Campto CS concentrate 20mg/ml 15ml vials, 1pc

Composition

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1 ml (1 bottle) contains:

Active ingredients:

irinotecan hydrochloride trihydrate is 20 mg (300 mg), which corresponds to an irinotecan content of 17.33 mg (259.95 mg).

Auxiliary substances:

sorbitol,

lactic acid,

sodium hydroxide and hydrochloric acid (up to pH 3.5),

d/i water.

Pharmacological action

Pharmacodynamics

Antitumor drug of plant origin. 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 the SN-38 metabolite stabilize the topoisomerase I complex with DNA, which prevents its replication. In vivo experiments have shown that irinotecan is also active against tumors expressing P-glycoprotein of multiple drug resistance (vincristine-and doxorubicin-resistant leukemias p388).

Pharmacokinetics

The pharmacokinetics of irinotecan and the SN-38 metabolite were studied with a 30-minute intravenous infusion of the drug at a dose of 100-750 mg / m2. The pharmacokinetic profile of irinotecan was independent of the dose.

Metabolism and distribution

Irinotecan is metabolized in the liver by the enzyme carboxyesterase to form the active metabolite SN-38.

The plasma distribution is two – or three-phase. The average T_1/2 in the first phase of the three-phase model is 12 min, in the second phase – 2.5 h, in the third phase-14.2 h. The_cmax of irinotecan and SN-38 was achieved by the end of the IV infusion at the recommended dose of 350 mg/m2 of body surface area for monotherapy.

Binding to plasma proteins is approximately 65% for irinotecan,95% for the SN-38 metabolite.

Urinary excretion within 24 hours,19.9% is excreted as unchanged irinotecan and 0.25% as the SN – 38 metabolite.

Pharmacokinetics In special clinical cases

, pharmacokinetic studies have confirmed the absence of the effect of 5-fluorouracil and calcium folinate on the pharmacokinetics of irinotecan.

Indications

Treatment of locally advanced or metastatic colon and rectal cancer:

• in combination with 5-fluorouracil and calcium folinate in patients who have not previously received chemotherapy;
• in monotherapy in patients with disease progression after conventional treatment.

Use during pregnancy and lactation

The drug is contraindicated for use during pregnancy and lactation (breastfeeding).

Patients of reproductive age should avoid conception during the use of the drug and, at least, for 3 months after its withdrawal.

Contraindications

• Hypersensitivity to irinotecan or other components of the drug;
• non-specific ulcerative colitis and / or intestinal patency disorders;
• severe suppression of bone marrow hematopoiesis;
• blood bilirubin level exceeding more than 3 times ULN;
• general condition of patients evaluated on the WHO scale>2;>
• pregnancy;
• lactation (breastfeeding).

Side effects

From the hematopoietic system: neutropenia – in 78.7% of patients with monotherapy (82.5% – with combined chemotherapy), including 22.6% of patients with severe neutropenia (neutrophil count less than 500/µl). Neutropenia is reversible and not cumulative. Complete neutrophil count recovery usually occurs on day 22 when Campto is used as monotherapy and on day 7-8 when Campto is used as part of combination therapy. Fever in combination with severe neutropenia was observed in 6.2% and 3.4% of patients, respectively. Infectious complications with monotherapy occurred in 10.3% of patients, in 5.3% of patients-in combination with severe neutropenia. Infectious complications with combination therapy occurred in approximately 2% of patients (0.5% of cycles), in approximately 2.1% of patients, and in 0.5% of cycles they were combined with severe neutropenia.

Anemia with monotherapy is observed in 58.7% of patients, with combined chemotherapy-in 97.2%.

Thrombocytopenia (platelet count less than 100,000 / µl) is observed in 7.4% of patients with monotherapy, with combination therapy-in 32.6% of patients. When using Campto as part of combined chemotherapy, severe thrombocytopenia was not observed. The platelet count is restored by day 22.

There was 1 case of thrombocytopenia in combination with the formation of antiplatelet antibodies.

From the digestive system: nausea, vomiting, diarrhea, abdominal pain, anorexia, mucositis, constipation. Rare cases of pseudomembranous colitis, intestinal obstruction, gastrointestinal bleeding, intestinal perforation, and elevated amylase or lipase levels have been reported.

When using the drug as monotherapy, severe diarrhea was observed in 20% of patients (in combination therapy-in 13.1%) who followed the recommendations for the treatment of diarrhea. The average time to the appearance of the first loose stool after Campto use was 5 days.

When Campto was used as monotherapy, approximately 10% of patients treated with antiemetics experienced severe nausea and vomiting. When Campto was used in combination therapy, severe nausea and vomiting were observed less frequently – in 2.1% and 2.8%, respectively.

Acute cholinergic syndrome: early diarrhea, abdominal pain, increased sweating, conjunctivitis, rhinitis, decreased blood pressure, vasodilation, lacrimation, drooling, chills, malaise, dizziness, visual disturbances, miosis, was observed in 9% of patients receiving Campto as monotherapy (in 1.4% – as part of combination therapy). All symptoms disappear after use of atropine.

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

Allergic reactions: rarely – skin rash, very rarely-anaphylactic shock.

Others: alopecia, fever, local reactions, transient increases in serum transaminases, ALP, bilirubin and creatinine. In rare cases, the development of renal failure, hypotension, circulatory insufficiency has been observed in patients who have experienced episodes of dehydration associated with diarrhea and/or vomiting, or in patients with sepsis.

Interaction

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

Pharmaceutical interaction

Campto 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.

The drug is administered as an intravenous infusion lasting at least 30 minutes and no more than 90 minutes.

In the treatment of colorectal cancer, Campto 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, Campto is used at a dose of 350 mg/m2 of body surface area every 3 weeks.

In combination therapy with prolonged infusion of 5-fluorouracil and calcium folinate, Campto is prescribed weekly at a dose of 80 mg / m2; once every 2 weeks-180 mg/m2; when administered in combination with a bolus of 5-fluorouracil and calcium folinate weekly – 125 mg / m2.

Campto should not be administered until the number of neutrophils in the peripheral blood does not exceed 1500 / µl, and until such complications of therapy as nausea, vomiting and diarrhea are completely stopped. 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 Campto or, if necessary,5-fluorouracil reduced by 15-20%.

Treatment of Campto can be continued until objective signs of progression of the tumor disease or the development of unacceptable toxic manifestations appear.

In patients with impaired liver function, if the level of bilirubin in the blood serum exceeds the upper limit of normal by no more than 1.5 times, due to the increased risk of developing severe neutropenia, the patient’s blood parameters should be carefully monitored. If the bilirubin level increases by more than 3 times, Campto treatment should be discontinued.

In patients with impaired renal function, treatment of Campto is not recommended, because the use in this category of patients has not been studied.

There are no special instructions for the use of Campto in elderly patients. With caution, the dose should be selected on a case-by-case basis.

The safety and efficacy of Campto in children are poorly understood.

Overdose

The main expected symptoms of overdose are neutropenia and diarrhea. If necessary, conduct symptomatic therapy. There is no specific antidote.

Special instructions

Treatment with the drug should be carried out in specialized chemotherapy departments and only under the supervision of a doctor who has experience with antitumor drugs.

The drug should be used with caution in patients who have previously received radiation therapy for the abdominal or pelvic region, patients who have previously experienced hyperleukocytosis, as well as patients with a general condition on the WHO scale≥2, female patients; in all these cases, the risk of diarrhea increases.

Diarrhea that occurs as a result of cytostatic action of the drug (delayed diarrhea) is usually noted no earlier than 24 hours after the introduction of Campto (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 loperamide in high doses (4 mg at the first dose, then 2 mg every 2 hours).

This therapy is continued for another 12 hours after the last episode of loose stools (but not more than 48 hours due to the risk of intestinal 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 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, start taking broad-spectrum antibiotics inside, and the patient is recommended to be hospitalized. If diarrhea and severe neutropenia occur simultaneously (the number of white blood cells is less than 500/µl), in addition to antidiarrheal therapy, broad-spectrum antibiotics are prescribed inside for preventive purposes.

Loperamide should not be administered prophylactically, including in patients who have had diarrhea during previous Campto injections.

The patient should be informed about the possibility of developing diarrhea. Patients should immediately inform their doctor about the occurrence of diarrhea (in order to immediately start antidiarrheal therapy).

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 ≤1000/µl) should immediately start antibiotic therapy in a hospital setting.

With the development of acute cholinergic syndrome in the absence of contraindications, subcutaneous use of atropine at a dose of 0.25 mg 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 severe cases), prophylactic use of atropine sulfate is recommended before the appointment of Campto.

Given that Campto contains sorbitol, the drug is not prescribed to patients with hereditary fructose intolerance.

In patients receiving Campto, a detailed clinical blood test should be performed weekly and liver function should be monitored.

Influence on the ability to drive vehicles and other mechanisms that require increased concentration of attention

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

Form of production

Concentrate for preparation of solution for infusions.

Storage conditions

In a dry place, at a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Irinotecan

Conditions of release from pharmacies

By prescription

Dosage form

infusion solution