Campto

Campto is an alkaloid with anti-tumor properties.

[1]

Indications of the campto

It is used in the treatment of cancer tumors in the rectum or colon region, which have a metastatic or locally occult nature.

Used in combination with calcium folinate, as well as fluorouracil in people who have not previously undergone chemotherapy.

It can also be administered with monotherapy of individuals who, after performing standard antitumor treatment procedures, progressed the disease.

Release form

The release occurs in the form of a concentrate, used in the preparation of infusion solutions, 2, 5 or 15 ml of the substance in flacon. The box contains 1 such bottle.

[2]

Pharmacodynamics

The component irinotecan is a semisynthetic derivative of camptothecin. It specifically slows down the activity of the cellular enzyme topoisomerase I. Within the tissues, the drug undergoes metabolic processes in which an active degradation product SN-38 is formed, which has a higher activity than irinotecan. Both these elements help stabilize the ligament of topoisomerase I along with DNA, so that its replication stops.

During in vivo tests, the activity of irinotecan against tumors expressing the P-glycoprotein component has been shown to have multiple therapeutic resistance (vincristine, and in addition doxorubicin-resistant leukemia type P388).

[3], [4],

Pharmacokinetics

The pharmacokinetic parameters of irinotecan, together with its active decay product, were studied by intravenous infusion of LS in a dose of 100-750 mg / m². It should be taken into account that the pharmacokinetics of irinotecan does not change depending on the dosage size of the preparation.

Metabolism of irinotecan is mostly caused by the hepatic enzyme carboxyl esterase.

The drug is distributed inside the plasma in 2 or 3 stages. The average half-life of drugs within the plasma (with a three-stage model) is 12 minutes at the first stage, 2.5 hours at the 2nd stage, and 14.2 hours at the third stage.

Peak values of the active substance and its metabolism product inside the plasma were noted at the end of the infusion procedure (a recommended dose of 350 mg / m² was administered).

Excretion of the unchanged component (about 19.9%) and its decay product (0.25%) occurs through the kidneys. Unchanged substance and its metabolite excreted also with bile (approximately 30% of drugs).

The binding with the blood plasma protein in irinotecan is approximately 65%, and in the SN-38 metabolism product it is 95%.

[5], [6], [7]

Dosing and administration

The drug is used in monotherapy, and in addition in combination with calcium folinate or fluorouracil. During the selection of the dosage and the regimen of application, the recommendations provided by the specialist literature should be taken into account. It is necessary to administer the medicine intravenously, with the help of infusion, which lasts in the range of 0.5-1.5 hours.

With monotherapy, Campto is used in a dose of 125 mg / m², with administration weekly for 1 month - in the form of an IV infusion lasting 1.5 hours. In this case, a 1-hour infusion of intravenous infusion in a 350 mg / m2 dose is administered at intervals of 3 weeks.

When combined with calcium folinate or fluorouracil, the dosage is 125 mg / m² once weekly, and a continuous infusion with a dose of 180 mg / m² is used once for 14 days.

Recommendations for adjusting portions.

With monotherapy, a reduction in the initial portion of the drug from 125 to 100 mg / m², and in addition from 350 to 300 mg / m² can be prescribed for older people (over 65 years old), and in addition to those who previously had extensive radiation therapy, those with a general condition of the patient is 2, and those who have increased bilirubin levels inside the blood. Under similar conditions, during the combined treatment, portions are reduced from 125 to 100 mg / m², and in addition from 180 to 150 mg / m².

It is necessary to use the medication before the moment when the level of neutrophils inside the peripheral blood becomes higher than 1500 cells / μl, and until the moment when such disorders as vomiting with nausea and, in particular, diarrhea are finally eliminated. The use of drugs before the elimination of all adverse symptoms can be postponed for 7-14 days. With the development during the treatment of individual disorders listed below, new portions of Campto, as well as fluorouracil (if such a need exists) need to be reduced by 15-20%.

The disorders that arise in the treatment of:

• inhibition of hematopoietic processes within the bone marrow, which is strong (the neutrophil count is less than 500 / μl, the number of white blood cells is less than 1,000 / μl, the platelet count is less than 100,000 / μL);
• neutropenic fever (the number of neutrophils is 1 000 / μL and below, while the patient has a temperature above 38 ° C);
• complications of an infectious nature;
• diarrhea in severe degree;
• other non-hematological toxicity, having a 3-4 degree of severity.

After the emergence of objective symptoms of tumor progression or the appearance of unacceptable toxic symptoms, it is required to stop the use of the medication.

People with eating disorders in the liver.

If the bilirubin index inside the blood serum exceeds the maximum permissible limits of the norm by a factor of 1.5, due to the increased probability of occurrence of neutropenia in the expressed form, it is necessary to closely monitor the blood values of the patient. If the bilirubin values are increased more than three times, it is necessary to completely abandon the use of drugs.

Diagram of preparation of infusion fluid for administration.

Cooking solution is necessary according to the rules of asepsis.

The required amount of the drug is diluted in 5% dextrose solution or 0.9% sodium chloride solution (0.25 L is required), and then reshape them, shaking the bottle or the container. Before using the drug, you should carefully inspect the liquid to check its transparency. If a precipitate is found in the solution, it can not be used.

Enter the medicine immediately after the procedure for dilution of the substance.

When carrying out the dilution procedure using aseptic rules (for example, using laminar air flow), the medicine may be stored for 12 hours (together with the infusion period) at standard temperature, and also within 24 hours after opening the container with drug substance at temperature indices within 2-8 ° С.

[11]

Use of the campto during pregnancy

It is forbidden to appoint Campto to pregnant women.

Contraindications

The main contraindications:

• the presence of intolerance with respect to irinotecan or other elements of the medication;
• disorders of intestinal permeability or ulcerative form of colitis;
• inhibition of hematopoietic processes within the bone marrow to a significant extent;
• bilirubin indices inside the blood serum exceeding the upper permissible limit more than three times;
• Patients whose general condition is rated by WHO> 2;
• lactation period.

Caution is required for such violations:

• the presence in the anamnesis of the procedures of radiotherapy, conducted on the site of the peritoneum or pelvis;
• leukocytosis;
• appointment to women (due to increased risk of diarrhea);
• kidney failure (no information on safety of use);
• hypovolemia;
• the presence of a tendency to develop thromboembolism or thrombosis;
• appointment to elderly patients.

[8], [9]

Side effects of the campto

The use of medication can cause some side-effects:

• disorders of the hematopoietic function: leuco- or neutropenia is often noted, as well as anemia. In this case, neutropenia is reversible and does not accumulate inside the body. The level of neutrophils is fully restored on the 22nd day of drug use in monotherapy, and also on the 7-8th day when combined with chemotherapy. Development of severe form of thrombocytopenia was not noted. The platelet count is also restored on the 22nd day of treatment. There was also a single case of thrombocytopenia, together with the formation of antibodies that are antiplatelet;
• disorders in the gastrointestinal tract: the emergence of vomiting, constipation, diarrhea, abdominal pain, nausea, and in addition the development of mucositis and anorexia. Rarely, pseudomembranous form of colitis, intestinal blockage, intestinal perforation, bleeding in the gastrointestinal tract, and in addition an increase in lipase or amylase activity were noted. Diarrhea that develops more than 24 hours after using the drug (delayed form of the disorder) is a toxic symptom and depends on the size of the medication. An acute form of the cholinomimetic syndrome can develop which manifests itself in the form of abdominal pains, early diarrhea, runny nose, conjunctivitis, bradycardia, a decrease in the level of blood pressure, and in addition, in the form of hyperhidrosis, increased intestinal peristalsis, vasodilation, sensation of malaise, chills, or drooling, dizziness and miosis. All these signs pass after the administration of atropine to the patient;
• disturbances in the work of the National Assembly: asthenia and paresthesia, and in addition, convulsions or twitching of the muscles that are involuntary;
• problems with respiratory function: febrile state, dyspnea, infiltrates in the lungs;
• signs of allergy: occasionally there are rashes on the skin. Single-onset anaphylaxis;
• others: the development of alopecia or speech disorders, and in addition a temporary increase in the activity of AP and transaminases, as well as the creatinine and bilirubin values inside the blood serum. Occasionally, renal insufficiency, decreased blood pressure or insufficient blood flow in people who have experienced cases of dehydration due to vomiting / diarrhea, or in persons with sepsis are noted.

[10]

Overdose

When intoxication, one should expect the development of neutropenia or diarrhea.

The drug has no antidote. It is required to carry out symptomatic procedures. In case of an overdose, the injured person should be hospitalized, and then closely monitor the work of important organs for life.

[12], [13]

Interactions with other drugs

Because irinotecan is able to exert an anticholinesterase effect, the duration of neuromuscular blockade after combination with suxamethonium salts may increase. There is also an antagonistic effect on neuromuscular blockade when combined with non-depolarizing nature of muscle relaxants.

Combination with myelosuppressors or the use of Campto against radiation therapy leads to an increased toxic effect on the bone marrow (development of leuko-or thrombocytopenia).

The combination with GCS (such as dexamethasone) leads to an increased likelihood of hyperglycaemia (especially in people with diabetes mellitus or decreased glucose tolerance), as well as lymphocytopenia.

Simultaneous use with diuretics can lead to increased dehydration, which develops due to vomiting and diarrhea. The combination with laxative drugs potentiates the severity of diarrhea and its frequency.

Combination with prochlorperazine increases the risk of developing symptoms of akathisia.

The combination with medicines that are of a vegetative nature (at the heart of a holed hole), and in addition to anticonvulsants inducing the activity of the CYP3A element (such as phenobarbital with carbamazepine and phenytoin), leads to a decrease in the metabolic product of drugs (SN-38) inside the plasma .

Combination of the drug with atazanavir, drugs slowing down the activity of CYP3A4 and UGT1A1 enzymes, and also with ketoconazole leads to an increase in the plasma values of the active product of SN-38 metabolism.

It is forbidden to mix the substance irinotecan with other medicines inside one vial.

Introduction to people who use antitumor drugs, vaccines (live or weakened), can lead to the development of severe or even fatal infections. It is required to refuse vaccination with live vaccines to people who use irinotecan. It is allowed to inject an inactivated or killed vaccine, but the body's reaction to it can be weakened.

[14]

Storage conditions

Campto is required to be kept out of the reach of children and penetrating the sunlight spot. It is forbidden to freeze a medicinal substance. The temperature is a maximum of 25 ° C.

[15],

Shelf life

Campto can be used for 3 years since the release of the drug.

Application for children

The medicine can be used only by adult patients.

Analogues

The following drugs are analogues of the medicine: Irinotecan, Irinotecan-Filaxis and Irinotecan Pliva-Lachema with Irinotecan-Teva, and in addition to Irnokam, Iriten, Kapmtotecan and Kampeter.

[16], [17], [18], [19], [20]