Iriten - instructions for use, dose, side effects, contraindications

Active substance:
irinotecan hydrochloride trihydrate in terms of irinotecan hydrochloride	0.02 g
Excipients:
D-sorbitol	0.045 g
lactic acid	0.0009 g
sodium hydroxide 0.5 M or 1 M (10% solution)	to pH 3.5
water for injections	up to 1 ml

Description:

Transparent yellowish liquid.

Pharmacotherapeutic group:Antitumor agent - alkaloid

ATX: & nbsp

L.01.X.X.19 Irynotekan

Pharmacodynamics:

Irinotecan, a semisynthetic derivative of camptothecin, is a specific inhibitor of the cellular enzyme topoisomerase I. In tissues, the drug is metabolized to form an active metabolite SN-38, which excels in its activity Irynotekan. Irynotekan and metabolite SN-38 stabilize the topoisomerase I complex with DNA, which prevents its replication.

Pharmacokinetics:

The pharmacokinetic profile of irinotecan is dose independent.

Metabolized mainly in the liver under the action of the enzyme carboxyesterase to the active metabolite SN-38.

The distribution of the drug in the plasma is two- or three-phase. The average half-life of the drug in the first phase is 12 minutes, in the second phase - 2.5 hours and in the last phase - 14.2 hours. The maximum plasma concentration of irinotecan and SN-38 was reached by the end of intravenous infusion at a recommended dose of 350 mg / m². With urine within 24 hours, an average of 20% of unchanged drug and 0.25% in the form of a metabolite SN-38.About 30% of the drug is excreted in bile, both in unchanged form and in the form of a metabolite SN-38 glucoronide.

The association with blood plasma proteins for irinotecan is approximately 65%, for its active metabolite SN-38 - 95%.

5-fluorouracil and calcium folinate do not affect the pharmacokinetics of irinotecan.

Indications:

Locally or metastatic cancer of the colon and rectum:

- in combination with 5-fluorouracil and calcium folinate in patients who had not previously received chemotherapy;

- in monotherapy in patients with disease progression after conventional treatment.

Contraindications:

- Hypersensitivity to irinotecan or other components of the drug;

- chronic inflammatory bowel disease and / or intestinal obstruction;

- marked suppression of bone marrow hematopoiesis;

- the level of bilirubin in the serum, exceeding the upper limit of the norm (VGN) by more than 1.5 times;

- general condition of patients, assessed by WHO scale> 2;

- pregnancy and the period of breastfeeding;

- children's age (data on safety and effectiveness in children are absent).

Carefully:

- Radiation therapy (in the anamnesis) on the abdominal cavity or pelvis;

- leukocytosis;

- female patients (increased risk of diarrhea).

Dosing and Administration:

The drug is intended only for adults.

Iriten is administered as an intravenous infusion lasting at least 30 minutes and not more than 90 minutes.

When choosing a dose and mode of administration in each individual case, you should refer to the special literature.

In the monotherapy regime: Iriten is applied at a dose of 350 mg / m² every 3 weeks.

As part of combined chemotherapy The dose of Iriten is:

- with 5-fluorouracil and calcium folinate at a weekly administration of 80 mg / m^2;

- when administered by continuous infusion once every 2 weeks - 180 mg / m²;

- in combination with jet injection of 5-fluorouracil and calcium folinate - 125 mg / m²weekly.

Doses and regimens for the administration of 5-fluorouracil and calcium folinate are described in detail in the literature.

Iriten should not be administered until the amount of neutrophils in the peripheral blood exceeds 1500 cells / μl, and until such complications as nausea, vomiting and especially diarrhea are completely eliminated. The administration of the drug before the resolution of all side effects can be postponed for 1-2 weeks.

If the development of treatment with expressed inhibition of bone marrow hematopoiesis (the number of neutrophils less than 500 / μl, and / or the number of leukocytes less than 1000 / μl, and / or the number of platelets less than 100,000 / μl), febrile neutropenia (the number of neutrophils 1000 / μL of blood and less in combination with an increase in body temperature of more than 38 ° C), infectious complications, severe diarrhea, or other non-hematologic toxicity of 3-4 degrees, subsequent doses of iritene and, if necessary, 5-fluorouracil should be reduced by 15-20%.

Patients with impaired hepatic function. At a level of bilirubin in the blood serum exceeding the upper limit of the norm no more than 1.5 times, in connection with an increased risk of development of severe neutropenia, blood parameters in the patient should be closely monitored. If the level of bilirubin is increased more than 1.5 times, treatment with Iriten should be stopped.

Patients with impaired renal function. Treatment with iritene is not recommended, as there is no data on the use of irinotecan in this category of patients.

Elderly patients. There are no specific instructions for the use of irinotecan in the elderly.The dose of the drug in each case should be selected with caution.

Instructions for preparing a solution for infusions

The necessary amount of the preparation should be diluted in 250 ml of a 0.5% solution of dextrose or 0.9% sodium chloride solution and the resulting solution is mixed by rotating the vial. Before administration, the solution should be visually inspected for clarity. If a sediment is found, the preparation must be destroyed.

The solution should be used immediately after dilution.

If the dilution is carried out in accordance with aseptic rules (for example, in a laminar air flow installation), the Iritene solution can be used in case of storage at room temperature for 12 hours (including infusion time) and in case of storage at a temperature of 2-8 ° C for 24 hours after opening the vial with concentrate.

Side effects:

On the part of the organs of hematopoiesis: neutropenia is observed on average in 80% of patients, including half of them there is a decrease in neutrophils of less than 1000 cells in 1 μl. Restoration of the number of neutrophils is usually observed in 7-20 days from the beginning 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 is described.

From the side of the digestive system: Late diarrhea that occurs more than 24 hours (on average 5 days) after drug administration is a dose-limiting toxic effect and is observed in approximately 87% of patients, with a severe degree in 38%. Nausea and vomiting occurs usually on the first day of administration or after 24 hours in 85% of patients. Dehydration was reported on the background of vomiting and diarrhea, very rarely with the development of renal failure, hypotension and heart failure. Possible abdominal pain, anorexia, mucositis, constipation.

Acute cholinergic syndrome is observed in 9% of patients during the first 24 hours after the administration of the drug and manifested by diarrhea, abdominal pain, increased sweating, miosis, vision disorder, lacrimation, drooling, lowering of blood pressure, dizziness, chills and general malaise.

From the central nervous system: involuntary muscle twitching or cramps, paresthesia, asthenia.

Allergic reactions: rarely - a skin rash and very rarely - the development of anaphylactic shock.

Other: shortness of breath, alopecia, fever, local reactions.

Overdose:

The main expected manifestations of an overdose are neutropenia and diarrhea.

The specific antidote to irinotecan is unknown. Treatment is symptomatic. In case of an overdose, the patient should be hospitalized and closely monitor the function of vital organs.

Interaction:

As 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 nondepolarizing muscle relaxants.

Iriten should not be mixed with other drugs in one bottle.

Special instructions:

Treatment with Iriten should be carried out in specialized chemotherapy departments under the supervision of a doctor who has experience working with antitumor drugs.

In patients receiving Iriten, it is necessary to do a detailed clinical blood test every week and monitor liver function.

Diarrhea that occurs as a consequence of the cytotoxic effect of the drug is usually noted no earlier than 24 hours after the administration of iritene (in most patients, an average of 5 days).When the first episode of a loose stool appears, it is necessary to administer a copious drink containing electrolytes and immediately perform antidiarrheal therapy, including taking loperamide in high doses (4 mg at the first dose and then 2 mg every 2 hours). This therapy is continued for at least 12 hours after the last episode of a loose stool, but no more than 48 hours because of the possibility of developing a small intestine paresis. If it regarded as severe diarrhea (more than 6 episodes of watery stools during days or expressed tenesmus), and if accompanied by fever or vomiting, the patient must be urgently admitted to the ICU for the comprehensive treatment comprising administering to broad spectrum antibiotics. At moderate or mild diarrhea (less than 6 episodes of watery stools during days and moderate tenesmus), which is not stopped during the first 48 hours must begin receiving broad-spectrum antibiotics inside. With the simultaneous occurrence of diarrhea and severe neutropenia (the number of white blood cells is less than 500 / mm3), in addition to antidiarrheal therapy, antibiotics of a wide spectrum of action are prescribed internally for prophylactic purposes.

Loperamide should not be prescribed prophylactically, including to patients who have had diarrhea during previous Ireten injections.

The patient must be warned in advance about the possibility of developing delayed diarrhea. Patients should immediately inform their doctor about the occurrence of diarrhea and immediately begin appropriate treatment.

If the treatment of diarrhea is inadequate, a condition threatening the patient's life may develop, especially if diarrhea develops against a background of neutropenia.

Patients with febrile neutropenia (body temperature ≥38 ° C and neutrophil count ≤1000 / μL) should immediately begin the introduction of broad-spectrum antibiotics in hospital settings.

Acute cholinergic syndrome usually occurs during the administration of the drug or within the first 24 hours after administration is quickly and effectively suppressed by subcutaneous administration of 0.25 mg of atropine (caution in patients with bronchial asthma).

The dosage form of the drug as an auxiliary substance contains sorbitol, and therefore Iriten can not be used in patients with hereditary intolerance to fructose.

During treatment with Iriten and at least three months after cessation of therapy, reliable contraceptive measures should be applied.

If you get Iriten solution or infusion solution on your skin or mucous membranes, immediately wash your skin with soap and water, mucous membranes simply with water.

Effect on the ability to drive transp. cf. and fur:

Patients should be warned about the possibility of appearing during the treatment Iritenom dizziness and visual disorders, which develop within 24 hours after the administration of the drug. If these symptoms occur, patients are advised to refrain from driving and practicing other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Concentrate for solution for infusion, 20 mg / ml.

Packaging:

For 100 mg / 5 ml; 40 mg / 2 ml; 300 mg / 15 ml in bottles of dark glass. For 1 bottle with the attached instructions for use in a cardboard bundle. For 5 or 10 bottles with instructions for use in a cardboard bundle with partitions or special nests.

For 50, 85 or 100 bottles with instructions for use, based on one instruction for 10 bottles, in a box of cardboard (for hospitals).

Storage conditions:

At a temperature of no higher than 30 ° C, in a place protected from light and inaccessible to children.

Shelf life:

3 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N003769 / 01

Date of registration:29.12.2009 / 29.07.2016

Expiration Date:Unlimited

The owner of the registration certificate:LENS-PHARM, LLC LENS-PHARM, LLC Russia

Manufacturer: & nbsp

VEROPHARM SA Russia

Information update date: & nbsp28.11.2017

Illustrated instructions

Instructions

Iriten (Iriten)