Irin

Irin is a therapeutic drug from a subgroup of antineoplastic drugs. Its main active ingredient is irinotecan hydrochloride, which is part 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 to treat colorectal cancer, and also in the development of attacks caused by Lennox-Gastaut syndrome.

It can be used as monotherapy or in combination with capecitabine, leucovorin, 5-fluorouracil, and cetuximab or bevacizumab.

Release form

The product is available in the form of an injection liquid, in 5 ml vials.

Pharmacodynamics

Compared to other antitumor agents, it has greater cytotoxicity against certain types of cancer, including those that have not responded to the drugs vinblastine and doxorubicin.

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

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

Pharmacokinetics

Intraplasmic drug breakdown corresponds to a 2- or even 3-phase model. The plasma half-life term at stage 1 is 12 minutes, at stage 2 – 2.5 hours, and at stage 3 – 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 participates in metabolic processes with the formation of the active breakdown product SN-38. Metabolic processes mainly occur within the liver.

The mean urinary excretion of the metabolic element SN-38 over a 24-hour period is 0.25%. The pharmacokinetics of irinotecan are independent of the dosage size.

Dosing and administration

Irin is used in the form of an infusion drug, it is administered into the central or peripheral vein. Only an experienced medical specialist should perform dilution and infusion. The dosage is selected by an experienced oncologist. The drug should be diluted in a glucose or NaCl solution.

Often the medication is used once every 3 weeks; more rarely, a regimen with administration once every 1 week is used. In case of combined treatment – once every 2 weeks. The infusion is administered at a rate of 0.5-1.5 hours.

In case of monotherapy, the dose size is generally 0.35 g/m2. During combination therapy, 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 should not be prescribed during pregnancy (it is allowed only if there are vital indications).

If you need to use medications while breastfeeding, you need to stop breastfeeding for a while.

Contraindications

Main contraindications:

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

It is prohibited to use together with medicines containing St. John's wort. There may also be other contraindications when combined with other antineoplastics.

Side effects Irin

Side effects include:

• dizziness, nervousness, cephalgia;
• visual, speech or thinking disorders;
• vomiting, diarrhea;
• neutro- or leukopenia.

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

In addition, the following may occur:

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

Overdose

If the dose is exceeded twice, the patient may die (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 and therefore may increase the duration of neuromuscular blockade when suxamethonium is used.

When combined with non-depolarizing muscle relaxants, an antagonistic effect on neuromuscular transmission is possible.

Some tests have shown 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, and pharmacodynamic properties. In addition to the induction of hemoprotein P4503A enzymes, potentiation of glucuronidation and an increase in the intensity of biliary excretion may affect the decrease in the exposure of irinotecan with its breakdown products.

The drug should be used with caution in people who are simultaneously taking drugs that inhibit (e.g. ketoconazole) or induce (e.g. phenytoin or carbamazepine with phenobarbital) the metabolic processes of drugs that occur with the help of hemoprotein P450 3A. It is necessary to avoid combining inducers/inhibitors of this metabolic pathway, since this may affect the metabolic processes Irina.

St. John's wort should not be used together with the drug because it reduces plasma SN-38 values.

Storage conditions

Irin should be stored at temperatures no higher than 25°C.

Shelf life

Irin can be used within a 2-year period from the date of production of the medicinal substance.