Ирнокам®

General characteristics. Structure:

1 ml 1 фл.
irinotekana of a hydrochloride trihydrate - 20 mg 40 mg
Excipients: sorbitol, lactic acid, glacial acetic acid, sodium hydroxide (for maintenance of level рН), water for and. 2 ml – bottles of dark glass (1) – a pack cardboard.
Concentrate for preparation of solution for in/in introductions transparent, pale yellow or yellow color.
1 ml 1 фл.
irinotekana of a hydrochloride trihydrate - 20 mg 100 mg
Excipients: sorbitol, lactic acid, glacial acetic acid, sodium hydroxide (for maintenance of level рН), water for and. 5 ml – bottles of dark glass (1) – a pack cardboard.

Pharmacological properties:

Antineoplastic drug, alkaloid, semi-synthetic derivative kamptotetsina. Is specific inhibitor of cellular enzyme of I.Действие topoisomerase of drug it is connected with presence of both an irinotekan, and its active metabolite of SN_38 which surpasses an irinotekan in the activity. Irinotekan and a metabolite of SN_38 stabilize a topoisomerase I complex with DNA that interferes with its replication.

Indications to use:

Locally-spread or metastatic cancer thick and rectum: in a combination with 5_ftoruratsilom and calcium folinaty at the patients who were earlier not receiving chemotherapy; as monotherapy at patients with progressing of a disease after the standard treatment.

Route of administration and doses:

Drug is intended only for adults.
Ирнокам® it is entered in a look into infusions lasting not less than 30 min. and no more than 90 min. At the choice of a dose and mode of introduction in each individual case it is necessary to address special literature.
In the monotherapy mode Irnokam appoint in a dose 350 mg/sq.m each 3 weeks.
As a part of the combined chemotherapy Irnokam's dose makes:
with 5_ftoruratsilom and calcium folinaty at weekly introduction – 80 mg/sq.m;
at introduction by long infusion of 1 times to 2 weeks – 180 mg/sq.m;
in a combination with jet introduction of a 5-ftoruratsil and calcium of a folinat – 125 mg/sq.m weekly.
Doses and the mode of introduction of a 5-ftoruratsil and folinat of calcium are in detail described in special literature.
Irnokam's introduction should not be carried out until the quantity of neutrophils in peripheral blood does not exceed 1500/mkl, and such complications as nausea, vomiting and especially diarrhea will not be completely stopped yet. Administration of drug until permission of all by-effects can be postponed for 1_2 weeks. At development against the background of treatment of the expressed oppression of a marrowy hemopoiesis (quantity of neutrophils <500/mkl, and/or quantity of leukocytes <1000/mkl, and/or quantity of thrombocytes <100 000/mkl), a febrile neutropenia (quantity of neutrophils _1000/mkl blood in combination with fervescence more than 38 °C), infectious complications, heavy diarrhea or other not hematologic toxicity 3_4 degrees the subsequent doses of Irnokam and in need of a 5-ftoruratsil it is necessary to reduce by 15_20%.
At patients with abnormal liver functions at the bilirubin level in blood serum exceeding VGN no more than by 1.5 times in connection with the increased risk of development of the expressed neutropenia it is necessary to control carefully blood indicators at the patient. At increase in level of bilirubin more than by 1.5 times – treatment by Irnokam should be stopped.
At renal failures of Irnokam® it is not recommended to appoint since data on use of an irinotekan for this category of patients are absent. Any special application instructions of an irinotekan at patients of advanced age are absent. The drug dose in each case should be selected with care.
Rules of preparation of solution for infusions
To dilute necessary amount of drug in 250 ml 0.5% of solution of a dextrose or 0.9% of solution of sodium of chloride and to mix the received solution by rotation of a bottle. Before introduction solution should be examined visually on transparency. In case of detection of a deposit, drug has to be destroyed. Solution has to be used at once after cultivation. If cultivation is executed with observance of rules of an asepsis (for example, in installation of a laminar air flow), Irnokam's solution can be used in case of storage at the room temperature, during 12 h (including time of infusions); in case of storage at a temperature of 2_8 °C – during 24 h after opening of a bottle with a concentrate.

Features of use:

Treatment by Irnokam should be carried out in specialized chemotherapeutic departments under observation of the doctor having experience with antineoplastic drugs.
At the patients receiving Irnokam® it is necessary to do weekly developed clinical blood test and to monitor function of a liver.
The diarrhea arising as a result of cytotoxic effect of drug is usually noted not earlier than 24 h after Irnokam's introduction (at most of patients on average in 5 days). At emergence of the first episode of a liquid chair purpose of the plentiful drink containing electrolytes, and immediate performing the antidiarrheal therapy including reception of loperamide in high doses is necessary (4 mg in the first reception and then on 2 mg each 2 h). This therapy is continued during not less than 12 h after the last episode of a liquid chair, but by no more than 48 h because of a possibility of development of paresis of a small intestine. If diarrhea is regarded as heavy (more than 6 episodes of a liquid chair within a day or the expressed tenesmus), and also if it is followed by vomiting or fever, the patient has to be urgently hospitalized in intensive care unit for performing the complex treatment including introduction of antibiotics of a broad spectrum of activity. At moderate or slight diarrhea (less than 6 episodes of a liquid chair within a day and moderate tenesmus) which is not stopped during the first 48 h it is necessary to begin reception of antibiotics of a broad spectrum of activity inside. At simultaneous developing of diarrhea and the expressed neutropenia (quantity of leukocytes less than 500 cells / мкл) in addition to antidiarrheal therapy with the preventive purpose antibiotics of a broad spectrum of activity inside appoint.
It is not necessary to appoint loperamide preventively, including to patients at whom diarrhea was noted during the previous introductions of Irnokam.
The patient needs to be warned about a possibility of development in it of the delayed diarrhea in advance.
At inadequate treatment of diarrhea the state, life-threatening can develop
the patient, especially, if diarrhea developed against the background of a neutropenia.
To patients with a febrile neutropenia (body temperature of _38 °C and quantity of neutrophils _1000/mkl) introduction of antibiotics of a broad spectrum of activity in the conditions of a hospital has to be urgently begun.
The acute cholinergic syndrome which is usually arising during administration of drug or in the first 24 h after introduction is quickly and effectively stopped п / to introduction of 0.25 mg of atropine (to be careful at patients with bronchial asthma). The dosage form of drug as excipient contains sorbitol in this connection Irnokam® cannot be applied at patients with hereditary intolerance of fructose. At hit of solution of Irnokam or infusion solution on skin or mucous membranes skin should be washed out immediately water with soap, mucous membranes – simply water.
Influence on ability to driving of motor transport and to control of mechanisms
Patients need to be warned about a possibility of emergence during treatment by Irnokam of dizziness and visual frustration which develop during 24 h after administration of drug. At emergence of these symptoms patients are recommended to refrain from driving and occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From bodies of a hemopoiesis: the neutropenia is observed on average at 80% of patients, including at a half of them decrease in neutrophils less than 1000 cells / мкл is noted. Recovery of number of neutrophils is usually observed in 7_20 days from an initiation of treatment. Anemia of varying severity occurs on average at 60% of patients, thrombocytopenia – at 7% of patients. One case of thrombocytopenia with formation of antithrombocytic antibodies is described.
From the alimentary system: the late diarrhea arising more than in 24 h (on average in 5 days) after administration of drug, is the toxic manifestation limiting a dose and is observed approximately at 87% of patients, at the same time heavy degree – at 38%. Nausea and vomiting arise usually in the first day of introduction or later 24 h at 85% of patients. It was reported about development of dehydration against the background of vomiting and diarrhea, it is very rare with development of a renal failure, hypotension and heart failure. Abdominal pains, anorexia, mukozita, a lock are possible.
Acute cholinergic syndrome: it is observed at 9% of patients during the first 24 h after administration of drug and shown by diarrhea, abdominal pains, the strengthened sweating, a miosis, a visual disturbance, dacryagogue, hypersalivation, decrease in the ABP, dizziness, a fever and a febricula.
From TsNS: involuntary muscular twitchings or spasms, paresthesias,
adynamy.
Allergic reactions: seldom – skin rash; very seldom – development of an acute anaphylaxis.
Others: asthma, alopecia, fervescence, local reactions.

Interaction with other medicines:

Since иринотекан has antikholinesterazny activity, increase in duration of neuromuscular blockade at combined use with succinylcholine and antagonistic interaction concerning neuromuscular blockade is possible at a combination to not depolarizing muscle relaxants.
Ирнокам® it is not necessary to mix with other drugs rolled into one. 5_ftoruratsil and calcium фолинат do not influence pharmacokinetics of an irinotekan.

Contraindications:

Chronic inflammatory diseases of intestines and/or disturbance of intestinal passability;
the expressed oppression of a marrowy hemopoiesis; the bilirubin level in blood serum exceeding more than by 1.5 times of VGN; the general condition of patients estimated on a scale of WHO> 2; pregnancy; lactation period; children's age (data on safety and efficiency at children are absent); hypersensitivity to an irinotekan or other components of drug.
With care it is necessary to appoint drug at radiation therapy (in the anamnesis) to area of an abdominal cavity or a basin, at a leukocytosis; to female patients (the risk of development of diarrhea increases).

PREGNANCY AND LACTATION
Drug is contraindicated to use at pregnancy and in the period of a lactation. During treatment by Irnokam and, at least, within 3 months after the therapy termination, reliable measures of contraception have to be applied.

Overdose:

Symptoms: the neutropenia and diarrhea are possible.
Treatment: performing symptomatic therapy. In case of overdose of the patient it is necessary to hospitalize and to carefully control functions of vitals. The specific antidote to an irinotekan is not known.

Storage conditions:

List B. Drug should be stored in the unavailable to children, dry, protected from light place at a temperature not above 25 °C. A period of validity – 2 years.

Issue conditions:

According to the recipe

Packaging:

Concentrate for preparation of solution for infusions, 20 mg/ml. On 2 ml in the bottles of dark glass of a class 1 (USP) corked by rubber bungs and which are pressed out by aluminum caps with safety plastic covers of green color. On 1 bottle place in a pack cardboard.

On 5 ml in the bottles of dark glass of a class 1 (USP) corked by rubber bungs and which are pressed out by aluminum caps with safety plastic covers of violet color. On 1 bottle place in a pack cardboard.

Packaging of "in bulk". On 12 bottles in a box from a corrugated cardboard with cardboard lattices. On 12 boxes in a box from a corrugated cardboard.

In case of drug packaging by Naukoprofi branch of RONTs of N. N. Blochin of the Russian Academy of Medical Science. On 2 ml in the bottles of dark glass of a class 1 (USP) corked by rubber bungs and which are pressed out by aluminum caps with safety plastic covers of green color. On 1 bottle place in a pack cardboard.

On 5 ml in the bottles of dark glass of a class 1 (USP) corked by rubber bungs and which are pressed out by aluminum caps with safety plastic covers of violet color. On 1 bottle place in a pack cardboard.