Composition, form of production and packaging
Concentrate for the preparation of a solution for infusions in the form of a clear solution from colorless with a yellowish hue to light yellow or light greenish-yellow color.
1 ml of 1 fl.
irinotecan hydrochloride trihydrate 20 mg 40 mg,
which corresponds to the content of irinotecan 17.33 mg 34.66 mg
Excipients: sorbitol, lactic acid, sodium hydroxide and hydrochloric acid (up to pH 3.5), water d / u.
2 ml - bottles of polypropylene brown (1) - packs of cardboard.
Concentrate for the preparation of a solution for infusions in the form of a clear solution from colorless with a yellowish hue to light yellow or light greenish-yellow color.
1 ml of 1 fl.
irinotecan hydrochloride trihydrate 20 mg 100 mg,
which corresponds to the content of irinotecan 17.33 mg 86.65 mg
Excipients: sorbitol, lactic acid, sodium hydroxide and hydrochloric acid (up to pH 3.5), water d / u.
5 ml - bottles of polypropylene brown (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2008.
PHARMACHOLOGIC EFFECT
Antitumor drug of plant origin. Irinotecan, a semi-synthetic 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 metabolite SN-38 stabilize the topoisomerase I complex with DNA, which prevents its replication.
In vivo experiments, it has been shown that irinotecan is also active against tumors that express P-glycoprotein of multiple drug resistance (vincristine and doxorubicin-resistant leukemias P388).
PHARMACOKINETICS
The pharmacokinetics of irinotecan and metabolite SN-38 was studied with a 30-minute intravenous infusion of the drug at a dose of 100-750 mg / m 2 . The pharmacokinetic profile of irinotecan did not depend on the dose.
Metabolism and distribution
Irinotecan is metabolized in the liver by the action of the carboxyesterase enzyme to form the active metabolite SN-38.
The distribution in the plasma is two- or three-phase. The mean T 1/2 in the first phase of the three-phase model is 12 minutes, in the second phase 2.5 hours, in the third phase 14.2 hours. C max irinotecan and SN-38 was achieved by the end of IV infusion in the recommended dose for the monotherapy 350 mg / m 2 of the body surface.
Binding to plasma proteins is approximately 65% ​​for irinotecan, 95% for the metabolite SN-38.
Excretion
C urine for 24 hours displays 19.9% ​​in the form of unchanged irinotecan and 0.25% - in the form of metabolite SN-38.
Pharmacokinetics in special clinical cases
Pharmacokinetic studies confirmed the absence of the effect of 5-fluorouracil and calcium folinate on the pharmacokinetics of irinotecan.
INDICATIONS
Treatment of locally advanced or metastatic cancer of the colon and rectum:
- in combination with 5-fluorouracil and calcium folinate in patients who have not previously received chemotherapy;
- with monotherapy in patients with progression of the disease after conventional treatment.
DOSING MODE
The drug is prescribed only to adults .
The drug is administered as an IV infusion lasting at least 30 minutes and not more than 90 minutes.
In the treatment of colorectal cancer, Campto is used both as a monotherapy, and in combination with 5-fluorouracil and calcium folinate. When choosing a dose and mode of administration, you should refer to the special literature.
In the monotherapy regime, Campto is used at a dose of 350 mg / m 2 body surface every 3 weeks.
In the combination therapy with prolonged infusion of 5-fluorouracil and calcium folinate, Campto is prescribed weekly at a dose of 80 mg / m 2 ; Once in 2 weeks - 180 mg / m 2 ; when administered in combination with a bolus of 5-fluorouracil and calcium folinate weekly - 125 mg / m 2 .
Introduction Campto should not be performed until the amount of neutrophils in the peripheral blood exceeds 1500 / Ојl, and until such time as the complications of therapy such as nausea, vomiting and diarrhea are completely stopped. The administration of the drug before the resolution of all side effects can be postponed for 1-2 weeks.
In the event that the expressed inhibition of bone marrow hematopoiesis develops (the number of neutrophils is less than 500 / Ојl, and / or the number of white blood cells is less than 1000 / Ојl, and / or the platelet count is less than 100,000 / Ојl), or febrile neutropenia (the number of neutrophils 1000 / Ојl and less in combination with fever above 38 В° C), or infectious complications, or severe diarrhea, or other non-hematological toxicity of 3-4 degrees, subsequent doses of Campto or, if necessary, 5-fluorouracil reduce by 15-20%.
Treatment of Campto can continue until the appearance of objective signs of progression of the tumor disease or the development of unacceptable toxic manifestations.
In patients with impaired hepatic function with a serum level of bilirubin exceeding the upper limit of the norm by no more than 1.5 times, due to the increased risk of severe neutropenia, the blood counts in the patient should be closely monitored. With an increase in the level of bilirubin more than 3 times - treatment of Campto should be discontinued.
In patients with impaired renal function, treatment with Kampto is not recommended, because the use in this category of patients has not been studied.
There are no special instructions for the use of the drug Campto in elderly patients . Care should be taken in each case.
The safety and effectiveness of the use of the drug Campto in children are not well understood.
SIDE EFFECT
From the hemopoietic system: neutropenia - in 78.7% of patients with monotherapy (in 82.5% - with combined chemotherapy), incl. 22.6% of patients had severe neutropenia (neutrophil count less than 500 / ОјL). Neutropenia is reversible and not cumulative. The complete recovery of neutrophil counts usually occurs on day 22 with the application of Campto as monotherapy and on day 7-8 with the use of Campto as part of a combination therapy. Fever in combination with severe neutropenia was noted in 6.2% and 3.4% of patients, respectively. Infectious complications with monotherapy took place in 10.3% of patients, in 5.3% of patients - in combination with severe neutropenia. Infectious complications in combination therapy occurred in approximately 2% of patients (0.5% of cycles), approximately 2.1% of patients and in 0.5% of cycles they were associated with severe neutropenia.
Anemia in monotherapy is noted in 58.7% of patients, with combined chemotherapy - in 97.2%.
Thrombocytopenia (the number of platelets is less than 100,000 / Ојl) is observed in 7.4% of patients with monotherapy, in combination therapy in 32.6% of patients.When using Kampto as part of combined chemotherapy, severe thrombocytopenia was not observed. The number of platelets is restored by day 22.
There was 1 case of thrombocytopenia in combination with the formation of antiplatelet antibodies.
On the part of the digestive system: nausea, vomiting, diarrhea, abdominal pain, anorexia, mucositis, constipation. There have been reports of rare cases of pseudomembranous colitis, intestinal obstruction, bleeding from the gastrointestinal tract, intestinal perforation, increased levels of amylase or lipase.
When using the drug as a monotherapy, severe diarrhea was observed in 20% of patients (in the combination therapy - in 13.1%), which followed recommendations for the treatment of diarrhea. The average time before the appearance of the first liquid stool after the introduction of Campto was 5 days.
With the use of Campto in monotherapy, approximately 10% of patients who used anti-emetics showed marked nausea and vomiting. With the use of Campto as part of a combination therapy, severe nausea and vomiting were less common, in 2.1% and 2.8%, respectively.
Acute cholinergic syndrome: early diarrhea, abdominal pain, increased sweating, conjunctivitis, rhinitis, decreased blood pressure, vasodilation, lacrimation, salivation, chills, malaise, dizziness, visual disturbance, miosis, was observed in 9% of patients receiving Campto as a monotherapy 1.4% in combination therapy). All symptoms pass after the administration of atropine.
From the side of the central nervous system and peripheral nervous system: involuntary muscle twitching or convulsions, paresthesia, asthenia.
Allergic reactions: rarely - skin rash, very rarely - anaphylactic shock.
Other: alopecia, fever, local reactions, transient increase in the level of transaminases, alkaline phosphatase, bilirubin and creatinine in serum. In rare cases, there was a development of renal failure, arterial hypotension, circulatory insufficiency in patients who had had episodes of dehydration associated with diarrhea and / or vomiting, or in patients with sepsis.
CONTRAINDICATIONS
- hypersensitivity to irinotecan or other components of the drug;
- nonspecific ulcerative colitis and / or intestinal obstruction;
- marked suppression of bone marrow hematopoiesis;
- the level of bilirubin in the blood, exceeding more than 3 times the IGN;
- the general condition of patients assessed by the WHO scale> 2;
- Pregnancy;
- lactation (breastfeeding).
PREGNANCY AND LACTATION
The drug is contraindicated for use in pregnancy and lactation (breastfeeding).
Patients of reproductive age should avoid conception during the use of the drug and, at least, within 3 months after its withdrawal.
APPLICATION FOR FUNCTIONS OF THE LIVER
In patients with impaired renal function, treatment with Kampto is not recommended, because the use in this category of patients has not been studied.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In patients with impaired hepatic function with a serum level of bilirubin exceeding the upper limit of the norm by no more than 1.5 times, due to the increased risk of severe neutropenia, the blood counts in the patient should be closely monitored. With an increase in the level of bilirubin by more than 1.5 times, the treatment should be stopped.
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 administered with caution to patients who received previous radiation therapy in the abdominal or pelvic area, patients who previously had hyperleukocytosis, as well as patients with a general condition on the WHO-2 scale, to female patients; in all these cases, the risk of diarrhea increases.
Diarrhea that occurs as a consequence of the cytostatic effect of the drug (delayed diarrhea) is usually noted no earlier than 24 hours after the administration of Campto (in most patients, an average of 5 days).
When the first episode of a loose stool occurs, it is necessary to administer a copious drink containing electrolytes and immediately perform antidiarrheal therapy, including loperamide in high doses (4 mg for the first dose, then 2 mg every 2 hours). This therapy is continued for another 12 hours after the last episode of a loose stool (but no more than 48 hours because of the risk of intestinal paresis). If diarrhea is regarded as severe (more than 6 episodes of loose stool during the day or severe tenesmus), and 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 stool during the day and moderate tenesmus), which does not stop within the first 48 hours, the intake of broad-spectrum antibiotics begins, and the patient is recommended to be hospitalized. With the simultaneous occurrence of diarrhea and severe neutropenia (the number of white blood cells is less than 500 / Ојl), in addition to antidiarrheal therapy with a preventive purpose, antibiotics of a wide spectrum of action are administered inside.
Do not prescribe loperamide prophylactically, incl. patients who had diarrhea during the previous administration of Campto.
The patient should be informed about the possibility of developing diarrhea. Patients should immediately inform their physician about the occurrence of diarrhea (to immediately begin antidiarrheal therapy).
If the treatment of diarrhea is inadequate, a condition threatening the patient's life may develop, especially if diarrhea develops against a background of neutropenia.
Patients with febrile neutropenia (body temperature ≥ 38 ° and neutrophil count ≤ 1000 / μL) should immediately begin antibiotic therapy in a hospital setting.
With the development of acute cholinergic syndrome in the absence of contraindications is shown s / c atropine at a dose of 0.25 mg. Care should be taken when using the drug in patients with bronchial asthma. Patients who have a history of indication of the development of acute cholinergic syndrome (including in severe form), before the appointment of Campot recommended the prophylactic use of atropine sulfate.
Given that Campto contains sorbitol, the drug is not prescribed to patients with hereditary intolerance to fructose.
Patients receiving Campto should undergo a weekly clinical blood test and monitor liver function.
Impact on the ability to drive vehicles and manage mechanisms
Patients should be cautioned about the possible appearance during the treatment of Camptus dizziness and visual disorders that develop within 24 hours after the introduction of Campto. If these symptoms occur, patients are advised to refrain from driving and other mechanisms.
OVERDOSE
The main expected symptoms of an overdose are neutropenia and diarrhea. If necessary, conduct symptomatic therapy. There is no specific antidote.
DRUG INTERACTION
Since Campto has anticholinesterase activity, it is possible to increase the duration of neuromuscular blockade with concomitant use with suxamethonium and antagonistic interaction with neuromuscular blockade when combined with nondepolarizing muscle relaxants.
Pharmaceutical interaction
Campto should not be mixed with other drugs in one bottle.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children and protected from light, at a temperature of no higher than 25 В° C. Shelf life - 3 years.
The prepared solution should be used immediately after dilution.
If dilution is performed in accordance with aseptic rules (for example, in a laminar air flow installation), the Campto solution can be used for storage at room temperature for 12 hours (including infusion time) and at a temperature of 2 В° to 8 В° C for 24 h after opening the vial with concentrate.
