atropine (subcutaneously at a dose of 0.25 mg);
- cardiovascular system: sometimes - lowering blood pressure, hypovolemic shock due to dehydration; rarely - increased blood pressure during or after the end of the infusion;
- skin and subcutaneous fat: very often - reversible alopecia; sometimes mild skin reactions;
- allergic reactions: sometimes - skin rash; extremely rare - anaphylactic shock;
- respiratory organs: sometimes - rhinitis, shortness of breath, pulmonary infiltrates;
- others: very often - an increase in body temperature; often - increased fatigue; rarely - the addition of secondary infections, local post-infusion reactions, weight loss, hypomagnesemia, increased serum urea nitrogen and gamma glutamyltransferase (GGT) activity, hypovolemia, dehydration, chest pain, urinary tract infections, fainting, sepsis, syndrome lysis of the tumor;
- laboratory parameters: very often - a temporary increase in the activity of alkaline phosphatase (ALP), serum transaminases or bilirubin levels (combination therapy); often - a transient increase in the activity of alkaline phosphatase, serum transaminases or bilirubin level (monotherapy), an increase in serum creatinine; rarely - hyponatremia and hypokalemia; extremely rarely - an increase in the activity of serum lipase and / or amylase.
Diarrhea (delayed) that occurs later than 24 hours after administration of the drug is a dose-dependent toxic effect of Irinotecan. When using the drug in monotherapy mode, severe diarrhea was detected in 20% of patients (during combination therapy - 13.1%).
When prescribing the drug in monotherapy, about 10% of patients taking antiemetic drugs experienced severe vomiting and nausea, when using irinotecan during combined chemotherapy - in 2.8 and 2.1% of patients, respectively.
Neutropenia was observed in 78.7% of patients with monotherapy (in 82.5% - against the background of combined chemotherapy), including in 22.6% - it was pronounced (the number of neutrophils was less than 500 cells / μL). This adverse reaction was reversible and not cumulative. The full number of neutrophils was restored, as a rule, on day 22 when using irinotecan in monotherapy mode, and on days 7–8 - as part of combined chemotherapy. Fever simultaneously with severe neutropenia during monotherapy was recorded in 6.2% of patients, and in 3.4% of patients as part of a combination treatment. Against the background of irinotecan monotherapy, infectious complications were observed in 10.3% of patients, while in combination with severe neutropenia - in 5.3%.
Overdose
Diarrhea and neutropenia can be expected manifestations of overdose. Treatment for this condition is prescribed symptomatic. In case of an overdose, it is recommended to hospitalize the patient and monitor the function of vital organs. The specific antidote for irinotecan is currently unknown.
special instructions
Drug therapy is required to be carried out in specialized chemotherapy departments and only under the supervision of a specialist who has experience with antiblastoma drugs.
During treatment with irinotecan, it is necessary to monitor liver activity and complete blood count every week.
Diarrhea caused by the cytotoxic effect of Irinotecan, as a rule, occurs no earlier than 24 hours after its administration, and in a larger number of patients - after about 5 days. With the development of the first episode of loose stools, the patient needs to drink plenty of fluids containing electrolytes, and immediate appropriate treatment, including the use of high doses of loperamide - the first dose of 4 mg and then every 2 hours at 2 mg. Such therapy should still be continued for at least 12 hours after the last episode of loose stools, but not longer than 48 hours due to the increased risk of paresis of the small intestine. With severe diarrhea, when more than 6 episodes of loose stools or pronounced tenesmus are observed during the day, and vomiting or fever occurs,the patient requires urgent hospitalization in the intensive care unit for complex treatment with the introduction of broad-spectrum antibiotics. If there are less than 6 episodes of loose stools per day and mild tenesmus, diarrhea is considered moderate or mild, but if it cannot be stopped within 48 hours, the patient should also be hospitalized and given oral antibiotics.
If diarrhea is accompanied by severe neutropenia (leukocyte count below 500 cells / μl), antidiarrheal therapy is combined with oral administration of broad-spectrum antibiotics for prophylaxis. For prophylactic purposes, loperamide should not be prescribed, including in patients who have had diarrhea in previous cycles of irinotecan treatment.
The patient should be aware of the risk of developing delayed diarrhea during therapy, when it occurs, it is necessary to urgently consult a doctor and begin appropriate treatment.
Before each cycle of therapy with Irinotecan, it is recommended to take antiemetics for prevention.
Patients with hereditary fructose intolerance should not use the drug, since it contains sorbitol as an additional component.
During the period of treatment, as well as for 3 months after its termination, women and men of reproductive age must use reliable methods of contraception.
In case of contact of Irinotecan on the skin, it should be urgently washed with soap and water, in case of contact with mucous membranes and eyes - only with clean water. In the process of diluting the concentrate, gloves, a mask and goggles must be used.
Influence on the ability to drive vehicles and complex mechanisms
During the period of treatment with Irinotecan within 24 hours after its administration, the risk of visual disturbances and dizziness should be taken into account. In the case of the development of such symptoms, patients need to refrain from driving motor vehicles and other potentially dangerous, complex mechanisms.
Application during pregnancy and lactation
During pregnancy and lactation, the use of an antineoplastic agent is contraindicated.
Pediatric use
In pediatric practice, Irinotecan is not used, since there is no data confirming the safety and efficacy of drug therapy in children and adolescents.
With impaired renal function
Treatment with Irinotecan is contraindicated in patients with renal insufficiency, since there are no data on the efficacy and safety of its use in this category of patients.
For violations of liver function
Patients with a serum bilirubin concentration in the blood exceeding more than 1.5 or 3 times (depending on the manufacturer) VGN, treatment with Irinotecan is contraindicated. With an increase in the serum bilirubin level no more than 1.5 times, the threat of severe neutropenia increases, and therefore requires careful monitoring of blood counts.
Use in the elderly
There are no special instructions for using the drug Irinotecan in the elderly. Patients in this age group need to select the dose individually, with extreme caution.
Drug interactions
- suxamethonium salts: an increase in the duration of neuromuscular blockade is possible due to the anticholinesterase activity exhibited by irinotecan;
- non-depolarizing muscle relaxants: possible antagonistic interaction in relation to neuromuscular blockade;
- myelosuppressive drugs and radiation therapy: the toxic effect of irinotecan on the bone marrow increases (including the development of thrombocytopenia and leukopenia);
- glucocorticosteroid drugs (GCS), including dexamethasone: the threat of lymphocytopenia, hyperglycemia (especially in the presence of diabetes mellitus or glucose intolerance) is aggravated;
- prochlorperazine: increases the likelihood of symptoms of akathisia;
- diuretics: may increase dehydration resulting from vomiting and diarrhea;
- laxatives: the incidence or severity of diarrhea may increase;
- atazanavir, an inhibitor of the CYP3A4 and UGT1A1 enzymes, ketoconazole: the plasma level of the active metabolite SN-38 in the blood increases;
- anticonvulsants - inducers of the CYP3A4 isoenzyme (phenytoin, phenobarbital, carbamazepine), drugs based on St. John's wort (Hypericum perforatum): the plasma concentration of the active metabolite SN-38 decreases; these combinations are not recommended;
- live (attenuated) vaccines: serious or fatal infections may develop; during treatment with irinotecan, it is necessary to refrain from vaccination with live vaccines; an inactivated or killed vaccine may be administered, but the response to such administration may be impaired.
Irinotecan should not be mixed in the same bottle with other medicines.
Analogs
Irinotecan's analogues are Irinotecan Medak, Irinax, Irinotecan-Teva, Irinotecan Pliva-Lahema, Iriten, Kamptera, Irnokam, Kolotekan, Campto TsS, etc.
Terms and conditions of storage
Store in a place protected from light and moisture, out of reach of children, at a temperature not exceeding 25 ° C.
The shelf life is 2 or 3 years (depending on the manufacturer).
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Irinotecan
The few reviews about Irinotecan are mostly positive. Patients report positive dynamics when using the drug for the treatment of rectal and colon cancer both in monotherapy mode and in combination with calcium folinate and fluorouracil.
The disadvantage of an anticancer agent is a high risk of side effects, especially diarrhea, neutropenia, and anemia.
Price for Irinotecan in pharmacies
The price of Irinotecan, a concentrate for the preparation of a solution for infusion (20 mg / ml), can be 1600–5000 rubles. per bottle, 5 ml.
Irinotecan: prices in online pharmacies
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Drug name Price Pharmacy |
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Irinotecan 20 mg / ml concentrate for preparation of solution for infusion 2 ml 1 pc. 1909 RUB Buy |
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Irinotecan 20 mg / ml concentrate for preparation of solution for infusion 5 ml 1 pc. 3463 RUB Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
