Irin

Irin is a therapeutic drug from the subgroup of drugs of the antineoplastic type. Its main active ingredient is irinotecan hydrochloride, which is a member of the irinotecan group of substances (they are semi-artificial derivatives of the camptothecin component).

The drug has pronounced antitumor properties, and in addition, it specifically slows down the activity of isomerase enzymes, which have an active effect on DNA topology (topoisomerases). [1]

Indications Irin

It is used for the treatment of colorectal cancer , and in addition, with the development of seizures caused by Lennox-Gastaut syndrome .

Can be used alone or in combination with capecitabine, leucovorin, 5-fluorouracil, and cetuximab or bevacizumab.

Release form

The release is realized in the form of an injection liquid, inside 5 ml vials.

Pharmacodynamics

In comparison with other anticancer substances, it has a greater cytotoxicity against some types of cancers, including those that have not succumbed to the influence of the drugs vinblastine and doxorubicin.

Another pronounced medicinal effect of irinotecan hydrochloride is its ability to suppress the action of a hydrolytic enzyme, acetylcholinesterase. [2]

Cytotoxic activity depends on the stage of the cell cycle and the time of exposure. [3]

Pharmacokinetics

Intraplasmic disintegration of the drug corresponds to a 2 or even 3-phase model. The term plasma half-life at the 1st stage is 12 minutes, at the 2nd - 2.5 hours, and at the 3rd - 14.2 hours. Over a period of 24 hours, 19.9% of the applied dosage is excreted in the urine.

Protein synthesis of SN-38 and irinotecan in vitro is 95% and 65%.

After intravenous injection, irinotecan is involved in metabolic processes with the formation of an active degradation product of SN-38. Metabolic processes mainly take place inside the liver.

The average rate of excretion of the metabolic element SN-38 with urine over a period of 24 hours is 0.25%. The pharmacokinetics of irinotecan does not depend on the size of the dosage.

Dosing and administration

Irin is used in the form of an infusion medication, it is injected into the region of the central or peripheral vein. Dilution and infusion should only be performed by an experienced healthcare professional. The dosage is selected by an experienced oncologist. It is necessary to dilute the medicine in a glucose or NaCl solution.

Often, the medication is applied 1 time in 3 weeks; more rarely, the regimen is used with the introduction of 1 time per 1 week. With combined treatment - 1 time in 2 weeks. The infusion is administered at a rate of 0.5-1.5 hours.

In the case of monotherapy, the serving size is generally 0.35 g / m2. During complex treatment, the drug is usually administered at a dosage of 0.18 g / m2.

• Application for children

The medication is not used in pediatrics.

Use Irin during pregnancy

Irin cannot be prescribed during pregnancy (it is allowed only if there are vital indications).

If you need to use drugs during hepatitis B, you need to stop breastfeeding for a while.

Contraindications

The main contraindications:

• the presence of severe intolerance to the active ingredient of the drug or its additional elements;
• chronic intestinal inflammation, intestinal blockage;
• hyperbilirubinemia;
• severe form of bone marrow failure;
• the general indicators of the patient's health are below the 2 mark (in accordance with the WHO index);
• severe form of neutropenia.

It is forbidden to use it together with medicines that contain St. John's wort. There may also be other contraindications when combined with other antineoplastics.

Side effects Irin

Among the side symptoms:

• dizziness, nervousness, cephalalgia;
• disorders of vision, speech or thinking;
• vomiting, diarrhea;
• neutro- or leukopenia.

When used together with other drugs, disorders characteristic of that medication may appear. Administration with bevacizumab causes an increase in blood pressure values.

In addition, there may be:

• thromboembolism or thrombosis;
• myocardial infarction or ischemic heart disease;
• neutropenic fever.

Overdose

If the portion is exceeded twice, the patient's death is possible (1-fold case). In addition, severe diarrhea or severe neutropenia may develop.

The medicine has no antidote. It is necessary to prevent the development of infections and acute dehydration.

Interactions with other drugs

Irinotecan has an anticholinesterase effect, therefore it can increase the duration of neuromuscular blockade in the case of using suxamethonium.

When combined with muscle relaxants of a non-depolarizing type, an antagonistic effect with respect to neuromuscular transmission is possible.

Some tests have revealed that when combined with anticonvulsants that induce the effect of CYP3A (for example, phenobarbital with carbamazepine or phenytoin), there is a decrease in the exposure of SN-38 with irinotecan, SN-38-glucuronide, as well as pharmacodynamic properties. In addition to the induction of hemoprotein P450ZA enzymes, the potentiation of glucuronidation and an increase in the intensity of biliary excretion can affect the decrease in the exposure of irinotecan to its degradation products.

The medication should be used with caution in people who simultaneously use drugs that inhibit (for example, ketoconazole) or induce (for example, phenytoin or carbamazepine with phenobarbital) the metabolic processes of drugs that occur with the help of hemoprotein P450 3A. It is necessary to abandon the combination of inducers / inhibitors of this metabolic pathway, since this can affect the metabolic processes of Irina.

St. John's wort is forbidden to be used in conjunction with the medicine, since it reduces the plasma values of SN-38.

Storage conditions

Irin must be kept at a temperature of no more than 25 ° C.

Shelf life

Irin can be applied within a 2-year term from the date of manufacture of the drug substance.