BETABIOFERON-1b

General characteristics. Structure:

Active ingredient: 1 ampoule contains 0.3 mg (9 600 000 MO) of recombinant interferon a beta of-1 b;

1 ml of solution contains 0.25 mg (8 000 000) of recombinant interferon a beta – 1 b;

excipients: glucose monohydrate, albumine of human 20%.

Physics – chemical properties: the lyophilized  powder from white till beige color, free from alien particles.

Pharmacological properties:

Pharmacodynamics. Owns the antiviral and immunoregulating  activity. Activity of interferon a beta – 1b is species-specific. Mechanisms of effect of interferon a beta – 1b at multiple sclerosis are not finalized. However it is known that the biological effect of Interferon a beta – 1b is caused by its interaction with the specific receptors revealed on a surface of cells of the person. Interferon binding the beta – 1b with these receptors induces an expression of a number of substances which are considered as mediators of biological effects of interferon a beta - 1b. Interferon the beta – 1b reduces the connecting ability and an expression of receptors to interferon scale, strengthens their disintegration. Besides, interferon the beta – 1b increases suppressor activity of mononuklearny cells of peripheral  blood. Use of drug at multiple sclerosis with repeatedly progressing current allows to detain further progressing of a disease and approach of disability, including heavy, for up to 12 months. This effect is observed at patients both with exacerbations of diseases, and without them, and also with any degree of an invalidism. Both at remitiruyushchy, and at repeatedly progressing multiple sclerosis, treatment by drug reduces frequency (to 30%) and weight of exacerbations of a disease, number of hospitalization and the need for treatment of GKS, and also extends remission duration.

By results of a magnetic and resonant tomography of a brain at patients with the remitiruyushchy  and repeatedly progressing multiple sclerosis against the background of treatment with drug established its considerable positive influence which is expressed  in reduction of weight of pathological process, and also considerable reduction of formation of the new active centers.

Pharmacokinetics. After hypodermic introduction in a dose of 8 000 MO of concentration of interferon beta 1b in blood low or are not defined in general. After hypodermic introduction in a dose of 16 000 MO the maximum level in a blood plasma makes about 40 ME/ml in 1-8 h after introduction. Absolute биодоступнисть at hypodermic introduction makes about 50%. At intravenous administration of interferon beta 1b the clearance and an elimination half-life of drug average 30 ml/min. and 5 h respectively. Administration of drug every other day does not lead to increase in its level in a blood plasma, and its pharmacokinetics throughout a therapy course, obviously, does not change. At hypodermic introduction in a dose of 8 000 ME every other day at healthy volunteers levels of markers of the biological answer (neopterine, β2-микроглобулина and immunoresupresivny IL-10 cytokine) considerably increased in comparison with initial indicators in 6-12 h after  introduction of the first dose of drug, reached a maximum in 40-124 h and remained raised throughout  7-day (168 h) the observation period. Communication between levels in a blood plasma of interferon beta 1b or levels of the markers induced by it and the mechanism of effect of drug at multiple sclerosis is not established.

Indications to use:

Multiple sclerosis with a recurrent remitiruyushchim current type which is characterized not less than two aggravations within 3 previous years and lack of signs of its continuous progressing current between a recurrence.

Route of administration and doses:

8 000 000 ME of the prepared solution are entered subcutaneously, every other day. For receiving solution of drug with Betabioferonom-1b enter 1,2 ml of solvent into an ampoule (0,54% chloride sodium solution). Powder has to  be dissolved entirely without stirring; before use it is necessary to examine ready solution. In the presence of particles or discoloration solution cannot be applied. At present there is unresolved a therapy duration question. In controlled clinical trial the effect of treatment remained for all 3 years of observations.

Features of use:

Patients should be informed that  the depression and suicide thoughts with the advent of which it is necessary to see a doctor immediately can be side effects of Betabioferona-1b. In rare instances these states can lead to suicide attempts. In the presence of a depression and suicide thoughts it is necessary to stop treatment immediately. At patients with a depression, at persons in whose anamnesis there is an instruction on a depression or spasms and also at patients who receive antiepileptic  means, Betabioferon-1b it is necessary to apply with care. Drug should be used with care at patients with heart diseases , in particular, at patients with heart failure ІІІ - the IV functional class on classification of NÝHA, at patients with cardiomyopathies. If communication of a cardiomyopathy which developed in the course of treatment, using Betabioferona-1b is supposed, drug should be cancelled.

At treatment of Betabioferonom-1b   serious reactions of hypersensitivity (an anaphylaxis, a bronchospasm, a small tortoiseshell) in rare instances can develop. To purpose of Betabioferona-1b and against the background of treatment it is necessary to carry out regularly developed blood test, including definitions of a leukocytic formula, and also to define activity of ASAT, ALAT and γ-glutamiltransferaza. In case of increase in activity of transaminases in blood serum it is necessary to make careful observation and inspection of the patient. Drug needs to be cancelled at substantial increase of activity of liver   enzymes or emergence of symptoms of hepatitis. In the absence of clinical signs of injury of a liver, after normalization of activity of liver enzymes it is possible to try to recover therapy under careful control of function of a liver.  There are no clinical data on use of Betabioferona-1b for patients with the broken function of a liver or kidneys. In isolated cases the pancreatitis which is often caused by a gipertriglitseridemiya was observed. In clinical trials at 41% of patients with remitiruyushchy  multiple sclerosis emergence of serumal neutralized antibodies to interferon beta 1b was noted (two consecutive caption ≥ 20). In a research at patients with  repeatedly progressing multiple sclerosis emergence of neutralized antibodies is revealed in 28% of cases. Influence of antibody formation on clinical performance of Betabioferona-1b is studied at present. The available results are contradictory and do not allow to draw an unambiguous conclusion. Signs of negative influence of neutralized antibodies on disease at for the second time the progressing multiple sclerosis are not revealed. In vitro is established that neutralized antibodies against recombinant interferon beta 1b interact also with natural interferon a beta, though to a lesser extent. In vivo this effect was not studied therefore its clinical value is unknown.

Information about patients which completed therapy of Betabioferonom-1b despite emergence of neutralized antibodies, is not numerous and unconvincing. At patients who received Betabioferon-1b necrosis cases in the place of an injection are described. With the advent of the multiple or big centers of a necrosis treatment of Betabioferonom-1b should be stopped before their full healing. Sometimes special treatment which can continue up to 6 months is necessary. In the presence of one center and lack of a big necrosis treatment of Betabioferonom-1b can be continued. To reduce risk of development of a necrosis in the place of an injection, it is necessary to follow strictly rules of an asepsis when performing injections, and also to constantly change places of an injection. It is necessary to adhere to care at treatment of Betabioferonom-1b at patients with a miyelosupressiya, anemia or thrombocytopenia.

Use of cytokines for patients with a monoclonal gammapathy sometimes was followed by system increase in permeability of capillaries with shocklike  symptoms and a lethal outcome. It is unknown whether Betabioferon-1b is capable to cause damage of a fruit at treatment of women during pregnancy or and to influence reproductive function of the person. In controlled clinical trials at patients with multiple sclerosis misbirth cases were noted. So, Betabioferon-1b is contraindicated during pregnancy. Women of reproductive age at treatment by this drug should use reliable methods of contraception.

In case of approach of pregnancy during treatment of Betabioferonom-1b or pregnancy planning the woman should be informed on potential risk and to recommend the treatment termination. It is unknown whether interferon beta 1b with breast milk ekstretirutsya. Considering potentiality of development of serious undesirable reactions to Betabioferon-1b in children of chest age, it is necessary to stop feeding  by a breast or to cancel drug. The side effects from TsNS caused by use of Betabioferona-1b at sensitive persons can affect ability to management  of transport and to work with potentially dangerous mechanisms. Efficiency and safety of use of Betabioferona-1b for children and teenagers up to 18 years were not studied, in this regard patients of this age group should not appoint drug.

Side effects:

The leukopenia, lymphopenia, neutropenia, anemia, thrombocytopenia are possible. The expressed thrombocytopenia, the message on development of a cardiomyopathy was in rare instances noted; pain behind a breast, tachycardia or palpitation. In rare instances against the background of treatment of Betabioferonom-1b were noted dysfunction of a thyroid gland (a hyperthyroidism, and also a hypothyroidism). Nausea and vomiting are possible. In isolated cases pancreatitis was observed.

Grippopodobny symptoms (fever, fever, mialgiya, febricula, perspiration). There can be heavy reactions of hypersensitivity (such reactions as a bronchospasm, an anaphylaxis and urticaria are in rare instances observed). When using drug increase in activity Asat, Alat and γ-glutamiltransferaza can be observed; hepatitis cases are described. At treatment of Betabioferonom-1b the hypocalcemia and a hyperuricemia, in rare instances — a gipertriglitseridemiya, an asthma were in certain cases observed.

Depression, feeling of alarm, emotional lability, depersonalization, spasms, suicide tendencies and confusion of consciousness. Cases of increase in a muscle tone are known. Women at a menopause can have a disturbance of a menstrual cycle. Local reactions in the form of a hyperemia, hypostases, discoloration of skin, an inflammation, pain, hypersensitivity, a necrosis, a lymphadenopathy, increase in the ABP.

Interaction with other medicines:

Influence of Betabioferona-1b in a dose (8 000 000 MO) every other day on metabolism of medicinal substances at patients with multiple sclerosis it is not studied. At treatment of exacerbations of a disease at patients who received Betabioferon-1b, portability of corticosteroids or AKTG which applied courses up to 28 days was good.

Use of Betabioferona-1b along with other immunodepresant, except GKS, was not studied. Interferona reduce activity hepatic cytochrome of P450-dependent enzymes at the person and animals. It is necessary to adhere to care at purpose of Betabioferona-1b in a combination with medical supplies which have a narrow therapeutic index which clearance substantially depends on hepatic  system of P450 cytochrome (for example, antiepileptic means). It is also necessary to adhere to care at simultaneous use of any drugs which influence system of a krovoobrazovaniye.

Contraindications:

The pregnancy period, the feeding period a breast, reactions of hypersensitivity to natural or recombinant interferon a beta or human albumine in the anamnesis, heavy depressions and/or suicide attempts in the anamnesis. A liver disease in a decompensation phase, epilepsy in the absence of effect of treatment.

Overdose:

Cases of overdose are not described.

Storage conditions:

In the unavailable to children, dry, protected from light place, at a temperature from 2 °C to 8 °C. A period of storage of the prepared solution – till 3 o'clock at a temperature of 2 °C - 8 °C. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

The powder lyophilized  on 0.3 mg (9 600 000 ME) of antiviral activity in ampoules No. 10 complete with solvent (sodium chloride of 0,54%) on 2 ml in ampoules No. 10 in a pack with a corrugated partition or a polymeric insert from a film polyvinyl chloride.