Campto

Campto is an alkaloid with antitumor properties.

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Indications Campto

It is used in the treatment of cancerous tumors in the rectum or colon, which are metastatic or locally advanced.

It is used in combination with calcium folinate and fluorouracil in people who have not previously undergone chemotherapy.

It can also be prescribed as monotherapy for individuals who have experienced disease progression after standard antitumor treatment procedures.

Release form

The product is released as a concentrate used in the preparation of infusion solutions, 2, 5 or 15 ml of the substance in vials. The box contains 1 such vial.

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Pharmacodynamics

The component irinotecan is a semi-synthetic derivative of the substance camptothecin. It specifically slows down the activity of the cellular enzyme topoisomerase I. Inside the tissues, the drug undergoes metabolic processes, during which an active product of SN-38 decay is formed, which has a higher activity than irinotecan. Both of these elements help stabilize the topoisomerase I binding to DNA, due to which its replication stops.

In vivo tests demonstrated the activity of irinotecan against tumors expressing the P-glycoprotein component with multiple therapeutic resistance (vincristine- and doxorubicin-resistant leukemia type P388).

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Pharmacokinetics

The pharmacokinetic parameters of irinotecan together with its active decay product were studied by intravenous administration by a half-hour infusion of the drug in a portion 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 drug.

Irinotecan is metabolized primarily by the liver enzyme carboxylesterase.

The drug is distributed inside the plasma in 2 or 3 stages. The average half-life of the drug inside the plasma (with a three-stage model) at stage 1 is 12 minutes, at stage 2 – 2.5 hours, and at stage 3 – 14.2 hours.

Peak plasma concentrations of the active substance and its metabolite were observed at the end of the infusion procedure (the recommended dose of 350 mg/m² was administered).

Excretion of the unchanged component (approximately 19.9%) and its breakdown product (0.25%) occurs via the kidneys. The unchanged substance and its metabolite are also excreted with bile (approximately 30% of the drug).

Plasma protein binding of irinotecan is approximately 65%, while that of the metabolite SN-38 is 95%.

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Dosing and administration

The medication is used in monotherapy, and also in combination with calcium folinate or fluorouracil. When selecting the dosage and application scheme, it is necessary to take into account the recommendations provided in the special literature. The medication must be administered intravenously, using an infusion that lasts within 0.5-1.5 hours.

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

When combining the drug with calcium folinate or fluorouracil, the dosage when administered weekly is 125 mg/m², and when used once every 14 days, a long-term infusion with a dose of 180 mg/m² is administered.

Recommendations for portion adjustments.

In monotherapy, a decrease in the initial dose of the drug from 125 to 100 mg/m², and also from 350 to 300 mg/m² can be prescribed to elderly people (over 65 years old), and also to those who have previously undergone extensive radiation therapy, those whose general condition level is 2, and those who have increased bilirubin levels in the blood. Under similar conditions, during combined treatment, the dose is reduced from 125 to 100 mg/m², and also from 180 to 150 mg/m².

The medication should be used until the level of neutrophils in the peripheral blood becomes higher than 1500 cells/mcl, and also until such disorders as vomiting with nausea and, in particular, diarrhea are completely eliminated. The use of the drug until all side effects are eliminated may be postponed for 7-14 days. If certain disorders listed below develop during therapy, new doses of Campto, as well as fluorouracil (if necessary) should be reduced by 15-20%.

Disorders arising during treatment:

• suppression of hematopoietic processes within the bone marrow, which is highly pronounced (neutrophil count is less than 500/μl; white blood cell count is less than 1,000/μl; platelet count is less than 100,000/μl);
• neutropenic fever (neutrophil count is 1000/μl or lower; the patient has a temperature above 38°C);
• complications of infectious nature;
• severe diarrhea;
• other non-hematological toxicity of 3-4 degrees of severity.

After the occurrence of objective symptoms of tumor progression or the appearance of unacceptable toxic signs, it is necessary to stop using the medication.

People with liver disorders.

If the bilirubin level in the blood serum exceeds the maximum permissible limits of the norm by 1.5 times, due to the increased probability of severe neutropenia, it is necessary to closely monitor the patient's blood values. If the bilirubin values are increased more than threefold, it is necessary to completely stop using the drug.

Scheme for preparing infusion fluid for administration.

The solution must be prepared according to aseptic rules.

The required amount of the medicine is diluted in a 5% dextrose solution or 0.9% sodium chloride solution (0.25 l is required), and then mixed by shaking the bottle or container. Before using the medicine, carefully inspect the liquid to check its transparency. If sediment is found in the solution, it cannot be used.

The medicine must be administered immediately after the procedure of diluting the substance.

When the dilution procedure is carried out using aseptic rules (for example, using a laminar air flow), the drug may be stored for 12 hours (including the infusion period) at standard temperature, as well as for 24 hours after opening the container with the drug at temperatures within 2-8°C.

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Use Campto during pregnancy

It is prohibited to prescribe Campto to pregnant women.

Contraindications

Main contraindications:

• the presence of intolerance to irinotecan or other components of the drug;
• intestinal obstruction or ulcerative colitis;
• suppression of hematopoietic processes within the bone marrow to a significant degree;
• serum bilirubin levels exceeding the upper permissible limit by more than three times;
• patients whose general condition is assessed according to the WHO rating >2;
• lactation period.

Caution is required in the following cases:

• history of radiation therapy procedures performed on the peritoneum or pelvis;
• leukocytosis;
• appointment for women (due to the increased risk of diarrhea);
• renal failure (no information regarding safety of use);
• hypovolemia;
• the presence of a tendency to develop thromboembolism or thrombosis;
• appointment to elderly patients.

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Side effects Campto

The use of the medication may cause the appearance of certain side effects:

• hematopoietic dysfunction: leukopenia or neutropenia, as well as anemia, are often observed. Neutropenia is reversible and does not accumulate in the body. The neutrophil level is fully restored on the 22nd day of using the drug in monotherapy, as well as on the 7-8th day with combined use with chemotherapy. The development of severe thrombocytopenia was not noted. The platelet count also recovers on the 22nd day of treatment. A single case of thrombocytopenia development along with the formation of antibodies of an antiplatelet nature was also registered;
• Gastrointestinal disorders: vomiting, constipation, diarrhea, abdominal pain, nausea, and also the development of mucositis and anorexia. Rarely, pseudomembranous colitis, intestinal obstruction, intestinal perforation, gastrointestinal bleeding, and also 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 dose of the drug. An acute form of cholinomimetic syndrome may develop, which manifests itself in the form of abdominal pain, early diarrhea, runny nose, conjunctivitis, bradycardia, decreased blood pressure, and also in the form of hyperhidrosis, increased intestinal peristalsis, vasodilation, a feeling of malaise, chills, visual impairment, lacrimation or salivation, dizziness and miosis. All these symptoms disappear after the patient is given atropine;
• disorders of the nervous system: asthenia and paresthesia, as well as convulsions or muscle twitching of an involuntary nature;
• problems with respiratory function: fever, dyspnea, pulmonary infiltrates;
• signs of allergy: skin rashes occasionally occur. Anaphylaxis develops occasionally;
• Others: development of alopecia or speech disorders, as well as temporary increase in the activity of alkaline phosphatase and transaminases, as well as creatinine and bilirubin levels in the blood serum. Rarely, renal failure, decreased blood pressure or insufficient blood flow are observed in people who have suffered cases of dehydration due to vomiting/diarrhea, or in people suffering from sepsis.

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Overdose

In case of intoxication, the development of neutropenia or diarrhea should be expected.

The drug has no antidote. Symptomatic procedures are required. In case of overdose, the victim must be hospitalized, and then the functioning of vital organs must be closely monitored.

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Interactions with other drugs

Because irinotecan is capable of exerting an anticholinesterase effect, the duration of neuromuscular blockade may increase after combination with suxamethonium salts. An antagonistic effect on neuromuscular blockade is also noted when used in combination with non-depolarizing muscle relaxants.

Combination with myelosuppressants or the use of Campto during radiation therapy leads to increased toxic effects on the bone marrow (development of leukopenia or thrombocytopenia).

Combination with GCS (such as dexamethasone) increases the likelihood of hyperglycemia (especially in people with diabetes mellitus or reduced glucose tolerance) and lymphopenia.

Simultaneous use with diuretics may lead to increased dehydration, developing due to vomiting and diarrhea. Combination with laxatives potentiates the severity of diarrhea and its frequency.

Combination with prochlorperazine increases the risk of developing akathisia symptoms.

Combination with herbal medicines (based on St. John's wort), and also with anticonvulsants that induce the activity of the CYP3A element (such as phenobarbital with carbamazepine and phenytoin), leads to a decrease in the indicators of the drug metabolism product (SN-38) in the plasma.

The combination of the drug with atazanavir, drugs that inhibit the activity of CYP3A4 and UGT1A1 enzymes, and also with ketoconazole leads to an increase in plasma values of the active metabolic product SN-38.

It is prohibited to mix the substance irinotecan with other drugs in the same bottle.

Administration of a vaccine (live or attenuated) to people who use antitumor drugs may cause severe or even fatal infections. Vaccination with live vaccines should be avoided in people using irinotecan. Administration of an inactivated or killed vaccine is permitted, but the body's response to it may be weakened.

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Storage conditions

Campto should be kept out of reach of children and sunlight. Do not freeze the medicinal substance. Temperature – maximum 25°C.

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Shelf life

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

Application for children

The medicine can only be used by adult patients.

Analogues

The following drugs are analogs of the drug: Irinotecan, Irinotecan-Filaxis and Irinotecan Pliva-Lahema with Irinotecan-Teva, and in addition Irnokam, Iriten, Kamptotecan and Kamptera.

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