Митотакс®

General characteristics. Structure:

Concentrate for preparation of solution for infusions in the form of transparent, colourless or pale yellow slightly viscous liquid.
1 ml 1 фл.
paklitakset 6 mg 30 mg
Excipients: macrogoal глицерилгидроксистеарат, ethanol, citric acid. 5 ml – bottles of colourless glass (1) – a pack cardboard.
Concentrate for preparation of solution for infusions in the form of transparent, colourless or pale yellow slightly viscous liquid.
1 ml 1 фл.
paklitakset 6 mg 100 mg
Excipients: macrogoal глицерилгидроксистеарат, ethanol, citric acid.
16.7 ml – bottles of colourless glass (1) – a pack cardboard.
16.7 ml – bottles of colourless glass (1) – planimetric strip packagings (1) – packs cardboard.
Concentrate for preparation of solution for infusions in the form of transparent, colourless or
Pale yellow slightly viscous liquid.
1 ml 1 фл.
paklitakset 6 mg 250 mg
Excipients: macrogoal глицерилгидроксистеарат, ethanol, citric acid.
41.7 ml – bottles of colourless glass (1) – a pack cardboard.
41.7 ml – bottles of colourless glass (1) – planimetric strip packagings (1) – packs cardboard.
Concentrate for preparation of solution for infusions in the form of transparent, colourless or pale yellow slightly viscous liquid.
1 ml 1 фл.
paklitakset 6 mg 300 mg
Excipients: macrogoal глицерилгидроксистеарат, ethanol, citric acid.
50 ml – bottles of colourless glass (1) – a pack cardboard.
50 ml – bottles of colourless glass (1) – planimetric strip packagings (1) – packs cardboard.

Pharmacological properties:

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, preventing a depolymerization, their structure and to slow down dynamic reorganization in interphase that breaks mitotic function of a cell. Besides, paklitakset induces formation of abnormal accumulations or "bunches" of microtubules throughout all cellular cycle and a set of star-shaped accumulations (aster) during a mitosis. Causes dozozavisimy suppression of a marrowy hemopoiesis. In pilot studies it is established that drug has mutagen and embriotoksichesky properties, causes decrease in reproductive function.

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

Route of administration and doses:

For prevention of development of the expressed allergic reactions by all patient before infusion premedication with use of GKS, antihistaminic drugs has to be carried out (including antagonists histamine N2_retseptorov): 20 mg of dexamethasone (or its equivalent) inside or in oil for 12 h and 6 h before administration of the drug Mitotaks®, 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 the drug Mitotaks®.
At the choice of the mode and doses in each individual case it is necessary to be guided by data of special literature.
Митотакс® enter in/in in a look 3_chasovoy or 24_chasovoy infusions 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 (at ovarian cancer and not small-celled lung cancer) or doxorubicine (at a breast cancer). Repeated administrations of the drug Mitotaks® are carried out at the maintenance of neutrophils in peripheral blood _1500/mkl and thrombocytes _100 000/mkl.
To patients at whom after the previous introductions of a paklitaksel the expressed neutropenia was observed (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 a dose of the drug Mitotaks® by 20%.
Rules of preparation, introduction and storage of solution
Solution for infusions is prepared just before introduction. A concentrate 0.9% part with solution of sodium of chloride, 5% solution of a dextrose or a combination of 5% of solution of a dextrose from 0.9% chloride sodium solution, or a combination of 5% of solution of a dextrose in Ringer's solution. Final concentration of a paklitaksel in solution has to make 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 can remain. At preparation, storage and administration of the drug Mitotaks® it is necessary to use the equipment which does not contain details from PVC. Solutions of the drug Mitotaks® should be prepared and stored in glass, polypropylene or polyolefin systems and to enter through infusional systems with an internal surface from polyethylene, and also via the membrane filter connected to system with a size of time no more than 0.22 microns.

Features of use:

Treatment by the drug Mitotaks® has to be performed under observation of the doctor having experience with antineoplastic chemotherapeutic drugs. If Mitotaks® is used in a combination with Cisplatinum, at first it is necessary to enter Mitotaks®, 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 infusion), control of an ECG (including prior to treatment).
In case of development of heavy reactions of hypersensitivity, infusion of drug of Mitotaks 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.
Митотакс® 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 a paklitaksel 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 8_11 day, normalization occurs for the 22nd day.
Allergic reactions: skin rash, rushes of blood to face skin and an upper part of a thorax, a Quincke's disease, a bronchospasm, a generalized small tortoiseshell, decrease in the ABP, pain behind a breast. Isolated cases of a fever and dorsodynias are described.
From outside сердечно&сосудистой systems: 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 hypotonia.
From outside костно&мышечной systems: 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 (the nuclear heating plant is more often), ShchF and bilirubin in blood serum. Cases of development of a gepatonekroz and hepatic encephalopathy are described.
Dermatological reactions: an alopecia, it is rare – 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). Inhibitors of a microsomal oxidation (including кетоконазол, verapamil, diazepam, quinidine, cyclosporine) suppress metabolism of a paklitaksel.
Simultaneous use with Cimetidinum, ranitidine, dexamethasone or Dimedrol does not influence linkng of a paklitaksel with proteins of a blood plasma. 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 containers, and extent of washing away of DEGP increases at increase in concentration of solution and over time.

Contraindications:

Initial maintenance of neutrophils less 1500/mkl;
pregnancy;
period of a lactation (breastfeeding);
hypersensitivity to a paklitaksel or other components of drug (including to the polyhydroxyethylated castor oil).
With care it is necessary to appoint drug at thrombocytopenia (less than 100 000/mkl), 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.

PREGNANCY AND LACTATION
Drug is contraindicated at pregnancy and during breastfeeding. Patients during treatment by the drug Mitotaks® and, at least, within 3 months after the end of therapy should use reliable methods of contraception.

Overdose:

Symptoms: marrow aplasia, peripheral neuropathy, mukozita.
Treatment: symptomatic. The antidote to a paklitaksel is not known.

Storage conditions:

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

Issue conditions:

According to the recipe

Packaging:

Concentrate for preparation of solution for infusions, 6 mg/ml. On 5, 16,7, 41,7 or 50 ml in the colourless glass bottles corked by rubber bungs and which are pressed out by aluminum caps with safety plastic lids (gray color for bottles on 5 ml, red — on 16,7 ml, violet — on 41,7 ml and green — on 50 ml).

On 1 bottle place in a pack cardboard.

On 1 bottle (16,7, 41,7 or 50 ml) in a blister strip packaging place in a pack cardboard.