Producer: CJSC Generium Russia
Code of automatic telephone exchange: B02BD02
Release form: Liquid dosage forms. Lyophilisate for preparation of solution for intravenous administration.
General characteristics. Structure:
Active ingredient: 250 ME, 500 ME, 1000 ME or 2000 ME мороктоког alpha.
Excipients: sodium chloride, sucrose, histidine, Calcii chloridum dihydrate, half-oxameasures 407.
1 bottle with solvent contains: chloride sodium solution of 0,9% for injections.
Pharmacodynamics. Active agent of drug - recombinant blood-coagulation factors of VIII with the remote B-domain (мороктоког an alpha), represents a glycoprotein with a molecular weight about 165 000 дальтон.
The recombinant blood-coagulation factors of VIII are produced by the modified intertwined line of cells of CHO 2H5 received by transfection of cells of ovaries of the Chinese hamster and allocated with use of technologies of recombinant DNA.
Recombinant blood-coagulation factors of VIII as well as endogenous, participates in the internal mechanism of a blood coagulation, forming in the presence of platelet phospholipids and the ionized calcium a complex with blood-coagulation factors of IX. This complex activates blood-coagulation factors of X. The last provides transformation of a prothrombin to thrombin which, in turn, turns fibrinogen into fibrin that leads to formation of a blood clot.
Мороктоког the alpha has similar pharmacological properties from one of forms of an internal cause of a blood coagulation VIII therefore it can be used for replacement therapy at deficit of a factor of coagulation of VIII at patients with hemophilia And for the purpose of reduction of expressiveness of a hemorrhagic syndrome.
Pharmacokinetics. In pharmacokinetic parameters the recombinant factor of VIII with the remote V-domain (мороктоког an alpha) is equivalent to a full-chained recombinant factor of VIII (to an oktokog an alpha) and to a plasma factor of VIII.
Level of activity of a factor VIII in plasma after Oktofaktor's introduction to earlier treated patients with hemophilia And makes 76-112%. Oktofaktor's activity in plasma decreases on a two-phase exponent. In an initial phase there is a distribution of drug from a vascular bed in other liquids of an organism to plasma elimination half-life from 3 to 6 h; from about 2/3 to 3/4 factors of VIII remain in a system blood-groove. In the subsequent slow phase (which probably reflects consumption of a factor of VIII) the elimination half-life averages 12,69 h, and the average time of deduction of Oktofaktor in an organism of 17 - 38 h. Average value of clearance corresponds to 2,94 dl/h.
Indications to use:
Treatment and prevention of bleedings at patients with hemophilia And (inborn insufficiency of blood-coagulation factors of VIII) at the age of 18 years are also more senior.
Note: drug Oktofaktor does not contain Villebrand's factor therefore it is not shown for treatment of an angiohemophilia.
Route of administration and doses:
Oktofaktor is entered intravenously struyno slowly within 5-10 minutes after lyophilisate cultivation by the enclosed solvent. The dose of blood-coagulation factors of VIII is measured in the international units (IU). 1 ME activities of a factor of coagulation of VIII it is equivalent to quantity of a factor of coagulation of VIII in 1 ml of a blood plasma of the healthy person. Activity of a factor of coagulation of VIII in a blood plasma is expressed as a percentage (rather normal values of a blood plasma of the person) or in ME per unit of volume (ME/dl). Calculation of a dose of blood-coagulation factors of VIII is based on empirically obtained data on the fact that 1 ME factors of the VIII/kg body weight are raised by activity of this factor in a blood plasma on average on 2 ME/dl that makes about 2% of normal activity.
The single dose of Oktofaktor is calculated by the following formula:
Necessary quantity of ME of a factor of VIII = Body weight (in kg) x Necessary increase in activity of a factor of VIII (% or ME/dl) x 0,5 (ME/kg on ME/dl),
where to size 0,5 (ME/kg on ME/dl) there corresponds the doubled increment of extent of recovery of activity, usually observable after introduction of a factor of VIII.
Owing to distinction of extent of recovery of activity of in vivo and an elimination half-life of drug, specific features of reaction of patients to treatment by recombinant blood-coagulation factors of VIII are possible.
During replacement therapy by drug Oktofaktor, and also extensive operative measures it is necessary to control activity of a factor of coagulation by VIII in a blood plasma laboratory methods.
At development of the hemorrhagic manifestations given in the table activity of a factor of VIII in a blood plasma should not fall below the specified levels (to % of norm or to ME/dl) during the corresponding span.
The table of calculation of doses of Oktofaktor at different types of bleedings and operative measures.
For long-term prevention of bleedings at the patients suffering from a severe form of hemophilia And, the average dose of drug makes 20-40 ME/kg with an introduction interval each 2-3 days. In some situations, for example, at patients of young age, reduction of intervals between introductions or increase in a dose of drug can be required.
Oktofaktor's use more than 1 time a day, as a rule, is not required.
Features of use:
At the patients receiving treatment by drugs of blood-coagulation factors VIII formation of active neutralized antibodies (inhibitors) relating to immunoglobulins G is sometimes possible. Clinically it can be shown in the form of the insufficient response to therapy. The caption of inhibitors is measured in Betezd's (BE) units on blood plasma ml. The analysis on availability of inhibitors to blood-coagulation factors of VIII is carried out at impossibility to reach the expected level of activity of blood-coagulation factors VIII or to stop bleeding at introduction of adequately calculated dose. With high concentration of inhibitors to blood-coagulation factors of VIII (> 10 BE) therapy by Oktofaktor can be inefficient. In this case increase in a dose of drug or performing the corresponding specific therapy can be required. The risk of products of inhibitors is maximum during the first 20 days of exposure of drug.
Intravenous administration of proteinaceous drugs including Oktofaktora, can be followed by hypersensitivity reaction development. At development of any allergic or anaphylactic reactions it is necessary to stop immediately Oktofaktor's introduction and to begin the corresponding treatment.
Researches at elderly people were not conducted. A drug dose at patients 55 years are more senior it is necessary to select individually.
Influence on ability to manage vehicles. Researches of influence of drug on ability to driving and work with the mechanisms demanding the increased concentration of attention were not conducted.
By results of preclinical trials, including toksikometrichesky and pathomorphologic, Oktofaktor belongs to the class of low-toxic medicines. Also absence at Oktofaktor of irritant action, mutagen and pyrogenic properties was established.
Use of a moroktokog an alpha in certain cases can be followed by development of a number of side effects of the following categories: very frequent (with a frequency of ≥1/10), frequent (with a frequency from ≥1/100 to <1/10) and infrequent (with a frequency from ≥1/1000 to <1/100). In each category of frequency side effects are given in an order of decrease in degree of their gravity.
System disturbances and complications in an injection site. Frequent: adynamy, fever. Infrequent: a fever, an inflammation in the place of an injection, reaction in the place of an injection, pain in the place of an injection.
Disturbances from blood and lymphatic system. Very frequent: products of inhibitors of blood-coagulation factors of VIII at the patients who were earlier not receiving blood-coagulation factors. Frequent: products of inhibitors of blood-coagulation factors of VIII at the patients who were earlier receiving blood-coagulation factors.
Disturbances of food and metabolism. Infrequent: anorexia.
Changes of laboratory indicators. Infrequent: increase in activity of aspartate aminotransferase, increase in activity of alaninaminotranspherase, increase in concentration of bilirubin, increase in activity of a kreatinfosfokinaza.
Surgeries and medical procedures. Frequent: complications from vascular access.
Against the background of treatment moroktokogy an alpha also messages on emergence of the following undesirable phenomena were received: paresthesias, fatigue, decrease in clearness of sight, acne, gastritis, gastroenteritis and pains.
Hypersensitivity and allergic reactions (possible manifestations which can be: a Quincke's disease, a burning sensation and tightening in the place of an injection, a fever, a hyperemia, urticaria, a headache, a lowering of arterial pressure, block, nausea, concern, tachycardia, feeling of a prelum in a thorax, feeling of a pricking, vomiting, goose breathing) were noted during treatment moroktokogy an alpha infrequently. In certain cases they can progress before development of a heavy anaphylaxis, including shock.
Interaction with other medicines:
The research of medicinal interaction was not conducted.
Hypersensitivity to proteins of hamsters, and also intolerance of any of the components which are a part of drug. The age is younger than 18 years (experience of use is absent).
Cases of overdose are not described.
Period of validity: drug – 2 years, solvent – 3 years. Not to use after the term specified on packaging. To store in the place protected from light, at a temperature from 2 to 8 °C. Not to freeze. Storage of drug in original packaging at a temperature not above 25 °C no more than 24 watch is allowed. To store in the places unavailable to children.
According to the recipe
Lyophilisate for preparation of solution for intravenous administration on 250 ME, 500 ME, 1000 ME or 2000 ME in the glass bottles corked by rubber bungs with a running in caps aluminum-plastic with control of the first opening. On 5 ml of solvent (chloride sodium solution of 0,9% for injections) in the glass bottles corked by rubber bungs with a running in caps aluminum-plastic with control of the first opening. 1 bottle with drug and 1 bottle with solvent in a blister strip packaging from a film polyvinyl chloride or polietilentereftalatny. 1 blister strip packaging complete with account medical materials: the syringe without needle, 2 needles for cultivation, the filter injection, a catheter for peripheral veins, the plaster fixing a napkin sorption sterile, 2 napkins spirit and the application instruction in a pack from a cardboard. Each component of account medical materials is placed in sterile one-time packaging from a film polyvinyl chloride and the paper laminated. On joints of a cover and a bottom with front and back sides of a pack paste self-adhesive labels for control of the first opening.