Iriten, vial 100mg, 5ml

Composition

Active ingredient:

irinotecan hydrochloride trihydrate;

Auxiliary substances:

D-sorbitol,

lactic acid,

sodium hydroxide,

D/i water.

Pharmacological action

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

Pharmacokinetics

The pharmacokinetic profile of irinotecan is dose-independent. The maximum plasma concentration of irinotecan and SN-38 was reached by the end of the intravenous infusion at the recommended dose of 350 mg / m2. Binding to plasma proteins for irinotecan is approximately 65%, for its active metabolite — SN-38 — 95%.

The distribution of the drug in plasma is two-or three-phase. It is mainly metabolized in the liver by the enzyme carboxylesterase to the active metabolite SN-38. The average T1 / 2 of the drug in the first phase is 12 minutes, in the second — 2.5 hours and in the last — 14.2 hours.

It is excreted in the urine for 24 hours in the form of an unchanged drug (20%) and in the form of SN-38 (0.25%). About 30% of the drug is excreted in the bile, both in unchanged form and in the form of glucuronide SN-38.5-fluorouracil and calcium folinate do not affect the pharmacokinetics of irinotecan.

Indications

Locally advanced or metastatic colon and rectal cancer: as monotherapy in patients with disease progression after conventional treatment; in combination with 5-fluorouracil and calcium folinate in patients who have not previously received chemotherapy.

Use during pregnancy and lactation

The drug is contraindicated for use during pregnancy and lactation (breastfeeding). Reliable contraceptive measures should be used during treatment with Iriten and for at least 3 months after discontinuation of therapy.

Contraindications

— a chronic inflammatory bowel disease and/or violations of intestinal permeability;

— significant inhibition of bone marrow hematopoiesis;

— the level of bilirubin in the blood serum in excess of CAH is more than 1.5 times;

the General condition of patients, as measured on a scale of who>2;

— pregnancy;

— lactation (breastfeeding);

— hypersensitivity to irinotecan or other components of the drug.

With caution, the drug should be prescribed for radiation therapy (in the anamnesis) on the abdominal or pelvic area, leukocytosis, and female patients (the risk of diarrhea increases).

Side effects

Hematopoietic disorders: neutropenia is observed in an average of 80% of patients, including half of them have a decrease in neutrophils to

On the part of the digestive system: late diarrhea that occurs more than 24 hours (on average 5 days) after use of the drug is a dose-limiting toxic manifestation and is observed in approximately 87% of patients, of which 38% are severe. Nausea and vomiting usually occur on the first day of use or after 24 hours in 85% of patients.

Dehydration has been reported with vomiting and diarrhoea, very rarely with renal failure, hypotension and heart failure. Possible abdominal pain, anorexia, mucositis, constipation.

Acute cholinergic syndrome is observed in 9% of patients within the first 24 hours after Iriten use and is manifested by diarrhea, abdominal pain, increased sweating, miosis, visual disturbances, lacrimation, drooling, decreased blood pressure, dizziness, chills and general malaise.

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

Allergic reactions: rarely-skin rash and very rarely-development of anaphylactic shock. Other: shortness of breath, alopecia, fever, local reactions.

Interaction

Since Iriten has anticholinesterase activity, it is possible to increase the duration of neuromuscular blockade when combined with suxamethonium and antagonistic interaction with respect to neuromuscular blockade when combined with non-depolarizing muscle relaxants.

Pharmaceutical interaction Iriten should not be mixed with other drugs in the same bottle.

How to take, course of use and dosage

The drug is prescribed only for adults. Iriten is administered as an intravenous infusion lasting at least 30 minutes and no more than 90 minutes. For colorectal cancer, Iriten is used both as monotherapy and in combination with 5-fluorouracil and calcium folinate. When choosing the dose and mode of use, you should refer to the special literature. In the monotherapy mode, Iriten is used at a dose of 350 mg/m2 of body surface area every 3 weeks.

As part of combination therapy with prolonged infusion of 5-fluorouracil and calcium folinate, Iriten is prescribed weekly at a dose of 80 mg/m2; 1 time in 2 weeks – 180 mg/m2; when administered in combination with a bolus of 5-fluorouracil and calcium folinate weekly – 125 mg/m2. Iriten should not be administered until the number of neutrophils in the peripheral blood does not exceed 1500 cells/µl, and until such complications as such as nausea, vomiting, and especially diarrhea. use of the drug until all side effects are resolved can be postponed for 1-2 weeks.

If the treatment is developing significant inhibition of bone marrow hematopoiesis (the number of neutrophils less than 500/µl, and/or white blood cell count less than 1000/µl and/or a platelet count less than 100,000/µl), or febrile neutropenia (neutrophil count of 1000/µl and less in combination with a fever over 38°C), or infectious complications, or severe diarrhea, or other non-hematologic toxicity grade 3-4, subsequent doses of Iritana or, if necessary,5-fluorouracil reduced by 15-20%.

Treatment with Iriten is continued until objective signs of progression of the tumor disease or the development of unacceptable toxic manifestations appear. Patients with impaired liver function with a serum bilirubin level exceeding the ULN by no more than 1.5 times, due to an increased risk of developing severe neutropenia, should carefully monitor peripheral blood parameters.

If the bilirubin level increases by more than 1.5 times ULN, treatment with Iriten should be discontinued. Patients with impaired renal function should not be treated with Iriten, since the use of the drug in this category of patients has not been studied. There are no special instructions for the use of Iriten in elderly patients. The dose of the drug in each specific case should be selected with caution.

The safety and efficacy of Iriten in children are poorly understood. Rules for preparing the solution for intravenous infusions Iriten solution should be prepared under aseptic conditions. The required amount of the drug is diluted in 250 ml of 5% dextrose solution or 0.9% sodium chloride solution and the resulting solution is mixed by rotating the container or bottle. Before use, the solution should be visually examined for transparency.

If sediment is detected, the preparation must be destroyed. The Iritene solution should be used immediately after dilution. If dilution is performed in accordance with the rules of asepsis (for example, in a laminar air flow unit), the Iritene solution can be used when stored at room temperature for 12 hours (including infusion time) and when stored at a temperature of 2° to 8°C – for 24 hours after opening the concentrate bottle.

Overdose

Since Iriten has anticholinesterase activity, it is possible to increase the duration of neuromuscular blockade when combined with suxamethonium and antagonistic interaction with respect to neuromuscular blockade when combined with non-depolarizing muscle relaxants.

Pharmaceutical interaction Iriten should not be mixed with other drugs in the same bottle.

Special instructions

Treatment with Iriten should be carried out in specialized chemotherapy departments under the supervision of a doctor who has experience with antitumor drugs. In patients receiving Iriten, a detailed clinical blood test should be performed weekly and liver function should be monitored.

Diarrhea that occurs as a result of the cytotoxic effect of the drug (delayed diarrhea) is usually noted no earlier than 24 hours after Iriten use (in most patients, on average, after 5 days). When the first episode of loose stools occurs, it is necessary to prescribe a plentiful drink containing electrolytes and immediately conduct 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 loose stools, but not more than 48 hours due to the possibility of developing small bowel paresis. If diarrhea is considered severe (more than 6 episodes of loose stools during the day or severe tenesmus), as well as if it is accompanied by vomiting or fever, the patient should be urgently hospitalized for complex treatment, including the introduction of broad-spectrum antibiotics.

With moderate or mild diarrhea (less than 6 episodes of loose stools during the day and moderate tenesmus), which does not stop within the first 48 hours, it is necessary to start taking broad-spectrum antibiotics inside, while the patient is recommended to be hospitalized.In case of simultaneous occurrence of diarrhea and severe neutropenia (the number of white blood cells is less than 500/µl), in addition to antidiarrheal therapy, broad-spectrum antibiotics are prescribed inside for prophylactic purposes.

Loperamide should not be administered prophylactically, including in patients who have had diarrhea during previous Iriten use. The patient should be warned in advance about the possibility of developing delayed diarrhea. Patients should immediately inform their doctor about the occurrence of diarrhea and immediately start appropriate treatment. If diarrhoea is not adequately treated, a life-threatening condition may develop, especially if the diarrhoea develops on the background of neutropenia. Patients with febrile neutropenia (body temperature >38°C and neutrophil count less than 1000/µl) should be immediately initiated with broad-spectrum antibiotics in a hospital setting.

With the development of acute cholinergic syndrome in the absence of contraindications, the appointment of 0.25 mg of atropine sulfate subcutaneously is indicated. Caution should be exercised when using the drug in patients with bronchial asthma. In patients with a history of acute cholinergic syndrome, including those in severe form, prophylactic use of antiemetic drugs is recommended before the appointment of Iriten.

Since the dosage form of the drug contains D-sorbitol as an auxiliary substance, Iriten should not be used in patients with hereditary fructose intolerance. Caution should be exercised when preparing the Iriten solution and handling the product. Wear gloves, a mask, and glasses.

If the Iriten solution or infusion solution gets on the skin or mucous membranes, the skin should be immediately washed with soap and water, and the mucous membranes should be simply washed with water.

Influence on the ability to drive motor vehicles and manage mechanisms

Patients should be warned about the possibility of dizziness and visual disturbances during treatment with Iriten, which develop within 24 hours after use of the drug. If these symptoms occur, patients are advised to refrain from driving a car or other mechanisms.

Form of production

Concentrate for preparation of solution for infusions.

Storage conditions

In a dark place, at a temperature not exceeding 25 °C.

Shelf life

2 years

Active ingredient

Irinotecan

Conditions of release from pharmacies

By prescription

Dosage form

infusion solution