Intaksel

General characteristics. Structure:

Active ingredient: 6 mg of a paklitaksel.

Excipients: a macrogoal глицерилгидроксистеарат, ethanol anhydrous - 49.7% about/about.

Pharmacological properties:

Pharmacodynamics. The antineoplastic drug of a plant origin received in the semi-synthetic way from Taxus Baccata plant.

The mechanism of action is connected with ability to stimulate assembly of microtubules from dimeric molecules of a tubulin, to stabilize their structure and to slow down dynamic reorganization in interphase that breaks mitotic function of a cell.

Causes dozozavisimy suppression of a marrowy hemopoiesis. On experimental data has mutagen and embriotoksichesky properties, causes decrease in reproductive function.

Pharmacokinetics. At in introduction during 3 h in a dose of 135 mg/sq.m of Cmax makes 2170 ng/ml, AUC - 7952 нг/ч/мл; at introduction of the same dose during 24 h - 195 ng/ml and 6300 нг/ч/мл, respectively. Cmax and AUC of a dozozavisima: at 3-hour infusions increase in a dose up to 175 mg/sq.m leads to increase in these parameters for 68% and 89%, and at 24-hour - for 87% and 26%, respectively.

Communication with proteins of plasma - 88-98%. Semi-distribution time from blood in fabric - 30 min. Easily gets and it is absorbed by fabrics, collects preferential in a liver, a spleen, a pancreas, a stomach, intestines, heart, muscles.

It is metabolized in a liver by a hydroxylation with participation of isoenzymes of P450 CYP2D8 cytochrome (with formation of a metabolite - 6 - alpha гидроксипаклитаксел) and CYP3CA4 (with formation of metabolites 3 - couple - gidroksipaklitaksel and 6 alpha, 3 - couple - digidroksipaklitaksel). It is removed preferential with bile - 90%. At repeated infusions does not kumulirut.

T1/2 and the general clearance are variable and depend on a dose and duration in/in introductions: 13.1-52.7 h and 12.2-23.8 l/h/sq.m, respectively. Later in/in infusions (1-24 h) the general removal by kidneys makes 1.3-12.6% of a dose (15-275 mg/sq.m) that indicates existence of intensive extrarenal clearance.

Indications to use:

— ovarian cancer: therapy of the first line of patients with a common form of a disease or a residual tumor (more than 1 cm) after a laparotomy (in a combination with Cisplatinum) and therapy of the second line at metastasises after the standard therapy which did not yield a positive take;

— a breast cancer (existence of the affected lymph nodes after a standard combination therapy (adjuvant treatment)); after the disease recurrence, within 6 months after the beginning of adjuvant therapy - therapy of the first line; a metastatic breast cancer after inefficient standard therapy - therapy of the second line;

— not small-celled lung cancer (therapy of the first line of patients to whom performing surgical treatment and/or radiation therapy is not planned (in a combination with Cisplatinum));

— Kaposha's sarcoma at patients AIDS (therapy of the second line, after inefficient therapy by liposomal anthracyclines).

Route of administration and doses:

For the warning of heavy hypersensitivity reactions to all patients premedication with use of GKS, antihistaminic drugs and antagonists of H2-histamine receptors has to be carried out. For example, 20 mg of dexamethasone (or its equivalent) inside approximately for 12 h and 6 h before administration of drug Intaksel, 50 mg of a difengidramin (or its equivalent) in/in and 300 mg of Cimetidinum or 50 mg of ranitidine in/in in 30-60 min. prior to administration of drug Intaksel.

At the choice of the mode and doses in each individual case it is necessary to be guided by data of special literature.

Intaksel enter in/in in the form of 3-hour or 24-hour infusion in a dose of 175 mg/sq.m or 135 mg/sq.m respectively, with an interval between introductions of 3 weeks. Drug is used in the form of monotherapy or in a combination with Cisplatinum (ovarian cancer and not small-celled lung cancer) or doxorubicine (breast cancer).

The recommended drug dose Intaksel for treatment of sarcoma of Kaposha at patients about AIDS makes 100 mg/sq.m in the form of 3-hour infusion each 2 weeks.

Administration of drug Intaksel should not be repeated until the maintenance of neutrophils does not make, at least, 1500/mkl blood, and the maintenance of thrombocytes, at least, 100 000/mkl blood. To patients at whom after introduction Intaksela was observed the expressed neutropenia (the maintenance of neutrophils <500/mkl blood within 7 days or longer time) or a severe form of a peripheral neuropathy, during the subsequent courses of treatment it is necessary to lower Intaksel's dose by 20%. Solution for infusion is prepared just before introduction, parting a concentrate of 0.9% with chloride sodium solution, either 5% dextrose solution, or 5% dextrose solution in 0.9% chloride sodium solution for injections, or 5% dextrose solution in Ringer's solution to final concentration from 0.3 to 1.2 mg/ml. The prepared solutions can opalestsirovat because of the dosage form of a basis carrier which is present at structure, and after filtering opalescence of solution remains.

At preparation, storage and administration of drug Intaksel it is necessary to use the equipment which does not contain details from PVC.

Intaksel it is necessary to enter through system with the built-in membrane filter (the size of a time no more than 0.22 microns).

Features of use:

Use at pregnancy and feeding by a breast. Drug is contraindicated at pregnancy and in the period of a lactation (breastfeeding).

Use at abnormal liver functions. With care appoint drug at a liver failure.

Use for children. Safety and efficiency of drug of Intaksel at children is not established.

Special instructions. Treatment by drug Intaksel has to be performed under observation of the doctor having experience with antineoplastic chemotherapeutic drugs.

At use in combinations with Cisplatinum, at first it is necessary to enter Intaksel, and then Cisplatinum.

During treatment it is regularly necessary to control a pattern of peripheral blood, the ABP, ChSS and number of dykhaniye (especially for the first hour of infusions), ECG control (and prior to treatment).

In case of development of heavy reactions of hypersensitivity drug infusion Intaksel it is necessary to stop and begin immediately a symptomatic treatment, and it is not necessary to administer the drug repeatedly.

In cases of development of disturbances of AV conductivity, at repeated introductions it is necessary to carry out continuous cardiomonitoring.

Patients during treatment by drug Intaksel and, at least, within 3 months after the end of therapy should use reliable methods of contraception.

Intaksel is cytotoxic substance during the work with which it is necessary to be careful, use gloves and to avoid its hit on skin or mucous membranes which in such cases need to be washed out carefully soap and water, or (eyes) a large amount of water.

Use in pediatrics. Safety and efficiency of drug of Intaksel at children is not established.

Influence on ability to driving of motor transport and to control of mechanisms. During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Frequency and expressiveness of side effects have dozozavisimy character.

From system of a hemopoiesis: neutropenia, thrombocytopenia, anemia. Suppression of function of marrow, mainly a granulotsitarny sprout, was the main toxic effect limiting a drug dose. The maximum decrease in level of neutrophils is usually observed for the 8-11th day, normalization occurs for the 22nd day.

Hypersensitivity reactions: during the first hours after Intaksel's introduction the hypersensitivity reactions which are shown a bronchospasm, decrease in the ABP, thorax pains, rushes of blood to the person, skin rashes, a generalized small tortoiseshell, a Quincke's disease can be observed. Isolated cases of a fever and dorsodynias are described.

From cardiovascular system: decrease in the ABP, is more rare increase in the ABP, bradycardia or tachycardia, disturbance of a rhythm, AV blockade, a ventricular bigeminal pulse, changes on an ECG, thrombosis of venous vessels.

From respiratory system: intersticial pneumonia, a pneumosclerosis, an embolism of a pulmonary artery, and also more frequent development of a beam pneumonitis in the patients who are at the same time taking a course of radiation therapy.

From a nervous system: peripheral neuropathy (mainly paresthesias); seldom - convulsive attacks like grand mal, an ataxy, encephalopathy, damage of an optic nerve, the vegetative neuropathy which is shown paralytic impassability of intestines and orthostatic hypotension.

From a musculoskeletal system: arthralgia, mialgiya.

From the alimentary system: nausea, vomiting, diarrhea, mukozita, anorexia, lock; there are single messages on acute intestinal impassability, perforation of intestines, fibrinferment of a mesenteric artery, ischemic colitis; increase in activity of hepatic transaminases (ACT is more often), ShchF and bilirubin in blood serum. Cases of development of a gepatonekroz and hepatic encephalopathy are described.

From skin and integuments: alopecia; seldom - disturbance of pigmentation or decolouration of a nail bed.

From sense bodys: decrease in visual acuity, conjunctivitis, the raised dacryagogue.

Local reactions: thrombophlebitis, pain, hypostasis, an erythema, an induration and a xanthopathy in the place of an injection; the ekstravazation can cause an inflammation and a necrosis of hypodermic cellulose.

Others: an adynamy and a febricula, decrease in tolerance to infections (any etiology).

Interaction with other medicines:

Cisplatinum reduces the general clearance of a paklitaksel by 20% (at the same time more expressed miyelosupressiya is observed in case paklitakset enter after Cisplatinum).

Co-administration with Cimetidinum, ranitidine, dexamethasone or difengidraminy does not influence communication of a paklitaksel with proteins of a blood plasma.

Inhibitors of a microsomal oxidation (including кетоконазол, Cimetidinum, verapamil, diazepam, quinidine, cyclosporine) suppress metabolism of a paklitaksel.

The polyhydroxyethylated castor oil which is a part of a paklitaksel can cause extraction of DEGP [di - (2 hexyl) phthalate] from the plasticized polyvinyl chloride (PVC) containers, and extent of washing away of DEGP increases at increase in concentration of solution and over time.

Contraindications:

— the initial maintenance of neutrophils less 1500/mkl at patients with solid tumors;

— initial (or registered in the course of treatment) the maintenance of neutrophils less 1000/mkl at patients with Kaposha's sarcoma at patients AIDS;

— pregnancy;

— period of a lactation (breastfeeding);

— hypersensitivity to a paklitaksel or other components of drug (including to the polyhydroxyethylated castor oil).

With care appoint drug at oppression of a marrowy hemopoiesis (including after himio-or radiation therapy), a liver failure, acute infectious diseases (including shingles, chicken pox, herpes), a heavy current of an ischemic heart disease, a myocardial infarction (in the anamnesis), arrhythmias.

Overdose:

Symptoms: marrow aplasia, peripheral neuropathy, mukozita.

Treatment: symptomatic. The antidote to a paklitaksel is unknown.

Storage conditions:

Drug should be stored in the unavailable to children, protected from light place at a temperature not above 25 °C. Not to freeze. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

In bottles from transparent glass on 30 mg / 5 ml, 100 mg / 17 ml or 260 mg / 43,4 ml; in a cardboard pack 1 bottle.